Study to Demonstrate the Efficacy, Safety and Tolerability of an Intravenous Regimen of Secukinumab Compared to Placebo in Subjects With Active axSpA

• ClinicalTrials.gov Identifier: NCT04156620
• Recruitment Status: Completed
• First Posted: November 7, 2019
• Results First Posted: January 23, 2024
• Last Update Posted: January 23, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Ankylosing Spondylitis
• Interventions: Drug: Secukinumab; Drug: Placebo
• Enrollment: 527

Participant Flow

Recruitment Details
Pre-assignment Details	769 participants were screened for the study and 527 participants were randomized. However, one participant was mis-randomized and discontinued prior to dosing and is not included in the table below.

Arm/Group Title	AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.
Arm/Group Description	Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)
Period Title: Overall Study
Started	264	262
Completed Period 1 [1]	255	253
Started Period 2 [2]	255	251 [3]
Completed Period 2	233	235
Completed [4]	227	233
Not Completed	37	29
Reason Not Completed
Adverse event - TP 1	5	2
Lost to follow-up TP 1	1	1
Progressive disease - TP 1	0	1
Subject decision - TP 1	3	5
Adverse event - TP 2	5	6
Death - TP 2	1	0
Lost to follow-up - TP 2	5	2
Physician decision - TP 2	4	2
Pregnancy - TP 2	1	1
Subject decision - TP 2	11	9
New therapy for study indication - TP 2	1	0
[1] Baseline up to Week 16; [2] Week 16 up Week 52; [3] 2 patients completed Period 1 but discontinued prior to Period 2; [4] Completed up to Week 60 (follow-up)

Baseline Characteristics

Arm/Group Title		AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.	Total
Arm/Group Description		Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)	Total of all reporting groups
Overall Number of Baseline Participants		264	262	526
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	264 participants	262 participants	526 participants
< 65 years		253 95.8%	257 98.1%	510 97.0%
65 - 75 years		8 3.0%	4 1.5%	12 2.3%
>= 75 years		3 1.1%	1 0.4%	4 0.8%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	264 participants	262 participants	526 participants
	Female	99 37.5%	84 32.1%	183 34.8%
	Male	165 62.5%	178 67.9%	343 65.2%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	264 participants	262 participants	526 participants
White		180 68.2%	179 68.3%	359 68.3%
Black or African American		7 2.7%	6 2.3%	13 2.5%
Asian		59 22.3%	47 17.9%	106 20.2%
American Indian or Alaska Native		17 6.4%	25 9.5%	42 8.0%
Multiple		1 0.4%	5 1.9%	6 1.1%
Disease condition; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	264 participants	262 participants	526 participants
Ankylosing spondylitis		208 78.8%	205 78.2%	413 78.5%
Non-radiographic axial spondylarthritis		56 21.2%	57 21.8%	113 21.5%
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	264 participants	262 participants	526 participants
		77.61 (18.006)	78.08 (18.444)	77.85 (18.210)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved an ASAS40 (Assessment of SpondyloArthritis International Society Criteria)
Description	ASAS40 is ≥ 40% and an absolute improvement from baseline of ≥20 units (range 0-100) in ≥ 3 of the following 4 domains: back pain [10 cm visual analogue scale (VAS)], patient global assessment of disease activity (10 cm VAS), physical function (BASFI; range 0-100) and inflammation (mean score of items 5 and 6 of the BASDAI; both 10 cm VAS) without any worsening in the remaining domain. ASAS consists of 6 domains (4 main and 2 additional): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the BAS Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the BAS Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set with missing responses for any reason imputed as non-responders.

Arm/Group Title	AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.
Arm/Group Description:	Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)
Overall Number of Participants Analyzed	264	262
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	40.85; (34.94 to 46.76)	22.94; (17.86 to 28.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AIN457 6 mg/kg - 3 mg/kg i.v., Placebo - AIN457 3 mg/kg i.v.
	Comments	Week 16
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Marginal difference
	Estimated Value	17.91
	Confidence Interval	(2-Sided) 95%; 10.12 to 25.71
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP) Major Improvement
Description	ASDAS-CRP was utilized to assess disease activity status. Parameters used for the ASDAS included: total back pain (BASDAI question 2), patient's global assessment of disease activity, peripheral pain/swelling (BASDAI question 3), duration of morning stiffness (BASDAI question 6) and CRP in mg/L. Disease activity states: inactive disease, moderate disease activity, high disease activity, and very high disease activity. The three values selected to separate these states are: < 1.3 between inactive disease and moderate disease activity; < 2.1 between moderate disease activity and high disease activity; and > 3.5 between high disease activity and very high disease activity. Selected cutoffs for improvement scores are a change of ≥ 1.1 unit for "minimal clinically important improvement" and a change of ≥ 2.0 units for "major improvement" .
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set with missing responses for any reason imputed as non-responders.

Arm/Group Title	AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.
Arm/Group Description:	Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)
Overall Number of Participants Analyzed	264	262
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	27.99; (22.86 to 33.12)	7.54; (4.44 to 10.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AIN457 6 mg/kg - 3 mg/kg i.v., Placebo - AIN457 3 mg/kg i.v.
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Marginal difference
	Estimated Value	20.45
	Confidence Interval	(2-Sided) 95%; 14.45 to 26.44
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	The Change From Baseline in Total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Description	BASDAI consists of a 0 through 10 scale (0 indicating no problem and 10 indicating the worst problem, captured as a continuous VAS), which was used to answer six questions pertaining to the five major symptoms of AS: fatigue, spinal pain, peripheral joint pain / swelling,, areas of localized tenderness (enthesitis, or inflammation of tendons and ligaments), morning stiffness duration, morning stiffness severity. To give each symptom equal weight, the mean of the two scores relating to morning stiffness is taken into account (questions 5 and 6). The resulting 0 to 10 score is added to the scores for questions 1 through 4. The resulting 0 to 50 score is divided by 5 to give a final 0 10 BASDAI score.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.
Arm/Group Description:	Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)
Overall Number of Participants Analyzed	253	247
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	-2.70 (0.144)	-1.69 (0.144)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AIN457 6 mg/kg - 3 mg/kg i.v., Placebo - AIN457 3 mg/kg i.v.
	Comments	Week 16
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean change
	Estimated Value	-1.01
	Confidence Interval	(2-Sided) 95%; -1.38 to -0.64
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.189
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Percentage of Participants Who Achieved an ASAS 5/6 (Assessment of Spondylarthritis International Society Criteria)
Description	The ASAS 5/6 improvement criteria is an improvement of ≥20% in at least five of all six domains. A higher score on the VAS signifies higher severity. ASAS consists of 6 domains (4 main and 2 additional): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the BAS Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the BAS Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set with missing responses for any reason imputed as non-responders.

Arm/Group Title	AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.
Arm/Group Description:	Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)
Overall Number of Participants Analyzed	264	262
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participaants
	43.92; (37.94 to 49.90)	21.77; (16.77 to 26.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AIN457 6 mg/kg - 3 mg/kg i.v., Placebo - AIN457 3 mg/kg i.v.
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Marginal difference
	Estimated Value	22.15
	Confidence Interval	(2-Sided) 95%; 14.36 to 29.95
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	The Change From Baseline in Total Bath Ankylosing Spondylitis Functional Index (BASFI)
Description	The BASFI is a set of 10 questions designed to determine the degree of functional limitation in subjects with AS. The questions were chosen on the basis of predominant input from subjects with AS. The first eight questions consider activities related to functional anatomy. The final two questions assess the subjects' ability to cope with everyday life. A 0-10 scale (captured as a continuous VAS) is used to answer the questions. The BASFI score is the mean of the ten scales - a value between 0 and 10.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.
Arm/Group Description:	Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)
Overall Number of Participants Analyzed	253	247
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	-2.33 (0.147)	-1.39 (0.148)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AIN457 6 mg/kg - 3 mg/kg i.v., Placebo - AIN457 3 mg/kg i.v.
	Comments	Week 16
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean change
	Estimated Value	-0.94
	Confidence Interval	(2-Sided) 95%; -1.33 to -0.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.194
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	The Change From Baseline in Short Form-36 Physical Component Summary (SF-36 PCS)
Description	The Short Form-36 Physical Component Summary (SF-36 PCS) is an instrument to measure health-related quality of life among healthy patients and patients with acute and chronic conditions. It consists of eight subscales (domains) that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role- Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed. The eight domains are based on a scale from 0-100 while PCS and MCS are norm-based scores with a mean of 50 and a standard deviation of 10. Higher scores indicate a higher level of functioning. A positive change from baseline score indicates an improvement.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.
Arm/Group Description:	Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)
Overall Number of Participants Analyzed	254	247
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	7.70 (0.473)	4.69 (0.473)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AIN457 6 mg/kg - 3 mg/kg i.v., Placebo - AIN457 3 mg/kg i.v.
	Comments	Week 16
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean change
	Estimated Value	3.01
	Confidence Interval	(2-Sided) 95%; 1.80 to 4.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.615
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	The Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQol)
Description	The ASQoL is a self-administered questionnaire designed to assess health-related quality of life in adult subjects with AS. The ASQoL contains 18 items with a dichotomous yes/no response option. A single point is assigned for each "yes" response and no points for each "no" response, resulting in overall scores that range from 0 (least severity) to 18 (highest severity). As such, lower scores indicate better quality of life. Items include an assessment of mobility/energy, self care and mood/emotion. The recall period is "at the moment".
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.
Arm/Group Description:	Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)
Overall Number of Participants Analyzed	254	247
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	-4.65 (0.291)	-2.88 (0.290)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AIN457 6 mg/kg - 3 mg/kg i.v., Placebo - AIN457 3 mg/kg i.v.
	Comments	Week 16
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean change
	Estimated Value	-1.77
	Confidence Interval	(2-Sided) 95%; -2.51 to -1.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.373
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	The Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP)
Description	This assessment (laboratory assessment) was performed in order to identify the presence of inflammation, to determine its severity and to monitor the response to treatment. Exponentially transformed LSM, the geometric mean ratio of post-baseline/baseline. A value <1 indicates a reduced CRP
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.
Arm/Group Description:	Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)
Overall Number of Participants Analyzed	246	248
Least Squares Mean (Standard Error); Unit of Measure: ratio
	0.39 (1.063)	0.89 (1.062)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AIN457 6 mg/kg - 3 mg/kg i.v., Placebo - AIN457 3 mg/kg i.v.
	Comments	Week 16
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Relative LS mean change
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.51
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Percentage of Participants Who Achieved an ASAS20 (Assessment of SpondyloArthritis International Society Criteria)
Description	The ASAS Response Criteria (ASAS20) is defined as an improvement of ≥20% and ≥1 unit on a scale of 10 in at least three of the four main domains and no worsening of ≥20% and ≥1 unit on a scale of 10 in the remaining domain. A higher score on the VAS signifies higher severity. ASAS consists of 6 domains (4 main and 2 additional): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the BAS Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the BAS Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set with missing responses for any reason imputed as non-responders.

Arm/Group Title	AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.
Arm/Group Description:	Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)
Overall Number of Participants Analyzed	264	262
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	63.94; (58.19 to 69.70)	40.53; (34.62 to 46.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AIN457 6 mg/kg - 3 mg/kg i.v., Placebo - AIN457 3 mg/kg i.v.
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Marginal difference
	Estimated Value	23.41
	Confidence Interval	(2-Sided) 95%; 15.61 to 31.66
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	The Percentage of Participants Achieving Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP) Inactive Disease.
Description	ASDAS-CRP was utilized to assess disease activity status. Parameters used for the ASDAS included: total back pain (BASDAI question 2), patient's global assessment of disease activity, peripheral pain/swelling (BASDAI question 3), duration of morning stiffness (BASDAI question 6) and CRP in mg/L. Disease activity states: inactive disease, moderate disease activity, high disease activity, and very high disease activity. The three values selected to separate these states are: < 1.3 between inactive disease and moderate disease activity; < 2.1 between moderate disease activity and high disease activity; and > 3.5 between high disease activity and very high disease activity. Selected cutoffs for improvement scores are a change of ≥ 1.1 unit for "minimal clinically important improvement" and a change of ≥ 2.0 units for "major improvement"
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set with missing responses for any reason imputed as non-responders.

Arm/Group Title	AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.
Arm/Group Description:	Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)
Overall Number of Participants Analyzed	264	262
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	15.66; (11.53 to 19.78)	3.08; (1.00 to 5.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AIN457 6 mg/kg - 3 mg/kg i.v., Placebo - AIN457 3 mg/kg i.v.
	Comments	Week 16
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Marginal difference
	Estimated Value	12.58
	Confidence Interval	(2-Sided) 95%; 7.96 to 17.19
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Percentage of Participants Who Achieved ASAS20 (Assessment of Spondylarthritis International Society Criteria) Partial Remission.
Description	ASAS partial remission criteria are defined as a value not above 2 units in each of the four main ASAS domains on a scale of 0-10. ASAS consists of 6 domains (4 main and 2 additional): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the BAS Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the BAS Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set with missing responses for any reason imputed as non-responders.

Arm/Group Title	AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.
Arm/Group Description:	Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)
Overall Number of Participants Analyzed	264	262
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	14.76; (10.49 to 19.03)	4.20; (1.77 to 6.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AIN457 6 mg/kg - 3 mg/kg i.v., Placebo - AIN457 3 mg/kg i.v.
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Marginal difference
	Estimated Value	10.56
	Confidence Interval	(2-Sided) 95%; 5.64 to 15.47
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Change From Baseline in Pittsburgh Sleep Quality Index (PSQI)
Description	The PSQI is a self-report questionnaire that assesses sleep quality over a 1-month time interval. Consisting of 19 items, the PSQI measures several different aspects of sleep, offering seven component scores and one composite score. The component scores consist of subjective sleep quality, sleep latency (i.e., how long it takes to fall asleep), sleep duration, habitual sleep efficiency (i.e., the percentage of time in bed that one is asleep), sleep disturbances, use of sleeping medication, and daytime dysfunction. Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denoted a healthier sleep quality.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	AIN457 6 mg/kg - 3 mg/kg i.v.	Placebo - AIN457 3 mg/kg i.v.
Arm/Group Description:	Participants received AIN457 (secukinumab) 6 mg/kg i.v. at baseline, followed by AIN457 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit, Weeks 4, 8, and 12, followed by AIN457 (secukinumab) 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)
Overall Number of Participants Analyzed	249	246
Least Squares Mean (Standard Error); Unit of Measure: scores on a scale
	-2.42 (0.222)	-1.76 (0.221)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AIN457 6 mg/kg - 3 mg/kg i.v., Placebo - AIN457 3 mg/kg i.v.
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0234
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean change
	Estimated Value	-0.66
	Confidence Interval	(2-Sided) 95%; -1.24 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.292
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Adverse events were reported for a maximum of 478 days for participants on AIN457 (including placebo switchers) and 182 days for participants on placebo which includes the 84 days in safety follow up.
Adverse Event Reporting Description	Any subjects randomized to Placebo were counted under 'Placebo' before being switched to AIN457 and under 'Any AIN457' after being switched to AIN457. It was pre-specified in the Study Protocol to monitor/assess Adverse Events irrespective of AIN457 dose level.
Arm/Group Title	Any AIN457	Placebo Until Week 16
Arm/Group Description	Participants received secukinumab (AIN457) 6 mg/kg i.v. at baseline, followed by secukinumab 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52); placebo participants who switched at Week 16 received secukinumab 3 mg/kg i.v. every four weeks starting at Week 16 through Week 48 (exposure through Week 52)	Participants received i.v. placebo at baseline visit), Weeks 4, 8, and 12 , followed by the administration of secukinumab 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52
All-Cause Mortality
	Any AIN457	Placebo Until Week 16
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/517 (0.19%)	0/261 (0.00%)
Serious Adverse Events
	Any AIN457	Placebo Until Week 16
	Affected / at Risk (%)	Affected / at Risk (%)
Total	32/517 (6.19%)	3/261 (1.15%)
Blood and lymphatic system disorders
Anaemia † 1	1/517 (0.19%)	0/261 (0.00%)
Cardiac disorders
Acute left ventricular failure † 1	1/517 (0.19%)	0/261 (0.00%)
Coronary artery occlusion † 1	1/517 (0.19%)	0/261 (0.00%)
Myocardial infarction † 1	2/517 (0.39%)	0/261 (0.00%)
Tachycardia † 1	1/517 (0.19%)	0/261 (0.00%)
Ear and labyrinth disorders
Tympanic membrane perforation † 1	1/517 (0.19%)	0/261 (0.00%)
Eye disorders
Choroiditis † 1	1/517 (0.19%)	0/261 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	2/517 (0.39%)	0/261 (0.00%)
Colitis † 1	1/517 (0.19%)	0/261 (0.00%)
Colitis ulcerative † 1	2/517 (0.39%)	0/261 (0.00%)
Crohn's disease † 1	1/517 (0.19%)	0/261 (0.00%)
Small intestinal obstruction † 1	1/517 (0.19%)	0/261 (0.00%)
General disorders
Chest pain † 1	1/517 (0.19%)	0/261 (0.00%)
Non-cardiac chest pain † 1	1/517 (0.19%)	0/261 (0.00%)
Hepatobiliary disorders
Cholecystitis † 1	0/517 (0.00%)	1/261 (0.38%)
Immune system disorders
Drug hypersensitivity † 1	1/517 (0.19%)	0/261 (0.00%)
Infections and infestations
Anal abscess † 1	1/517 (0.19%)	0/261 (0.00%)
Appendicitis † 1	1/517 (0.19%)	0/261 (0.00%)
COVID-19 pneumonia † 1	1/517 (0.19%)	0/261 (0.00%)
Cellulitis † 1	2/517 (0.39%)	0/261 (0.00%)
Dengue fever † 1	1/517 (0.19%)	0/261 (0.00%)
Lower respiratory tract infection † 1	1/517 (0.19%)	0/261 (0.00%)
Parainfluenzae virus infection † 1	1/517 (0.19%)	0/261 (0.00%)
Pneumonia † 1	1/517 (0.19%)	0/261 (0.00%)
Sepsis † 1	1/517 (0.19%)	0/261 (0.00%)
Tonsillitis † 1	0/517 (0.00%)	1/261 (0.38%)
Injury, poisoning and procedural complications
Hand fracture † 1	1/517 (0.19%)	0/261 (0.00%)
Lower limb fracture † 1	1/517 (0.19%)	0/261 (0.00%)
Stab wound † 1	0/517 (0.00%)	1/261 (0.38%)
Investigations
Weight decreased † 1	1/517 (0.19%)	0/261 (0.00%)
Musculoskeletal and connective tissue disorders
Fistula † 1	1/517 (0.19%)	0/261 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer † 1	1/517 (0.19%)	0/261 (0.00%)
Seminoma † 1	1/517 (0.19%)	0/261 (0.00%)
Psychiatric disorders
Depression suicidal † 1	1/517 (0.19%)	0/261 (0.00%)
Reproductive system and breast disorders
Ovarian cyst ruptured † 1	0/517 (0.00%)	1/261 (0.38%)
Respiratory, thoracic and mediastinal disorders
Asthma † 1	1/517 (0.19%)	0/261 (0.00%)
Skin and subcutaneous tissue disorders
Dermatitis atopic † 1	1/517 (0.19%)	0/261 (0.00%)
1 Term from vocabulary, MedDRA (25.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Any AIN457	Placebo Until Week 16
	Affected / at Risk (%)	Affected / at Risk (%)
Total	172/517 (33.27%)	35/261 (13.41%)
Gastrointestinal disorders
Diarrhoea † 1	18/517 (3.48%)	5/261 (1.92%)
Nausea † 1	12/517 (2.32%)	2/261 (0.77%)
Infections and infestations
COVID-19 † 1	65/517 (12.57%)	10/261 (3.83%)
Nasopharyngitis † 1	32/517 (6.19%)	7/261 (2.68%)
Pharyngitis † 1	13/517 (2.51%)	1/261 (0.38%)
Rhinitis † 1	11/517 (2.13%)	2/261 (0.77%)
Upper respiratory tract infection † 1	22/517 (4.26%)	6/261 (2.30%)
Urinary tract infection † 1	11/517 (2.13%)	1/261 (0.38%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	20/517 (3.87%)	1/261 (0.38%)
Nervous system disorders
Headache † 1	17/517 (3.29%)	9/261 (3.45%)
1 Term from vocabulary, MedDRA (25.1); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

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.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: + 1 862 778 8300
• EMail: Novartis.email@Novartis.com

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT04156620
• Other Study ID Numbers: CAIN457P12301
• First Submitted: October 8, 2019
• First Posted: November 7, 2019
• Results First Submitted: November 24, 2023
• Results First Posted: January 23, 2024
• Last Update Posted: January 23, 2024