A Study of Lebrikizumab (LY3650150) in Participants With Moderate-to-Severe Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of lebrikizumab compared with placebo in participants with moderate-to-severe atopic dermatitis.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial to Evaluate the Efficacy and Safety of Lebrikizumab in Patients With Moderate-to-Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Biological: Lebrikizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years or older. Chronic AD as defined by Hanifin and Rajka (1980) that has been present for ≥1 year before the screening visit . Eczema Area and Severity Index (EASI) score ≥16 at the screening and the baseline visit. Investigator Global Assessment (IGA) score ≥3 (scale of 0 to 4) at the screening and the baseline visit. ≥10% body surface area (BSA) of AD involvement at the screening and the baseline visit. Exclusion Criteria: Treatment with any of the following agents within 4 weeks prior to the baseline visit: Immunosuppressive/immunomodulating drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.) Phototherapy and photochemotherapy (PUVA) for AD. Treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) within 1 week prior to the baseline visit. Treatment with: An investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, prior to the baseline visit. Dupilumab within 3 months prior to baseline visit. Cell-depleting biologics, including rituximab, within 6 months prior to the baseline visit. Other biologics within 5 half-lives (if known) or 16 weeks prior to baseline visit (whichever is longer). Use of prescription moisturizers within 7 days of the baseline visit.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 125 milligrams (mg) Lebrikizumab - Every 4 Weeks (Q4W)<br>125 mg Lebrikizumab administered subcutaneously (SC) once Q4W. Baseline: Loading dose 250 mg Lebrikizumab SC (two injections SC 1-milliliter (mL) of 125 mg/mL Lebrikizumab and 1-mL placebo). Week 2: Four 1-mL SC injections placebo. Weeks 4, 8, 12: 125 mg SC Lebrikizumab and 1-mL SC placebo. Weeks 6, 10, 14: Two 1-mL SC placebo. | Biological: Lebrikizumab<br>* Sterile liquid solution administered subcutaneously.<br>* Other names: DRM06;Drug: Placebo<br>* Solution administered subcutaneously.<br>|
| Experimental: 250 mg Lebrikizumab - Q4W<br>250 mg Lebrikizumab administered SC once Q4W. Baseline: Loading dose of 500 mg (four 1-mL SC injections of 125 mg/mL Lebrikizumab). Week 2: Four 1-mL SC injections of placebo. Weeks 4, 8, 12: 250 mg (two 1-mL injections of 125 mg/mL Lebrikizumab). Weeks 6, 10, 14: Two 1-mL injections of placebo. | Biological: Lebrikizumab<br>* Sterile liquid solution administered subcutaneously.<br>* Other names: DRM06;Drug: Placebo<br>* Solution administered subcutaneously.<br>|
| Experimental: 250 mg Lebrikizumab - Every 2 Weeks (Q2W)<br>250 mg Lebrikizumab administered SC once Q2W. Baseline and Week 2: Loading dose of 500 mg (four 1-mL SC injections of 125 mg/mL Lebrikizumab). Week 4, 6, 8, 10, 12, 14: 250 mg (two 1-mL SC injections of 125 mg/mL Lebrikizumab). | Biological: Lebrikizumab<br>* Sterile liquid solution administered subcutaneously.<br>* Other names: DRM06;Drug: Placebo<br>* Solution administered subcutaneously.<br>|
| Placebo Comparator: Group 4 - Placebo<br>Placebo administered SC once Q2W. Baseline and Week 2: Four 1-mL SC injections of placebo. Week 4, 6, 8, 10, 12, 14: Two 1-mL SC injections of placebo. | Drug: Placebo<br>* Solution administered subcutaneously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Eczema Area and Severity Index (EASI) | The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). Least Square (LS) Means were calculated using analysis of covariance (ANCOVA) with the factor of treatment and the baseline EASI as covariate. Note: Missing values were imputed using Markov Chain Monte Carlo (MCMC) multiple imputation. | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a 75% Improvement From Baseline in EASI (EASI75) at Week 16 | The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score. | Week 16 | 
| Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) and a Reduction ≥2 Points From Baseline to Week 16 (5-point Scale) | The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification. | Week 16 | 
| Percentage of Participants With EASI <7 at Week 16 | The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). | Week 16 | 
| Percentage of Participants Achieving EASI50 at Week 16 | The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI responder is defined as a participant who achieves a ≥ 50% improvement from baseline in the EASI score. | Week 16 | 
| Percentage of Participants Achieving EASI90 at Week 16 | The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI responder is defined as a participant who achieves a ≥ 90% improvement from baseline in the EASI score | Week 16 | 
| Percent Change From Baseline in the Sleep Loss Scale Score | The Sleep Loss Scale is used by the participants to report the impact of itching on their sleep every night. Participants responded to the question to what extent did your itching interfere with your sleep last night. The scale ranged from 0 to 4, with 0 (not at all) to 4 (unable to sleep at all). Higher scores indicated a greater impact and worse outcome. Assessments were recorded daily by the participant using an electronic diary. Least Squares (LS) Means were calculated using ANCOVA with the factor of treatment and the baseline sleep-loss scale as covariates. | Baseline, Week 16 | 
| Percent Change From Baseline in Pruritus Numeric Rating Score (NRS) | The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable. Pruritus assessments were recorded daily by the participant using an electronic diary. LS Means were calculated using ANCOVA with the factor of treatments and the baseline pruritus NRS as covariates. | Baseline, Week 16 | 
| Percentage of Participants With Pruritus NRS Change of ≥3 at Week 16 | The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable. Assessments were recorded daily by the participant using an electronic diary. The percentage of participants who are dichotomized to success (pruritus NRS greater than or equal to 3-point improvement) at Week 16 will be analyzed using a Cochran-Mantel-Haenszel (CMH) test. | Week 16 | 
| Percentage of Participants With Pruritus NRS Change of ≥4 From Baseline to Week 16 | The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable. Assessments were recorded daily by the participant using an electronic diary. The percentage of participants who are dichotomized to success (pruritus NRS greater than or equal to 4-point improvement) at Week 16 will be analyzed using a Cochran-Mantel-Haenszel (CMH) test. | Week 16 | 
| Change From Baseline in Body Surface Area (BSA) Involved With Atopic Dermatitis (AD) | The body surface area (BSA) affected by AD will be assessed for 4 separate body regions: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. BSA was calculated using the participant's palm using the 1% rule, 1 palm was equivalent to 1% with estimates of the number of palms it takes to cover the affected AD area. Maximum number of palms were 10 palms for head and neck (10%), 20 palms for upper extremities (20%), 30 palms for trunk, including axilla and groin (30%), 40 palms for lower extremities, including buttocks (40%). Percent of BSA for a body region was calculated as = total number of palms in a body region * % surface area equivalent to 1 palm. Overall percent BSA of all 4 body regions ranges from 0% to 100 % with higher values representing greater severity of AD. | Baseline, Week 16 | 
| Change From Baseline in Atopic Dermatitis Impact Questionnaire (ADIQ) Score | The ADIQ is a 17-item questionnaire used to assess the participant's AD-specific health-related quality of life. Each item is rated on a 5-point scale from 0 to 4, with higher numbers indicating greater burden. The questionnaire assesses AD's impact on emotions, energy, activities of daily living, and social activities. The ADIQ has a recall specification of 7 days. Assessments were recorded by the participant using an electronic diary and transferred to the clinical database.The ADIQ score is calculated by summing the score of each of the 14 questions resulting in a maximum of 56 and a minimum of 0, with higher scores indicating greater burden. | Baseline, Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eczema