A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Nemolizumab in Subjects With Moderate-to-Severe Atopic Dermatitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Galderma R&D
- 入组人数
- 787
- 试验地点
- 138
- 主要终点
- Percentage of Participants With Investigator's Global Assessment (IGA) Success at Week 16: Severe Pruritus Population
研究概览
简要总结
The main purpose of the study was to assess the efficacy and safety of nemolizumab after a 16-week treatment period in adult and adolescent subjects with moderate-to-severe atopic dermatitis (AD) not adequately controlled with topical treatments.
详细描述
This was a randomized, double-blind, placebo-controlled, multi-center, parallel-group study in adult and adolescent subjects of age 12 years and above with moderate-to-severe AD. Eligible subjects had documented history of inadequate response to topical AD medication(s). Approximately 750 subjects were randomized in 2:1 to receive either nemolizumab or placebo, stratified by baseline disease severity (Investigator's Global Assessment (IGA) = 3, moderate; IGA = 4, severe) and peak pruritus numeric rating scale (PP NRS) severity (PP NRS >= 7; PP NRS < 7). A minimum of 250 subjects were randomized in each PP NRS strata. All nemolizumab-treated subjects who were clinical responders at Week 16 (i.e., the end of initial treatment [Initial Treatment Period]/beginning of Maintenance Period) were re-randomized (1:1:1) to different treatment regimens (nemolizumab injections Q4W or every 8 weeks (Q8W) [with placebo injections at Weeks 20, 28, 36, and 44 to maintain the blind] or placebo Q4W). A clinical responder was defined as a subject at Week 16 with an IGA of 0 (clear) or 1 (almost clear) or a >=75% improvement in EASI from baseline (EASI-75). All placebo-treated subjects who responded to placebo during the Initial Treatment Period continued to receive placebo Q4W in the Maintenance Period.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Treatment
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects aged greater than and equal to (>=) 12 years at the screening visit.
- •Chronic atopic dermatitis (according to American Academy of Dermatology Consensus Criteria) that has been present for at least 2 years before the screening visit.
- •Eczema Area and Severity Index (EASI) score >=16 at the screening and baseline visits.
- •Investigator Global Assessment (IGA) score >= 3 (scale of 0 to 4) at the screening and baseline visits.
- •AD involvement >= 10 percent (%) of body surface area (BSA) at screening and baseline visits.
- •Peak Pruritus Numerical Rating Scale (PPNRS) score of at least 4.0 at the screening and baseline visits.
- •Documented recent history of inadequate response to topical medications (topical corticosteroids [TCS] with or without Topical calcineurin inhibitors [TCI]).
- •Female subjects of childbearing potential (that is, fertile, following menarche and until becoming postmenopausal unless permanently sterile) must agree either to be strictly abstinent throughout the study and for 12 weeks after the last study drug injection or to use an adequate and approved method of contraception throughout the study and for 12 weeks after the last study drug injection.
排除标准
- •Body weight (<) 30 kilograms (kg)
- •Exacerbation of asthma requiring hospitalization in the preceding 12 months. Uncontrolled asthma in the preceding 3 months.
- •Cutaneous infection within 1 week before the baseline visit, any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics or antifungals within 2 weeks before the baseline visit, or any confirmed or suspected coronavirus disease (COVID)-19 infection within 2 weeks before the screening or baseline visit.
- •Pregnant women, breastfeeding women, or women planning a pregnancy during the clinical study.
- •Note: Subjects with chronic,stable use of prophylactic treatment for recurrent herpes viral infection can be included in this clinical study.
- •History of hypersensitivity (including anaphylaxis) to an immunoglobulin product (plasma-derived or recombinant, e.g., monoclonal antibody) or to any of the study drug excipients.
- •Any clinically significant issue, based on investigator judgement.
研究组 & 干预措施
Placebo
Placebo administered via subcutaneous injection
干预措施: Placebo (Drug)
Nemolizumab
Nemolizumab administered via subcutaneous injection
干预措施: Nemolizumab (Drug)
结局指标
主要结局
Percentage of Participants With Investigator's Global Assessment (IGA) Success at Week 16: Severe Pruritus Population
时间窗: Week 16
IGA success was defined as an IGA score of 0 (clear) or 1 (almost clear) and at least a 2-grade improvement from baseline to Week 16. The IGA is a 5-point scale ranging from 0 (clear) to 4 (severe) used by the Investigator or trained designee to evaluate the global severity of AD and the clinical response to treatment. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered a treatment failure. Participants with missing data at Week 16 were considered non-responders.
Percentage of Participants With >=75% Improvement in Eczema Area and Severity Index (EASI-75) at Week 16: ITT Population
时间窗: Week 16
EASI-75 was defined as \>=75 percent(%) improvement in EASI from baseline to Week 16. EASI evaluates severity of participants AD based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD(erythema, induration/papulation, excoriation and lichenification)scored separately for each of 4 body regions (head \& neck, upper limbs, trunk \& lower limbs on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI total score is composite score ranging from 0 to 72. Higher scores represent greater severity of AD. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered a treatment failure. Participants with missing data at Week 16 were considered non-responders.
Percentage of Participants With >=75% Improvement in Eczema Area and Severity Index (EASI-75) at Week 16: Severe Pruritus Population
时间窗: Week 16
EASI-75 was defined as \>=75 percent(%) improvement in EASI from baseline to Week 16. EASI evaluates severity of participants AD based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD(erythema, induration/papulation, excoriation and lichenification)scored separately for each of 4 body regions (head \& neck, upper limbs, trunk \& lower limbs on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI total score is composite score ranging from 0 to 72. Higher scores represent greater severity of AD. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered a treatment failure. Participants with missing data at Week 16 were considered non-responders.
Percentage of Participants With Investigator's Global Assessment (IGA) Success at Week 16: Intent-To-Treat (ITT) Population
时间窗: Week 16
IGA success was defined as an IGA score of 0 (clear) or 1 (almost clear) and at least a 2-grade improvement from baseline to Week 16. The IGA is a 5-point scale ranging from 0 (clear) to 4 (severe) used by the Investigator or trained designee to evaluate the global severity of atopic dermatitis (AD) and the clinical response to treatment. If a participant received any rescue therapy, the data after receipt of rescue therapy was considered treatment failure. Participants with missing data at Week 16 were considered non-responders.
次要结局
- Percentage of Participants With an Improvement of Sleep Disturbance Numeric Rating Scale (SD NRS) >=4 at Week 16: Severe Pruritus Population(Week 16)
- Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 4: ITT Population(Week 4)
- Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 16: ITT Population(Week 16)
- Percentage of Participants With <2 Points in Weekly Average PP NRS at Week 16: ITT Population(Week 16)
- Percentage of Participants With an Improvement of Sleep Disturbance Numeric Rating Scale (SD NRS) >=4 at Week 16: ITT Population(Week 16)
- Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 1: Severe Pruritus Population(Week 1)
- Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 16: Severe Pruritus Population(Week 16)
- Percentage of Participants With <2 Points in Weekly Average PP NRS at Week 16: Severe Pruritus Population(Week 16)
- Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 4: Severe Pruritus Population(Week 4)
- Percentage of Participants With Peak Pruritus Numeric Rating Scale (PP NRS) <2 at Week 4: ITT Population(Week 4)
- Percentage of Participants With Peak Pruritus Numeric Rating Scale (PP NRS) <2 at Week 4: Severe Pruritus Population(Week 4)
- Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 2: ITT Population(Week 2)
- Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 2: Severe Pruritus Population(Week 2)
- Percentage of Participants With Improvement of >=4 Points in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS) at Week 1: ITT Population(Week 1)