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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 280
- 试验地点
- 57
- 主要终点
- Percent Change From Baseline in Eczema Area and Severity Index (EASI)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Lebrikizumab (Biological)
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.
干预措施: Placebo (Drug)
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.
干预措施: Lebrikizumab (Biological)
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.
干预措施: Placebo (Drug)
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).
干预措施: Lebrikizumab (Biological)
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).
干预措施: Placebo (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change From Baseline in Eczema Area and Severity Index (EASI)
时间窗: 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.
次要结局
- 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)