A Phase II Study of M2951 in SLE

• ClinicalTrials.gov Identifier: NCT02975336
• Recruitment Status: Terminated
• First Posted: November 29, 2016
• Results First Posted: December 17, 2020
• Last Update Posted: April 12, 2021
• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborator: Merck KGaA, Darmstadt, Germany
• Information provided by (Responsible Party): EMD Serono ( EMD Serono Research & Development Institute, Inc. )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus
• Interventions: Drug: Placebo; Drug: M2951
• Enrollment: 469

Participant Flow

Recruitment Details	A total of 1053 participants with Systemic Lupus Erythematosus (SLE) were screened. Out of which 469 participants were randomized in ratio of 1:1:1:1 to 1 of 4 treatment groups: Placebo; M2951 25mg QD, M2951 75 mg QD and M2951 50 mg BID. 283 out of 348 participants that completed Double-Blind Placebo-Controlled (DBPC) period, entered the Long-Term Extension (LTE) period of study.
Pre-assignment Details

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID	LTE: Placebo/ M2951 50 mg BID	LTE Period: M2951 25 mg QD/ M2951 50 mg BID	LTE Period: M2951 75 mg QD/ M2951 50 mg BID	LTE: M2951 50 mg BID/ M2951 50 mg BID
Arm/Group Description	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.	Participants who received Placebo in DBPC period were switched to receive 50 mg M2951 orally BID in LTE period for 104 weeks.	Participants who received 25 mg of M2951 orally QD in DBPC period were switched to receive 50 mg M2951 orally BID in LTE period for 104 weeks.	Participants who received 75 mg of M2951 orally QD in DBPC period were switched to receive 50 mg M2951 orally BID in LTE period for 104 weeks.	Participants who received 50 mg of M2951 orally BID in DBPC period continued to receive same dose of M2951 orally BID in LTE period for 104 weeks.
Period Title: DBPC (52 Weeks)
Started	117	118	117	117	0	0	0	0
Completed	85	89	90	84	0	0	0	0
Not Completed	32	29	27	33	0	0	0	0
Reason Not Completed
Adverse Event	16	17	13	18	0	0	0	0
Lost to Follow-up	2	1	2	4	0	0	0	0
Protocol Violation	4	1	3	1	0	0	0	0
Lack of Efficacy	4	4	2	3	0	0	0	0
Withdrawal by Subject	1	0	1	3	0	0	0	0
Premature termination of the study	5	6	6	4	0	0	0	0
Period Title: LTE (104 Weeks)
Started	0	0	0	0	62	69	80	72
Completed	0	0	0	0	0	0	0	0
Not Completed	0	0	0	0	62	69	80	72
Reason Not Completed
Adverse Event	0	0	0	0	7	4	2	0
Lost to Follow-up	0	0	0	0	0	1	0	0
Lack of Efficacy	0	0	0	0	0	1	2	0
Other	0	0	0	0	55	63	76	72

Baseline Characteristics

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID	Total
Arm/Group Description		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		117	118	117	117	469
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	117 participants	118 participants	117 participants	117 participants	469 participants
		40.2 (12.49)	38.8 (12.45)	41.5 (12.52)	42.2 (11.78)	40.7 (12.34)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	117 participants	118 participants	117 participants	117 participants	469 participants
	Female	110 94.0%	112 94.9%	111 94.9%	112 95.7%	445 94.9%
	Male	7 6.0%	6 5.1%	6 5.1%	5 4.3%	24 5.1%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	117 participants	118 participants	117 participants	117 participants	469 participants
	Hispanic or Latino	45 38.5%	51 43.2%	47 40.2%	42 35.9%	185 39.4%
	Not Hispanic or Latino	72 61.5%	67 56.8%	70 59.8%	75 64.1%	284 60.6%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	117 participants	118 participants	117 participants	117 participants	469 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	23 19.7%	17 14.4%	21 17.9%	13 11.1%	74 15.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	10 8.5%	12 10.2%	11 9.4%	12 10.3%	45 9.6%
	White	66 56.4%	73 61.9%	68 58.1%	83 70.9%	290 61.8%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	18 15.4%	16 13.6%	17 14.5%	9 7.7%	60 12.8%

Outcome Measures

1. Primary Outcome

Title	DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 52
Description	SRI-4 response was defined as greater than or equal to (>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score, no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and no treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to Systemic Lupus Erythematosus (SLE) divided into 9 organ systems. For each organ system A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The modified Intent To Treat (mITT) analysis set included all randomized participants who had received at least one dose of Investigational Medicinal Product (IMP) [Evobrutinib or placebo] and have at least one Baseline and one post Baseline disease assessment (among the following: Systemic Lupus Erythematosus Disease Activity Index flare index [SFI], SLEDAI 2K, PGA, BILAG 2004, Cutaneous Lupus Erythematosus Disease Area and Severity Index [CLASI]).

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	114	115	116	114
Measure Type: Count of Participants; Unit of Measure: Participants
	52 45.6%	64 55.7%	60 51.7%	55 48.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5462
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95%; 0.91 to 2.64
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5462
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95%; 0.76 to 2.18
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5462
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.93
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6) at Week 52
Description	SRI-6 response was defined as >= 6-point reduction in SLEDAI-2K total score, no new BILAG A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system :A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "overall number of participants analyzed" signifies those participants who achieved SLEDAI-2K total score >= 10 at screening (High Disease Activity [HDA] participants).

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	56	54	65	55
Measure Type: Count of Participants; Unit of Measure: Participants
	22 39.3%	27 50.0%	30 46.2%	24 43.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5462
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.50
	Confidence Interval	(2-Sided) 95%; 0.69 to 3.24
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5462
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.42
	Confidence Interval	(2-Sided) 95%; 0.68 to 2.97
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5462
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.27
	Confidence Interval	(2-Sided) 95%; 0.59 to 2.75
	Estimation Comments	[Not Specified]

3. Primary Outcome

Title	DBPC Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Description	Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: events between first dose of study drug that were absent before treatment/that worsened relative to pre-treatment state up to 56 weeks. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs and serious TEAEs were reported.
Time Frame	Baseline up to Week 56

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo).

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	117	118	117	117
Measure Type: Count of Participants; Unit of Measure: Participants
Any TEAEs	96 82.1%	103 87.3%	100 85.5%	99 84.6%
Any serious TEAE	10 8.5%	13 11.0%	11 9.4%	9 7.7%

4. Primary Outcome

Title	DBPC Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Description	Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs by severity were reported.
Time Frame	Baseline up to Week 56

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo).

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	117	118	117	117
Measure Type: Count of Participants; Unit of Measure: Participants
Grade 1	76 65.0%	80 67.8%	79 67.5%	76 65.0%
Grade 2	63 53.8%	77 65.3%	72 61.5%	78 66.7%
Grade 3	24 20.5%	29 24.6%	24 20.5%	21 17.9%
Grade 4	1 0.9%	1 0.8%	0 0.0%	2 1.7%
Grade 5	0 0.0%	1 0.8%	1 0.9%	0 0.0%

5. Primary Outcome

Title	DBPC Period: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Description	Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, respiratory rate, weight and height. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.
Time Frame	Baseline up to Week 56

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo).

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	117	118	117	117
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	0 0.0%	0 0.0%

6. Primary Outcome

Title	DBPC Period: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
Description	12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.
Time Frame	Baseline up to Week 56

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo).

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	117	118	117	117
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	0 0.0%	0 0.0%

7. Primary Outcome

Title	DBPC Period: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Description	Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.
Time Frame	Baseline up to Week 56

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo).

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	117	118	117	117
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	0 0.0%	0 0.0%

8. Primary Outcome

Title	DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 2.
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	114	116	115	113
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG	14.56 (5.367)	13.75 (4.652)	14.37 (5.536)	12.81 (3.847)
IgA	2.62 (1.207)	2.75 (1.374)	2.78 (1.328)	2.66 (1.137)
IgM	1.12 (0.662)	1.22 (0.890)	1.09 (0.697)	1.18 (0.776)

9. Primary Outcome

Title	DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 4
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 4.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	114	114	114	115
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG	14.92 (5.497)	13.60 (4.590)	14.21 (4.828)	12.73 (3.771)
IgA	2.71 (1.284)	2.73 (1.349)	2.82 (1.293)	2.64 (1.109)
IgM	1.12 (0.699)	1.18 (0.824)	1.06 (0.676)	1.16 (0.745)

10. Primary Outcome

Title	DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 12
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 12.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	110	106	110	105
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG:	14.91 (5.312)	12.92 (4.332)	13.64 (4.035)	12.38 (3.520)
IgA	2.72 (1.321)	2.73 (1.340)	2.88 (1.363)	2.68 (1.021)
IgM	1.11 (0.683)	1.05 (0.700)	0.95 (0.610)	1.02 (0.695)

11. Primary Outcome

Title	DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 24
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 24.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	96	97	101	96
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG	15.01 (5.190)	13.75 (4.783)	13.79 (4.165)	12.86 (3.725)
IgA	2.79 (1.430)	2.89 (1.460)	2.98 (1.391)	2.78 (1.091)
IgM	1.07 (0.609)	1.01 (0.686)	0.89 (0.583)	0.98 (0.656)

12. Primary Outcome

Title	DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 36
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 36.
Time Frame	Week 36

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	92	91	97	86
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG	14.81 (5.217)	13.54 (4.242)	13.67 (3.934)	12.65 (3.480)
IgA	2.72 (1.378)	2.89 (1.418)	3.01 (1.420)	2.86 (1.073)
IgM	1.06 (0.630)	1.01 (0.669)	0.85 (0.541)	0.95 (0.656)

13. Primary Outcome

Title	DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 52
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 52
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed		78	83	85	76
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG	Number Analyzed	78 participants	83 participants	85 participants	76 participants
		15.21 (5.105)	13.90 (4.087)	14.32 (4.542)	13.01 (3.723)
IgA	Number Analyzed	78 participants	83 participants	85 participants	76 participants
		2.82 (1.438)	2.95 (1.596)	3.17 (1.596)	2.95 (1.159)
IgM	Number Analyzed	78 participants	83 participants	84 participants	76 participants
		1.08 (0.624)	0.94 (0.645)	0.82 (0.487)	0.96 (0.670)

14. Primary Outcome

Title	DBPC Period: Mean Absolute Value of Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 56
Description	Mean absolute value of serum levels of IgG, IgA, IgM were assessed at Week 56
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	37	36	31	33
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG	14.82 (5.504)	14.25 (4.435)	14.25 (4.626)	13.12 (4.507)
IgA	2.95 (1.549)	3.01 (1.459)	2.89 (1.655)	3.03 (1.164)
IgM	1.11 (0.642)	1.01 (0.601)	0.95 (0.624)	1.31 (0.869)

15. Primary Outcome

Title	DBPC Period: Mean Absolute Total B Cell Count at Week 4
Description	Mean total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence activated cell sorting was performed for the analysis of B cell counts.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	98	99	99	99
Mean (Standard Deviation); Unit of Measure: Cells per microliter
	150 (126.9)	236 (197.4)	296 (243.8)	229 (232.9)

16. Primary Outcome

Title	DBPC Period: Mean Absolute Total B Cell Count at Week 24
Description	Mean absolute total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence activated cell sorting was performed for the analysis of B cell counts.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	89	90	87	88
Mean (Standard Deviation); Unit of Measure: Cells per microliter
	161 (125.8)	184 (152.6)	204 (158.3)	151 (129.2)

17. Primary Outcome

Title	DBPC Period: Mean Absolute Total B Cell Count at Week 52
Description	Mean absolute total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence activated cell sorting was performed for the analysis of B cell counts.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	68	66	76	66
Mean (Standard Deviation); Unit of Measure: Cells per microliter
	169 (121.9)	167 (168.7)	180 (170.7)	119 (84.1)

18. Primary Outcome

Title	DBPC Period: Mean Absolute Total B Cell Count at Week 56
Description	Mean absolute total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence activated cell sorting was performed for the analysis of B cell counts.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	35	30	27	30
Mean (Standard Deviation); Unit of Measure: Cells per microliter
	164 (113.3)	129 (100.0)	156 (127.1)	104 (71.9)

19. Primary Outcome

Title	DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 2

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	114	116	115	113
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG	-0.51 (1.726)	-0.06 (1.361)	-0.15 (1.772)	-0.40 (1.025)
IgA	-0.11 (0.435)	-0.04 (0.431)	-0.01 (0.381)	-0.03 (0.268)
IgM	0.00 (0.197)	-0.05 (0.194)	-0.04 (0.155)	-0.07 (0.116)

20. Primary Outcome

Title	DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 4
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	114	114	114	115
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG	-0.26 (1.760)	-0.16 (1.463)	-0.24 (1.657)	-0.45 (1.150)
IgA	-0.01 (0.205)	-0.04 (0.334)	0.03 (0.447)	-0.03 (0.301)
IgM	0.01 (0.195)	-0.09 (0.175)	-0.07 (0.192)	-0.08 (0.159)

21. Primary Outcome

Title	DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 12
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	110	106	110	105
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG	-0.36 (2.073)	-0.62 (1.827)	-0.72 (2.552)	-0.93 (1.640)
IgA	0.00 (0.325)	-0.02 (0.360)	0.06 (0.518)	-0.03 (0.340)
IgM	-0.01 (0.194)	-0.20 (0.301)	-0.18 (0.277)	-0.20 (0.250)

22. Primary Outcome

Title	DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 24
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	96	97	101	96
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG	-0.21 (2.318)	0.11 (2.234)	-0.46 (2.912)	-0.57 (2.363)
IgA	0.06 (0.332)	0.14 (0.390)	0.19 (0.565)	0.04 (0.563)
IgM	-0.01 (0.264)	-0.23 (0.369)	-0.23 (0.321)	-0.25 (0.346)

23. Primary Outcome

Title	DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 36
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 36

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	92	91	97	86
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG	-0.15 (2.130)	0.02 (2.487)	-0.43 (2.572)	-0.69 (2.189)
IgA	-0.02 (0.361)	0.22 (0.453)	0.24 (0.583)	0.08 (0.459)
IgM	-0.04 (0.255)	-0.25 (0.416)	-0.25 (0.284)	-0.28 (0.392)

24. Primary Outcome

Title	DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 52
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed		78	83	85	76
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG	Number Analyzed	78 participants	83 participants	85 participants	76 participants
		0.41 (2.898)	0.29 (2.361)	0.35 (2.688)	-0.31 (2.344)
IgA	Number Analyzed	78 participants	83 participants	85 participants	76 participants
		0.19 (0.420)	0.32 (0.492)	0.39 (0.767)	0.18 (0.469)
IgM	Number Analyzed	78 participants	83 participants	84 participants	76 participants
		-0.02 (0.235)	-0.25 (0.303)	-0.21 (0.318)	-0.33 (0.456)

25. Primary Outcome

Title	DBPC Period: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 56
Description	Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Time Frame	Baseline and Week 56

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	37	36	31	33
Mean (Standard Deviation); Unit of Measure: gram per liter (g/L)
IgG	0.74 (2.907)	1.06 (2.607)	0.74 (1.987)	-0.40 (2.823)
IgA	0.23 (0.468)	0.48 (0.600)	0.35 (0.488)	0.26 (0.498)
IgM	0.01 (0.266)	-0.15 (0.219)	-0.11 (0.225)	-0.21 (0.488)

26. Primary Outcome

Title	DBPC Period: Change From Baseline in Total B Cell Count at Week 4
Description	Change from baseline in Total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	90	88	88	91
Mean (Standard Deviation); Unit of Measure: Cells per microliter
	-5 (93.7)	65 (146.6)	87 (146.2)	67 (109.1)

27. Primary Outcome

Title	DBPC Period: Change From Baseline in Total B Cell Count at Week 24
Description	Change from baseline in Total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	80	82	73	81
Mean (Standard Deviation); Unit of Measure: Cells per microliter
	2 (98.1)	5 (112.0)	3 (103.2)	-7 (134.7)

28. Primary Outcome

Title	DBPC Period: Change From Baseline in Total B Cell Count at Week 52
Description	Change from baseline in Total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	57	60	63	60
Mean (Standard Deviation); Unit of Measure: Cells per microliter
	-14 (103.0)	-19 (133.3)	-14 (147.5)	-52 (215.7)

29. Primary Outcome

Title	DBPC Period: Change From Baseline in Total B Cell Count at Week 56
Description	Change from baseline in Total B cell count were assessed. Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
Time Frame	Baseline and Week 56

Outcome Measure Data

Analysis Population Description

The Safety analysis set included all participants who received at least 1 dose of IMP (Evobrutinib or Placebo). Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	30	27	24	24
Mean (Standard Deviation); Unit of Measure: Cells per microliter
	7 (96.2)	-70 (138.2)	-75 (192.1)	-48 (85.8)

30. Secondary Outcome

Title	DBPC Period: Time to First Severe British Isles Lupus Assessment Group (BILAG) A Flare
Description	BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. BILAG evaluated by scoring each of a list of signs and symptoms as: improving (1); same (2); worse (3); new (4); not present (0); not done (ND). Total BILAG score is sum of scores of 9 domains where A=12, B=8, C=1, D=0, and E=0. Total score ranges from 0 to 108 with a higher score indicating greater lupus activity. Time to first severe flare, where a severe flare is defined as at least one BILAG A (Severe disease activity) score in any organ system due to items that are new or worse, compared to the BILAG evaluation at the previous visit, during the 52-Week Treatment. It was measured using Kaplan-Meier (KM) estimates.
Time Frame	Baseline up to Week 56

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	14	16	11	12
Median (Full Range); Unit of Measure: Days
	NA [1]; (29.0 to 337.0)	NA [1]; (29.0 to 367.0)	NA [1]; (29.0 to 225.0)	NA [1]; (28.0 to 162.0)

[1]

NA indicated that median was not reached as the number of participants with events were too low in respect to number of participants censored to estimate the value.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7034
	Comments	[Not Specified]
	Method	Cox proportional hazards model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 0.57 to 2.40
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5462
	Comments	[Not Specified]
	Method	Cox proportional hazards model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.31 to 1.52
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5462
	Comments	[Not Specified]
	Method	Cox proportional hazards model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.42 to 1.97
	Estimation Comments	[Not Specified]

31. Secondary Outcome

Title	DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 52 in Serologically Active (SA) Subgroup
Description	SRI-4 response was defined as greater than or equal to (>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score, no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and no treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to Systemic Lupus Erythematosus (SLE), divided into 9 organ systems. For each organ system A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants with positive anti-double-stranded deoxyribonucleic acid (antidsDNA) and/or low complement levels at screening (Serologically active subgroup).

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	59	65	60	63
Measure Type: Count of Participants; Unit of Measure: Participants
	28 47.5%	38 58.5%	29 48.3%	34 54.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5462
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.52
	Confidence Interval	(2-Sided) 95%; 0.74 to 3.15
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5462
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.49 to 2.13
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5462
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.35
	Confidence Interval	(2-Sided) 95%; 0.65 to 2.81
	Estimation Comments	[Not Specified]

32. Secondary Outcome

Title	DBPC Period: Number of Participants With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6) at Week 52 in Serologically Active Subgroup
Description	SRI-6 response was defined as >= 6-point reduction in SLEDAI-2K total score, no new BILAG A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system :A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale = from 0(very well) to 100(very poor).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants with positive anti-double-stranded deoxyribonucleic acid (antidsDNA) and/or low complement levels at screening (Serologically active subgroup).

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	59	65	60	63
Measure Type: Count of Participants; Unit of Measure: Participants
	17 28.8%	25 38.5%	23 38.3%	23 36.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2434
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.60
	Confidence Interval	(2-Sided) 95%; 0.73 to 3.54
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2389
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.62
	Confidence Interval	(2-Sided) 95%; 0.73 to 3.63
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1952
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.71
	Confidence Interval	(2-Sided) 95%; 0.76 to 3.85
	Estimation Comments	[Not Specified]

33. Secondary Outcome

Title	DBPC Period: Time to First British Isles Lupus Assessment Group (BILAG) A or 2B Moderate to Severe Flare
Description	BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. BILAG evaluated by scoring each of a list of signs and symptoms as: improving (1); same (2); worse (3); new (4); not present (0); not done (ND). Total BILAG score is sum of scores of 9 domains where A=12, B=8, C=1, D=0, and E=0. Total score ranges from 0 to 108 with a higher score indicating greater lupus activity. A Moderate to Severe (BILAG A or 2B) flare is defined as at least one BILAG A (severe disease activity) grade or two BILAG B (moderate disease activity) grade in any organ system due to items that are new or worse, compared to the BILAG evaluation at the previous visit, during the 52 week treatment. It was measured using Kaplan-Meier (KM) estimates.
Time Frame	Baseline up to Week 56

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	18	27	19	19
Median (Full Range); Unit of Measure: Days
	NA [1]; (29.0 to 337.0)	NA [1]; (27.0 to 365.0)	NA [1]; (29.0 to 308.0)	NA [1]; (28.0 to 334.0)

[1]

NA indicated that median was not reached as the number of participants with events were too low in respect to number of participants censored to estimate the value.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0987
	Comments	[Not Specified]
	Method	Cox proportional hazards model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95%; 0.87 to 2.89
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9201
	Comments	[Not Specified]
	Method	Cox proportional hazards model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.51 to 1.85
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5645
	Comments	[Not Specified]
	Method	Cox proportional hazards model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.60 to 2.20
	Estimation Comments	[Not Specified]

34. Secondary Outcome

Title	DBPC Period: Number of Participants With British Isles Lupus Assessment Group (BILAG) 2004 Flare-Free Status During the 52-Week Treatment Period
Description	A participant has a flare-free status if no flare has been reported during the 52-week treatment period. Participants who discontinued treatment prior to Week 52, without having a flare are counted as not being flare free at Week 52. A flare was defined as either 1 or more new BILAG-2004 A (severe disease activity) or 2 or more new BILAG-2004 B (moderate disease activity) items compared to the previous visit. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected.
Time Frame	up to Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	114	115	116	114
Measure Type: Count of Participants; Unit of Measure: Participants
	41 36.0%	35 30.4%	37 31.9%	33 28.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3743
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.44 to 1.37
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6445
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.50 to 1.54
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2634
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.41 to 1.28
	Estimation Comments	[Not Specified]

35. Secondary Outcome

Title	DBPC Period: Annualized Flare Rate
Description	A flare was defined as either 1 or more new BILAG-2004 A (severe disease activity) or 2 or more new BILAG-2004 B (moderate disease activity) items compared to the previous visit. The occurrence of a new flare was checked for each available visit versus the previous available visit up to Week 52. If no new flares occurred, the number of flares was set to 0. Otherwise all flares were counted leading to the maximum number of flares of 13. The annualized flare rate was calculated as the number of flares divided by the flare exposure time in days multiplied with 365.25 (1 year). The flare exposure time is the time up to Week 52 (date of BILAG-2004 assessment at Week 52) or up to the date of last available BILAG 2004 assessment.
Time Frame	Baseline up to Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	114	115	116	114
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Annualized flare rate ratio
	0.15; (0.06 to 0.39)	0.23; (0.09 to 0.59)	0.13; (0.05 to 0.33)	0.19; (0.07 to 0.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2989
	Comments	Nominal p-value
	Method	Negative binomial regression
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95%; 0.66 to 3.81
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7325
	Comments	Nominal p-value
	Method	Negative binomial regression
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.33 to 2.19
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5910
	Comments	Nominal p-value
	Method	Negative binomial regression
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95%; 0.51 to 3.22
	Estimation Comments	[Not Specified]

36. Secondary Outcome

Title	DBPC Period: Number of Participants With Low Disease Activity Status, Defined by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score of Less Than or Equal (<= ) 2 at Week 52
Description	Low disease activity is defined as SLEDAI-2K score <=2. SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms at the time of assessment or during the previous 30 days. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	114	115	116	114
Measure Type: Count of Participants; Unit of Measure: Participants
	26 22.8%	32 27.8%	39 33.6%	28 24.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3635
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95%; 0.72 to 2.47
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0329
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.94
	Confidence Interval	(2-Sided) 95%; 1.06 to 3.56
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7619
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.59 to 2.07
	Estimation Comments	[Not Specified]

37. Secondary Outcome

Title	DBPC Period: Number of Participants With Low Disease Activity Status, Defined by Clinical Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score of Less Than or Equal (<= ) 2 at Week 52
Description	Low disease activity is defined as SLEDAI-2K score <=2. SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms at the time of assessment or during the previous 30 days. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms). Clinical SLEDAI-2K score is equal to the SLEDAI-2K score from electronic case report form (eCRF) excluding the components 'Increased Deoxyribonucleic acid (DNA) Binding' and 'Low Complement'.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	114	115	116	114
Measure Type: Count of Participants; Unit of Measure: Participants
	42 36.8%	50 43.5%	52 44.8%	41 36.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2642
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 0.79 to 2.35
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1489
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.49
	Confidence Interval	(2-Sided) 95%; 0.87 to 2.57
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9285
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.56 to 1.70
	Estimation Comments	[Not Specified]

38. Secondary Outcome

Title	DBPC Period: Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Description	SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms at the time of assessment or during the previous 30 days. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).
Time Frame	Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and have at least 1 Baseline and 1 post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed		111	115	115	113
Mean (Standard Deviation); Unit of Measure: Units on a Scale
Week 4	Number Analyzed	111 participants	115 participants	115 participants	113 participants
		-1 (1.9)	-1 (2.1)	0 (1.9)	-1 (2.2)
Week 8	Number Analyzed	111 participants	111 participants	112 participants	109 participants
		-2 (3.1)	-2 (3.2)	-2 (3.0)	-2 (3.2)
Week 12	Number Analyzed	109 participants	106 participants	109 participants	104 participants
		-3 (3.8)	-3 (3.3)	-3 (3.2)	-3 (3.4)
Week 16	Number Analyzed	104 participants	102 participants	107 participants	98 participants
		-4 (3.7)	-3 (3.4)	-3 (3.4)	-3 (3.6)
Week 20	Number Analyzed	101 participants	99 participants	103 participants	96 participants
		-4 (4.1)	-4 (3.8)	-4 (3.4)	-4 (3.4)
Week 24	Number Analyzed	98 participants	95 participants	101 participants	94 participants
		-4 (4.0)	-4 (3.7)	-4 (3.6)	-3 (3.4)
Week 28	Number Analyzed	93 participants	94 participants	99 participants	89 participants
		-4 (3.9)	-4 (3.6)	-4 (3.5)	-4 (3.5)
Week 32	Number Analyzed	92 participants	91 participants	97 participants	88 participants
		-4 (4.0)	-4 (3.5)	-4 (3.7)	-4 (3.4)
Week 36	Number Analyzed	91 participants	90 participants	95 participants	113 participants
		-4 (4.3)	-5 (3.5)	-5 (3.6)	-4 (3.5)
Week 40	Number Analyzed	90 participants	90 participants	95 participants	87 participants
		-5 (4.1)	-5 (3.6)	-5 (3.8)	-4 (3.3)
Week 44	Number Analyzed	89 participants	90 participants	92 participants	86 participants
		-4 (4.0)	-5 (3.7)	-5 (3.9)	-4 (3.5)
Week 48	Number Analyzed	89 participants	90 participants	92 participants	85 participants
		-4 (4.1)	-5 (3.7)	-5 (3.8)	-5 (3.3)
Week 52	Number Analyzed	85 participants	89 participants	91 participants	84 participants
		-5 (4.0)	-5 (3.7)	-5 (3.7)	-5 (3.9)

39. Secondary Outcome

Title	DBPC Period: Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) Score at Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Description	CLASI is an validated measurement instrument for lupus erythematosus developed for use in clinical studies that consists of separate scores for the activity of the disease (CLASI-A). The CLASI activity score is calculated on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The CLASI activity score ranges from 0-70, with higher scores indicating more severe skin disease. Severity categories based on the CLASI activity score are as follows: mild (0-9), moderate (10-20), and severe (21-70).
Time Frame	Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and have at least 1 Baseline and 1 post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed		111	113	115	113
Mean (Standard Deviation); Unit of Measure: Units on a Scale
Week 2	Number Analyzed	110 participants	113 participants	113 participants	109 participants
		-1 (1.9)	-1 (1.6)	0 (1.6)	0 (1.2)
Week 4	Number Analyzed	111 participants	113 participants	115 participants	113 participants
		-1 (1.9)	-1 (3.5)	-1 (2.4)	-1 (2.2)
Week 8	Number Analyzed	110 participants	109 participants	110 participants	107 participants
		-2 (2.8)	-1 (4.2)	-1 (2.3)	-1 (2.5)
Week 12	Number Analyzed	107 participants	104 participants	107 participants	101 participants
		-2 (2.8)	-2 (3.3)	-2 (3.2)	-2 (2.7)
Week 16	Number Analyzed	104 participants	102 participants	107 participants	98 participants
		-2 (3.1)	-2 (3.9)	-2 (3.3)	-2 (2.7)
Week 20	Number Analyzed	99 participants	96 participants	102 participants	95 participants
		-3 (3.6)	-3 (4.4)	-3 (3.4)	-2 (2.9)
Week 24	Number Analyzed	97 participants	95 participants	100 participants	92 participants
		-3 (3.5)	-3 (4.7)	-3 (3.6)	-2 (2.7)
Week 28	Number Analyzed	92 participants	91 participants	96 participants	89 participants
		-3 (3.7)	-3 (4.6)	-3 (3.4)	-2 (2.7)
Week 32	Number Analyzed	91 participants	91 participants	96 participants	87 participants
		-3 (3.5)	-3 (4.4)	-3 (3.6)	-3 (3.2)
Week 36	Number Analyzed	90 participants	89 participants	95 participants	86 participants
		-3 (3.5)	-3 (4.6)	-3 (3.4)	-3 (3.6)
Week 40	Number Analyzed	90 participants	90 participants	92 participants	85 participants
		-3 (3.0)	-3 (4.6)	-3 (3.6)	-3 (3.8)
Week 44	Number Analyzed	89 participants	90 participants	92 participants	85 participants
		-3 (3.2)	-3 (4.5)	-3 (3.7)	-3 (3.8)
Week 48	Number Analyzed	88 participants	89 participants	91 participants	83 participants
		-3 (3.2)	-3 (4.7)	-3 (3.7)	-3 (3.9)
Week 52	Number Analyzed	84 participants	86 participants	89 participants	84 participants
		-3 (3.6)	-4 (4.8)	-3 (3.7)	-3 (4.0)

40. Secondary Outcome

Title	DBPC Period: Number of Participants With Response Based on BILAG-Based Composite Lupus Assessment (BICLA) at Week 52
Description	BICLA response defined as participants meeting following criteria: [1] At least one gradation of improvement in baseline BILAG scores in all body systems with moderate or severe disease activity at entry (example: all A (severe disease) scores falling to B (moderate), C (mild), or D (no activity) and all B scores falling to C or D; [2] No new BILAG A or more than one new BILAG B scores; [3] No worsening of total SLEDAI-2K score from baseline; [4] No significant deterioration (=<10%) in physician's global assessment and [5] No treatment failure (initiation of non-protocol treatment).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who have at least 1 BILAG A or 2 BILAG B grades at Baseline (BICLA Subpopulation).

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	76	73	76	70
Measure Type: Count of Participants; Unit of Measure: Participants
	30 39.5%	29 39.7%	33 43.4%	24 34.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9061
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.49 to 1.88
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6053
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.61 to 2.31
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5200
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.40 to 1.59
	Estimation Comments	[Not Specified]

41. Secondary Outcome

Title	DBPC Period: Change From Baseline in British Isles Lupus Assessment Group (BILAG)-2004 Score at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Description	BILAG 2004 disease activity Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. BILAG evaluated by scoring each of a list of signs and symptoms as: improving (1); same (2); worse (3); new (4); not present (0); not done (ND). Total BILAG score is sum of scores of 9 domains where A=12, B=8, C=1, D=0, and E=0. Total score ranges from 0 to 108 with a higher score indicating greater lupus activity.
Time Frame	Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and have at least 1 Baseline and 1 post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed		110	111	109	109
Mean (Standard Deviation); Unit of Measure: Units on a Scale
Week 4	Number Analyzed	108 participants	108 participants	108 participants	105 participants
		-4 (5.8)	-4 (6.1)	-3 (6.3)	-4 (6.2)
Week 8	Number Analyzed	110 participants	111 participants	109 participants	109 participants
		-6 (6.0)	-5 (7.0)	-6 (6.3)	-6 (6.1)
Week 12	Number Analyzed	109 participants	106 participants	107 participants	104 participants
		-7 (6.7)	-7 (6.8)	-6 (7.0)	-6 (6.2)
Week 16	Number Analyzed	104 participants	102 participants	105 participants	98 participants
		-7 (6.9)	-7 (7.6)	-6 (6.8)	-6 (5.9)
Week 20	Number Analyzed	101 participants	99 participants	102 participants	96 participants
		-7 (6.8)	-7 (7.3)	-7 (7.6)	-6 (6.2)
Week 24	Number Analyzed	97 participants	95 participants	100 participants	94 participants
		-8 (6.9)	-7 (6.5)	-8 (7.7)	-6 (6.3)
Week 28	Number Analyzed	93 participants	94 participants	98 participants	89 participants
		-8 (6.7)	-8 (6.9)	-8 (7.4)	-7 (6.2)
Week 32	Number Analyzed	92 participants	91 participants	96 participants	89 participants
		-9 (6.7)	-8 (7.3)	-8 (7.9)	-7 (6.0)
Week 36	Number Analyzed	91 participants	90 participants	95 participants	88 participants
		-8 (7.1)	-8 (7.2)	-8 (7.4)	-7 (6.7)
Week 40	Number Analyzed	88 participants	90 participants	95 participants	87 participants
		-9 (6.8)	-8 (6.7)	-9 (7.7)	-7 (6.6)
Week 44	Number Analyzed	88 participants	90 participants	92 participants	85 participants
		-9 (7.2)	-9 (7.2)	-9 (7.9)	-7 (6.7)
Week 48	Number Analyzed	89 participants	90 participants	92 participants	85 participants
		-8 (7.1)	-8 (7.2)	-9 (7.6)	-7 (6.5)
Week 52	Number Analyzed	85 participants	89 participants	91 participants	84 participants
		-8 (7.0)	-9 (6.8)	-9 (7.8)	-7 (6.7)

42. Secondary Outcome

Title	DBPC Period: Change From Baseline in Physician's Global Assessment (PGA) Score at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Description	The Physician's Global Assessment of Disease Activity was recorded using the 100 millimeter horizontal Visual Analog Scale (VAS). Physician rated participant's disease activity on a scale ranged from 0-100 millimeter (mm), where 0 indicated no disease activity and 100 represented maximum disease activity.
Time Frame	Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and have at least 1 Baseline and 1 post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed		111	115	115	113
Mean (Standard Deviation); Unit of Measure: Millimeter
Week 4	Number Analyzed	111 participants	115 participants	115 participants	113 participants
		-8 (11.7)	-8 (14.1)	-9 (13.4)	-9 (12.1)
Week 8	Number Analyzed	110 participants	109 participants	111 participants	107 participants
		-13 (16.2)	-14 (16.5)	-13 (15.5)	-14 (15.9)
Week 12	Number Analyzed	107 participants	104 participants	107 participants	101 participants
		-18 (17.4)	-18 (18.8)	-19 (18.3)	-18 (16.9)
Week 16	Number Analyzed	104 participants	102 participants	105 participants	98 participants
		-21 (17.6)	-20 (19.7)	-21 (18.7)	-19 (18.0)
Week 20	Number Analyzed	99 participants	96 participants	102 participants	95 participants
		-23 (19.2)	-21 (19.5)	-24 (17.9)	-20 (18.6)
Week 24	Number Analyzed	97 participants	95 participants	100 participants	92 participants
		-24 (17.8)	-24 (20.0)	-25 (19.2)	-21 (18.0)
Week 28	Number Analyzed	92 participants	91 participants	96 participants	89 participants
		-26 (17.6)	-26 (20.3)	-26 (18.6)	-24 (17.8)
Week 32	Number Analyzed	91 participants	91 participants	96 participants	87 participants
		-26 (17.8)	-26 (20.8)	-26 (19.0)	-26 (17.5)
Week 36	Number Analyzed	90 participants	89 participants	95 participants	86 participants
		-26 (17.9)	-26 (20.9)	-29 (18.3)	-26 (18.3)
Week 40	Number Analyzed	90 participants	90 participants	91 participants	85 participants
		-27 (16.9)	-27 (19.1)	-30 (19.7)	-25 (18.1)
Week 44	Number Analyzed	89 participants	90 participants	92 participants	85 participants
		-28 (16.6)	-28 (20.1)	-30 (20.7)	-26 (16.6)
Week 48	Number Analyzed	88 participants	89 participants	91 participants	83 participants
		-29 (16.5)	-29 (19.5)	-32 (18.8)	-28 (18.3)
Week 52	Number Analyzed	84 participants	86 participants	89 participants	84 participants
		-29 (16.2)	-31 (20.7)	-33 (19.2)	-27 (18.1)

43. Secondary Outcome

Title	DBPC Period: Change From Baseline in Study 36-Item Short Form Health Survey Version 2 (SF-36v2) Physical Component Summary Score and Mental Component Summary Scores at Week 4, 8, 12, 16, 24, 32, 40 and 52
Description	The 36-Item Short-Form Health Survey (SF-36) was a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) was based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0 - 100 (100 = highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100 = highest level of physical functioning).
Time Frame	Baseline, Week 4, 8, 12, 16, 24, 32, 40 and 52

Outcome Measure Data

Analysis Population Description

Quality of Life analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed		110	114	112	113
Mean (Standard Deviation); Unit of Measure: Units on a Scale
Physical Component Summary Score at Week 4	Number Analyzed	110 participants	114 participants	112 participants	113 participants
		1.2 (5.42)	2.5 (7.40)	3.5 (6.01)	2.2 (5.86)
Physical Component Summary Score at Week 8	Number Analyzed	107 participants	108 participants	109 participants	106 participants
		1.8 (6.35)	3.5 (7.69)	3.0 (6.61)	2.2 (6.63)
Physical Component Summary Score at Week 12	Number Analyzed	106 participants	102 participants	103 participants	101 participants
		2.4 (6.44)	3.7 (7.71)	4.2 (6.68)	3.0 (6.99)
Physical Component Summary Score at Week 16	Number Analyzed	101 participants	101 participants	105 participants	96 participants
		3.3 (7.04)	4.0 (7.56)	4.4 (5.81)	3.4 (6.77)
Physical Component Summary Score at Week 24	Number Analyzed	96 participants	95 participants	99 participants	95 participants
		3.4 (7.08)	4.6 (7.57)	5.4 (7.63)	2.8 (7.15)
Physical Component Summary Score at Week 32	Number Analyzed	90 participants	91 participants	93 participants	88 participants
		3.5 (8.03)	3.8 (7.36)	5.4 (7.24)	3.8 (6.89)
Physical Component Summary Score at Week 40	Number Analyzed	88 participants	89 participants	91 participants	86 participants
		4.2 (7.11)	4.6 (7.97)	5.7 (7.76)	4.1 (8.59)
Physical Component Summary Score at Week 52	Number Analyzed	86 participants	84 participants	87 participants	82 participants
		3.7 (8.32)	5.4 (7.05)	6.5 (8.58)	4.8 (7.76)
Mental Component Summary Score at Week 4	Number Analyzed	110 participants	114 participants	112 participants	113 participants
		3.9 (9.38)	1.7 (9.25)	1.9 (7.93)	2.4 (7.68)
Mental Component Summary Score at Week 8	Number Analyzed	107 participants	108 participants	109 participants	106 participants
		2.5 (8.59)	2.2 (8.81)	1.6 (8.48)	3.6 (9.04)
Mental Component Summary Score at Week 12	Number Analyzed	106 participants	102 participants	103 participants	101 participants
		3.1 (10.07)	3.1 (8.45)	0.8 (10.39)	2.9 (8.89)
Mental Component Summary Score at Week 16	Number Analyzed	101 participants	101 participants	105 participants	96 participants
		3.6 (9.84)	2.5 (8.39)	2.8 (9.39)	2.9 (9.13)
Mental Component Summary Score at Week 24	Number Analyzed	96 participants	95 participants	99 participants	95 participants
		2.9 (9.75)	2.4 (8.41)	3.4 (9.68)	2.7 (8.87)
Mental Component Summary Score at Week 32	Number Analyzed	90 participants	91 participants	93 participants	88 participants
		3.5 (8.55)	1.8 (9.51)	2.8 (9.71)	4.3 (9.03)
Mental Component Summary Score at Week 40	Number Analyzed	88 participants	89 participants	91 participants	86 participants
		4.5 (8.81)	1.5 (10.55)	3.2 (9.81)	4.0 (9.85)
Mental Component Summary Score at Week 52	Number Analyzed	86 participants	84 participants	87 participants	82 participants
		3.8 (9.45)	1.7 (9.91)	3.9 (11.21)	4.6 (9.80)

44. Secondary Outcome

Title	DBPC Period: Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire at Week 4, 8, 12, 16, 24, 32, 40 and 52
Description	The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L profile defines health in terms of mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each dimension has five levels: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, and 5: extreme problems. Responses were used to generate a weighted summary index (EQ-5D index), which ranges from 0 (dead) to 1.00 (perfect health). A higher score indicates better health and positive changes from baseline indicate improvement of health.
Time Frame	Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52

Outcome Measure Data

Analysis Population Description

Quality of Life analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed		110	114	112	113
Mean (Standard Deviation); Unit of Measure: Units on a Scale
Week 4	Number Analyzed	110 participants	114 participants	112 participants	113 participants
		0.036 (0.1626)	0.045 (0.1931)	0.036 (0.1618)	0.038 (0.1908)
Week 8	Number Analyzed	107 participants	108 participants	109 participants	106 participants
		0.034 (0.2164)	0.064 (0.2505)	0.046 (0.1842)	0.061 (0.1603)
Week 12	Number Analyzed	106 participants	102 participants	103 participants	101 participants
		0.061 (0.2014)	0.070 (0.2189)	0.055 (0.1912)	0.065 (0.1732)
Week 16	Number Analyzed	101 participants	101 participants	105 participants	96 participants
		0.083 (0.1818)	0.072 (0.2252)	0.067 (0.2287)	0.056 (0.1738)
Week 24	Number Analyzed	96 participants	95 participants	99 participants	95 participants
		0.080 (0.1901)	0.067 (0.2271)	0.086 (0.2110)	0.055 (0.1817)
Week 32	Number Analyzed	90 participants	91 participants	93 participants	88 participants
		0.083 (0.1758)	0.067 (0.2262)	0.075 (0.2009)	0.071 (0.1941)
Week 40	Number Analyzed	88 participants	89 participants	91 participants	86 participants
		0.093 (0.1521)	0.061 (0.1850)	0.090 (0.1853)	0.084 (0.2172)
Week 52	Number Analyzed	86 participants	84 participants	87 participants	82 participants
		0.096 (0.2092)	0.078 (0.2197)	0.102 (0.2224)	0.096 (0.2051)

45. Secondary Outcome

Title	DBPC Period: Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Visual Analog Scale (VAS) at Week 4, 8, 12, 16, 24, 32, 40 and 52
Description	The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L profile defines health in terms of mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each dimension has five levels: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, and 5: extreme problems. The responses were used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 was the worst health you can imagine and 100 was the best health you can imagine.
Time Frame	Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52

Outcome Measure Data

Analysis Population Description

Quality of Life analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed		110	114	112	113
Mean (Standard Deviation); Unit of Measure: Millimeter
Week 4	Number Analyzed	110 participants	114 participants	112 participants	113 participants
		3 (16.8)	2 (19.0)	4 (17.6)	4 (18.2)
Week 8	Number Analyzed	107 participants	108 participants	109 participants	106 participants
		3 (18.8)	6 (20.0)	4 (14.5)	6 (16.5)
Week 12	Number Analyzed	106 participants	102 participants	103 participants	101 participants
		5 (19.7)	6 (17.4)	5 (17.2)	4 (16.8)
Week 16	Number Analyzed	101 participants	101 participants	105 participants	96 participants
		7 (19.3)	5 (18.1)	6 (18.5)	4 (15.5)
Week 24	Number Analyzed	96 participants	95 participants	99 participants	95 participants
		7 (18.7)	5 (18.4)	9 (20.4)	4 (17.3)
Week 32	Number Analyzed	90 participants	91 participants	93 participants	88 participants
		8 (17.2)	4 (21.1)	7 (17.8)	7 (16.6)
Week 40	Number Analyzed	88 participants	89 participants	91 participants	86 participants
		8 (18.1)	6 (18.1)	10 (19.5)	8 (18.9)
Week 52	Number Analyzed	86 participants	84 participants	87 participants	82 participants
		8 (19.9)	8 (18.6)	10 (21.3)	10 (18.9)

46. Secondary Outcome

Title	DBPC Period: Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score at Week 4, 8, 12, 16, 24, 32, 40 and 52
Description	The Lupus QoL assessment is a 34 item questionnaire across 8 domains that is designed to find out how systemic lupus erythematosus (SLE) affects a participant's life. Domains include physical health, pain, planning, intimate relationships, burden to others, emotional health, body image, and fatigue. Participants indicate their responses on a 5-point Likert response format, where 4=never, 3=occasionally, 2= a good bit of the time, 1=most of the time, and 0=worst of the time. Summary scores can be calculated for all 8 domains. A LupusQoL score for each domain was reported on a 0 to 100 scale, with greater values indicating better health related QoL.
Time Frame	Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52

Outcome Measure Data

Analysis Population Description

Quality of Life analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed		110	114	112	113
Mean (Standard Deviation); Unit of Measure: Units on a scale
Physical Health Week 4	Number Analyzed	110 participants	114 participants	112 participants	113 participants
		1.9 (12.58)	4.7 (17.68)	4.0 (14.04)	3.5 (13.43)
Physical Health Week 8	Number Analyzed	107 participants	108 participants	109 participants	106 participants
		2.8 (15.20)	6.3 (19.94)	3.8 (17.64)	4.6 (14.69)
Physical Health Week 12	Number Analyzed	106 participants	102 participants	103 participants	101 participants
		4.8 (16.75)	6.7 (19.78)	5.6 (15.95)	5.7 (14.94)
Physical Health Week 16	Number Analyzed	101 participants	101 participants	105 participants	96 participants
		6.6 (17.45)	6.1 (18.71)	7.4 (17.61)	6.2 (15.59)
Physical Health Week 24	Number Analyzed	96 participants	95 participants	99 participants	95 participants
		6.9 (17.17)	7.2 (18.59)	8.4 (20.47)	6.1 (13.63)
Physical Health Week 32	Number Analyzed	90 participants	91 participants	93 participants	88 participants
		5.7 (16.82)	6.7 (19.45)	9.4 (17.21)	7.0 (16.21)
Physical Health Week 40	Number Analyzed	88 participants	89 participants	91 participants	86 participants
		7.6 (15.32)	8.2 (17.38)	9.6 (19.10)	7.1 (17.98)
Physical Health Week 52	Number Analyzed	86 participants	84 participants	87 participants	82 participants
		7.1 (20.39)	9.0 (18.44)	11.6 (19.88)	7.9 (18.73)
Pain Week 4	Number Analyzed	110 participants	114 participants	112 participants	113 participants
		3.6 (16.30)	6.7 (21.81)	9.0 (20.90)	5.7 (16.26)
Pain Week 8	Number Analyzed	107 participants	108 participants	109 participants	106 participants
		4.8 (18.71)	9.9 (24.65)	7.3 (21.76)	6.7 (18.31)
Pain Week 12	Number Analyzed	106 participants	102 participants	103 participants	101 participants
		7.5 (19.04)	8.8 (24.00)	9.8 (23.35)	5.5 (14.73)
Pain Week 16	Number Analyzed	101 participants	101 participants	105 participants	96 participants
		9.4 (18.58)	8.3 (25.60)	10.5 (26.33)	6.9 (15.47)
Pain Week 24	Number Analyzed	96 participants	95 participants	99 participants	95 participants
		9.4 (19.95)	9.3 (24.31)	13.0 (28.18)	6.2 (17.02)
Pain Week 32	Number Analyzed	90 participants	91 participants	93 participants	88 participants
		6.7 (23.74)	9.2 (24.60)	12.8 (22.87)	8.7 (17.18)
Pain Week 40	Number Analyzed	88 participants	89 participants	91 participants	86 participants
		11.0 (19.43)	10.9 (23.68)	15.3 (23.81)	9.6 (20.51)
Pain Week 52	Number Analyzed	86 participants	84 participants	87 participants	82 participants
		10.2 (21.37)	12.9 (22.64)	14.9 (26.11)	9.6 (19.99)
Planning Week 4	Number Analyzed	110 participants	114 participants	112 participants	113 participants
		4.8 (20.14)	4.9 (19.64)	5.4 (24.30)	4.6 (18.73)
Planning Week 8	Number Analyzed	107 participants	108 participants	109 participants	106 participants
		5.5 (23.32)	8.4 (23.25)	5.8 (25.14)	3.9 (22.98)
Planning Week 12	Number Analyzed	106 participants	102 participants	103 participants	101 participants
		7.8 (23.58)	5.8 (23.39)	6.8 (25.74)	5.1 (20.55)
Planning Week 16	Number Analyzed	101 participants	101 participants	105 participants	96 participants
		8.3 (21.65)	5.3 (24.12)	6.5 (28.00)	6.3 (22.91)
Planning Week 24	Number Analyzed	96 participants	95 participants	99 participants	95 participants
		7.9 (22.92)	8.1 (23.55)	11.5 (29.08)	5.6 (21.79)
Planning Week 32	Number Analyzed	90 participants	91 participants	93 participants	88 participants
		6.5 (24.82)	7.6 (22.66)	9.9 (25.90)	6.9 (22.07)
Planning Week 40	Number Analyzed	88 participants	89 participants	91 participants	86 participants
		9.0 (20.69)	7.8 (23.19)	11.6 (26.17)	8.0 (23.52)
Planning Week 52	Number Analyzed	86 participants	84 participants	87 participants	82 participants
		9.9 (22.38)	7.0 (23.12)	9.9 (28.29)	10.5 (21.59)
Intimate Relationship Week 4	Number Analyzed	74 participants	88 participants	80 participants	71 participants
		3.4 (26.11)	1.6 (28.29)	4.7 (24.06)	3.2 (24.06)
Intimate Relationship Week 8	Number Analyzed	70 participants	81 participants	75 participants	61 participants
		8.2 (30.31)	4.2 (28.44)	9.7 (29.10)	3.7 (18.73)
Intimate Relationship Week 12	Number Analyzed	70 participants	75 participants	65 participants	59 participants
		5.5 (27.31)	4.7 (25.65)	2.3 (30.37)	6.4 (21.32)
Intimate Relationship Week 16	Number Analyzed	60 participants	72 participants	69 participants	53 participants
		8.8 (26.77)	1.6 (30.76)	3.8 (32.46)	4.2 (22.99)
Intimate Relationship Week 24	Number Analyzed	59 participants	70 participants	62 participants	47 participants
		6.4 (30.12)	2.1 (28.79)	6.7 (30.76)	5.3 (26.29)
Intimate Relationship Week 32	Number Analyzed	54 participants	66 participants	54 participants	52 participants
		2.5 (28.77)	1.3 (31.78)	6.5 (29.41)	1.4 (27.86)
Intimate Relationship Week 40	Number Analyzed	49 participants	61 participants	55 participants	48 participants
		12.0 (27.59)	6.6 (27.91)	6.4 (32.53)	7.8 (22.72)
Intimate Relationship Week 52	Number Analyzed	51 participants	60 participants	49 participants	45 participants
		7.4 (26.48)	4.4 (28.36)	8.4 (29.58)	8.9 (24.52)
Burden to Others Week 4	Number Analyzed	110 participants	114 participants	112 participants	113 participants
		5.8 (23.83)	5.2 (22.84)	6.8 (24.85)	2.2 (24.24)
Burden to Others Week 8	Number Analyzed	107 participants	108 participants	109 participants	106 participants
		5.6 (22.42)	9.3 (27.17)	5.7 (25.80)	8.0 (25.79)
Burden to Others Week 12	Number Analyzed	106 participants	102 participants	103 participants	101 participants
		8.6 (25.86)	6.7 (28.00)	7.4 (25.93)	7.3 (24.74)
Burden to Others Week 16	Number Analyzed	101 participants	101 participants	105 participants	96 participants
		11.8 (26.17)	8.1 (23.32)	6.7 (25.80)	7.4 (24.30)
Burden to Others Week 24	Number Analyzed	96 participants	95 participants	99 participants	95 participants
		10.3 (28.68)	9.0 (24.12)	11.8 (27.15)	5.8 (26.21)
Burden to Others Week 32	Number Analyzed	90 participants	91 participants	93 participants	88 participants
		10.6 (29.42)	6.8 (24.09)	9.6 (27.14)	8.4 (28.21)
Burden to Others Week 40	Number Analyzed	88 participants	89 participants	91 participants	86 participants
		16.1 (25.07)	12.4 (21.91)	12.4 (28.74)	12.1 (25.78)
Burden to Others Week 52	Number Analyzed	86 participants	84 participants	87 participants	82 participants
		15.3 (26.96)	10.7 (22.13)	13.0 (30.04)	10.5 (25.89)
Emotional Health Week 4	Number Analyzed	110 participants	114 participants	112 participants	113 participants
		6.4 (15.37)	4.7 (18.48)	4.2 (18.45)	1.8 (16.73)
Emotional Health Week 8	Number Analyzed	107 participants	108 participants	109 participants	106 participants
		4.5 (15.15)	7.0 (19.26)	2.3 (19.51)	5.3 (15.53)
Emotional Health Week 12	Number Analyzed	106 participants	102 participants	103 participants	101 participants
		6.3 (17.23)	7.6 (21.08)	4.9 (20.99)	4.7 (16.39)
Emotional Health Week 16	Number Analyzed	101 participants	101 participants	105 participants	96 participants
		8.3 (15.86)	7.5 (19.59)	7.4 (18.56)	6.2 (18.32)
Emotional Health Week 24	Number Analyzed	96 participants	95 participants	99 participants	95 participants
		7.1 (17.31)	5.6 (24.02)	8.9 (20.97)	4.3 (20.04)
Emotional Health Week 32	Number Analyzed	90 participants	91 participants	93 participants	88 participants
		6.3 (17.07)	4.3 (23.55)	9.0 (22.66)	6.0 (20.56)
Emotional Health Week 40	Number Analyzed	88 participants	89 participants	91 participants	86 participants
		8.4 (16.08)	8.3 (19.94)	7.6 (21.52)	6.7 (19.14)
Emotional Health Week 52	Number Analyzed	86 participants	84 participants	87 participants	82 participants
		8.5 (17.43)	6.4 (21.31)	8.2 (22.77)	7.6 (18.80)
Body Image Week 4	Number Analyzed	96 participants	97 participants	92 participants	93 participants
		3.1 (17.70)	8.4 (24.41)	2.5 (24.60)	4.0 (18.79)
Body Image Week 8	Number Analyzed	90 participants	92 participants	91 participants	85 participants
		5.7 (18.37)	7.5 (23.40)	-1.3 (27.06)	6.5 (17.30)
Body Image Week 12	Number Analyzed	88 participants	84 participants	83 participants	85 participants
		6.5 (18.57)	7.1 (21.07)	2.3 (26.86)	6.6 (16.53)
Body Image Week 16	Number Analyzed	84 participants	82 participants	85 participants	81 participants
		6.7 (18.10)	7.6 (23.11)	-0.4 (25.31)	5.7 (20.39)
Body Image Week 24	Number Analyzed	75 participants	79 participants	75 participants	77 participants
		6.7 (20.84)	10.2 (20.47)	5.8 (27.31)	6.7 (21.80)
Body Image Week 32	Number Analyzed	71 participants	76 participants	68 participants	73 participants
		5.1 (20.08)	8.1 (23.71)	3.3 (24.99)	5.8 (21.54)
Body Image Week 40	Number Analyzed	71 participants	76 participants	66 participants	72 participants
		7.7 (14.11)	8.2 (23.99)	4.6 (26.67)	9.0 (18.31)
Body Image Week 52	Number Analyzed	74 participants	68 participants	66 participants	67 participants
		6.6 (16.92)	9.8 (21.46)	5.1 (27.30)	7.8 (21.56)
Fatigue Week 4	Number Analyzed	110 participants	114 participants	112 participants	113 participants
		4.4 (16.71)	4.3 (18.98)	6.2 (19.91)	3.9 (17.08)
Fatigue Week 8	Number Analyzed	107 participants	108 participants	109 participants	106 participants
		5.0 (19.22)	7.1 (21.31)	4.9 (20.61)	4.5 (16.78)
Fatigue Week 12	Number Analyzed	106 participants	102 participants	103 participants	101 participants
		6.7 (18.22)	5.8 (21.30)	7.3 (23.11)	5.0 (16.08)
Fatigue Week 16	Number Analyzed	101 participants	101 participants	105 participants	96 participants
		7.7 (17.61)	6.6 (21.39)	7.1 (24.16)	4.1 (15.81)
Fatigue Week 24	Number Analyzed	96 participants	95 participants	99 participants	95 participants
		7.5 (19.06)	4.8 (23.34)	9.0 (26.00)	3.6 (14.20)
Fatigue Week 32	Number Analyzed	90 participants	91 participants	93 participants	88 participants
		7.0 (19.20)	3.7 (22.71)	8.5 (22.96)	4.1 (17.24)
Fatigue Week 40	Number Analyzed	88 participants	89 participants	91 participants	86 participants
		11.3 (20.03)	6.1 (25.28)	11.0 (25.18)	5.3 (16.73)
Fatigue Week 52	Number Analyzed	86 participants	84 participants	87 participants	82 participants
		8.9 (21.15)	4.5 (24.78)	11.2 (22.56)	6.7 (17.89)

47. Secondary Outcome

Title	DBPC Period: Number of Participants With Patient Global Impression of Change (PGIC) Scale Score of Any Improvement, no Change and Any Worsening
Description	The PGIC is a self-rated scale that asks the participant to describe the change in activity limitations, symptoms, emotions, and overall quality of life (QoL) related to the participants painful condition on the following scale: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse) and 7 (very much worse). Number of participants in the PGIC categories of any improvement (that is PGIC scale score 1, 2 or 3), no change (that is PGIC scale score 4) and any worsening (that is PGIC scale score 5, 6 or 7) are reported.
Time Frame	Week 4, 8, 12, 16, 24, 32, 40, and 52

Outcome Measure Data

Analysis Population Description

Quality of Life analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here,"Number Analyzed" signified those participants who were evaluable at given time points.

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed		112	114	113	113
Measure Type: Count of Participants; Unit of Measure: Participants
Week 4	Number Analyzed	112 participants	114 participants	113 participants	113 participants
	Any Improvement	69 61.6%	78 68.4%	81 71.7%	71 62.8%
	No Change	33 29.5%	27 23.7%	23 20.4%	34 30.1%
	Any Worsening	8 7.1%	9 7.9%	8 7.1%	8 7.1%
	Missing	2 1.8%	0 0.0%	1 0.9%	0 0.0%
Week 8	Number Analyzed	110 participants	110 participants	110 participants	109 participants
	Any Improvement	80 72.7%	81 73.6%	85 77.3%	75 68.8%
	No Change	22 20.0%	18 16.4%	19 17.3%	28 25.7%
	Any Worsening	5 4.5%	9 8.2%	5 4.5%	3 2.8%
	Missing	3 2.7%	2 1.8%	1 0.9%	3 2.8%
Week 12	Number Analyzed	108 participants	105 participants	107 participants	104 participants
	Any Improvement	78 72.2%	82 78.1%	81 75.7%	77 74.0%
	No Change	23 21.3%	13 12.4%	15 14.0%	20 19.2%
	Any Worsening	5 4.6%	7 6.7%	7 6.5%	4 3.8%
	Missing	2 1.9%	3 2.9%	4 3.7%	3 2.9%
Week 16	Number Analyzed	104 participants	101 participants	105 participants	98 participants
	Any Improvement	75 72.1%	81 80.2%	87 82.9%	79 80.6%
	No Change	23 22.1%	13 12.9%	16 15.2%	15 15.3%
	Any Worsening	3 2.9%	7 6.9%	2 1.9%	2 2.0%
	Missing	3 2.9%	0 0.0%	0 0.0%	2 2.0%
Week 24	Number Analyzed	98 participants	95 participants	101 participants	95 participants
	Any Improvement	67 68.4%	77 81.1%	87 86.1%	73 76.8%
	No Change	23 23.5%	12 12.6%	7 6.9%	17 17.9%
	Any Worsening	6 6.1%	6 6.3%	5 5.0%	5 5.3%
	Missing	2 2.0%	0 0.0%	2 2.0%	0 0.0%
Week 32	Number Analyzed	91 participants	91 participants	95 participants	89 participants
	Any Improvement	70 76.9%	70 76.9%	80 84.2%	72 80.9%
	No Change	16 17.6%	15 16.5%	8 8.4%	13 14.6%
	Any Worsening	4 4.4%	6 6.6%	5 5.3%	3 3.4%
	Missing	1 1.1%	0 0.0%	2 2.1%	1 1.1%
Week 40	Number Analyzed	89 participants	89 participants	93 participants	87 participants
	Any Improvement	67 75.3%	69 77.5%	80 86.0%	73 83.9%
	No Change	19 21.3%	12 13.5%	7 7.5%	9 10.3%
	Any Worsening	2 2.2%	8 9.0%	4 4.3%	4 4.6%
	Missing	1 1.1%	0 0.0%	2 2.2%	1 1.1%
Week 52	Number Analyzed	88 participants	89 participants	90 participants	85 participants
	Any Improvement	66 75.0%	64 71.9%	76 84.4%	64 75.3%
	No Change	14 15.9%	18 20.2%	6 6.7%	13 15.3%
	Any Worsening	6 6.8%	1 1.1%	5 5.6%	4 4.7%
	Missing	2 2.3%	6 6.7%	3 3.3%	4 4.7%

48. Secondary Outcome

Title	DBPC Period: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 4, 8, 12, 16, 24, 32, 40 and 52
Description	The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assess self reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.
Time Frame	Baseline, Week 4, 8, 12, 16, 24, 32, 40, and 52

Outcome Measure Data

Analysis Population Description

Quality of Life analysis set included all randomized participants who had received at least 1 dose of IMP (Evobrutinib or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed		110	114	112	113
Mean (Standard Deviation); Unit of Measure: Units on a scale
Week 4	Number Analyzed	110 participants	114 participants	112 participants	113 participants
		3 (8.0)	2 (7.8)	4 (9.1)	3 (7.7)
Week 8	Number Analyzed	107 participants	108 participants	109 participants	106 participants
		3 (8.7)	3 (8.3)	3 (9.1)	5 (8.2)
Week 12	Number Analyzed	106 participants	102 participants	103 participants	101 participants
		3 (10.0)	4 (9.7)	3 (9.7)	4 (8.1)
Week 16	Number Analyzed	101 participants	101 participants	105 participants	96 participants
		4 (9.8)	3 (9.8)	4 (10.2)	3 (8.4)
Week 24	Number Analyzed	96 participants	95 participants	99 participants	95 participants
		3 (9.9)	4 (8.5)	5 (10.3)	3 (7.5)
Week 32	Number Analyzed	90 participants	91 participants	93 participants	88 participants
		4 (9.6)	4 (9.5)	5 (9.7)	4 (6.8)
Week 40	Number Analyzed	88 participants	89 participants	91 participants	86 participants
		4 (8.8)	3 (8.6)	6 (9.9)	4 (8.5)
Week 52	Number Analyzed	86 participants	84 participants	87 participants	82 participants
		4 (9.9)	4 (7.9)	5 (9.7)	5 (8.7)

49. Secondary Outcome

Title	DBPC Period: Number of Participants With Change From Baseline in Prednisone Equivalent Corticosteroid (CS) Dose by >=25% to a Dose of <=7.5 Milligram Per Day (mg/Day), With no BILAG A or 2B Flare in Disease Activity at Week 52
Description	BILAG A or 2B flare is defined as at least one BILAG A grade or two BILAG B grade in any organ system due to items that are new or worse, compared to the BILAG evaluation at the previous visit, during the 52 week treatment period. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to systemic lupus erythematosus (SLE), divided into 9 organ systems. For each organ system based on alphabetic score: A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	68	68	70	71
Measure Type: Count of Participants; Unit of Measure: Participants
	19 27.9%	23 33.8%	20 28.6%	21 29.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Rate difference
	Estimated Value	5.9
	Confidence Interval	(2-Sided) 95%; -9.7 to 21.2
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -14.5 to 15.6
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Rate difference
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -13.5 to 16.6
	Estimation Comments	[Not Specified]

50. Secondary Outcome

Title	DBPC Period: Change From Baseline to Week 52 in Prednisone Equivalent Corticosteroid (CS) Daily Dose at at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Description	Change From Baseline in Prednisone-equivalent CS Daily Dose at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 were reported.
Time Frame	Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. . Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.

Arm/Group Title		DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:		Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed		113	113	116	114
Mean (Standard Deviation); Unit of Measure: Milligram (mg)
Week 1	Number Analyzed	48 participants	58 participants	60 participants	52 participants
		0.21 (1.443)	0.00 (0.000)	0.00 (0.000)	0.00 (0.000)
Week 2	Number Analyzed	113 participants	113 participants	116 participants	114 participants
		0.10 (1.206)	-0.07 (0.524)	0.00 (0.000)	-0.13 (1.405)
Week 4	Number Analyzed	111 participants	113 participants	115 participants	111 participants
		0.01 (1.267)	-0.45 (2.879)	-0.04 (0.739)	-0.15 (1.428)
Week 6	Number Analyzed	57 participants	47 participants	55 participants	55 participants
		-1.07 (3.563)	-0.64 (3.275)	-0.59 (2.095)	-0.70 (3.484)
Week 8	Number Analyzed	108 participants	110 participants	110 participants	105 participants
		-0.57 (2.588)	-1.24 (3.915)	-1.09 (3.640)	-1.02 (3.422)
Week 10	Number Analyzed	55 participants	49 participants	61 participants	55 participants
		-1.43 (3.985)	-2.04 (5.146)	-1.56 (4.137)	-2.50 (4.971)
Week 12	Number Analyzed	107 participants	102 participants	107 participants	99 participants
		-1.26 (3.260)	-1.85 (4.158)	-1.73 (4.574)	-1.97 (4.150)
Week 14	Number Analyzed	60 participants	51 participants	63 participants	57 participants
		-2.00 (4.569)	-2.70 (5.428)	-1.87 (4.489)	-2.76 (5.125)
Week 16	Number Analyzed	102 participants	101 participants	104 participants	97 participants
		-1.67 (4.427)	-2.70 (4.955)	-2.47 (5.365)	-2.40 (4.535)
Week 20	Number Analyzed	98 participants	94 participants	101 participants	94 participants
		-1.94 (4.054)	-2.82 (4.905)	-2.64 (5.489)	-2.53 (4.727)
Week 24	Number Analyzed	93 participants	95 participants	99 participants	91 participants
		-1.99 (4.228)	-2.64 (5.066)	-2.61 (5.568)	-2.34 (5.330)
Week 28	Number Analyzed	92 participants	91 participants	97 participants	89 participants
		-2.23 (4.439)	-2.97 (4.981)	-3.07 (6.068)	-2.46 (5.371)
Week 32	Number Analyzed	92 participants	90 participants	95 participants	88 participants
		-2.45 (4.584)	-3.13 (5.193)	-3.18 (6.161)	-2.44 (5.347)
Week 36	Number Analyzed	90 participants	90 participants	95 participants	87 participants
		-2.42 (4.835)	-3.31 (5.327)	-3.18 (6.136)	-2.37 (5.445)
Week 40	Number Analyzed	90 participants	90 participants	92 participants	86 participants
		-2.08 (6.149)	-3.21 (5.280)	-3.24 (6.218)	-2.67 (5.202)
Week 44	Number Analyzed	89 participants	90 participants	92 participants	85 participants
		-2.42 (4.833)	-3.21 (5.280)	-3.27 (6.254)	-2.56 (5.121)
Week 48	Number Analyzed	86 participants	89 participants	91 participants	84 participants
		-2.38 (4.895)	-3.22 (5.310)	-3.37 (6.265)	-2.62 (5.136)
Week 52	Number Analyzed	99 participants	100 participants	100 participants	96 participants
		-1.70 (5.470)	-2.94 (5.534)	-3.09 (5.981)	-2.63 (5.673)

51. Secondary Outcome

Title	DBPC Period: Number of Participants With Reduction From Baseline in Prednisone Equivalent Corticosteroid (CS) Daily Dose by > 0 to 25%, >25% to 50%, >50% to 100% or an Increase at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52
Description	Number of Participants With Reduction From Baseline in Prednisone-equivalent Corticosteroid (CS) Daily Dose by > 0 to 25%, >25% to 50%, >50% to 100% or an Increase at Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 were reported.
Time Frame	Baseline, Week 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	114	115	116	114
Measure Type: Count of Participants; Unit of Measure: Participants
Reduction of dose by >0-25% Week 1	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Reduction of dose by >0-25% Week 2	1 0.9%	2 1.7%	0 0.0%	0 0.0%
Reduction of dose by >0-25% Week 4	1 0.9%	5 4.3%	2 1.7%	1 0.9%
Reduction of dose by >0-25% Week 6	3 2.6%	4 3.5%	3 2.6%	4 3.5%
Reduction of dose by >0-25% Week 8	6 5.3%	6 5.2%	5 4.3%	6 5.3%
Reduction of dose by >0-25% Week 10	0 0.0%	3 2.6%	4 3.4%	5 4.4%
Reduction of dose by >0-25% Week 12	5 4.4%	11 9.6%	8 6.9%	6 5.3%
Reduction of dose by >0-25% Week 14	2 1.8%	2 1.7%	4 3.4%	5 4.4%
Reduction of dose by >0-25% Week 16	5 4.4%	10 8.7%	5 4.3%	6 5.3%
Reduction of dose by >0-25% Week 20	5 4.4%	10 8.7%	5 4.3%	5 4.4%
Reduction of dose by >0-25% Week 24	4 3.5%	10 8.7%	5 4.3%	5 4.4%
Reduction of dose by >0-25% Week 28	2 1.8%	8 7.0%	5 4.3%	4 3.5%
Reduction of dose by >0-25% Week 32	1 0.9%	7 6.1%	4 3.4%	3 2.6%
Reduction of dose by >0-25% Week 36	1 0.9%	5 4.3%	4 3.4%	3 2.6%
Reduction of dose by >0-25% Week 40	1 0.9%	5 4.3%	3 2.6%	3 2.6%
Reduction of dose by >0-25% Week 44	1 0.9%	5 4.3%	3 2.6%	3 2.6%
Reduction of dose by >0-25% Week 48	0 0.0%	5 4.3%	4 3.4%	3 2.6%
Reduction of dose by >0-25% Week 52	1 0.9%	5 4.3%	4 3.4%	4 3.5%
Reduction of dose by >25- 50% Week 1	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Reduction of dose by >25- 50% Week 2	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Reduction of dose by >25- 50% Week 4	1 0.9%	2 1.7%	1 0.9%	0 0.0%
Reduction of dose by >25- 50% Week 6	4 3.5%	1 0.9%	2 1.7%	0 0.0%
Reduction of dose by >25- 50% Week 8	5 4.4%	9 7.8%	6 5.2%	5 4.4%
Reduction of dose by >25- 50% Week 10	7 6.1%	6 5.2%	4 3.4%	10 8.8%
Reduction of dose by >25- 50% Week 12	14 12.3%	9 7.8%	10 8.6%	15 13.2%
Reduction of dose by >25- 50% Week 14	7 6.1%	6 5.2%	2 1.7%	8 7.0%
Reduction of dose by >25- 50% Week 16	16 14.0%	12 10.4%	9 7.8%	16 14.0%
Reduction of dose by >25- 50% Week 20	13 11.4%	11 9.6%	8 6.9%	14 12.3%
Reduction of dose by >25- 50% Week 24	12 10.5%	9 7.8%	8 6.9%	13 11.4%
Reduction of dose by >25- 50% Week 28	14 12.3%	12 10.4%	9 7.8%	16 14.0%
Reduction of dose by >25- 50% Week 32	15 13.2%	11 9.6%	8 6.9%	16 14.0%
Reduction of dose by >25- 50% Week 36	15 13.2%	13 11.3%	6 5.2%	15 13.2%
Reduction of dose by >25- 50% Week 40	15 13.2%	15 13.0%	6 5.2%	16 14.0%
Reduction of dose by >25- 50% Week 44	15 13.2%	15 13.0%	6 5.2%	16 14.0%
Reduction of dose by >25- 50% Week 48	15 13.2%	14 12.2%	6 5.2%	17 14.9%
Reduction of dose by >25- 50% Week 52	16 14.0%	12 10.4%	7 6.0%	17 14.9%
Reduction of dose by >50-100% Week 1	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Reduction of dose by >50-100% Week 2	0 0.0%	0 0.0%	0 0.0%	1 0.9%
Reduction of dose by >50-100% Week 4	0 0.0%	1 0.9%	0 0.0%	1 0.9%
Reduction of dose by >50-100% Week 6	1 0.9%	1 0.9%	0 0.0%	1 0.9%
Reduction of dose by >50-100% Week 8	1 0.9%	3 2.6%	4 3.4%	3 2.6%
Reduction of dose by >50-100% Week 10	2 1.8%	3 2.6%	3 2.6%	4 3.5%
Reduction of dose by >50-100% Week 12	1 0.9%	6 5.2%	6 5.2%	6 5.3%
Reduction of dose by >50-100% Week 14	5 4.4%	6 5.2%	7 6.0%	7 6.1%
Reduction of dose by >50-100% Week 16	5 4.4%	13 11.3%	13 11.2%	9 7.9%
Reduction of dose by >50-100% Week 20	7 6.1%	13 11.3%	14 12.1%	11 9.6%
Reduction of dose by >50-100% Week 24	7 6.1%	14 12.2%	13 11.2%	11 9.6%
Reduction of dose by >50-100% Week 28	9 7.9%	14 12.2%	15 12.9%	11 9.6%
Reduction of dose by >50-100% Week 32	11 9.6%	16 13.9%	16 13.8%	12 10.5%
Reduction of dose by >50-100% Week 36	10 8.8%	17 14.8%	18 15.5%	11 9.6%
Reduction of dose by >50-100% Week 40	10 8.8%	15 13.0%	18 15.5%	11 9.6%
Reduction of dose by >50-100% Week 44	10 8.8%	15 13.0%	18 15.5%	10 8.8%
Reduction of dose by >50-100% Week 48	9 7.9%	15 13.0%	19 16.4%	10 8.8%
Reduction of dose by >50-100% Week 52	9 7.9%	17 14.8%	19 16.4%	12 10.5%
Increased from Baseline Week 1	1 0.9%	0 0.0%	0 0.0%	0 0.0%
Increased from Baseline Week 2	2 1.8%	0 0.0%	0 0.0%	0 0.0%
Increased from Baseline Week 4	2 1.8%	1 0.9%	1 0.9%	0 0.0%
Increased from Baseline Week 6	1 0.9%	1 0.9%	0 0.0%	0 0.0%
Increased from Baseline Week 8	2 1.8%	1 0.9%	1 0.9%	0 0.0%
Increased from Baseline Week 10	1 0.9%	1 0.9%	0 0.0%	0 0.0%
Increased from Baseline Week 12	1 0.9%	1 0.9%	1 0.9%	0 0.0%
Increased from Baseline Week 14	1 0.9%	0 0.0%	0 0.0%	0 0.0%
Increased from Baseline Week 16	1 0.9%	1 0.9%	1 0.9%	0 0.0%
Increased from Baseline Week 20	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Increased from Baseline Week 24	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Increased from Baseline Week 28	0 0.0%	0 0.0%	0 0.0%	1 0.9%
Increased from Baseline Week 32	0 0.0%	0 0.0%	0 0.0%	1 0.9%
Increased from Baseline Week 36	0 0.0%	0 0.0%	0 0.0%	1 0.9%
Increased from Baseline Week 40	1 0.9%	0 0.0%	0 0.0%	1 0.9%
Increased from Baseline Week 44	0 0.0%	0 0.0%	0 0.0%	1 0.9%
Increased from Baseline Week 48	0 0.0%	0 0.0%	0 0.0%	1 0.9%
Increased from Baseline Week 52	2 1.8%	0 0.0%	0 0.0%	2 1.8%

52. Secondary Outcome

Title	DBPC Period: Cumulative Prednisone Equivalent Corticosteroid (CS) Dose at Week 52
Description	Cumulative Prednisone-equivalent Corticosteroid (CS) Dose was calculated at Week 52.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	114	115	116	114
Mean (Standard Deviation); Unit of Measure: Milligrams
	2267.66 (1507.652)	2209.46 (1922.557)	2137.70 (1618.688)	2205.56 (1737.092)

53. Secondary Outcome

Title	DBPC Period: Number of Participants With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 mg Prednisone Equivalent Per Day or Less With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 52
Description	SRI-4 response was defined as greater than or equal to (>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score, no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and no treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to Systemic Lupus Erythematosus (SLE), divided into 9 organ systems. For each organ system A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	56	59	63	57
Measure Type: Count of Participants; Unit of Measure: Participants
	43 76.8%	45 76.3%	43 68.3%	41 71.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7728
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.46 to 2.82
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3314
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.28 to 1.54
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7205
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.36 to 2.04
	Estimation Comments	[Not Specified]

54. Secondary Outcome

Title	DBPC Period: Number of Participants With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 mg Prednisone Equivalent Per Day or Less With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6) at Week 52
Description	SRI-6 response was defined as >= 6-point reduction in SLEDAI-2K total score, no new BILAG A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to SLE, divided into 9 organ systems. For each organ system :A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale =from 0(very well) to 100(very poor).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "overall number of participants analyzed" signifies those participants who achieved SLEDAI-2K total score >= 10 at screening (HDA participants) and evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	27	28	35	24
Measure Type: Count of Participants; Unit of Measure: Participants
	18 66.7%	19 67.9%	23 65.7%	15 62.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8364
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.35 to 3.71
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8287
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.37 to 3.45
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7621
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 0.35 to 4.16
	Estimation Comments	[Not Specified]

55. Secondary Outcome

Title	DBPC Period: Number of Participants With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to 7.5 mg Prednisone Equivalent Per Day or Less With Response Based on SRI-4 at Week 52 in Serologically Active Subgroup
Description	SRI-4 response was defined as greater than or equal to (>=) 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score, no worsening (less than 10 percent increase) from baseline in Physician's Global Assessment of Disease Activity (PGA) and no treatment failure. SLEDAI-2K assessment consists of 24 items with total score of 0(no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. BILAG Index: assessing clinical signs, symptoms, or laboratory parameters related to Systemic Lupus Erythematosus (SLE), divided into 9 organ systems. For each organ system A=severe disease, B=moderate disease, C=mild stable disease, D=inactive, but previously active, E=inactive and never affected. The PGA assess disease activity on a visual analogue scale = from very well(0)-very poor(100).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI. Here, "Overall Number of Participants Analyzed" signifies those participants with positive antidsDNA and/or low complement levels at screening (Serologically active subgroup) and evaluable for this outcome measure.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	26	33	32	34
Measure Type: Count of Participants; Unit of Measure: Participants
	21 80.8%	25 75.8%	22 68.8%	25 73.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8464
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.23 to 3.31
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4170
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95%; 0.16 to 2.12
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9988
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.27 to 3.74
	Estimation Comments	[Not Specified]

56. Secondary Outcome

Title	DBPC Period: Number of Participants With Lupus Low Disease Activity State (LLDAS) at Week 52
Description	Lupus low disease activity state will be measured as: SLEDAI-2K <= 4; No activity in any major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever); No new features of disease activity compared with the previous assessment; Prednisone-equivalent <= 7.5 milligram per day; Unchanged background immunosuppressive therapy.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The mITT analysis set included all randomized participants who had received at least one dose of IMP (Evobrutinib or placebo) and have at least one Baseline and one post Baseline disease assessment among the following: SFI, SLEDAI 2K, PGA, BILAG 2004, CLASI.

Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID
Arm/Group Description:	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.
Overall Number of Participants Analyzed	114	115	116	114
Measure Type: Count of Participants; Unit of Measure: Participants
	29 25.4%	32 27.8%	35 30.2%	29 25.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 25 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6970
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.62 to 2.04
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 75 mg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3234
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.34
	Confidence Interval	(2-Sided) 95%; 0.75 to 2.42
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DBPC Period: Placebo, DBPC Period: M2951 50 mg BID
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9846
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.82
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Double-Blind Placebo-Controlled: Baseline up to Week 56 Long-Term Extension: Up to Week 108
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID	LTE: Placebo/ M2951 50 mg BID	LTE Period: M2951 25 mg QD/ M2951 50 mg BID	LTE Period: M2951 75 mg QD/ M2951 50 mg BID	LTE: M2951 50 mg BID/ M2951 50 mg BID
Arm/Group Description	Participants received placebo matched to M2951 orally for 52 weeks.	Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 52 weeks.	Participants received 75 mg of M2951 orally QD for 52 weeks.	Participants received 50 mg of M2951 orally twice daily (BID) for 52 weeks.	Participants who received Placebo in DBPC period were switched to receive 50 mg M2951 orally BID in LTE period for 104 weeks.	Participants who received 25 mg of M2951 orally QD in DBPC period were switched to receive 50 mg M2951 orally BID in LTE period for 104 weeks.	Participants who received 75 mg of M2951 orally QD in DBPC period were switched to receive 50 mg M2951 orally BID in LTE period for 104 weeks.	Participants who received 50 mg of M2951 orally BID in DBPC period continued to receive same dose of M2951 orally BID in LTE period for 104 weeks.
All-Cause Mortality
	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID	LTE: Placebo/ M2951 50 mg BID	LTE Period: M2951 25 mg QD/ M2951 50 mg BID	LTE Period: M2951 75 mg QD/ M2951 50 mg BID	LTE: M2951 50 mg BID/ M2951 50 mg BID
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/117 (0.00%)	1/118 (0.85%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Serious Adverse Events
	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID	LTE: Placebo/ M2951 50 mg BID	LTE Period: M2951 25 mg QD/ M2951 50 mg BID	LTE Period: M2951 75 mg QD/ M2951 50 mg BID	LTE: M2951 50 mg BID/ M2951 50 mg BID
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	10/117 (8.55%)	13/118 (11.02%)	11/117 (9.40%)	9/117 (7.69%)	5/62 (8.06%)	5/69 (7.25%)	5/80 (6.25%)	7/72 (9.72%)
Blood and lymphatic system disorders
Bone marrow failure * 1	0/117 (0.00%)	0/118 (0.00%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Pancytopenia * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	1/117 (0.85%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Anaemia * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	1/62 (1.61%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Leukopenia * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	1/80 (1.25%)	0/72 (0.00%)
Lymphadenitis * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	1/62 (1.61%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Thrombocytopenia * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	1/62 (1.61%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Cardiac disorders
Pericarditis lupus * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Ear and labyrinth disorders
Vertigo * 1	1/117 (0.85%)	0/118 (0.00%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Eye disorders
Cataract * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	1/72 (1.39%)
Gastrointestinal disorders
Abdominal pain * 1	0/117 (0.00%)	0/118 (0.00%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Ascites * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	1/117 (0.85%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Colitis * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Lupus enteritis * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	1/117 (0.85%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Pancreatitis * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Dental cyst * 1	1/117 (0.85%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Diarrhoea * 1	1/117 (0.85%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Abdominal adhesions * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	1/72 (1.39%)
General disorders
Non-cardiac chest pain * 1	0/117 (0.00%)	2/118 (1.69%)	0/117 (0.00%)	2/117 (1.71%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Chest pain * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Hepatobiliary disorders
Cholelithiasis * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	1/117 (0.85%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	1/72 (1.39%)
Hepatitis * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	1/62 (1.61%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Infections and infestations
Otitis media * 1	0/117 (0.00%)	0/118 (0.00%)	2/117 (1.71%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Campylobacter sepsis * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Cellulitis * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	1/117 (0.85%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Clostridium difficile infection * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Diverticulitis * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Gastroenteritis * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Giardiasis * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Pneumonia * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	1/117 (0.85%)	0/62 (0.00%)	0/69 (0.00%)	1/80 (1.25%)	1/72 (1.39%)
Pyelonephritis acute * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Soft tissue infection * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Upper respiratory tract infection * 1	0/117 (0.00%)	0/118 (0.00%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Herpes zoster * 1	1/117 (0.85%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Osteomyelitis * 1	1/117 (0.85%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	1/62 (1.61%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Urinary tract infection * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	2/69 (2.90%)	0/80 (0.00%)	0/72 (0.00%)
Appendicitis * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	1/72 (1.39%)
Bronchitis * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	1/80 (1.25%)	0/72 (0.00%)
Pneumonia mycoplasmal * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	1/72 (1.39%)
Subperiosteal abscess * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	1/62 (1.61%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Injury, poisoning and procedural complications
Ligament injury * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	1/117 (0.85%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Post procedural complication * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	1/72 (1.39%)
Post procedural haemorrhage * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	1/72 (1.39%)
Wound * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	1/72 (1.39%)
Investigations
Liver function test increased * 1	0/117 (0.00%)	0/118 (0.00%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Transaminases increased * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	1/117 (0.85%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Platelet count decreased * 1	1/117 (0.85%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Metabolism and nutrition disorders
Hypoglycaemia * 1	0/117 (0.00%)	0/118 (0.00%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Back pain * 1	0/117 (0.00%)	0/118 (0.00%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Intervertebral disc protrusion * 1	0/117 (0.00%)	0/118 (0.00%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Musculoskeletal chest pain * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Osteoarthritis * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Osteonecrosis * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	1/72 (1.39%)
Systemic lupus erythematosus * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	1/117 (0.85%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Osteonecrosis of jaw * 1	1/117 (0.85%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	1/62 (1.61%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
SLE arthritis * 1	1/117 (0.85%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer * 1	1/117 (0.85%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Basal cell carcinoma * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	1/62 (1.61%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Nervous system disorders
Dizziness * 1	0/117 (0.00%)	0/118 (0.00%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	1/80 (1.25%)	0/72 (0.00%)
Headache * 1	2/117 (1.71%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Presyncope * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Syncope * 1	0/117 (0.00%)	0/118 (0.00%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Ischaemic stroke * 1	1/117 (0.85%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Cerebral infarction * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	1/62 (1.61%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Cerebral venous sinus thrombosis * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	1/62 (1.61%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Renal and urinary disorders
Acute kidney injury * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Lupus nephritis * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	1/62 (1.61%)	1/69 (1.45%)	0/80 (0.00%)	0/72 (0.00%)
Urinary retention * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	1/80 (1.25%)	0/72 (0.00%)
Reproductive system and breast disorders
Pelvic pain * 1	0/117 (0.00%)	0/118 (0.00%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Uterine polyp * 1	1/117 (0.85%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	1/69 (1.45%)	0/80 (0.00%)	0/72 (0.00%)
Metrorrhagia * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	1/69 (1.45%)	0/80 (0.00%)	0/72 (0.00%)
Ovarian cyst * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	1/80 (1.25%)	0/72 (0.00%)
Respiratory, thoracic and mediastinal disorders
Asthma * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	1/117 (0.85%)	0/62 (0.00%)	0/69 (0.00%)	1/80 (1.25%)	0/72 (0.00%)
Skin and subcutaneous tissue disorders
Cutaneous vasculitis * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Dermatosis * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Dermatitis contact * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	1/72 (1.39%)
Urticaria * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	1/69 (1.45%)	0/80 (0.00%)	0/72 (0.00%)
Vascular disorders
Hypertension * 1	0/117 (0.00%)	0/118 (0.00%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Malignant hypertension * 1	0/117 (0.00%)	1/118 (0.85%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Hypotension * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	1/80 (1.25%)	0/72 (0.00%)
Hypovolaemic shock * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	1/72 (1.39%)
1 Term from vocabulary, MedDRA V22.1/23.0; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	DBPC Period: Placebo	DBPC Period: M2951 25 mg QD	DBPC Period: M2951 75 mg QD	DBPC Period: M2951 50 mg BID	LTE: Placebo/ M2951 50 mg BID	LTE Period: M2951 25 mg QD/ M2951 50 mg BID	LTE Period: M2951 75 mg QD/ M2951 50 mg BID	LTE: M2951 50 mg BID/ M2951 50 mg BID
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	76/117 (64.96%)	85/118 (72.03%)	75/117 (64.10%)	78/117 (66.67%)	22/62 (35.48%)	34/69 (49.28%)	35/80 (43.75%)	23/72 (31.94%)
Blood and lymphatic system disorders
Lymphopenia * 1	9/117 (7.69%)	4/118 (3.39%)	6/117 (5.13%)	2/117 (1.71%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Neutropenia * 1	4/117 (3.42%)	1/118 (0.85%)	2/117 (1.71%)	6/117 (5.13%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Gastrointestinal disorders
Diarrhoea * 1	11/117 (9.40%)	12/118 (10.17%)	17/117 (14.53%)	10/117 (8.55%)	3/62 (4.84%)	5/69 (7.25%)	7/80 (8.75%)	2/72 (2.78%)
Nausea * 1	7/117 (5.98%)	8/118 (6.78%)	9/117 (7.69%)	5/117 (4.27%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Vomiting * 1	4/117 (3.42%)	9/118 (7.63%)	8/117 (6.84%)	3/117 (2.56%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Abdominal pain upper * 1	5/117 (4.27%)	6/118 (5.08%)	8/117 (6.84%)	5/117 (4.27%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Abdominal pain * 1	3/117 (2.56%)	7/118 (5.93%)	3/117 (2.56%)	5/117 (4.27%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Gastritis * 1	3/117 (2.56%)	6/118 (5.08%)	3/117 (2.56%)	4/117 (3.42%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
General disorders
Influenza like illness * 1	5/117 (4.27%)	7/118 (5.93%)	9/117 (7.69%)	7/117 (5.98%)	4/62 (6.45%)	0/69 (0.00%)	2/80 (2.50%)	0/72 (0.00%)
Infections and infestations
Urinary tract infection * 1	16/117 (13.68%)	21/118 (17.80%)	26/117 (22.22%)	21/117 (17.95%)	4/62 (6.45%)	7/69 (10.14%)	7/80 (8.75%)	6/72 (8.33%)
Nasopharyngitis * 1	8/117 (6.84%)	13/118 (11.02%)	15/117 (12.82%)	7/117 (5.98%)	5/62 (8.06%)	5/69 (7.25%)	7/80 (8.75%)	5/72 (6.94%)
Upper respiratory tract infection * 1	12/117 (10.26%)	15/118 (12.71%)	6/117 (5.13%)	8/117 (6.84%)	3/62 (4.84%)	6/69 (8.70%)	3/80 (3.75%)	0/72 (0.00%)
Pharyngitis * 1	8/117 (6.84%)	5/118 (4.24%)	4/117 (3.42%)	4/117 (3.42%)	0/62 (0.00%)	3/69 (4.35%)	6/80 (7.50%)	1/72 (1.39%)
Gastroenteritis * 1	6/117 (5.13%)	4/118 (3.39%)	2/117 (1.71%)	2/117 (1.71%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Herpes zoster * 1	2/117 (1.71%)	2/118 (1.69%)	6/117 (5.13%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Bronchitis * 1	0/117 (0.00%)	0/118 (0.00%)	0/117 (0.00%)	0/117 (0.00%)	0/62 (0.00%)	4/69 (5.80%)	5/80 (6.25%)	3/72 (4.17%)
Investigations
Alanine aminotransferase increased * 1	3/117 (2.56%)	8/118 (6.78%)	6/117 (5.13%)	6/117 (5.13%)	5/62 (8.06%)	4/69 (5.80%)	1/80 (1.25%)	2/72 (2.78%)
Lipase increased * 1	2/117 (1.71%)	4/118 (3.39%)	6/117 (5.13%)	6/117 (5.13%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Aspartate aminotransferase increased * 1	3/117 (2.56%)	8/118 (6.78%)	3/117 (2.56%)	4/117 (3.42%)	3/62 (4.84%)	4/69 (5.80%)	1/80 (1.25%)	2/72 (2.78%)
Gamma-glutamyltransferase increased * 1	6/117 (5.13%)	4/118 (3.39%)	4/117 (3.42%)	7/117 (5.98%)	3/62 (4.84%)	3/69 (4.35%)	1/80 (1.25%)	4/72 (5.56%)
Amylase increased * 1	5/117 (4.27%)	2/118 (1.69%)	4/117 (3.42%)	8/117 (6.84%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Transaminases increased * 1	3/117 (2.56%)	3/118 (2.54%)	3/117 (2.56%)	6/117 (5.13%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Musculoskeletal and connective tissue disorders
Back Pain * 1	3/117 (2.56%)	4/118 (3.39%)	5/117 (4.27%)	9/117 (7.69%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Nervous system disorders
Headache * 1	20/117 (17.09%)	17/118 (14.41%)	19/117 (16.24%)	17/117 (14.53%)	1/62 (1.61%)	7/69 (10.14%)	2/80 (2.50%)	5/72 (6.94%)
Dizziness * 1	3/117 (2.56%)	5/118 (4.24%)	4/117 (3.42%)	6/117 (5.13%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Respiratory, thoracic and mediastinal disorders
Epistaxis * 1	6/117 (5.13%)	2/118 (1.69%)	1/117 (0.85%)	0/117 (0.00%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
Vascular disorders
Hypertension * 1	0/117 (0.00%)	6/118 (5.08%)	4/117 (3.42%)	1/117 (0.85%)	0/62 (0.00%)	0/69 (0.00%)	0/80 (0.00%)	0/72 (0.00%)
1 Term from vocabulary, MedDRA V22.1/23.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

Primary and Secondary endpoints were planned to be analyze only for Double-Blind Placebo-controlled period.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

 

Results Point of Contact

• Name/Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany
• Phone: +49-6151-72-5200
• EMail: service@emdgroup.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

• Responsible Party: EMD Serono ( EMD Serono Research & Development Institute, Inc. )
• ClinicalTrials.gov Identifier: NCT02975336
• Other Study ID Numbers: MS200527-0018; 2016-002950-19 ( EudraCT Number )
• First Submitted: November 23, 2016
• First Posted: November 29, 2016
• Results First Submitted: November 18, 2020
• Results First Posted: December 17, 2020
• Last Update Posted: April 12, 2021