A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-CENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PF-04965842 MONOTHERAPY IN SUBJECTS AGED 12 YEARS AND OLDER, 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
- 387
- 试验地点
- 87
- 主要终点
- Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to 2 Points Improvement From Baseline at Week 12
研究概览
简要总结
B7451012 is a Phase 3 study to evaluate PF-04965842 in patients aged 12 years and older with a minimum body weight of 40 kg who have moderate to severe atopic dermatitis. The efficacy and safety of two dosage strengths of PF-04965842, 100 mg and 200 mg taken orally once daily, will be evaluated relative to placebo over 12 weeks of study participation. Eligible patients will have an option to enter a long-term extension study after completing 12 weeks of treatment.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •12 years of age or older with a minimum body weight of 40 kg
- •Diagnosis of atopic dermatitis (AD) for at least 1 year and current status of moderate to severe disease (>= the following scores: BSA 10%, IGA 3, EASI 16, Pruritus NRS 4)
- •Recent history of inadequate response or inability to tolerate topical AD treatments or require systemic treatments for AD control
排除标准
- •Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study
- •Prior treatment with JAK inhibitors
- •Other active nonAD inflammatory skin diseases or conditions affecting skin
- •Medical history including thrombocytopenia, coagulopathy or platelet dysfunction, Q wave interval abnormalities, current or history of certain infections, cancer, 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
PF-04965842 100 mg
干预措施: PF-04965842 100 mg (Drug)
PF-04965842 200 mg
干预措施: PF-04965842 200 mg (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to 2 Points Improvement From Baseline at Week 12
时间窗: Baseline, Week 12
IGA assesses severity of AD on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriation and slight oozing/crusting; 4= severe AD with deep dark red lesions, severe erythema, papulation/induration, lichenification, excoriation and moderate to severe oozing/crusting. Assessment excluded sole, palms and scalp.
Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response of >=75 Percent (%) Improvement From Baseline at Week 12
时间窗: Baseline, Week 12
EASI evaluates severity of participants' AD (excluded scalp, palms, soles) 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 and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % 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, higher scores = greater severity of AD.
次要结局
- Percentage of Participants With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale for Severity of Pruritus at Week 2, 4 and 12: Per Protocol Analysis Set (PPAS)(Baseline, Week 2, 4, 12)
- Percentage of Participants With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Week 2, 4, 8 and 12: Full Analysis Set (FAS)(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 2, 4, 8 and 12: Full Analysis Set(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis Total Score at Week 12: Per Protocol Analysis Set(Baseline, Week 12)
- Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale for Severity of Pruritus(Baseline up to Week 12)
- Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement From Baseline at Week 2, 4 and 8(Baseline, Week 2, 4, 8)
- Percentage of Participants Achieving Investigator's Global Assessment Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Week 2, 4 and 8(Baseline, Week 2, 4, 8)
- Percentage of Participants Achieving Investigator's Global Assessment Response of Clear (0) at Week 2, 4, 8 and 12(Week 2, 4, 8, 12)
- Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement From Baseline at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement From Baseline at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in Eczema Area and Severity Index Total Score at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in Percentage Body Surface Area at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants With Percentage Body Surface Area Less Than (<) 5% at Week 2, 4, 8 and 12(Week 2, 4, 8, 12)
- Percentage of Participants With Scoring Atopic Dermatitis (SCORAD) Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants With Scoring Atopic Dermatitis Response of >=75% Improvement From Baseline at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in Scoring Atopic Dermatitis: Visual Analogue Scale of Sleep Loss at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in Scoring Atopic Dermatitis: Total Score at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants Achieving >=1 Point Improvement From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants With Baseline Dermatology Life Quality Index Score >=2 and Achieving <2 DLQI Score at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants With Baseline Children's Dermatology Life Quality Index Score >=2 and Achieving <2 CDLQI Score at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants With Baseline Dermatology Life Quality Index Score >=4 and Achieving >=4 Point Improvement From Baseline in DLQI Score at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants With Baseline Children's Dermatology Life Quality Index Score >=2.5 and Achieving >=2.5 Point Improvement From Baseline in CDLQI Score at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in Hospital Anxiety and Depression Scale (HADS): Depression Subscale at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants With >=8 Points at Baseline and Achieving Score of <8 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Anxiety Subscale at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants With >=11 Points at Baseline and Achieving Score of <11 Points in Hospital Anxiety and Depression Scale: Depression Subscale at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Percentage of Participants Achieving 'Clear' or 'Almost Clear' and >=2 Points Improvement From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L): Index Value at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y): Index Value at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L)- Visual Analogue Scale Score at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y): Visual Analogue Scale Score at Week 2, 4, 8 and 12(Baseline, Week 2, 4, 8, 12)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) at Week 12(Baseline, Week 12)
- Change From Baseline in Pediatric Functional Assessment of Chronic Illness Therapy Fatigue Scale (Peds-FACIT-F) at Week 12(Baseline, Week 12)
- Change From Baseline in Short Form-36v2 (SF-36v2) Acute Summary Score at Week 12: Physical Component Summary(Baseline, Week 12)
- Change From Baseline in Short Form-36v2 Acute Summary Score at Week 12: Mental Component Summary(Baseline, Week 12)
- Plasma Concentration Versus Time Summary of PF-04965842(Day 1 of Week 4: 0 hour(Pre-dose), 0.5 hours post-dose; Day 1 of Week 12: 0.5, 4 hours post-dose)