A PHASE 3 RANDOMIZED WITHDRAWAL, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTI-CENTER STUDY INVESTIGATING THE EFFICACY AND SAFETY OF PF-04965842 IN SUBJECTS AGED 12 YEARS AND OVER, WITH MODERATE TO SEVERE ATOPIC DERMATITIS WITH THE OPTION OF RESCUE TREATMENT IN FLARING SUBJECTS
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 1,235
- 试验地点
- 235
- 主要终点
- Percentage of Participants With Loss of Response: Double-blind (DB) Period
研究概览
简要总结
B7451014 is a Phase 3 study to investigate PF-04965842 in patients aged 12 years and over with a minimum body weight of 40 kg who have moderate to severe atopic dermatitis. Subjects responding well to an initial open-label 12 week treatment of PF-04965842 (200 mg) taken orally once daily (QD) will be identified and randomized in a double-blind manner to receive 200 mg QD PF-04965842, 100 mg QD PF-04965842, or QD placebo. Efficacy and safety of 2 doses of PF-04965842 will be evaluated relative to placebo over 40 weeks. Subjects experiencing significant worsening of their symptoms, i.e., protocol-defined flare, enter 12 weeks rescue treatment and receive 200 mg PF-04965842 together with a marketed topical medicine. Eligible patients will have the option to enter a long-term extension study after completing the initial 12 week treatment, the 12 week rescue treatment, and the 40 week blinded treatment.
详细描述
Responder criteria for randomization at week 12 are defined as a) achieving an IGA of clear (0) or almost clear (1) (on a 5 point scale), b) a reduction from IGA baseline of 2 or more points, and c) reaching an EASI-75 response compared to baseline. Flare requiring rescue treatment is defined as a loss of at least 50% of the EASI response at Week 12 and an IGA score of 2 or higher.
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: BSA10%, 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 QD
Double-blind randomized treatment following open label run-in period.
干预措施: PF-04965842 100 mg (Drug)
PF-04965842 200 mg QD
Double-blind randomized treatment following open label run-in period.
干预措施: PF-04965842 200 mg (Drug)
Placebo QD
Double-blind randomized treatment following open label run-in period.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Loss of Response: Double-blind (DB) Period
时间窗: From Day 1 of up to Week 40 of double blind period
Percentage of participants with loss of response requiring rescue treatment during double blind period was determined. Loss of response denoted as flare and was define as a loss of at least 50% of EASI total score at Week 12 and with an IGA score of 2 or higher. EASI quantifies severity of participant's atopic dermatitis (AD) based on both severity of lesion clinical signs and % of body surface area (BSA) affected. EASI is a composite scoring by AD clinical evaluator of degree of erythema, induration/papulation, excoriation, and lichenification for each of 4 body regions. EASI total score range from 0.0 to 72.0, with higher scores representing greater severity of AD. IGA assesses severity of AD on 5-point scale (0 to 4, higher scores = more severity), reflecting global consideration of erythema, induration and scaling. Where, 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate and 4 = severe.
Time to Loss of Response: Double-blind Period
时间窗: From date of first dose of randomized treatment until the last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue) (maximum up to Week 40, visit window was extended +/- 45 Days due to COVID 19)
Time (in days) to loss of response based on achieving IGA \>=2 was measured from date of first dose of randomized treatment until last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue) and based on EASI, loss of at least 50% of EASI response at Week 12 and IGA score of 2 or higher. IGA assesses severity of AD on 5-point scale (0 to 4, higher scores=more severity), reflecting global consideration of erythema, induration and scaling with scores 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe. EASI quantifies severity of AD based on severity of lesion clinical signs and % of BSA affected. EASI composite score evaluates degree of erythema, induration/papulation, excoriation, and lichenification.
次要结局
- Time to First Loss of Response Based on Investigator's Global Assessment (IGA) Score of 2 or Higher: Double-blind Period(From date of first dose of randomized treatment until the last dose of randomized treatment (if not entered rescue) or first day of rescue treatment (if entered rescue) (maximum up to Week 40, visit window +/- 7 Days))
- Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and a Reduction of Greater Than or Equal to (>=) 2 Points From Baseline at Weeks 12, 16, 28, 40, and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=50% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=75% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=90% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=100% Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Percentage of Participants With Greater Than or Equal 4 Points Improvement in the Numerical Rating Scale (NRS) for Severity of Pruritus From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Percent Change From Baseline in Body Surface Area (BSA) at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Percent Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Total Score at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Change From Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analogue Scale (VAS) of Itch and Sleep Loss at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Percentage of Participants With >=50% Improvement From Baseline in Scoring Atopic Dermatitis (SCORAD) Response at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Percentage of Participants With >=75% Improvement From Baseline in Scoring Atopic Dermatitis (SCORAD) Response at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to (>=) 2 Points Improvement From Rescue Baseline at Rescue Weeks 2, 4, 8 and 12: Rescue Period(Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12)
- Percent Change From Rescue Baseline in Total Eczema Area and Severity Index (EASI) Score at Rescue Weeks 2, 4, 8 and 12: Rescue Period(Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12)
- Percentage of Participants Achieving Greater Than or Equal to 4 Points Improvement From Rescue Baseline in Peak Pruritus Numeric Rating Scale (PP-NRS) at Rescue Weeks 2, 4, 8 and 12: Rescue Period(Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12)
- Percent Change From Rescue Baseline in Percent Body Surface Area (BSA) at Rescue Weeks 2, 4, 8 and 12: Rescue Period(Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12)
- Percent Change From Rescue Baseline in Scoring Atopic Dermatitis (SCORAD) Visual Analog Scale (VAS) Score of Itch and Sleep Loss at Rescue Weeks 2, 4, 8 and 12: Rescue Period(Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12)
- Percentage of Participants With 50% Improvement in Scoring Atopic Dermatitis (SCORAD) From Rescue Baseline at Rescue Weeks 2, 4, 8 and 12: Rescue Period(Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12)
- Percentage of Participants With 75% Improvement in Scoring Atopic Dermatitis (SCORAD) From Rescue Baseline at Rescue Weeks 2, 4, 8 and 12: Rescue Period(Rescue Baseline: last observation collected between last dose of blinded treatment and Day 1 (first dose day) of rescue treatment, Rescue Weeks 2, 4, 8 and 12)
- Percentage of Participants Achieving Patient Global Assessment (PtGA) Response of 'Clear (0)' or 'Almost Clear (1)' and Greater Than or Equal to 2 Points Improvement From Baseline at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Change From Baseline in Dermatology Life Quality Index (DLQI) Score for Adults at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score for Adolescents at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety Scale at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Depression Scale at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Change From Baseline in Patient Oriented Eczema Measure (POEM) Score at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)
- Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Score at Weeks 12, 16, 28, 40 and 52: Double-blind Period(Baseline, Weeks 12, 16, 28, 40 and 52)