A PHASE 3B RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, ACTIVE CONTROLLED MULTI-CENTER STUDY ASSESSING THE EFFICACY AND SAFETY OF ABROCITINIB COMPARED WITH DUPILUMAB IN ADULT PARTICIPANTS ON BACKGROUND TOPICAL THERAPY WITH MODERATE TO SEVERE ATOPIC DERMATITIS
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 727
- 试验地点
- 149
- 主要终点
- Percentage of Participants Achieving Greater Than or Equal to (>=) 4 Points Improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) From Baseline at Week 2
研究概览
简要总结
This is a randomized, double-blind, double-dummy, active-controlled, multi-center study to assess the efficacy and safety of abrocitinib 200 mg (2 x 100 mg tablets) administered orally QD compared with dupilumab 300 mg administered by subcutaneous injection every other week (as per label guidelines) in adult participants on background topical therapy, with moderate to severe AD. The treatment duration is 26 weeks. A total of approximately 600 participants will be enrolled from approximately 220 sites globally. Approximately 600 participants will be randomly assigned to study intervention. There are primary efficacy assessments at Week 2 and Week 4, and a key secondary efficacy assessment at Week 16. Efficacy and safety endpoints will be assessed throughout the entire study. Exploratory endpoints related to hand eczema efficacy will be assessed throughout the study.
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)
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
- •18 years of age or older
- •Diagnosis of chronic atopic dermatitis (AD) for at least 6 months
- •Moderate to severe AD (BSA at least 10%, IGA at least 3, EASI at least 16, and PP-NRS severity score at least 4)
- •Recent history of inadequate response to treatment with medicated topical therapy for AD, or who have required systemic therapies for control of their disease
排除标准
- •Acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation
- •Have increased risk of developing venous thromboembolism
- •Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study
- •Prior treatment with systemic JAK inhibitors or IL-4 or IL-13 antagonists including dupilumab, lebrikizumab or tralokinumab
- •Other active non-AD inflammatory skin diseases or conditions affecting skin
- •Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, malignancies, current or history of certain infections, lymphoproliferative disorders and other medical conditions at the discretion of the investigator
- •Pregnant or breastfeeding women, or women of childbearing potential who are unwilling to use contraception
研究组 & 干预措施
Abrocitinib 200 mg plus placebo injection
Abrocitinib 200 mg daily through Week 26, plus placebo injections every other week through Week 24
干预措施: Abrocitinib 200 mg (Drug)
Dupilumab 300 mg plus placebo tablets
Dupilumab 300 mg every other week (2 injections on Day 1) through Week 24, plus placebo tablets daily through Week 26
干预措施: Dupilumab 300 mg (Combination Product)
结局指标
主要结局
Percentage of Participants Achieving Greater Than or Equal to (>=) 4 Points Improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) From Baseline at Week 2
时间窗: Week 2
The severity of itch (pruritus) due to atopic dermatitis (AD) was assessed using the PP-NRS, a validated horizontal NRS. Participants were asked to assess their worst itching due to AD over the past 24 hours on an NRS with scale ranging from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Percentage of Participants Achieving >= 90% Improvement From Baseline in Eczema Area and Severity Index (EASI-90) Response at Week 4
时间窗: Week 4
EASI quantifies severity of AD based on severity of lesion clinical signs and percentage (%) of body surface area (BSA) affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%) and 6 (90 to 100%). Total EASI score =0.1\*Ah\*(Eh+Ih+Exh+Lh) + 0.2\*Au\*(Eu+Iu+ExU+Lu) + 0.3\*At\*(Et+It+Ext+Lt) + 0.4\*Al\*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD.
次要结局
- Percentage of Participants Achieving PP-NRS4 From Baseline at Days 2 to 15(Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15)
- Percent Change From Baseline in the Percentage (%) Body Surface Area (BSA) Affected at Week 2, 4, 8, 12, 16, 20 and 26(Baseline (Day 1), Week 2, 4, 8, 12, 16, 20 and 26)
- Change From Baseline in Total Anxiety Score Measured Using the Hospital Anxiety and Depression Scale (HADS) at Week 12,16 and 26(Baseline (Day 1), Week 12, 16 and 26)
- Percentage of Participants Achieving EASI-90 Response at Week 16(Week 16)
- Percentage of Participants Achieving EASI-90 Response at Weeks 2, 8, 12, 20 and 26(Week 2, 8, 12, 20 and 26)
- Percentage of Participants Achieving PP-NRS4 From Baseline at Week 4, 8, 12, 16, 20 and 26(Week 4, 8, 12, 16, 20 and 26)
- Time to Achieve >=4 Points Improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4)(Baseline (Day 1) up to Week 30)
- Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 2, 12, 16, 20 and 26(Baseline (Day 1), Week 2, 12, 16, 20 and 26)
- Percentage of Participants Achieving >= 75% Improvement From Baseline in EASI (EASI-75) Response at Weeks 2, 4, 8, 12, 16, 20 and 26(Week 2, 4, 8, 12, 16, 20 and 26)
- Percentage of Participants Achieving Investigator's Global Assessment (IGA) Score of 'Clear' or 'Almost Clear' and >=2 Points Improvement From Baseline up to Week 26(Week 2, 4, 8, 12, 16, 20 and 26)
- Percent Change From Baseline in the SCORing Atopic Dermatitis (SCORAD) Total Score at Week 2, 4, 8, 12, 16, 20 and 26(Baseline (Day 1), Week 2, 4, 8, 12, 16, 20 and 26)
- Change From Baseline in Medical Outcomes Study - Sleep Scale (MOS-Sleep Scale) at Week 12, 16 and 26(Baseline (Day 1), Week 12, 16 and 26)
- Change From Baseline in Patient-Oriented Eczema Measure (POEM) Total Score at Week 12, 16 and 26(Baseline (Day 1), Week 12, 16 and 26)
- Change From Baseline in Skin Pain NRS at Week 2, 12, 16, 20 and 26(Baseline (Day 1), Week 2, 12, 16, 20 and 26)
- Medicated Topical Background Therapy-free Days(Day 1 up to Week 26)
- Percentage of Participants Achieving >=4 Points Improvement From Baseline in DLQI at Week 2, 12, 16, 20 and 26(Week 2, 12, 16, 20 and 26)
- Change From Baseline in Total Depression Score Measured Using the HADS at Week 12,16 and 26(Baseline (Day 1), Week 12, 16 and 26)
- Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Visual Analog Scale (VAS) Score at Week 12, 16 and 26(Baseline (Day 1), Week 12, 16 and 26)