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
Overview
- Phase
- Phase 2
- Intervention
- Lebrikizumab
- Conditions
- Atopic Dermatitis
- Sponsor
- Eli Lilly and Company
- Enrollment
- 280
- Locations
- 57
- Primary Endpoint
- Percent Change From Baseline in Eczema Area and Severity Index (EASI)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
125 milligrams (mg) Lebrikizumab - Every 4 Weeks (Q4W)
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.
Intervention: Lebrikizumab
125 milligrams (mg) Lebrikizumab - Every 4 Weeks (Q4W)
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.
Intervention: Placebo
250 mg Lebrikizumab - Q4W
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.
Intervention: Lebrikizumab
250 mg Lebrikizumab - Q4W
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.
Intervention: Placebo
250 mg Lebrikizumab - Every 2 Weeks (Q2W)
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).
Intervention: Lebrikizumab
250 mg Lebrikizumab - Every 2 Weeks (Q2W)
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).
Intervention: Placebo
Group 4 - Placebo
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Percent Change From Baseline in Eczema Area and Severity Index (EASI)
Time Frame: Baseline, 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). 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.
Secondary Outcomes
- Percentage of Participants With a 75% Improvement From Baseline in EASI (EASI75) at Week 16(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)(Week 16)
- Percentage of Participants With EASI <7 at Week 16(Week 16)
- Percentage of Participants Achieving EASI50 at Week 16(Week 16)
- Percentage of Participants Achieving EASI90 at Week 16(Week 16)
- Percent Change From Baseline in Pruritus Numeric Rating Score (NRS)(Baseline, Week 16)
- Percentage of Participants With Pruritus NRS Change of ≥3 at Week 16(Week 16)
- Percentage of Participants With Pruritus NRS Change of ≥4 From Baseline to Week 16(Week 16)
- Change From Baseline in Body Surface Area (BSA) Involved With Atopic Dermatitis (AD)(Baseline, Week 16)
- Percent Change From Baseline in the Sleep Loss Scale Score(Baseline, Week 16)
- Change From Baseline in Atopic Dermatitis Impact Questionnaire (ADIQ) Score(Baseline, Week 16)