Safety and Efficacy of Lebrikizumab (LY3650150) in Combination With Topical Corticosteroid in Moderate-to-Severe Atopic Dermatitis. (ADhere)

• ClinicalTrials.gov Identifier: NCT04250337
• Recruitment Status: Completed
• First Posted: January 31, 2020
• Results First Posted: May 2, 2022
• Last Update Posted: May 9, 2022
• Sponsor: Eli Lilly and Company
• Collaborator: Dermira, Inc.
• Information provided by (Responsible Party): Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Atopic Dermatitis
• Interventions: Biological: Lebrikizumab; Other: Placebo; Other: Topical Corticosteroid
• Enrollment: 228

Participant Flow

Recruitment Details

Pre-assignment Details

A participant is considered to have completed the study if he/she has completed the last scheduled visit: For participants continuing into Long-term Extension (LTE), upon completion of week 16 visit and rolling into LTE study; For participants not continuing into LTE, when participant had either week 16 or Early Termination (ET) visit, and safety follow up visit (12 weeks after last study drug administration)

Arm/Group Title	Placebo + Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description	Two placebo subcutaneous (SC) injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo every 2 weeks (Q2W) from Week 4 until Week 14. Topical Corticosteroid (TCS) will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response	500 milligram (mg) Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection of 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Period Title: Overall Study
Started	75	153
Received at Least One Dose of Study Drug	75	153
Completed	67	142
Not Completed	8	11
Reason Not Completed
Adverse Event	0	3
Lack of Efficacy	1	3
Physician Decision	1	0
Protocol Deviation	2	2
Withdrawal by Subject	4	3

Baseline Characteristics

Arm/Group Title		Placebo + Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid	Total
Arm/Group Description		Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo every Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections of lebrikizumab as a loading dose at Baseline and Week 2 followed by a single injection of 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response	Total of all reporting groups
Overall Number of Baseline Participants		75	153	228
Baseline Analysis Population Description		All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	75 participants	153 participants	228 participants
12 - <18		18	35	53
>= 18 - <65		52	103	155
>=65 - <75		5	10	15
>=75		0	5	5
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	75 participants	153 participants	228 participants
	Female	37	75	112
	Male	38	78	116
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	75 participants	153 participants	228 participants
	American Indian or Alaska Native	2	5	7
	Asian	13	18	31
	Native Hawaiian or Other Pacific Islander	0	3	3
	Black or African American	9	21	30
	White	49	96	145
	More than one race	1	8	9
	Unknown or Not Reported	1	2	3
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	75 participants	153 participants	228 participants
Canada		8 10.7%	14 9.2%	22 9.6%
United States		57 76.0%	111 72.5%	168 73.7%
Poland		8 10.7%	19 12.4%	27 11.8%
Germany		2 2.7%	9 5.9%	11 4.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With an Investigator's Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2-points From Baseline to Week 16.
Description	The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to Good Clinical Practice (GCP) issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	66	145
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	22.1; (11.6 to 32.7)	41.2; (33.0 to 49.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.011
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	18.3
	Confidence Interval	(2-Sided) 95%; 5.1 to 31.5
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Percentage of Participants Achieving Eczema Area and Severity Index (EASI-75) (≥75% Reduction From Baseline in EASI Score) at Week 16
Description	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	66	145
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	42.2; (30.1 to 54.4)	69.5; (61.9 to 77.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	26.4
	Confidence Interval	(2-Sided) 95%; 12.1 to 40.8
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Percentage of Participants Achieving EASI-90 (≥90% Reduction From Baseline in EASI Score) at Week 16
Description	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the EASI score.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	66	145
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	21.7; (11.4 to 32.0)	41.2; (33.0 to 49.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.008
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	18.9
	Confidence Interval	(2-Sided) 95%; 6.1 to 31.7
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Percent Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
Description	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." Least Squares (LS) Mean was calculated using analysis covariance (ANCOVA) model includes treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA score as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	63	139
Least Squares Mean (Standard Error); Unit of Measure: Percent change
	-35.47 (6.358)	-50.68 (4.546)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.017263
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-15.21
	Confidence Interval	(2-Sided) 95%; -27.7 to -2.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.373
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Percentage of Participants With a Pruritus NRS of ≥4-Points at Baseline Who Achieve a ≥4-Point Reduction From Baseline to Week 16
Description	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	57	130
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	31.9; (19.3 to 44.4)	50.6; (41.8 to 59.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.017
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	19.2
	Confidence Interval	(2-Sided) 95%; 4.3 to 34.1
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Percentage of Participants With a Pruritus NRS of ≥5-points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 16
Description	Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours with 0 indicating "No itch" and 10 indicating "Worst itch imaginable."
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	53	124
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	26.4; (14.5 to 38.3)	46.8; (38.0 to 55.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.007
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	21.6
	Confidence Interval	(2-Sided) 95%; 7.1 to 36.1
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Percent Change in EASI Score From Baseline at Week 16
Description	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). LS Mean was calculated using ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA score (IGA 3 versus 4) as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	66	145
Least Squares Mean (Standard Error); Unit of Measure: Percent Change
	-53.12 (5.097)	-76.76 (4.119)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.000003
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-23.64
	Confidence Interval	(2-Sided) 95%; -33.6 to -13.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.074
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Change From Baseline to Week 16 in Percent Body Surface Area (BSA)
Description	The BSA affected by AD will be assessed for 4 separate body regions: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. BSA was calculated using the participant's palm using the 1% rule, 1 palm was equivalent to 1% with estimates of the number of palms it takes to cover the affected AD area. Maximum number of palms were 10 palms for head and neck (10%), 20 palms for upper extremities (20%), 30 palms for trunk, including axilla and groin (30%), 40 palms for lower extremities, including buttocks (40%). Percent of BSA for a body region was calculated as = total number of palms in a body region * % surface area equivalent to 1 palm. Overall percent BSA of all 4 body regions ranges from 0% to 100 % with higher values representing greater severity of AD.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. The mixed model repeated measure (MMRM) include treatment, visit, the interaction of treatment by-visit, geographic region, age group, baseline IGA score. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	53	130
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	16.92 (2.287)	-29.19 (1.686)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-12.28
	Confidence Interval	(2-Sided) 95%; -17.07 to -7.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.428
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Percentage of Participants Achieving EASI-90 at Week 4
Description	The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the EASI score.
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	66	145
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	7.2; (0.5 to 13.8)	10.7; (5.6 to 15.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.454
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	3.5
	Confidence Interval	(2-Sided) 95%; -4.9 to 11.8
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Percent Change in Sleep-loss Score From Baseline to Week 16
Description	Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale [0 (not at all) to 4 (unable to sleep at all)]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. LS Mean was calculated using ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors. .
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	62	134
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-36.89 (12.217)	-57.03 (7.939)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.117607
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Markov Chain Monte Carlo (MCMC)
	Estimated Value	-20.14
	Confidence Interval	(2-Sided) 95%; -45.4 to 5.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 12.810
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Change From Baseline in Sleep-loss Score at Week 16
Description	Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale [0 (not at all) to 4 (unable to sleep at all)]. Higher scores indicated a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary. LS Mean was calculated using ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors. APD: All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	63	139
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-0.80 (0.132)	-1.10 (0.102)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.025293
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Markov Chain Monte Carlo (MCMC)
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95%; -0.6 to -0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.134
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Percentage of Participants With a Pruritus NRS of ≥4-points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4
Description	The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable.
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants, with baseline Pruritus NRS score of at least 4, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	57	130
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	9.3; (1.6 to 17.1)	23.5; (16.2 to 30.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.022
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	14.2
	Confidence Interval	(2-Sided) 95%; 3.8 to 24.7
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Percentage of Participants With a Pruritus NRS of ≥4-points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2
Description	The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable.
Time Frame	Baseline to Week 2

Outcome Measure Data

Analysis Population Description

All randomized participants, with baseline Pruritus NRS score of at least 4, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	57	130
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	7.1; (0.4 to 13.8)	8.5; (3.7 to 13.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.764
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; -7.3 to 9.7
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Percentage of Participants With a Pruritus NRS of ≥4-points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1
Description	The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable.
Time Frame	Baseline to Week 1

Outcome Measure Data

Analysis Population Description

All randomized participants, with baseline Pruritus NRS score of at least 4, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	57	130
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	1.8; (0.0 to 5.2)	3.8; (0.5 to 7.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.498
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; -2.9 to 6.7
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Percentage of Participants With a Pruritus NRS of ≥5-points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4
Description	The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable.
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants, with baseline Pruritus NRS score of at least 5, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	53	124
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	7.5; (0.4 to 14.7)	23.4; (15.9 to 30.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.014
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	15.6
	Confidence Interval	(2-Sided) 95%; 5.3 to 25.9
	Estimation Comments	[Not Specified]

16. Secondary Outcome

Title	Percentage of Participants With a Pruritus NRS of ≥5-points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2
Description	The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable.
Time Frame	Baseline to Week 2

Outcome Measure Data

Analysis Population Description

All randomized participants, with baseline Pruritus NRS score of at least 5, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	53	124
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	7.5; (0.4 to 14.7)	8.9; (3.9 to 13.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.818
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; -8.0 to 10.2
	Estimation Comments	[Not Specified]

17. Secondary Outcome

Title	Percentage of Participants With a Pruritus NRS of ≥5-points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1
Description	The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable.
Time Frame	Baseline to Week 1

Outcome Measure Data

Analysis Population Description

All randomized participants, with baseline Pruritus NRS score of at least 5, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	53	124
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	1.9; (0.0 to 5.5)	4.0; (0.6 to 7.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.499
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -3.1 to 7.1
	Estimation Comments	[Not Specified]

18. Secondary Outcome

Title	Percentage of Topical Corticosteroid (TCS)/Topical Calcineurin Inhibitors (TCI) Free Days From Baseline to Week 16
Description	Number of the total TCS/TCI free days divided by total number of days during the treatment period. The mixed model repeated measures (MMRM) includes treatment, visit, the interaction of treatment by-visit, geographic region, age group, baseline IGA score.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	53	131
Least Squares Mean (Standard Error); Unit of Measure: Percentage of Days
	23.88 (4.823)	31.17 (3.512)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.155
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	7.29
	Confidence Interval	(2-Sided) 95%; -2.78 to 17.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.104
	Estimation Comments	[Not Specified]

19. Secondary Outcome

Title	Median Time (Days) to TCS/TCI-free Use From Baseline to Week 16
Description	Days from first study drug injection to the day participant stopped using all TCS/TCI (if a participant started and stopped using low or midpotency TCS/TCI multiple times, use the last stop date as the stop date for this participant).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	66	145
Median (Full Range); Unit of Measure: days
	NA [1]; (1 to 112)	121.0; (2 to 121)

[1]

Less than 50 % of the participants reached TCS free within treatment window, median was not calculable.

20. Secondary Outcome

Title	Percent Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16
Description	The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), & subjective symptoms (C: 0-20) combine using A/5 + 7*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. LS Mean was calculated using the ANCOVA model with treatment group, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues. Missing Values were imputed using last observation carried forward (LOCF) method.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	65	140
Least Squares Mean (Standard Error); Unit of Measure: percent change
	-37.35 (4.415)	-55.04 (3.542)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-17.69
	Confidence Interval	(2-Sided) 95%; -26.37 to -9.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.403
	Estimation Comments	[Not Specified]

21. Secondary Outcome

Title	Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
Description	The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment, over the previous week. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life. LS Mean was calculated using the ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	51	109
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-6.46 (1.855)	-9.79 (1.815)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.001031
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-3.33
	Confidence Interval	(2-Sided) 95%; -5.3 to -1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.014
	Estimation Comments	[Not Specified]

22. Secondary Outcome

Title	Percentage of Participants With a DLQI Score ≥4 Points at Baseline Who Achieve a ≥4 Points
Description	The DLQI is a 10-item, validated questionnaire used to assess the impact of skin disease on the quality of life of an affected person. The 10 questions cover the following topics: symptoms, embarrassment, shopping and home care, clothes, social and leisure, sport, work or study, close relationships, sex, and treatment, over the previous week. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". Questions are scored from 0 to 3, giving a possible total score range from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). A high score is indicative of a poor quality of life. LS Mean was calculated using the ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	48	105
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	58.7; (44.1 to 73.2)	77.4; (69.3 to 85.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.036
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	17.2
	Confidence Interval	(2-Sided) 95%; 0.1 to 34.3
	Estimation Comments	[Not Specified]

23. Secondary Outcome

Title	Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) at Week 16 Health State Index
Description	The EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state. LS Mean was calculated using the ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues. Missing values were imputed using LOCF method.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	66	143
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
Health State Index UK	0.05 (0.025)	0.15 (0.019)
Health State Index US	0.03 (0.018)	0.10 (0.014)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	Health State Index UK
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; 0.06 to 0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.025
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	Health State Index US
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; 0.04 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.018
	Estimation Comments	[Not Specified]

24. Secondary Outcome

Title	Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) at Week 16 Visual Analog Score (VAS)
Description	The EQ-5D-5L is a 2-part measurement. The second part is assessed using a VAS that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. LS Mean was calculated using the ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues. Missing values were imputed using LOCF method.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	65	143
Least Squares Mean (Standard Error); Unit of Measure: millimeters (mm)
	6.51 (2.364)	10.13 (1.831)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.131
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	3.62
	Confidence Interval	(2-Sided) 95%; -1.08 to 8.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.386
	Estimation Comments	[Not Specified]

25. Secondary Outcome

Title	Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16
Description	POEM is a 7-item, validated, questionnaire used by the participant to assess disease symptoms over the last week. The participant is asked to respond to 7 questions on skin dryness, itching, flaking, cracking, sleep loss, bleeding and weeping. All 7 answers carry equal weight with a total possible score from 0 to 28 (answers scored as: No days=0; 1- 2 days = 1; 3-4 days = 2; 5-6 days = 3; everyday = 4). A high score is indicative of a poor quality of life. POEM responses will be captured using an electronic diary and transferred into the clinical database. LS Mean was calculated using MMRM model using treatment, baseline value, visit, the interaction of the baseline value-by-visit, the interaction of treatment by-visit as covariates, geographic region, age group, baseline IGA (3 versus 4) score as fixed.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	40	101
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-6.24 (1.038)	-10.23 (0.727)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-4.00
	Confidence Interval	(2-Sided) 95%; -6.26 to -1.74
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.145
	Estimation Comments	[Not Specified]

26. Secondary Outcome

Title	Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Week 16 - Adults
Description	PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. The PROMIS measures will be completed by the participant in the study clinic. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety. Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-scores with higher scores indicating greater severity of symptoms. LS Mean was calculated using the ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues. Missing values were imputed with the LOCF method.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	43	101
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-1.08 (1.367)	-1.88 (1.027)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.571
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95%; -3.58 to 1.98
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.407
	Estimation Comments	[Not Specified]

27. Secondary Outcome

Title	Change From Baseline in PROMIS Depression at Week 16 - Adults
Description	PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. The PROMIS measures will be completed by the participant in the study clinic. PROMIS depression has 8 questions on Emotion Distress-Depression. Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-scores with higher scores indicating greater severity of symptoms. LS Mean was calculated using the ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues. Missing values were imputed with the LOCF method.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	43	101
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-1.21 (1.098)	-1.38 (0.834)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.882
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -2.40 to 2.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.127
	Estimation Comments	[Not Specified]

28. Secondary Outcome

Title	Change From Baseline in PROMIS Anxiety at Week 16 - Pediatrics
Description	PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS anxiety has 8 questions on Emotion Distress-Anxiety (or Pediatric Anxiety Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-scores with higher scores indicating greater severity of symptoms. LS Mean was calculated using the ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues. Missing values were imputed using the LOCF method.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	13	31
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-4.92 (2.333)	-1.46 (1.732)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.171
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	3.46
	Confidence Interval	(2-Sided) 95%; -1.56 to 8.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.480
	Estimation Comments	[Not Specified]

29. Secondary Outcome

Title	Change From Baseline in PROMIS Depression at Week 16 - Pediatrics
Description	PROMIS® is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Participants ≤17 years will complete pediatric versions for the duration of the study. PROMIS depression has 8 questions on Emotion Distress-Depression (or Pediatric Depressive Symptom). Each question has 5 response options with values from 1 to 5. Total raw scores were converted to T-scores with higher scores indicating greater severity of symptoms. LS Mean was calculated using the ANCOVA model with treatment, baseline value, and stratification factors of geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues. Missing values were imputed using the LOCF method.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	13	31
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-6.43 (2.536)	-2.01 (1.916)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.109
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	4.43
	Confidence Interval	(2-Sided) 95%; -1.03 to 9.89
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.697
	Estimation Comments	[Not Specified]

30. Secondary Outcome

Title	Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 16 in Participants Who Have Self-reported Comorbid Asthma
Description	The ACQ-5 has been shown to reliably measure asthma control and distinguish participants with well-controlled asthma (score ≤0.75 points) from those with uncontrolled asthma (score ≥1.5 points). It consists of 5 questions that are scored on a 7- point Likert scale with a recall period of 1 week. The total ACQ-5 score is the mean score of all questions; a lower score represents better asthma control. LS Mean was calculated using ANCOVA with treatment, baseline value, geographic region, age group, baseline IGA (3 versus 4) score as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues. Missing values were imputed with the LOCF method.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	14	38
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	0.12 (0.116)	0.13 (0.076)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.922
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.22 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.116
	Estimation Comments	[Not Specified]

31. Secondary Outcome

Title	Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16
Description	The CDLQI questionnaire is designed for use in children (4 to 16 years of age). It consists of 10 items that are grouped into 6 domains: symptoms & feelings, leisure, school or holidays, personal relationships, sleep, & treatment. The scoring of each question is: Very much =3; Quite a lot = 2; Only a little = 1; Not at all = 0. CDLQI total score is calculated by summing all 10 items responses, and has a range of 0 to 30 (higher scores are indicative of greater impairment). LS Mean was calculated using MMRM model which includes treatment, baseline value, visit, the interaction of the baseline value-by-visit as covariates, the interaction of treatment by-visit, geographic region, age group, and baseline IGA (3 versus 4) score as fixed factors.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

All randomized participants, even if the participant does not take the assigned treatment, does not receive the correct treatment, or otherwise does not follow the protocol. One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Arm/Group Title	Placebo +Topical Corticosteroid	Lebrikizumab + Topical Corticosteroid
Arm/Group Description:	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14.TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.	500 mg Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 followed by a single injection 250 mg Lebrikizumab Q2W from Week 4 until Week 14. TCS will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
Overall Number of Participants Analyzed	11	24
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	-4.71 (1.170)	-9.33 (0.887)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo +Topical Corticosteroid, Lebrikizumab + Topical Corticosteroid
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-4.62
	Confidence Interval	(2-Sided) 95%; -7.22 to -2.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.271
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Baseline up to Week 28
Adverse Event Reporting Description	All randomized participants who received at least 1 dose of study treatment.
Arm/Group Title	Placebo +Topical Corticosteroid		Lebrikizumab + Topical Corticosteroid
Arm/Group Description	Two placebo SC injections as a loading dose at Baseline and Week 2 followed by a single injection of placebo Q2W from Week 4 until Week 14. Topical corticosteroid (TCS) will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.		500 mg Lebrikizumab (2 x 250 mg) subcutaneous (SC) injections as a loading dose at Baseline and Week 2 followed by a single injection of 250 mg Lebrikizumab every 2 weeks (Q2W) from Week 4 until Week 14. Topical corticosteroid (TCS) will be initiated at Baseline in all participants and may be tapered or stopped, or restarted as needed, based on treatment response.
All-Cause Mortality
	Placebo +Topical Corticosteroid		Lebrikizumab + Topical Corticosteroid
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/75 (0.00%)		0/153 (0.00%)
Serious Adverse Events
	Placebo +Topical Corticosteroid		Lebrikizumab + Topical Corticosteroid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/75 (1.33%)		2/153 (1.31%)
Cardiac disorders
Sinus node dysfunction † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Injury, poisoning and procedural complications
Fall † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Metabolism and nutrition disorders
Dehydration † 1	1/75 (1.33%)	1	0/153 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	1/75 (1.33%)	1	0/153 (0.00%)	0
1 Term from vocabulary, MedDRA 24.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Placebo +Topical Corticosteroid		Lebrikizumab + Topical Corticosteroid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/75 (34.67%)		66/153 (43.14%)
Blood and lymphatic system disorders
Eosinophilia † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Iron deficiency anaemia † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Lymphadenopathy † 1	1/75 (1.33%)	1	1/153 (0.65%)	1
Lymphocytosis † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Neutropenia † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Thrombocytopenia † 1	0/75 (0.00%)	0	2/153 (1.31%)	2
Eye disorders
Blepharitis † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Conjunctival haemorrhage † 1	1/75 (1.33%)	1	0/153 (0.00%)	0
Dry eye † 1	0/75 (0.00%)	0	3/153 (1.96%)	3
Eye irritation † 1	0/75 (0.00%)	0	1/153 (0.65%)	2
Lacrimation increased † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Vernal keratoconjunctivitis † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Xerophthalmia † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Gastrointestinal disorders
Diarrhoea † 1	1/75 (1.33%)	1	1/153 (0.65%)	1
Flatulence † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Gastrointestinal inflammation † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Nausea † 1	0/75 (0.00%)	0	2/153 (1.31%)	2
Vomiting † 1	0/75 (0.00%)	0	2/153 (1.31%)	2
General disorders
Injection site erythema † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Injection site pruritus † 1	0/75 (0.00%)	0	1/153 (0.65%)	2
Injection site rash † 1	0/75 (0.00%)	0	2/153 (1.31%)	2
Injection site reaction † 1	1/75 (1.33%)	1	2/153 (1.31%)	2
Injection site swelling † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Vaccination site pain † 1	1/75 (1.33%)	1	0/153 (0.00%)	0
Hepatobiliary disorders
Cholelithiasis † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Hepatic steatosis † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Hepatomegaly † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Immune system disorders
Drug hypersensitivity † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Infections and infestations
Bacteraemia † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Bacterial colitis † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Bronchitis † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Cellulitis † 1	1/75 (1.33%)	1	1/153 (0.65%)	1
Conjunctivitis † 1	0/75 (0.00%)	0	7/153 (4.58%)	8
Covid-19 † 1	0/75 (0.00%)	0	2/153 (1.31%)	2
Furuncle † 1	1/75 (1.33%)	1	0/153 (0.00%)	0
Herpes zoster † 1	0/75 (0.00%)	0	2/153 (1.31%)	2
Impetigo † 1	1/75 (1.33%)	1	2/153 (1.31%)	2
Nasopharyngitis † 1	5/75 (6.67%)	6	3/153 (1.96%)	5
Ophthalmic herpes simplex † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Oral herpes † 1	1/75 (1.33%)	1	2/153 (1.31%)	2
Tonsillitis † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Tooth abscess † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Tooth infection † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Upper respiratory tract infection † 1	2/75 (2.67%)	2	1/153 (0.65%)	1
Urinary tract infection † 1	0/75 (0.00%)	0	3/153 (1.96%)	3
Injury, poisoning and procedural complications
Concussion † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Corneal abrasion † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Fall † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Fibula fracture † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Ligament sprain † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Limb injury † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Muscle strain † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Suture related complication † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Vaccination complication † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Investigations
Alanine aminotransferase increased † 1	1/75 (1.33%)	1	1/153 (0.65%)	1
Aspartate aminotransferase increased † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Blood alkaline phosphatase increased † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Blood pressure increased † 1	1/75 (1.33%)	1	1/153 (0.65%)	2
Gamma-glutamyltransferase increased † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Weight increased † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Metabolism and nutrition disorders
Alcohol intolerance † 1	0/75 (0.00%)	0	1/153 (0.65%)	2
Hypercholesterolaemia † 1	1/75 (1.33%)	1	0/153 (0.00%)	0
Hyperglycaemia † 1	1/75 (1.33%)	1	0/153 (0.00%)	0
Hyperkalaemia † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Hypokalaemia † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Malnutrition † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Type 2 diabetes mellitus † 1	0/75 (0.00%)	0	2/153 (1.31%)	2
Vitamin d deficiency † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Musculoskeletal and connective tissue disorders
Back pain † 1	1/75 (1.33%)	1	0/153 (0.00%)	0
Bursitis † 1	1/75 (1.33%)	1	0/153 (0.00%)	0
Myalgia † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Spinal pain † 1	1/75 (1.33%)	1	0/153 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Keratoacanthoma † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Nervous system disorders
Cervical radiculopathy † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Dizziness † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Headache † 1	1/75 (1.33%)	1	7/153 (4.58%)	7
Ophthalmic migraine † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Syncope † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Psychiatric disorders
Attention deficit hyperactivity disorder † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Insomnia † 1	1/75 (1.33%)	1	0/153 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Asthma † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Chronic obstructive pulmonary disease † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Rhinitis allergic † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Rhinorrhoea † 1	1/75 (1.33%)	1	1/153 (0.65%)	1
Sinus congestion † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Skin and subcutaneous tissue disorders
Acne † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Alopecia areata † 1	1/75 (1.33%)	1	0/153 (0.00%)	0
Dermatitis † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Dermatitis acneiform † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Dermatitis atopic † 1	3/75 (4.00%)	3	3/153 (1.96%)	3
Dermatitis contact † 1	0/75 (0.00%)	0	1/153 (0.65%)	1
Eczema † 1	1/75 (1.33%)	1	1/153 (0.65%)	1
Hyperhidrosis † 1	1/75 (1.33%)	1	0/153 (0.00%)	0
Skin lesion inflammation † 1	1/75 (1.33%)	1	1/153 (0.65%)	1
Urticaria † 1	1/75 (1.33%)	1	1/153 (0.65%)	2
Vascular disorders
Hypertension † 1	1/75 (1.33%)	1	4/153 (2.61%)	4
1 Term from vocabulary, MedDRA 24.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

One investigational site with seventeen participants was excluded from analysis due to GCP issues.

Because of an error in the electronic data collection tool, the actual maximum score for each of the SCORAD symptoms was 9 instead of 10, resulting in a total maximum SCORAD score of 101 instead of 103. During the study, discussions with the SCORAD copyright owner resulted in a decision not to adjust the scale used or notify investigators as the altered scale was not expected to bias the results.

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: Chief Medical Officer
• Organization: Eli Lilly and Company
• Phone: 800-545-5979
• EMail: ClinicalTrials.gov@lilly.com

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT04250337
• Other Study ID Numbers: 17803; 2019-004300-34 ( EudraCT Number ); J2T-DM-KGAD ( Other Identifier: Eli Lilly and Company ); DRM06-AD06 ( Other Identifier: Dermira, Inc. )
• First Submitted: January 30, 2020
• First Posted: January 31, 2020
• Results First Submitted: March 14, 2022
• Results First Posted: May 2, 2022
• Last Update Posted: May 9, 2022