A PHASE 3 RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-CENTER STUDY INVESTIGATING THE EFFICACY AND SAFETY OF PF-04965842 AND DUPILUMAB IN COMPARISON WITH PLACEBO IN ADULT SUBJECTS 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
- 838
- 试验地点
- 213
- 主要终点
- Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=75 Percent (%) Improvement From Baseline at Week 12
研究概览
简要总结
B7451029 is a Phase 3 study to investigate PF-04965842 in adult patients who have moderate to severe atopic dermatitis and use background topical therapy. The efficacy 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. The efficacy of the two dosage strengths of PF-04965842 will be compared with dupilumab in terms of pruritus relief at 2 weeks. The two dosage strengths of PF-04965842 and dupilumab 300 mg injected subcutaneously once every two weeks (with a loading dose of 600 mg injected on the first day) will also be evaluated relative to placebo over 16 weeks. The safety of the investigational products will be evaluated over the duration of the study. Subjects will use non-medicated emollient at least twice a day and medicated topical therapy such as corticosteroids, calcineurin inhibitors or PDE4 inhibitors, as per protocol guidance, to treat active lesions during the study. Subjects who are randomized to receive one of the two dosage strengths of PF-04965842 will also receive placebo injectable study drug every two weeks until Week 16 and then will continue on receiving only the oral study drug for 4 weeks. Subjects who are randomized to receive dupilumab injections every two weeks will also receive oral placebo to be taken once daily until Week 16 and will then continue to receive only the oral placebo for 4 weeks. Subjects who are randomized to the placebo arms, will receive both daily oral placebo and injectable placebo every two weeks until Week 16, after which they will receive either 100 mg or 200 mg of PF-04965842 taken orally once daily for 4 weeks, dependent upon which arm they have been allocated to. Eligible subjects will have an option to enter a long-term extension study after completing 20 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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects aged 18 years or older at the time of informed consent
- •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 severity 4)
- •Documented recent history (within 6 months before the screening visit) of inadequate response to treatment with medicated topical therapy for AD for at least 4 weeks, or who have required systemic therapies for control of their disease.
- •Must be willing and able to comply with standardized background topical therapy, as per protocol guidelines throughout the study
- •Female subjects who are of childbearing potential must not be intending to become pregnant, currently pregnant, or lactating. The following conditions apply:
- •Female subjects of childbearing potential must have a confirmed negative pregnancy test prior to randomization;
- •Female subjects of childbearing potential must agree to use a highly effective method of contraception for the duration of the active treatment period and for at least 28 days after the last dose of investigational product.
- •Female subjects of non-childbearing potential must meet at least 1 of the following criteria:
- •Have undergone a documented hysterectomy and/or bilateral oophorectomy;
- •Have medically confirmed ovarian failure; or
- •Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state.
- •All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
- •If receiving concomitant medications for any reason other than AD, must be on a stable regimen prior to Day 1 and through the duration of the study
排除标准
- •Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
- •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
- •Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study
- •Other active nonAD inflammatory skin diseases or conditions affecting skin
- •Prior treatment with JAK inhibitors
- •Previous treatment with dupilumab
- •Unwilling to discontinue current AD medications prior to the study or require treatment with prohibited medications during the study
研究组 & 干预措施
PF-04965842 100 mg + Placebo Inj followed by PF-04965842 100mg
Once-daily oral PF-04965842 100 mg + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral PF-04965842 100 mg from Week 16 to Week 20
干预措施: PF-04965842 100 mg (Drug)
PF-04965842 100 mg + Placebo Inj followed by PF-04965842 100mg
Once-daily oral PF-04965842 100 mg + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral PF-04965842 100 mg from Week 16 to Week 20
干预措施: Injectable Placebo (Drug)
PF-04965842 200 mg + Placebo Inj followed by PF-04965842 200mg
Once-daily oral PF-04965842 200 mg + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral PF-04965842 200 mg from Week 16 to Week 20
干预措施: PF-04965842 200 mg (Drug)
PF-04965842 200 mg + Placebo Inj followed by PF-04965842 200mg
Once-daily oral PF-04965842 200 mg + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral PF-04965842 200 mg from Week 16 to Week 20
干预措施: Injectable Placebo (Drug)
Dupilumab Injection + Oral Placebo followed by Oral Placebo
Dupilumab injected subcutaneously once every 2 weeks + once-daily oral Placebo from Day 1 until Week 16 followed by once-daily oral Placebo from Week 16 to Week 20
干预措施: Dupilumab (Drug)
Dupilumab Injection + Oral Placebo followed by Oral Placebo
Dupilumab injected subcutaneously once every 2 weeks + once-daily oral Placebo from Day 1 until Week 16 followed by once-daily oral Placebo from Week 16 to Week 20
干预措施: Oral Placebo (Drug)
Oral Placebo + Placebo Inj followed by 100 mg PF-04965842
Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 100 mg PF-04965842 from Week 16 to Week 20
干预措施: PF-04965842 100 mg (Drug)
Oral Placebo + Placebo Inj followed by 100 mg PF-04965842
Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 100 mg PF-04965842 from Week 16 to Week 20
干预措施: Oral Placebo (Drug)
Oral Placebo + Placebo Inj followed by 100 mg PF-04965842
Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 100 mg PF-04965842 from Week 16 to Week 20
干预措施: Injectable Placebo (Drug)
Oral Placebo + Placebo Inj followed by 200 mg PF-04965842
Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 200 mg PF-04965842 from Week 16 to Week 20
干预措施: PF-04965842 200 mg (Drug)
Oral Placebo + Placebo Inj followed by 200 mg PF-04965842
Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 200 mg PF-04965842 from Week 16 to Week 20
干预措施: Oral Placebo (Drug)
Oral Placebo + Placebo Inj followed by 200 mg PF-04965842
Once-daily oral Placebo + Placebo injected subcutaneously once every 2 weeks from Day 1 until Week 16 followed by once-daily oral 200 mg PF-04965842 from Week 16 to Week 20
干预措施: Injectable Placebo (Drug)
结局指标
主要结局
Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response >=75 Percent (%) Improvement From Baseline at Week 12
时间窗: Baseline, Week 12
EASI evaluates severity of participants with 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.
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 Week 12
时间窗: Baseline (the last measurement prior to first dosing on Day 1), Week 12
IGA assessed severity of atopic dermatitis (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 scalp, palms and sole.
次要结局
- Change From Baseline in Percentage Body Surface Area (BSA) at Week 2, 4, 8, 12 and 16(Baseline, Week 2, 4, 8, 12 and 16)
- DLQI at Week 20(Week 20)
- Percentage of Participants With at Least 4 Points Improvement in the Numerical Rating Scale (NRS) for Severity of Pruritus From Baseline at Day 2-15, Week 2, 4, 8, 12 and 16(Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and Week 2, 4, 8, 12, 16)
- Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and a Reduction of >=2 Points From Baseline at Week 2, 4, 8 and 16(Baseline, Week 2, 4, 8 and 16)
- Percentage of Participants Achieving EASI Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16(Baseline, Week 2, 4, 8, 12 and 16)
- Percentage of Participants Achieving EASI Response >=75% Improvement From Baseline at Week 2, 4, 8 and 16(Baseline, Week 2, 4, 8 and 16)
- EQ-5D-5L- VAS Score at Week 20(Week 20)
- POEM at Week 20(Week 20)
- Percentage of Participants Achieving EASI Response >=90% Improvement From Baseline at Week 2, 4, 8, 12 and 16(Baseline, Week 2, 4, 8,12 and 16)
- Time From Baseline to First Achieve at Least 4 Points Improvement in the Severity of Pruritus NRS(Baseline up to Week 16)
- Change From Baseline in EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Index Value at Week 12 and 16(Baseline, Week 12 and 16)
- EQ-5D-5L- Index Value at Week 20(Week 20)
- Change From Baseline in Hospital Anxiety and Depression Scale (HADS) - Anxiety Scale at Week 12 and 16(Baseline, Weeks 12 and 16)
- Change From Baseline in HADS - Depression Scale at Week 12 and 16(Baseline, Week 12 and 16)
- Percentage of Participants Achieving EASI Response =100% Improvement From Baseline at Week 2, 4, 8, 12 and 16(Baseline, Week 2, 4, 8, 12 and 16)
- Percentage BSA at Week 18 and 20(Week 18 and 20)
- Change From Baseline in Patient Global Assessment (PtGA) at Week 2, 4, 8, 12 and 16(Baseline, Week 2, 4, 8, 12 and 16)
- Change From Baseline in EQ-5D-5L Visual Analogue Scale (VAS) Score at Week 12 and 16(Baseline, Week 12 and 16)
- Percentage of Participants With Scoring Atopic Dermatitis (SCORAD) Response >=50% Improvement From Baseline at Week 2, 4, 8, 12 and 16(Baseline, Week 2, 4, 8 12 and 16)
- Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 2, 12 and 16(Baseline, Week 2, 12 and 16)
- HADS - Depression Scale at Week 20(Week 20)
- PSAAD Total Score at Week 18 and 20(Week 18 and 20)
- HADS - Anxiety Scale at Week 20(Week 20)
- Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score Week 1 to Week 16(Baseline, Week 1 to Week 16)
- Change From Baseline in SCORAD Visual Analogue Scale (VAS) of Itch and Sleep Loss at Week 2, 4, 8 12 and 16(Baseline, Week 2, 4, 8 12 and 16)
- Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 12 and 16(Baseline, Week 12 and 16)
- Percentage of Participants With SCORAD Response >=75% Improvement From Baseline at Week 2, 4, 8 12 and 16(Baseline, Week 2, 4, 8 12 and 16)
- Least Square Mean of Number of Steroid-free Days From Baseline up to Week 16(Baseline up to Week 16)
- SCORAD VAS of Itch and Sleep Loss at Week 18 and 20(Week 18 and 20)