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Clinical Trial Results:
A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Lebrikizumab in Patients With Persistent Moderate to Severe Atopic Dermatitis That is Inadequately Controlled by Topical Corticosteroids

Summary
EudraCT number	2014-000049-56
Trial protocol	DE CZ ES FI NL PL
Global end of trial date	18 Apr 2016

Results information
Results version number	v1(current)
This version publication date	04 May 2017
First version publication date	04 May 2017
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

GS29250

ISRCTN number

US NCT number

NCT02340234

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com

Scientific contact

Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

29 Jun 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

18 Apr 2016

Was the trial ended prematurely?

Main objective of the trial

The main objective of the study was to evaluate the safety and efficacy of lebrikizumab used as adjunctive therapy with topical corticosteroids (TCS), compared with TCS in participants with persistent moderate to severe atopic dermatitis (AD).

Protection of trial subjects

The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice (GCP) according to the regulations and procedures described in the protocol. Approval from the Ethics Committee (EC)/Institutional Review Board (IRB) was obtained before study start. Roche also obtained approval from the relevant Competent Authority prior to starting the study. No modifications were made to the protocol after receipt of the EC/IRB approval.

Background therapy

Evidence for comparator

Actual start date of recruitment

18 May 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Korea, Republic of: 18

Country: Number of subjects enrolled

Taiwan: 14

Country: Number of subjects enrolled

Czech Republic: 15

Country: Number of subjects enrolled

Finland: 11

Country: Number of subjects enrolled

France: 18

Country: Number of subjects enrolled

Germany: 6

Country: Number of subjects enrolled

United Kingdom: 10

Country: Number of subjects enrolled

Netherlands: 8

Country: Number of subjects enrolled

Poland: 17

Country: Number of subjects enrolled

Spain: 20

Country: Number of subjects enrolled

Switzerland: 6

Country: Number of subjects enrolled

Australia: 20

Country: Number of subjects enrolled

Canada: 15

Country: Number of subjects enrolled

United States: 34

Worldwide total number of subjects

212

EEA total number of subjects

105

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

209

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 294 participants were screened, 212 participants were randomized, and 209 received at least one dose of study drug.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Lebrikizumab 250 mg Single Dose + TCS

Arm description

Participants received a single dose of lebrikizumab 250 milligrams (mg) subcutaneous (SC) injection on Day 1 followed by placebo on Week 4 and Week 8. Participants continued to apply TCS cream (triamcenolone acetonide 0.1 percent [%] or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.

Arm type

Experimental

Investigational medicinal product name

Lebrikizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Lebrikizumab administered as SC injection as per the schedule specified in the respective arms.

Investigational medicinal product name

Triamcinolone acetonide

Investigational medicinal product code

Other name

Pharmaceutical forms

Cream

Routes of administration

Cutaneous use

Dosage and administration details

Triamcinolone acetonide 0.1% cream was applied twice daily to active skin lesions.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo matched to lebrikizumab

Investigational medicinal product name

Hydrocortisone

Investigational medicinal product code

Other name

Pharmaceutical forms

Cream

Routes of administration

Cutaneous use

Dosage and administration details

Hydrocortisone 2.5% cream was applied twice daily to active skin lesions.

Lebrikizumab 125 mg Single Dose + TCS

Arm description

Participants received a single dose of lebrikizumab 125 mg SC injection on Day 1 followed by placebo on Week 4 and Week 8. Participants continued to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.

Arm type

Experimental

Investigational medicinal product name

Lebrikizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Lebrikizumab administered as SC injection as per the schedule specified in the respective arms.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo matched to lebrikizumab

Investigational medicinal product name

Triamcinolone acetonide

Investigational medicinal product code

Other name

Pharmaceutical forms

Cream

Routes of administration

Cutaneous use

Dosage and administration details

Triamcinolone acetonide 0.1% cream was applied twice daily to active skin lesions.

Investigational medicinal product name

Hydrocortisone

Investigational medicinal product code

Other name

Pharmaceutical forms

Cream

Routes of administration

Cutaneous use

Dosage and administration details

Hydrocortisone 2.5% cream was applied twice daily to active skin lesions.

Lebrikizumab 125 mg Q4W + TCS

Arm description

Participants received lebrikizumab 125 mg SC injection every 4 weeks (Q4W) for a total of 3 doses. Participants continued to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.

Arm type

Experimental

Investigational medicinal product name

Lebrikizumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Lebrikizumab administered as SC injection as per the schedule specified in the respective arms.

Investigational medicinal product name

Hydrocortisone

Investigational medicinal product code

Other name

Pharmaceutical forms

Cream

Routes of administration

Cutaneous use

Dosage and administration details

Hydrocortisone 2.5% cream was applied twice daily to active skin lesions.

Investigational medicinal product name

Triamcinolone acetonide

Investigational medicinal product code

Other name

Pharmaceutical forms

Cream

Routes of administration

Cutaneous use

Dosage and administration details

Triamcinolone acetonide 0.1% cream was applied twice daily to active skin lesions.

Placebo Q4W + TCS Cream

Arm description

Participants received placebo Q4W for a total of 3 doses. Participants continued to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo matched to lebrikizumab

Investigational medicinal product name

Hydrocortisone

Investigational medicinal product code

Other name

Pharmaceutical forms

Cream

Routes of administration

Cutaneous use

Dosage and administration details

Hydrocortisone 2.5% cream was applied twice daily to active skin lesions.

Investigational medicinal product name

Triamcinolone acetonide

Investigational medicinal product code

Other name

Pharmaceutical forms

Cream

Routes of administration

Cutaneous use

Dosage and administration details

Triamcinolone acetonide 0.1% cream was applied twice daily to active skin lesions.

Number of subjects in period 1	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Started	53	53	52	54
Treated	53	52	51	53
Completed	53	49	48	47
Not completed	0	4	4	7
Consent withdrawn by subject	-	2	1	3
Other unspecified	-	1	1	-
Adverse Event	-	-	1	1
Lost to follow-up	-	1	-	3
Lack of efficacy	-	-	1	-

Baseline characteristics

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Reporting group title

Lebrikizumab 250 mg Single Dose + TCS

Reporting group description

Reporting group title

Lebrikizumab 125 mg Single Dose + TCS

Reporting group description

Reporting group title

Lebrikizumab 125 mg Q4W + TCS

Reporting group description

Reporting group title

Placebo Q4W + TCS Cream

Reporting group description

Reporting group values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream	Total
Number of subjects	53	53	52	54	212
Age Categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	34.4 ( 12.3 )	34.9 ( 12.6 )	36.8 ( 12.2 )	38.8 ( 13.1 )	-
Gender Categorical
Units: Subjects
Female	22	18	16	18	74
Male	31	35	36	36	138

End points

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Reporting group title

Lebrikizumab 250 mg Single Dose + TCS

Reporting group description

Reporting group title

Lebrikizumab 125 mg Single Dose + TCS

Reporting group description

Reporting group title

Lebrikizumab 125 mg Q4W + TCS

Reporting group description

Reporting group title

Placebo Q4W + TCS Cream

Reporting group description

Subject analysis set title

Lebrikizumab 250 mg Single Dose + TCS

Subject analysis set type

Safety analysis

Subject analysis set description

Participants received a single dose of lebrikizumab 250 mg SC injection on Day 1 followed by placebo on Week 4 and Week 8. Participants continued to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.

Subject analysis set title

Lebrikizumab 125 mg Single Dose + TCS

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Lebrikizumab 125 mg Q4W + TCS

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Placebo Q4W + TCS Cream

Subject analysis set type

Safety analysis

Subject analysis set description

Primary: Percentage of Participants Who Achieved a 50 Percent (%) Reduction From Baseline in EASI Score (EASI-50) at Week 12

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End point title

Percentage of Participants Who Achieved a 50 Percent (%) Reduction From Baseline in EASI Score (EASI-50) at Week 12

End point description

The EASI score was used to measure the severity and extent of AD and measures erythema, induration-papulation, excoriation and lichenification on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head and neck, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no eruption) to 6 (greater than [>] 90 %-100% eruption). The total score is the sum of the four body-region scores, maximum=72, minimum=0, with higher scores reflecting greater disease severity. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score. mITT population.

End point type

Primary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	52	51	53
Units: percentage of participants
number (confidence interval 95%)	69.8 (57.45 to 82.17)	69.2 (56.69 to 81.78)	82.4 (71.89 to 92.82)	62.3 (49.21 to 75.31)

Statistical Analysis 1

Statistical analysis description

Cochran-Mantel-Haenszel (CMH) chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% confidence interval (CI) was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4361

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

7.55

Confidence interval

level

95%

sides

2-sided

lower limit

-10.43

upper limit

25.52

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4792

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

6.97

Confidence interval

level

95%

sides

2-sided

lower limit

-11.13

upper limit

25.07

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0261

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

20.09

Confidence interval

level

95%

sides

2-sided

lower limit

3.36

upper limit

36.81

Secondary: Percent Change From Baseline in EASI Score at Week 12

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End point title

Percent Change From Baseline in EASI Score at Week 12

End point description

The EASI score was used to measure the severity and extent of AD and measures erythema, induration-papulation, excoriation and lichenification on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head and neck, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no eruption) to 6 (> 90%-100% eruption). The total score is the sum of the four body-region scores, maximum=72, minimum=0, with higher scores reflecting greater disease severity. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score. mITT population. Here, number of subjects analysed (N)=participants analysed for this outcome.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	50	49	50
Units: percent change
least squares mean (standard error)	-57.7 ( 5.263 )	-58.46 ( 5.364 )	-70.5 ( 5.452 )	-53.14 ( 5.382 )

Statistical Analysis 1

Statistical analysis description

Adjusted mean and standard error of mean (SE) was calculated using linear mixed effects model including fixed effects of baseline value, treatment arm, visit, treatment by visit interaction, and geographic region; participant was included in the model as random effects with unstructured covariance structure.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5458

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-4.56

Confidence interval

level

95%

sides

2-sided

lower limit

-19.41

upper limit

10.3

Variability estimate

Standard error of the mean

Dispersion value

7.533

Statistical Analysis 2

Statistical analysis description

Adjusted mean and SE was calculated using linear mixed effects model including fixed effects of baseline value, treatment arm, visit, treatment by visit interaction, and geographic region; participant was included in the model as random effects with unstructured covariance structure.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4844

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-5.32

Confidence interval

level

95%

sides

2-sided

lower limit

-20.29

upper limit

9.65

Variability estimate

Standard error of the mean

Dispersion value

7.594

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0247

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-17.35

Confidence interval

level

95%

sides

2-sided

lower limit

-32.48

upper limit

-2.23

Variability estimate

Standard error of the mean

Dispersion value

7.671

Secondary: Absolute Change From Baseline in EASI Score at Week 12

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End point title

Absolute Change From Baseline in EASI Score at Week 12

End point description

The EASI score was used to measure the severity and extent of AD and measures erythema, induration-papulation, excoriation and lichenification on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head and neck, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no eruption) to 6 (> 90%-100% eruption). The total score is the sum of the four body-region scores, maximum=72, minimum=0, with higher scores reflecting greater disease severity. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score. mITT population. Here, N=participants analysed for this outcome.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	50	49	50
Units: units on scale
least squares mean (standard error)	-15.63 ( 1.343 )	-14.68 ( 1.367 )	-17.73 ( 1.39 )	-12.67 ( 1.372 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1256

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-2.96

Confidence interval

level

95%

sides

2-sided

lower limit

-6.75

upper limit

0.83

Variability estimate

Standard error of the mean

Dispersion value

1.922

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3022

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.82

upper limit

1.81

Variability estimate

Standard error of the mean

Dispersion value

1.936

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0105

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-5.06

Confidence interval

level

95%

sides

2-sided

lower limit

-8.91

upper limit

-1.2

Variability estimate

Standard error of the mean

Dispersion value

1.956

Secondary: Percentage of Participants Who Achieved a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 12

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End point title

Percentage of Participants Who Achieved a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 12

End point description

The EASI score was used to measure the severity and extent of AD and measures erythema, induration-papulation, excoriation and lichenification on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head and neck, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no eruption) to 6 (> 90%-100% eruption). The total score is the sum of the four body-region scores, maximum=72, minimum=0, with higher scores reflecting greater disease severity. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score. mITT population.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	52	51	53
Units: percentage of participants
number (confidence interval 95%)	49.1 (35.6 to 62.52)	38.5 (25.24 to 51.68)	54.9 (41.25 to 68.56)	34 (21.21 to 46.71)

Statistical Analysis 1

Statistical analysis description

CMH chi-square test was stratified by geographic region. 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.123

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

15.09

Confidence interval

level

95%

sides

2-sided

lower limit

-3.44

upper limit

33.63

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region. 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6627

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

4.5

Confidence interval

level

95%

sides

2-sided

lower limit

-13.87

upper limit

22.87

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region. 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.036

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

20.94

Confidence interval

level

95%

sides

2-sided

lower limit

2.26

upper limit

39.62

Secondary: Percentage of Participants Who Achieved an Investigator's Global Assessment (IGA) Score of 0 or 1 at Week 12

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End point title

Percentage of Participants Who Achieved an Investigator's Global Assessment (IGA) Score of 0 or 1 at Week 12

End point description

The IGA score is an assessment of the participant's disease state at the time of examination and does not attempt a comparison with any of the participant's previous disease states. The IGA utilizes a 6-point scale ranging from 0 to 5 where 0 = clear (no inflammatory signs of AD), 1 = almost clear (just perceptible erythema and papulation induration), 2 = mild (mild erythema and papulation induration; no oozing or crusting), 3 = moderate (moderate erythema and papulation induration; oozing and crusting may be present), 4 = severe (severe erythema and papulation induration; oozing and crusting is present) and 5 = very severe AD. mITT population.

End point type

Secondary

End point timeframe

Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	52	51	53
Units: percentage of participants
number (confidence interval 95%)	28.3 (16.17 to 40.43)	21.2 (10.05 to 32.25)	33.3 (20.4 to 46.27)	18.9 (8.33 to 29.4)

Statistical Analysis 1

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.263

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

9.43

Confidence interval

level

95%

sides

2-sided

lower limit

-6.63

upper limit

25.5

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7745

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

2.29

Confidence interval

level

95%

sides

2-sided

lower limit

-13.02

upper limit

17.59

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0976

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

14.47

Confidence interval

level

95%

sides

2-sided

lower limit

-2.22

upper limit

31.15

Secondary: Percentage of Participants With a Greater Than or Equal to (>/=) 2 Point Reduction From Baseline in IGA at Week 12

Top of page

End point title

Percentage of Participants With a Greater Than or Equal to (>/=) 2 Point Reduction From Baseline in IGA at Week 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	52	51	53
Units: percentage of participants
number (confidence interval 95%)	35.8 (22.94 to 48.76)	23.1 (11.63 to 34.53)	37.3 (23.99 to 50.52)	24.5 (12.94 to 36.11)

Statistical Analysis 1

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2154

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

11.32

Confidence interval

level

95%

sides

2-sided

lower limit

-6.02

upper limit

28.67

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8603

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-1.45

Confidence interval

level

95%

sides

2-sided

lower limit

-17.74

upper limit

14.84

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1673

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

12.73

Confidence interval

level

95%

sides

2-sided

lower limit

-4.89

upper limit

30.34

Secondary: Absolute Change From Baseline in IGA at Week 12

Top of page

End point title

Absolute Change From Baseline in IGA at Week 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	50	49	50
Units: units on scale
least squares mean (standard error)	-1.13 ( 0.125 )	-1.04 ( 0.128 )	-1.33 ( 0.13 )	-0.92 ( 0.128 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2281

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.22

Confidence interval

level

95%

sides

2-sided

lower limit

-0.57

upper limit

0.14

Variability estimate

Standard error of the mean

Dispersion value

0.179

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5038

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.48

upper limit

0.24

Variability estimate

Standard error of the mean

Dispersion value

0.181

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0258

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.41

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

-0.05

Variability estimate

Standard error of the mean

Dispersion value

0.182

Secondary: Percentage of Participants Who Achieved an Investigator Global Signs Assessment (IGSA) Score of 0 or 1 at Week 12

Top of page

End point title

Percentage of Participants Who Achieved an Investigator Global Signs Assessment (IGSA) Score of 0 or 1 at Week 12

End point description

The IGSA score is an assessment of AD signs. Investigator assesses signs in 2 steps: Step 1: Lesional assessment: Investigator chooses the lesional grade that best describes the participant’s involved skin, on average. Step 2: Consider Upgrade or Downgrade: based on skin lesion extent and location. Upgrade refers to the disease extends over the majority (>50% of a region) of one or more body regions, or is prominently affecting high visibility/functionally-important areas (face and hands). Downgrade refers to the disease localized to only one or two small areas (less than 1-2 palms) that are not highly visible or functionally important. A region is defined by i) arms combined, ii) legs combined, iii) trunk, and iv) head and neck, for a total of four regions. The IGSA utilizes a 5-point scale ranging from 0 (clear) to 5 (severe disease) where 0 = clear (no inflammatory signs of AD), 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe AD. mITT population.

End point type

Secondary

End point timeframe

Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	52	51	53
Units: percentage of participants
number (confidence interval 95%)	30.2 (17.83 to 42.55)	19.2 (8.52 to 29.94)	29.4 (16.91 to 41.92)	22.6 (11.37 to 33.91)

Statistical Analysis 1

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3945

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

7.55

Confidence interval

level

95%

sides

2-sided

lower limit

-9.18

upper limit

24.27

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.647

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-3.41

Confidence interval

level

95%

sides

2-sided

lower limit

-18.96

upper limit

12.14

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4395

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

6.77

Confidence interval

level

95%

sides

2-sided

lower limit

-10.06

upper limit

23.6

Secondary: Percentage of Participants With a >/=2 Point Reduction From Baseline in IGSA at Week 12

Top of page

End point title

Percentage of Participants With a >/=2 Point Reduction From Baseline in IGSA at Week 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	52	51	53
Units: percentage of participants
number (confidence interval 95%)	43.4 (30.05 to 56.74)	26.9 (14.87 to 38.98)	41.2 (27.67 to 54.68)	26.4 (14.55 to 38.28)

Statistical Analysis 1

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0729

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

16.98

Confidence interval

level

95%

sides

2-sided

lower limit

-0.88

upper limit

34.84

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1186

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

14.76

Confidence interval

level

95%

sides

2-sided

lower limit

-3.22

upper limit

32.74

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9636

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

0.51

Confidence interval

level

95%

sides

2-sided

lower limit

-16.41

upper limit

17.43

Secondary: Absolute Change From Baseline in IGSA at Week 12

Top of page

End point title

Absolute Change From Baseline in IGSA at Week 12

End point description

IGSA score is an assessment of AD signs. Investigator assesses signs in 2 steps: Step 1:Lesional assessment:Investigator chooses lesional grade that best describes participant’s involved skin, on average. Step 2: Consider Upgrade or Downgrade:based on skin lesion extent and location. Upgrade refers to disease extends over majority (>50% of a region) of one or more body regions, or is prominently affecting high visibility/functionally-important areas (face and hands). Downgrade refers to disease localized to only one or two small areas (less than 1-2 palms) that are not highly visible or functionally important. A region is defined by i) arms combined, ii) legs combined, iii) trunk, and iv) head and neck, for a total of four regions. IGSA utilizes a 5-point scale ranging from 0 (clear) to 5 (severe disease) where 0=clear(no inflammatory signs of AD), 1=almost clear, 2=mild, 3=moderate, 4=severe AD. mITT population. Here, N=participants analysed for this outcome.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	50	49	50
Units: units on scale
least squares mean (standard error)	-1.27 ( 0.136 )	-1.14 ( 0.139 )	-1.4 ( 0.141 )	-1.02 ( 0.14 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2027

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-0.63

upper limit

0.14

Variability estimate

Standard error of the mean

Dispersion value

0.195

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5316

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.51

upper limit

0.26

Variability estimate

Standard error of the mean

Dispersion value

0.197

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0568

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.38

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

0.01

Variability estimate

Standard error of the mean

Dispersion value

0.199

Secondary: Percent Change From Baseline in Severity Scoring of Atopic Dermatitis (SCORAD) Index Score at Week 12

Top of page

End point title

Percent Change From Baseline in Severity Scoring of Atopic Dermatitis (SCORAD) Index Score at Week 12

End point description

The SCORAD index scale combines 1) intensity of six lesion characteristics (erythema, edema/papulation, oozing/crusts, excoriations, lichenification, dryness) as assessed by the physician on a scale of 0 (absent) to 3 (severe) across four regions (head, trunk, upper and lower extremities); and 2) subjective symptoms of pruritus and sleep disturbance as reported by the participant on a visual analog scale (VAS) from 0 to 10 (increasing severity); along with 3) Physician assessment of affected areas (extent) in each region is made as percentage of body surface (head [10%], upper extremities [20%], trunk [30%], and lower extremities [40%]). The final SCORAD index score, ranging from 0 (absent disease) to 103 (severe disease), is calculated according to the weighted formula: (0.2 x area) + (3.5 x [sum of intensity score for each of the 6 items]) + participant's subjective score. mITT population. Here, N=participants analysed for this outcome.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	50	49	50
Units: percent change
least squares mean (standard error)	-42.63 ( 4.069 )	-38.72 ( 4.143 )	-53.45 ( 4.218 )	-35.41 ( 4.159 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2161

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-7.22

Confidence interval

level

95%

sides

2-sided

lower limit

-18.69

upper limit

4.25

Variability estimate

Standard error of the mean

Dispersion value

5.818

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5734

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-3.31

Confidence interval

level

95%

sides

2-sided

lower limit

-14.89

upper limit

8.27

Variability estimate

Standard error of the mean

Dispersion value

5.873

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0026

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-18.04

Confidence interval

level

95%

sides

2-sided

lower limit

-29.72

upper limit

-6.36

Variability estimate

Standard error of the mean

Dispersion value

5.923

Secondary: Absolute Change From Baseline in SCORAD Index Score at Week 12

Top of page

End point title

Absolute Change From Baseline in SCORAD Index Score at Week 12

End point description

The SCORAD index scale combines 1) intensity of six lesion characteristics (erythema, edema/papulation, oozing/crusts, excoriations, lichenification, dryness) as assessed by the physician on a scale of 0 (absent) to 3 (severe) across four regions (head, trunk, upper and lower extremities); and 2) subjective symptoms of pruritus and sleep disturbance as reported by the participant on a VAS from 0 to 10 (increasing severity); along with 3) Physician assessment of affected areas (extent) in each region is made as percentage of body surface (head [10%], upper extremities [20%], trunk [30%], and lower extremities [40%]). The final SCORAD index score, ranging from 0 (absent disease) to 103 (severe disease), is calculated according to the weighted formula: (0.2 x area) + (3.5 x [sum of intensity score for each of the 6 items]) + participant's subjective score. mITT population. Here, N=participants analysed for this outcome.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	50	49	50
Units: units on scale
least squares mean (standard error)	-26.17 ( 2.354 )	-22.98 ( 2.395 )	-31.84 ( 2.438 )	-20.6 ( 2.404 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0989

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-5.58

Confidence interval

level

95%

sides

2-sided

lower limit

-12.21

upper limit

1.06

Variability estimate

Standard error of the mean

Dispersion value

3.364

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4841

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-2.38

Confidence interval

level

95%

sides

2-sided

lower limit

-9.07

upper limit

4.31

Variability estimate

Standard error of the mean

Dispersion value

3.395

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0012

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-11.24

Confidence interval

level

95%

sides

2-sided

lower limit

-17.99

upper limit

-4.49

Variability estimate

Standard error of the mean

Dispersion value

3.423

Secondary: Percentage of Participants With a 50% or 75% Reduction From Baseline in SCORAD Index Score (SCORAD-50/SCORAD-75) at Week 12

Top of page

End point title

Percentage of Participants With a 50% or 75% Reduction From Baseline in SCORAD Index Score (SCORAD-50/SCORAD-75) at Week 12

End point description

The SCORAD index scale combines 1) intensity of six lesion characteristics (erythema, edema/papulation, oozing/crusts, excoriations, lichenification, dryness) as assessed by the physician on a scale of 0 (absent) to 3 (severe) across four regions (head, trunk, upper and lower extremities); and 2) subjective symptoms of pruritus and sleep disturbance as reported by the participant on a VAS from 0 to 10 (increasing severity); along with 3) Physician assessment of affected areas (extent) in each region is made as percentage of body surface (head [10%], upper extremities [20%], trunk [30%], and lower extremities [40%]). The final SCORAD index score, ranging from 0 (absent disease) to 103 (severe disease), is calculated according to the weighted formula: (0.2 x area) + (3.5 x [sum of intensity score for each of the 6 items]) + participant's subjective score. mITT population.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	52	51	53
Units: percentage of participants
number (confidence interval 95%)
SCORAD-50	47.2 (33.73 to 60.61)	34.6 (21.68 to 47.55)	51 (37.26 to 64.7)	26.4 (14.55 to 38.28)
SCORAD-75	11.3 (2.79 to 19.85)	13.5 (4.18 to 22.74)	21.6 (10.28 to 32.86)	13.2 (4.09 to 22.32)

Statistical Analysis 1: SCORAD-50

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0297

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

20.75

Confidence interval

level

95%

sides

2-sided

lower limit

2.82

upper limit

38.69

Statistical Analysis 2: SCORAD-50

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3817

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

8.2

Confidence interval

level

95%

sides

2-sided

lower limit

-9.35

upper limit

25.75

Statistical Analysis 3: SCORAD-50

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0117

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

24.57

Confidence interval

level

95%

sides

2-sided

lower limit

6.42

upper limit

42.71

Statistical Analysis 4: SCORAD-75

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

106

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7636

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-1.89

Confidence interval

level

95%

sides

2-sided

lower limit

-14.37

upper limit

10.6

Statistical Analysis 5: SCORAD-75

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

105

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9764

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

0.25

Confidence interval

level

95%

sides

2-sided

lower limit

-12.75

upper limit

13.26

Statistical Analysis 6: SCORAD-75

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

104

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2663

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

8.36

Confidence interval

level

95%

sides

2-sided

lower limit

-6.15

upper limit

22.87

Secondary: Percentage of Participants Who Achieved EASI-50 (50% Reduction From Baseline in EASI Score) at Week 12 and Maintained EASI-50 at Week 16

Top of page

End point title

Percentage of Participants Who Achieved EASI-50 (50% Reduction From Baseline in EASI Score) at Week 12 and Maintained EASI-50 at Week 16

End point description

The EASI score was used to measure the severity and extent of AD and measures erythema, induration-papulation, excoriation and lichenification on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head and neck, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no eruption) to 6 (> 90%-100% eruption). The total score is the sum of the four body-region scores, maximum=72, minimum=0, with higher scores reflecting greater disease severity. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score. mITT population. Here, N=participants who achieved EASI-50 at Week 12.

End point type

Secondary

End point timeframe

Baseline, Weeks 12, 16

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	37	36	42	33
Units: percentage of participants
number (confidence interval 95%)	94.6 (87.31 to 100)	80.6 (67.63 to 93.48)	95.2 (88.8 to 100)	81.8 (68.66 to 94.98)

Statistical Analysis 1

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0991

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

12.78

Confidence interval

level

95%

sides

2-sided

lower limit

-2.27

upper limit

27.82

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9529

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-1.26

Confidence interval

level

95%

sides

2-sided

lower limit

-19.7

upper limit

17.18

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0676

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

13.42

Confidence interval

level

95%

sides

2-sided

lower limit

-1.23

upper limit

28.07

Secondary: Percentage of Participants Who Achieved EASI-50 (50% Reduction From Baseline in EASI Score) at Week 12 and Maintained EASI-50 at Both Weeks 16 and 20

Top of page

End point title

Percentage of Participants Who Achieved EASI-50 (50% Reduction From Baseline in EASI Score) at Week 12 and Maintained EASI-50 at Both Weeks 16 and 20

End point description

The EASI score was used to measure the severity and extent of AD and measures erythema, induration-papulation, excoriation and lichenification on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head and neck, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no eruption) to 6 (> 90%-100% eruption). The total score is the sum of the four body-region scores, maximum=72, minimum=0, with higher scores reflecting greater disease severity. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score. mITT population. Here, N=participants who achieved EASI-50 at Week 12.

End point type

Secondary

End point timeframe

Baseline, Weeks 12, 16, 20

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	37	36	42	33
Units: percentage of participants
number (confidence interval 95%)	78.4 (65.11 to 91.64)	80.6 (67.63 to 93.48)	90.5 (81.6 to 99.35)	72.7 (57.53 to 87.92)

Statistical Analysis 1

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5771

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

5.65

Confidence interval

level

95%

sides

2-sided

lower limit

-14.5

upper limit

25.82

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3913

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

7.83

Confidence interval

level

95%

sides

2-sided

lower limit

-12.1

upper limit

27.78

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0477

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

17.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.15

upper limit

35.35

Secondary: Percentage of Participants Who Achieved IGA Score of 0 or 1 at Week 12 and Maintained IGA Score of 0 or 1 at Week 16

Top of page

End point title

Percentage of Participants Who Achieved IGA Score of 0 or 1 at Week 12 and Maintained IGA Score of 0 or 1 at Week 16

End point description

The IGA score is an assessment of AD severity. It is an assessment of the participant's disease state at the time of examination and does not attempt a comparison with any of the participant's previous disease states. The IGA utilizes a 6-point scale ranging from 0 (clear) to 5 (very severe disease) where 0 = clear (no inflammatory signs of AD), 1 = almost clear (just perceptible erythema and papulation induration), 2 = mild (mild erythema and papulation induration; no oozing or crusting), 3 = moderate (moderate erythema and papulation induration; oozing and crusting may be present), 4 = severe (severe erythema and papulation induration; oozing and crusting is present) and 5 = very severe AD. mITT population. Here, N=participants who achieved IGA score of 0 or 1 at Week 12.

End point type

Secondary

End point timeframe

Weeks 12, 16

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	15	11	17	10
Units: percentage of participants
number (confidence interval 95%)	60 (35.21 to 84.79)	72.7 (46.41 to 99.05)	82.4 (64.23 to 100)	80 (55.21 to 100)

Statistical Analysis 1

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.254

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-20

Confidence interval

level

95%

sides

2-sided

lower limit

-55.1

upper limit

15.06

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8809

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-7.27

Confidence interval

level

95%

sides

2-sided

lower limit

-43.4

upper limit

28.88

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6744

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

2.35

Confidence interval

level

95%

sides

2-sided

lower limit

-28.4

upper limit

33.06

Secondary: Percentage of Participants Who Achieved IGA Score of 0 or 1 at Week 12 and Maintained IGA Score of 0 or 1 at Both Weeks 16 and 20

Top of page

End point title

Percentage of Participants Who Achieved IGA Score of 0 or 1 at Week 12 and Maintained IGA Score of 0 or 1 at Both Weeks 16 and 20

End point description

End point type

Secondary

End point timeframe

Weeks 12, 16, 20

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	15	11	17	10
Units: percentage of participants
number (confidence interval 95%)	60 (35.21 to 84.79)	54.5 (25.12 to 83.97)	70.6 (48.93 to 92.25)	60 (29.64 to 90.36)

Statistical Analysis 1

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9409

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-39.2

upper limit

39.2

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9712

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-5.45

Confidence interval

level

95%

sides

2-sided

lower limit

-47.7

upper limit

36.83

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.582

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

10.59

Confidence interval

level

95%

sides

2-sided

lower limit

-26.7

upper limit

47.89

Secondary: Percentage of Participants Who Achieved IGSA Score of 0 or 1 at Week 12 and Maintained IGSA Score of 0 or 1 at Week 16

Top of page

End point title

Percentage of Participants Who Achieved IGSA Score of 0 or 1 at Week 12 and Maintained IGSA Score of 0 or 1 at Week 16

End point description

IGSA score is an assessment of AD signs. Investigator assesses signs in 2 steps: Step 1: Lesional assessment: Investigator chooses lesional grade that best describes participant’s involved skin, on average. Step 2: Consider Upgrade or Downgrade: based on skin lesion extent and location. Upgrade refers to disease extends over majority (>50% of a region) of one or more body regions, or is prominently affecting high visibility/functionally-important areas (face and hands). Downgrade refers to disease localized to only one or two small areas (less than 1-2 palms) that are not highly visible or functionally important. A region is defined by i) arms combined, ii) legs combined, iii) trunk, and iv) head and neck, for a total of four regions. IGSA utilizes a 5-point scale ranging from 0 (clear) to 5 (severe disease) where 0=clear (no inflammatory signs of AD), 1=almost clear, 2=mild, 3=moderate, 4=severe AD. mITT population. Here, N=participants who achieved IGSA score of 0 or 1 at Week 12.

End point type

Secondary

End point timeframe

Weeks 12, 16

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	16	10	15	12
Units: percentage of participants
number (confidence interval 95%)	62.5 (38.78 to 86.22)	80 (55.21 to 100)	73.3 (50.95 to 95.71)	83.3 (62.25 to 100)

Statistical Analysis 1

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1708

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-20.8

Confidence interval

level

95%

sides

2-sided

lower limit

-52.6

upper limit

10.91

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8752

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-3.33

Confidence interval

level

95%

sides

2-sided

lower limit

-35.9

upper limit

29.21

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9458

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-10

Confidence interval

level

95%

sides

2-sided

lower limit

-40.7

upper limit

20.75

Secondary: Percentage of Participants Who Achieved IGSA Score of 0 or 1 at Week 12 and Maintained IGSA Score of 0 or 1 at Both Weeks 16 and 20

Top of page

End point title

Percentage of Participants Who Achieved IGSA Score of 0 or 1 at Week 12 and Maintained IGSA Score of 0 or 1 at Both Weeks 16 and 20

End point description

IGSA score is an assessment of AD signs. Investigator assesses signs in 2 steps: Step 1: Lesional assessment: Investigator chooses lesional grade that best describes participant’s involved skin, on average. Step 2: Consider Upgrade or Downgrade: based on skin lesion extent and location. Upgrade refers to disease extends over majority (>50% of a region) of one or more body regions, or is prominently affecting high visibility/functionally-important areas (face and hands). Downgrade refers to disease localized to only one or two small areas (less than 1-2 palms) that are not highly visible or functionally important. A region is defined by i) arms combined, ii) legs combined, iii) trunk, and iv) head and neck, for a total of four regions. IGSA utilizes a 5-point scale ranging from 0 (clear) to 5 (severe disease) where 0=clear (no inflammatory signs of AD), 1=almost clear, 2=mild, 3=moderate, 4=severe AD. mITT population. Here, N=participants who achieved IGSA score of 0 or 1 at Week 12.

End point type

Secondary

End point timeframe

Weeks 12, 16, 20

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	16	10	15	12
Units: percentage of participants
number (confidence interval 95%)	56.3 (31.94 to 80.56)	60 (29.64 to 90.36)	60 (35.21 to 84.79)	50 (21.71 to 78.29)

Statistical Analysis 1

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9439

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

6.25

Confidence interval

level

95%

sides

2-sided

lower limit

-31

upper limit

43.55

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6297

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-31.5

upper limit

51.5

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5347

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-27.6

upper limit

47.62

Secondary: Percentage of Participants Who Achieved SCORAD-50 (50% Reduction From Baseline in SCORAD Index Score) at Week 12 and Maintained SCORAD-50 at Week 16

Top of page

End point title

Percentage of Participants Who Achieved SCORAD-50 (50% Reduction From Baseline in SCORAD Index Score) at Week 12 and Maintained SCORAD-50 at Week 16

End point description

The SCORAD index scale combines 1) intensity of six lesion characteristics (erythema, edema/papulation, oozing/crusts, excoriations, lichenification, dryness) as assessed by the physician on a scale of 0 (absent) to 3 (severe) across four regions (head, trunk, upper and lower extremities); and 2) subjective symptoms of pruritus and sleep disturbance as reported by the participant on a VAS from 0 to 10 (increasing severity); along with 3) Physician assessment of affected areas (extent) in each region is made as percentage of body surface (head [10%], upper extremities [20%], trunk [30%], and lower extremities [40%]). The final SCORAD index score, ranging from 0 (absent disease) to 103 (severe disease), is calculated according to the weighted formula: (0.2 x area) + (3.5 x [sum of intensity score for each of the 6 items]) + participant's subjective score. mITT population. Here, N=participants who achieved SCORAD-50 at Week 12.

End point type

Secondary

End point timeframe

Baseline, Weeks 12, 16

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	25	18	26	14
Units: percentage of participants
number (confidence interval 95%)	72 (54.4 to 89.6)	72.2 (51.53 to 92.91)	76.9 (60.73 to 93.12)	85.7 (67.38 to 100)

Statistical Analysis 1

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4875

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-13.7

Confidence interval

level

95%

sides

2-sided

lower limit

-39.1

upper limit

11.7

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3375

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-41.1

upper limit

14.15

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1334

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-8.79

Confidence interval

level

95%

sides

2-sided

lower limit

-33.3

upper limit

15.67

Secondary: Percentage of Participants Who Achieved SCORAD-50 (50% Reduction From Baseline in SCORAD Index Score) at Week 12 and Maintained SCORAD-50 at Both Weeks 16 and 20

Top of page

End point title

Percentage of Participants Who Achieved SCORAD-50 (50% Reduction From Baseline in SCORAD Index Score) at Week 12 and Maintained SCORAD-50 at Both Weeks 16 and 20

End point description

The SCORAD index scale combines 1) intensity of six lesion characteristics (erythema, edema/papulation, oozing/crusts, excoriations, lichenification, dryness) as assessed by the physician on a scale of 0 (absent) to 3 (severe) across four regions (head, trunk, upper and lower extremities); and 2) subjective symptoms of pruritus and sleep disturbance as reported by the participant on a VAS from 0 to 10 (increasing severity); along with 3) Physician assessment of affected areas (extent) in each region is made as percentage of body surface (head [10%], upper extremities [20%], trunk [30%], and lower extremities [40%]). The final SCORAD index score, ranging from 0 (absent disease) to 103 (severe disease), is calculated according to the weighted formula: (0.2 x area) + (3.5 x [sum of intensity score for each of the 6 items]) + participant's subjective score. mITT population. Here, N=participants who achieved SCORAD-50 at Week 12.

End point type

Secondary

End point timeframe

Baseline, Weeks 12, 16, 20

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	25	18	26	14
Units: percentage of participants
number (confidence interval 95%)	64 (45.18 to 82.82)	61.1 (38.59 to 83.63)	50 (30.78 to 69.22)	78.6 (57.08 to 100)

Statistical Analysis 1

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4852

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-14.6

Confidence interval

level

95%

sides

2-sided

lower limit

-43.1

upper limit

13.99

Statistical Analysis 2

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3375

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-17.5

Confidence interval

level

95%

sides

2-sided

lower limit

-48.6

upper limit

13.67

Statistical Analysis 3

Statistical analysis description

CMH chi-square test was stratified by geographic region (US/Canada versus Europe versus others). 95% CI was based on normal approximation for binomial proportion.

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1334

Method

Cochran-Mantel-Haenszel

Parameter type

Response Rate Difference

Point estimate

-28.6

Confidence interval

level

95%

sides

2-sided

lower limit

-57.4

upper limit

0.26

Secondary: Percent Change From Baseline in Total % Body Surface Area (BSA) Affected With AD at Week 12

Top of page

End point title

Percent Change From Baseline in Total % Body Surface Area (BSA) Affected With AD at Week 12

End point description

Affected BSA was assessed for each of the following four body regions: head and neck, upper limbs, trunk, and lower limbs. Affected BSA was assessed on a 7-point ordinal scale, where 0=no eruption, 1=<10%, 2=>10%-29%, 3=>30%-49%, 4=>50%-69%, 5=>70%-89%, and 6=>90%-100%. mITT population. Here, N=participants analysed for this outcome.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	50	49	50
Units: percent change
least squares mean (standard error)	-38.6 ( 8.069 )	-45.2 ( 8.206 )	-57.68 ( 8.35 )	-47.42 ( 8.242 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4453

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

8.83

Confidence interval

level

95%

sides

2-sided

lower limit

-13.93

upper limit

31.58

Variability estimate

Standard error of the mean

Dispersion value

11.541

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8487

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

2.22

Confidence interval

level

95%

sides

2-sided

lower limit

-20.7

upper limit

25.14

Variability estimate

Standard error of the mean

Dispersion value

11.625

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3835

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-10.25

Confidence interval

level

95%

sides

2-sided

lower limit

-33.39

upper limit

12.89

Variability estimate

Standard error of the mean

Dispersion value

11.736

Secondary: Absolute Change From Baseline in Pruritus as Measured by the Pruritus Visual Analog Scale (VAS) at Week 12

Top of page

End point title

Absolute Change From Baseline in Pruritus as Measured by the Pruritus Visual Analog Scale (VAS) at Week 12

End point description

Pruritus VAS score was measured as a part of SCORAD. Subjective symptoms of pruritus were reported by the participant on a VAS. VAS is an eleven point scale ranging from 0 (no pruritus) to 10 centimeters (cm) (most severe pruritus). mITT population. Here, N=participants analysed for this outcome.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	50	49	50
Units: cm
least squares mean (standard error)	-2.03 ( 0.325 )	-2.06 ( 0.331 )	-2.53 ( 0.336 )	-1.83 ( 0.332 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6591

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-1.12

upper limit

0.71

Variability estimate

Standard error of the mean

Dispersion value

0.464

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6223

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-1.16

upper limit

0.69

Variability estimate

Standard error of the mean

Dispersion value

0.469

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1391

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.63

upper limit

0.23

Variability estimate

Standard error of the mean

Dispersion value

0.472

Secondary: Percent Change From Baseline in Pruritus as Measured by the Pruritus VAS at Week 12

Top of page

End point title

Percent Change From Baseline in Pruritus as Measured by the Pruritus VAS at Week 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	50	49	50
Units: percent change
least squares mean (standard error)	-32.82 ( 5.953 )	-34.92 ( 6.143 )	-40.71 ( 6.188 )	-27.54 ( 6.124 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

103

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5374

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-5.28

Confidence interval

level

95%

sides

2-sided

lower limit

-22.12

upper limit

11.56

Variability estimate

Standard error of the mean

Dispersion value

8.54

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

100

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.396

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-7.38

Confidence interval

level

95%

sides

2-sided

lower limit

-24.5

upper limit

9.73

Variability estimate

Standard error of the mean

Dispersion value

8.679

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.132

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-13.17

Confidence interval

level

95%

sides

2-sided

lower limit

-30.34

upper limit

Variability estimate

Standard error of the mean

Dispersion value

8.706

Secondary: Absolute Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12

Top of page

End point title

Absolute Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12

End point description

The 5-D itch scale is a 5-item, validated questionnaire used to evaluate change in itch over time. The 5-D itch scale refers to the previous 2 weeks and the questions are organized into 5 domains: duration, degree, direction, disability, and distribution. The total 5-D itch score is calculated by summing each of the separately scored 5 domains. Total score ranges between 5 (no pruritus) and 25 (most severe pruritus). Higher scores mean greater impairment of the participant’s health-related QoL. mITT population. Here, N=participants analysed for this outcome.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	52	49	45	49
Units: units on scale
least squares mean (standard error)	-3.24 ( 0.557 )	-2.26 ( 0.57 )	-3.74 ( 0.581 )	-2.55 ( 0.57 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3842

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.27

upper limit

0.88

Variability estimate

Standard error of the mean

Dispersion value

0.798

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7226

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-1.31

upper limit

1.88

Variability estimate

Standard error of the mean

Dispersion value

0.809

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1446

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-1.19

Confidence interval

level

95%

sides

2-sided

lower limit

-2.79

upper limit

0.41

Variability estimate

Standard error of the mean

Dispersion value

0.813

Secondary: Percent Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12

Top of page

End point title

Percent Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	52	49	45	49
Units: percent change
least squares mean (standard error)	-15.23 ( 3.71 )	-10.57 ( 3.798 )	-20.51 ( 3.877 )	-13.05 ( 3.799 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6816

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-2.18

Confidence interval

level

95%

sides

2-sided

lower limit

-12.66

upper limit

8.3

Variability estimate

Standard error of the mean

Dispersion value

5.313

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6464

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

2.47

Confidence interval

level

95%

sides

2-sided

lower limit

-8.15

upper limit

13.09

Variability estimate

Standard error of the mean

Dispersion value

5.385

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1697

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-7.47

Confidence interval

level

95%

sides

2-sided

lower limit

-18.15

upper limit

3.22

Variability estimate

Standard error of the mean

Dispersion value

5.419

Secondary: Total Amount of TCS Used From Baseline to Week 12

Top of page

End point title

Total Amount of TCS Used From Baseline to Week 12

End point description

Total amount of TCS (Triamcinolone acetonide 0.1% cream or hydrocortisone 2.5% cream) used in grams from baseline to Week 12 was reported. mITT population. Here, n=participants who used triamcinolone acetonide 0.1% cream or hydrocortisone 2.5% cream at specified time-point per arm, respectively.

End point type

Secondary

End point timeframe

From Baseline to Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	52	51	53
Units: grams
arithmetic mean (standard deviation)
Triamcinolone acetonide 0.1% (n=33, 32, 42, 29)	608.7 ( 740 )	510.2 ( 478.5 )	669.4 ( 975 )	699.9 ( 687.5 )
Hydrocortisone 2.5% (n=27, 32, 32, 32)	28.2 ( 26.2 )	36.2 ( 68.2 )	29.3 ( 32.2 )	38.9 ( 66.6 )

No statistical analyses for this end point

Secondary: Total Amount of TCS Used From Week 12 to End of Study or Early Termination

Top of page

End point title

Total Amount of TCS Used From Week 12 to End of Study or Early Termination

End point description

Total amount of TCS (Triamcinolone acetonide 0.1% cream or hydrocortisone 2.5% cream) in grams used from Week 12 to the end of study or early termination was reported. mITT population. Here, n=participants who used triamcinolone acetonide 0.1% cream or hydrocortisone 2.5% cream at specified time-point per arm, respectively.

End point type

Secondary

End point timeframe

From Week 12 to end of study or early termination (up to 20 weeks)

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	52	51	53
Units: grams
arithmetic mean (standard deviation)
Triamcinolone acetonide 0.1% (n=36, 40, 43, 36)	459.4 ( 630.1 )	379.4 ( 443.5 )	279.4 ( 243.2 )	415.1 ( 414.4 )
Hydrocortisone 2.5% (n=32, 36, 34, 34)	15 ( 16.5 )	15 ( 25 )	19.4 ( 22.4 )	16 ( 19.9 )

No statistical analyses for this end point

Secondary: Percentage of Participants Who Experienced AD Disease Flares From Baseline to Week 12

Top of page

End point title

Percentage of Participants Who Experienced AD Disease Flares From Baseline to Week 12

End point description

Disease flare was defined as a measurable increase in extent or severity of lesions over a period of at least 3 days, under continued treatment and corresponding with a clinically significant increase in disease severity (as assessed by the treating physician and/or by the participant) necessitating an escalation in therapy, as defined by the protocol or initiated separately by the participant or a treating physician outside of the protocol. mITT population.

End point type

Secondary

End point timeframe

From Baseline to Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	53	52	51	53
Units: percentage of participants
number (not applicable)	5.7	0	2	5.7

No statistical analyses for this end point

Secondary: Absolute Change From Baseline in AD Symptoms at Week 12, as Assessed by the Atopic Dermatitis Symptom Diary (ADSD)

Top of page

End point title

Absolute Change From Baseline in AD Symptoms at Week 12, as Assessed by the Atopic Dermatitis Symptom Diary (ADSD)

End point description

The 8-item ADSD was used to assess participants’ AD symptoms; specifically, itchiness, skin pain, bleeding, skin sensitivity, skin irritation, skin flakiness, skin dryness, and weeping or oozing of clear fluid from the skin. The diary items were assessed on an 11-point numeric rating scale ranging from 0 (no symptom) to 10 (symptom as bad as one can imagine) and a Yes/No wake question. The diary had a recall specification of 24 hours. Scores of individual items were added to yield a total ADSD score (0-80), where higher scores mean worst symptom. mITT population. Here, N=participants analysed for this outcome.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	33	33	32	37
Units: units on scale
least squares mean (standard error)	-11.3 ( 1.963 )	-10.32 ( 1.815 )	-11.82 ( 1.837 )	-9.49 ( 1.96 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5143

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-1.82

Confidence interval

level

95%

sides

2-sided

lower limit

-7.31

upper limit

3.68

Variability estimate

Standard error of the mean

Dispersion value

2.776

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7552

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.83

Confidence interval

level

95%

sides

2-sided

lower limit

-6.12

upper limit

4.45

Variability estimate

Standard error of the mean

Dispersion value

2.671

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3878

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-2.33

Confidence interval

level

95%

sides

2-sided

lower limit

-7.66

upper limit

2.99

Variability estimate

Standard error of the mean

Dispersion value

2.691

Secondary: Percent Change From Baseline in AD Symptoms at Week 12, as Assessed by the ADSD

Top of page

End point title

Percent Change From Baseline in AD Symptoms at Week 12, as Assessed by the ADSD

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	33	33	32	37
Units: percent change
least squares mean (standard error)	-14.23 ( 12.981 )	-18.21 ( 12.011 )	-40.31 ( 12.224 )	-32.91 ( 12.897 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3096

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

18.68

Confidence interval

level

95%

sides

2-sided

lower limit

-17.56

upper limit

54.92

Variability estimate

Standard error of the mean

Dispersion value

18.315

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4058

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

14.7

Confidence interval

level

95%

sides

2-sided

lower limit

-20.18

upper limit

49.58

Variability estimate

Standard error of the mean

Dispersion value

17.626

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6782

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-7.4

Confidence interval

level

95%

sides

2-sided

lower limit

-42.59

upper limit

27.8

Variability estimate

Standard error of the mean

Dispersion value

17.791

Secondary: Absolute Change From Baseline in AD-Specific Health-Related Quality of Life (QoL) at Week 12, as Assessed by the Atopic Dermatitis Impact Questionnaire (ADIQ)

Top of page

End point title

Absolute Change From Baseline in AD-Specific Health-Related Quality of Life (QoL) at Week 12, as Assessed by the Atopic Dermatitis Impact Questionnaire (ADIQ)

End point description

The ADIQ is a 17-item questionnaire used to assess the participants’ AD-specific health-related QoL. The questionnaire assesses AD’s impact on emotions, energy, activities of daily living, and social activities. The ADIQ had a recall specification of 7 days. The questions were assessed on a 5-point likert scale: 0 (not at all), 1 (a little), 2 (somewhat), 3 (quite a bit), and 4 (extreme). Scores of individual items were added to yield a total ADIQ score (0-68), where higher scores mean greater impairment of the participant’s health-related QoL. mITT population. Here, N=participants analysed for this outcome.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	52	49	45	49
Units: units on scale
least squares mean (standard error)	-10.92 ( 1.551 )	-9.28 ( 1.58 )	-12.75 ( 1.607 )	-6.24 ( 1.578 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0357

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-4.68

Confidence interval

level

95%

sides

2-sided

lower limit

-9.05

upper limit

-0.32

Variability estimate

Standard error of the mean

Dispersion value

2.214

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1751

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-3.04

Confidence interval

level

95%

sides

2-sided

lower limit

-7.45

upper limit

1.37

Variability estimate

Standard error of the mean

Dispersion value

2.234

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0043

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-6.51

Confidence interval

level

95%

sides

2-sided

lower limit

-10.95

upper limit

-2.07

Variability estimate

Standard error of the mean

Dispersion value

2.251

Secondary: Percent Change From Baseline in AD-Specific Health-Related QoL at Week 12, as Assessed by the ADIQ

Top of page

End point title

Percent Change From Baseline in AD-Specific Health-Related QoL at Week 12, as Assessed by the ADIQ

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	52	49	45	49
Units: percent change
least squares mean (standard error)	-30.79 ( 8.989 )	-33.2 ( 9.153 )	-54.29 ( 9.173 )	-29.49 ( 9.133 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9193

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-26.59

upper limit

23.99

Variability estimate

Standard error of the mean

Dispersion value

12.818

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7742

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-3.72

Confidence interval

level

95%

sides

2-sided

lower limit

-29.23

upper limit

21.8

Variability estimate

Standard error of the mean

Dispersion value

12.934

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0568

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-24.81

Confidence interval

level

95%

sides

2-sided

lower limit

-50.33

upper limit

0.72

Variability estimate

Standard error of the mean

Dispersion value

12.94

Secondary: Absolute Change From Baseline in Health-Related QoL at Week 12, as Measured by the Dermatology Life Quality Index (DLQI)

Top of page

End point title

Absolute Change From Baseline in Health-Related QoL at Week 12, as Measured by the Dermatology Life Quality Index (DLQI)

End point description

The DLQI is a 10-item, validated questionnaire used routinely in clinical practice to evaluate the impact of dermatologic diseases on participants' lives. The DLQI refers to the previous 7 days and questions are categorized into six domains: symptoms and feelings (2 items), daily activities (2 items), leisure (2 items), work and school (1 item), personal relationships (2 items), and treatment (1 item). The questions were assessed on a 4-point likert scale: 0 (not at all), 1 (a little), 2 (a lot), and 3 (very much). Scores of individual items were added to yield a total DLQI score (0-30), where higher scores mean greater impairment of the participant’s health-related QoL. mITT population. Here, N=participants analysed for this outcome.

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	52	49	45	49
Units: units on scale
least squares mean (standard error)	-5.64 ( 0.653 )	-5.45 ( 0.665 )	-5.15 ( 0.678 )	-4.52 ( 0.666 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2313

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-1.12

Confidence interval

level

95%

sides

2-sided

lower limit

-2.96

upper limit

0.72

Variability estimate

Standard error of the mean

Dispersion value

0.933

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3229

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.93

Confidence interval

level

95%

sides

2-sided

lower limit

-2.79

upper limit

0.93

Variability estimate

Standard error of the mean

Dispersion value

0.943

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5045

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.63

Confidence interval

level

95%

sides

2-sided

lower limit

-2.51

upper limit

1.24

Variability estimate

Standard error of the mean

Dispersion value

0.949

Secondary: Percent Change From Baseline in Health-Related QoL at Week 12, as Measured by the DLQI

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End point title

Percent Change From Baseline in Health-Related QoL at Week 12, as Measured by the DLQI

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	52	49	45	49
Units: percent change
least squares mean (standard error)	-40.67 ( 6.691 )	-34.33 ( 6.929 )	-43.12 ( 7.017 )	-33.57 ( 6.928 )

Statistical Analysis 1

Statistical analysis description

Comparison groups

Lebrikizumab 250 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4621

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-7.09

Confidence interval

level

95%

sides

2-sided

lower limit

-26.04

upper limit

11.85

Variability estimate

Standard error of the mean

Dispersion value

9.637

Statistical Analysis 2

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Single Dose + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9383

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-0.76

Confidence interval

level

95%

sides

2-sided

lower limit

-20.04

upper limit

18.52

Variability estimate

Standard error of the mean

Dispersion value

9.809

Statistical Analysis 3

Statistical analysis description

Comparison groups

Lebrikizumab 125 mg Q4W + TCS v Placebo Q4W + TCS Cream

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.333

Method

Mixed models analysis

Parameter type

Adjusted Mean Difference

Point estimate

-9.55

Confidence interval

level

95%

sides

2-sided

lower limit

-28.91

upper limit

9.82

Variability estimate

Standard error of the mean

Dispersion value

9.85

Secondary: Number of Participants With Anti-Therapeutic Antibodies (ATA) to Lebrikizumab

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End point title

Number of Participants With Anti-Therapeutic Antibodies (ATA) to Lebrikizumab

End point description

Safety evaluable (SE) population was defined as participants who received at least one dose of the study treatment. Participants were analysed as per actual treatment received. Here, N=participants evaluable for this outcome. n=participants evaluable for specified category, per arm, respectively.

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1), post-baseline (pre-dose on Days 29, 85,141, study discontinuation visit [up to Day 141])

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	52	53	50	53
Units: participants
Baseline (n=51, 53, 50, 53)	4	1	5	2
Post-baseline (n=52,53,50,52)	8	19	11	2

No statistical analyses for this end point

Secondary: Number of Participants With ATA to Phospholipase B-Like 2 (PLBL2) Protein

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End point title

Number of Participants With ATA to Phospholipase B-Like 2 (PLBL2) Protein

End point description

Treatment-induced PLBL2 = a participant with negative or missing baseline PLBL2 result and at least one positive post-baseline PLBL2 result. Treatment-enhanced PLBL2 = a participant with positive PLBL2 result at baseline who had one or more post-baseline titer results that were at least 0.60 t.u. greater than the baseline titer result. SE population. Participants were analysed as per actual treatment received. Here, N=participants evaluable for this outcome. n=participants evaluable for specified category, per arm, respectively.

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1), post-baseline (pre-dose on Days 29, 85,141, study discontinuation visit [up to Day 141])

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	51	52	50	53
Units: participants
Baseline (n=51, 52, 50, 53)	1	0	2	1
Post-baseline:Treatment-induced (n=51, 48, 49, 50)	1	1	2	0
Post-baseline:Treatment-enhanced(n=51, 48, 49, 50)	0	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Participants With Disease Rebound

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End point title

Percentage of Participants With Disease Rebound

End point description

Disease rebound was defined as a significant worsening of disease severity after cessation of therapy to a severity level that is greater than prior to commencing therapy. SE population.

End point type

Secondary

End point timeframe

From Week 12 up to 20 weeks

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Number of subjects analysed	52	54	50	53
Units: percentage of participants
number (not applicable)	0	0	0	1.9

No statistical analyses for this end point

Secondary: Maximum Observed Serum Concentration (Cmax) of Lebrikizumab

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End point title

Maximum Observed Serum Concentration (Cmax) of Lebrikizumab

End point description

SE population, only participants who received lebrikizumab were to be analysed for this outcome. Here, N=participants analysed for this outcome.

End point type

Secondary

End point timeframe

After first dose of lebrikizumab at Week 1

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS
Number of subjects analysed	51	54	50
Units: micrograms per milliliter (mcg/mL)
arithmetic mean (standard deviation)	35.6 ( 10.8 )	17 ( 5.22 )	16.1 ( 5.19 )

No statistical analyses for this end point

Secondary: Time to Reach Cmax (Tmax) of Lebrikizumab

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End point title

Time to Reach Cmax (Tmax) of Lebrikizumab

End point description

SE population, only participants who received lebrikizumab were to be analysed for this outcome. Here, N=participants analysed for this outcome.

End point type

Secondary

End point timeframe

After first dose of lebrikizumab at Week 1

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS
Number of subjects analysed	51	54	50
Units: days
median (full range (min-max))	6.97 (4.88 to 14.9)	6.98 (4.92 to 14.6)	6.96 (1.98 to 10.3)

No statistical analyses for this end point

Secondary: Minimum Serum Concentration (Cmin) of Lebrikizumab

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End point title

Minimum Serum Concentration (Cmin) of Lebrikizumab

End point description

SE population, only participants who received lebrikizumab were to be analysed for this outcome. Here, N=participants analysed for this outcome. n=participants analysed at specified time-point.

End point type

Secondary

End point timeframe

Pre-dose (Hour 0) at Weeks 4, 8, 12

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS
Number of subjects analysed	52	53	50
Units: mcg/mL
arithmetic mean (standard deviation)
Week 4 (n=51, 53, 50)	21.4 ( 6.87 )	10.2 ( 3 )	9.15 ( 2.99 )
Week 8 (n=52, 50, 46)	9.53 ( 3.53 )	4.59 ( 2.12 )	13.6 ( 5.34 )
Week 12 (n=50, 49, 46)	3.77 ( 2.01 )	2.28 ( 1.72 )	14.4 ( 5.69 )

No statistical analyses for this end point

Secondary: Elimination Half-Life (t1/2) of Lebrikizumab

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End point title

Elimination Half-Life (t1/2) of Lebrikizumab

End point description

SE population, only participants who received lebrikizumab were to be analysed for this outcome. Here, N=participants analysed for this outcome.

End point type

Secondary

End point timeframe

Pre-dose (Hour 0) on Days 1, 8, 29, 43, 57, 85, 113, 141, study discontinuation visit (up to Day 141)

End point values	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS
Number of subjects analysed	52	52	48
Units: days
arithmetic mean (standard deviation)	22.2 ( 6.18 )	18.5 ( 5.06 )	20.9 ( 4.17 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Screening up to Week 20

Adverse event reporting additional description

SE population

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Lebrikizumab 250 mg Single Dose + TCS

Reporting group description

Participants received a single dose of lebrikizumab 250 milligrams (mg) subcutaneous (SC) injection on Day 1 followed by placebo on Week 4 and Week 8. Participants continued to apply TCS cream (triamcenolone acetonide 0.1% or hydrocortisone 2.5% cream) twice daily to active skin lesions throughout the 12-week treatment period.

Reporting group title

Lebrikizumab 125 mg Single Dose + TCS

Reporting group description

Reporting group title

Lebrikizumab 125 mg Q4W + TCS

Reporting group description

Reporting group title

Placebo Q4W + TCS Cream

Reporting group description

Serious adverse events	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 52 (0.00%)	3 / 54 (5.56%)	2 / 50 (4.00%)	2 / 53 (3.77%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 52 (0.00%)	1 / 54 (1.85%)	0 / 50 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoaesthesia
subjects affected / exposed	0 / 52 (0.00%)	1 / 54 (1.85%)	0 / 50 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Multiple sclerosis
subjects affected / exposed	0 / 52 (0.00%)	1 / 54 (1.85%)	0 / 50 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sensory loss
subjects affected / exposed	0 / 52 (0.00%)	1 / 54 (1.85%)	0 / 50 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Cyst
subjects affected / exposed	0 / 52 (0.00%)	1 / 54 (1.85%)	0 / 50 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Diplopia
subjects affected / exposed	0 / 52 (0.00%)	1 / 54 (1.85%)	0 / 50 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Inguinal hernia
subjects affected / exposed	0 / 52 (0.00%)	1 / 54 (1.85%)	0 / 50 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Rebound atopic dermatitis
subjects affected / exposed	0 / 52 (0.00%)	0 / 54 (0.00%)	0 / 50 (0.00%)	1 / 53 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolothiasis
subjects affected / exposed	0 / 52 (0.00%)	0 / 54 (0.00%)	1 / 50 (2.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Myopathy
subjects affected / exposed	0 / 52 (0.00%)	0 / 54 (0.00%)	1 / 50 (2.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Postoperative abcess
subjects affected / exposed	0 / 52 (0.00%)	0 / 54 (0.00%)	0 / 50 (0.00%)	1 / 53 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Lebrikizumab 250 mg Single Dose + TCS	Lebrikizumab 125 mg Single Dose + TCS	Lebrikizumab 125 mg Q4W + TCS	Placebo Q4W + TCS Cream
Total subjects affected by non serious adverse events
subjects affected / exposed	22 / 52 (42.31%)	23 / 54 (42.59%)	16 / 50 (32.00%)	19 / 53 (35.85%)
Nervous system disorders
Headache
subjects affected / exposed	4 / 52 (7.69%)	2 / 54 (3.70%)	4 / 50 (8.00%)	2 / 53 (3.77%)
occurrences all number	8	3	4	2
Eye disorders
Conjunctivitis allergic
subjects affected / exposed	2 / 52 (3.85%)	4 / 54 (7.41%)	2 / 50 (4.00%)	0 / 53 (0.00%)
occurrences all number	2	4	3	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	3 / 52 (5.77%)	3 / 54 (5.56%)	1 / 50 (2.00%)	0 / 53 (0.00%)
occurrences all number	4	3	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	4 / 52 (7.69%)	0 / 54 (0.00%)	0 / 50 (0.00%)	0 / 53 (0.00%)
occurrences all number	4	0	0	0
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	3 / 52 (5.77%)	0 / 54 (0.00%)	1 / 50 (2.00%)	3 / 53 (5.66%)
occurrences all number	3	0	1	3
Pruritus
subjects affected / exposed	2 / 52 (3.85%)	4 / 54 (7.41%)	3 / 50 (6.00%)	1 / 53 (1.89%)
occurrences all number	2	4	3	2
Infections and infestations
Conjunctivitis
subjects affected / exposed	0 / 52 (0.00%)	3 / 54 (5.56%)	0 / 50 (0.00%)	2 / 53 (3.77%)
occurrences all number	0	3	0	2
Nasopharyngitis
subjects affected / exposed	8 / 52 (15.38%)	10 / 54 (18.52%)	5 / 50 (10.00%)	8 / 53 (15.09%)
occurrences all number	10	13	8	9
Postoperative wound infection
subjects affected / exposed	1 / 52 (1.92%)	0 / 54 (0.00%)	0 / 50 (0.00%)	3 / 53 (5.66%)
occurrences all number	1	0	0	4
Rhinitis
subjects affected / exposed	3 / 52 (5.77%)	0 / 54 (0.00%)	1 / 50 (2.00%)	1 / 53 (1.89%)
occurrences all number	3	0	1	1
Upper respiratory tract infection
subjects affected / exposed	1 / 52 (1.92%)	7 / 54 (12.96%)	2 / 50 (4.00%)	5 / 53 (9.43%)
occurrences all number	1	7	4	6

More information

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Were there any global substantial amendments to the protocol? Yes

16 Jan 2015

- Antiviral medication to treat herpes zoster was deleted from the list of therapies permitted during the study. - Herpes zoster infection was added as a reason requiring study treatment discontinuation.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Lebrikizumab in Patients With Persistent Moderate to Severe Atopic Dermatitis That is Inadequately Controlled by Topical Corticosteroids

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants Who Achieved a 50 Percent (%) Reduction From Baseline in EASI Score (EASI-50) at Week 12

Primary: Percentage of Participants Who Achieved a 50 Percent (%) Reduction From Baseline in EASI Score (EASI-50) at Week 12

Secondary: Percent Change From Baseline in EASI Score at Week 12

Secondary: Percent Change From Baseline in EASI Score at Week 12

Secondary: Absolute Change From Baseline in EASI Score at Week 12

Secondary: Absolute Change From Baseline in EASI Score at Week 12

Secondary: Percentage of Participants Who Achieved a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 12

Secondary: Percentage of Participants Who Achieved a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 12

Secondary: Percentage of Participants Who Achieved an Investigator's Global Assessment (IGA) Score of 0 or 1 at Week 12

Secondary: Percentage of Participants Who Achieved an Investigator's Global Assessment (IGA) Score of 0 or 1 at Week 12

Secondary: Percentage of Participants With a Greater Than or Equal to (>/=) 2 Point Reduction From Baseline in IGA at Week 12

Secondary: Percentage of Participants With a Greater Than or Equal to (>/=) 2 Point Reduction From Baseline in IGA at Week 12

Secondary: Absolute Change From Baseline in IGA at Week 12

Secondary: Absolute Change From Baseline in IGA at Week 12

Secondary: Percentage of Participants Who Achieved an Investigator Global Signs Assessment (IGSA) Score of 0 or 1 at Week 12

Secondary: Percentage of Participants Who Achieved an Investigator Global Signs Assessment (IGSA) Score of 0 or 1 at Week 12

Secondary: Percentage of Participants With a >/=2 Point Reduction From Baseline in IGSA at Week 12

Secondary: Percentage of Participants With a >/=2 Point Reduction From Baseline in IGSA at Week 12

Secondary: Absolute Change From Baseline in IGSA at Week 12

Secondary: Absolute Change From Baseline in IGSA at Week 12

Secondary: Percent Change From Baseline in Severity Scoring of Atopic Dermatitis (SCORAD) Index Score at Week 12

Secondary: Percent Change From Baseline in Severity Scoring of Atopic Dermatitis (SCORAD) Index Score at Week 12

Secondary: Absolute Change From Baseline in SCORAD Index Score at Week 12

Secondary: Absolute Change From Baseline in SCORAD Index Score at Week 12

Secondary: Percentage of Participants With a 50% or 75% Reduction From Baseline in SCORAD Index Score (SCORAD-50/SCORAD-75) at Week 12

Secondary: Percentage of Participants With a 50% or 75% Reduction From Baseline in SCORAD Index Score (SCORAD-50/SCORAD-75) at Week 12

Secondary: Percentage of Participants Who Achieved EASI-50 (50% Reduction From Baseline in EASI Score) at Week 12 and Maintained EASI-50 at Week 16

Secondary: Percentage of Participants Who Achieved EASI-50 (50% Reduction From Baseline in EASI Score) at Week 12 and Maintained EASI-50 at Week 16

Secondary: Percentage of Participants Who Achieved EASI-50 (50% Reduction From Baseline in EASI Score) at Week 12 and Maintained EASI-50 at Both Weeks 16 and 20

Secondary: Percentage of Participants Who Achieved EASI-50 (50% Reduction From Baseline in EASI Score) at Week 12 and Maintained EASI-50 at Both Weeks 16 and 20

Secondary: Percentage of Participants Who Achieved IGA Score of 0 or 1 at Week 12 and Maintained IGA Score of 0 or 1 at Week 16

Secondary: Percentage of Participants Who Achieved IGA Score of 0 or 1 at Week 12 and Maintained IGA Score of 0 or 1 at Week 16

Secondary: Percentage of Participants Who Achieved IGA Score of 0 or 1 at Week 12 and Maintained IGA Score of 0 or 1 at Both Weeks 16 and 20

Secondary: Percentage of Participants Who Achieved IGA Score of 0 or 1 at Week 12 and Maintained IGA Score of 0 or 1 at Both Weeks 16 and 20

Secondary: Percentage of Participants Who Achieved IGSA Score of 0 or 1 at Week 12 and Maintained IGSA Score of 0 or 1 at Week 16

Secondary: Percentage of Participants Who Achieved IGSA Score of 0 or 1 at Week 12 and Maintained IGSA Score of 0 or 1 at Week 16

Secondary: Percentage of Participants Who Achieved IGSA Score of 0 or 1 at Week 12 and Maintained IGSA Score of 0 or 1 at Both Weeks 16 and 20

Secondary: Percentage of Participants Who Achieved IGSA Score of 0 or 1 at Week 12 and Maintained IGSA Score of 0 or 1 at Both Weeks 16 and 20

Secondary: Percentage of Participants Who Achieved SCORAD-50 (50% Reduction From Baseline in SCORAD Index Score) at Week 12 and Maintained SCORAD-50 at Week 16

Secondary: Percentage of Participants Who Achieved SCORAD-50 (50% Reduction From Baseline in SCORAD Index Score) at Week 12 and Maintained SCORAD-50 at Week 16

Secondary: Percentage of Participants Who Achieved SCORAD-50 (50% Reduction From Baseline in SCORAD Index Score) at Week 12 and Maintained SCORAD-50 at Both Weeks 16 and 20

Secondary: Percentage of Participants Who Achieved SCORAD-50 (50% Reduction From Baseline in SCORAD Index Score) at Week 12 and Maintained SCORAD-50 at Both Weeks 16 and 20

Secondary: Percent Change From Baseline in Total % Body Surface Area (BSA) Affected With AD at Week 12

Secondary: Percent Change From Baseline in Total % Body Surface Area (BSA) Affected With AD at Week 12

Secondary: Absolute Change From Baseline in Pruritus as Measured by the Pruritus Visual Analog Scale (VAS) at Week 12

Secondary: Absolute Change From Baseline in Pruritus as Measured by the Pruritus Visual Analog Scale (VAS) at Week 12

Secondary: Percent Change From Baseline in Pruritus as Measured by the Pruritus VAS at Week 12

Secondary: Percent Change From Baseline in Pruritus as Measured by the Pruritus VAS at Week 12

Secondary: Absolute Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12

Secondary: Absolute Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12

Secondary: Percent Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12

Secondary: Percent Change From Baseline in Pruritus as Measured by the 5-D Itch Scale at Week 12

Secondary: Total Amount of TCS Used From Baseline to Week 12

Secondary: Total Amount of TCS Used From Baseline to Week 12

Secondary: Total Amount of TCS Used From Week 12 to End of Study or Early Termination

Secondary: Total Amount of TCS Used From Week 12 to End of Study or Early Termination

Secondary: Percentage of Participants Who Experienced AD Disease Flares From Baseline to Week 12

Secondary: Percentage of Participants Who Experienced AD Disease Flares From Baseline to Week 12

Secondary: Absolute Change From Baseline in AD Symptoms at Week 12, as Assessed by the Atopic Dermatitis Symptom Diary (ADSD)

Secondary: Absolute Change From Baseline in AD Symptoms at Week 12, as Assessed by the Atopic Dermatitis Symptom Diary (ADSD)

Secondary: Percent Change From Baseline in AD Symptoms at Week 12, as Assessed by the ADSD

Secondary: Percent Change From Baseline in AD Symptoms at Week 12, as Assessed by the ADSD

Secondary: Absolute Change From Baseline in AD-Specific Health-Related Quality of Life (QoL) at Week 12, as Assessed by the Atopic Dermatitis Impact Questionnaire (ADIQ)

Secondary: Absolute Change From Baseline in AD-Specific Health-Related Quality of Life (QoL) at Week 12, as Assessed by the Atopic Dermatitis Impact Questionnaire (ADIQ)

Secondary: Percent Change From Baseline in AD-Specific Health-Related QoL at Week 12, as Assessed by the ADIQ

Secondary: Percent Change From Baseline in AD-Specific Health-Related QoL at Week 12, as Assessed by the ADIQ

Secondary: Absolute Change From Baseline in Health-Related QoL at Week 12, as Measured by the Dermatology Life Quality Index (DLQI)

Secondary: Absolute Change From Baseline in Health-Related QoL at Week 12, as Measured by the Dermatology Life Quality Index (DLQI)

Secondary: Percent Change From Baseline in Health-Related QoL at Week 12, as Measured by the DLQI

Secondary: Percent Change From Baseline in Health-Related QoL at Week 12, as Measured by the DLQI

Clinical Trial Results:
A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Lebrikizumab in Patients With Persistent Moderate to Severe Atopic Dermatitis That is Inadequately Controlled by Topical Corticosteroids