A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Proof-of-concept Study Evaluating Efficacy and Safety of Rilzabrutinib in Adult Patients With Moderate-to-severe Atopic Dermatitis Who Are Inadequate Responders or Intolerant to Topical Corticosteroids
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 124
- 试验地点
- 62
- 主要终点
- Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score
研究概览
简要总结
This was a parallel treatment, Phase 2, double-blind, 2-arm, placebo-controlled study with 2 staggered cohorts (2 arms in each cohort) to evaluate the efficacy and safety of rilzabrutinib in adult participants (aged at least 18 years) with moderate-to-severe AD and intolerance or inadequate response to topical corticosteroids (TCS).
The total study duration per participant was expected to be approximately 21 weeks, including up to 4 weeks of screening, 16 weeks of on-treatment double-blind period, 1 week of post-treatment follow-up.
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
- •AD as defined by the American Academy of Dermatology Consensus Criteria.
- •History of AD for at least 12 months prior to baseline as determined by the Investigator through patient interview.
- •Eczema Area and Severity Index (EASI) score ≥ 12 at screening and at baseline.
- •IGA score ≥ 3 (on the 0 to 4 IGA scale) at baseline.
- •BSA of AD involvement ≥ 10% at baseline.
- •Documented inadequate response or intolerance to TCS within 6 months prior to baseline visit
- •Baseline PP-NRS score for maximum itch intensity ≥
- •All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •For optional substudy only: Willingness to have 2 tape strips for comparison of baseline and treatment response.
排除标准
- •Skin comorbidities that may interfere with study assessments such as psoriasis, tinea corporis, lupus erythematosus.
- •Conditions that may predispose the patient to excessive bleeding.
- •Any other clinically significant disease, condition, or medical history that, in the opinion of the Investigator, would interfere with participant safety, trial evaluations, and/or trial procedures.
- •Laboratory abnormalities at the screening visit
- •History of serious infections requiring intravenous therapy with the potential for recurrence (as judged by the Site Investigator and the Sponsor Medical Monitor), with less than 4 weeks interval between resolution of serious infection and first dose of study drug, or currently active moderate to severe infection at Screening (Grade 2 or higher) including active coronavirus disease 2019 (COVID-19).
- •Live vaccine except Bacille Calmette Guerin-vaccination within 28 days prior to Day 1 or plan to receive one during the trial; Bacille Calmette Guerin-vaccination within 12 months prior to Screening.
- •COVID-19 vaccine within 14 days prior to Study Day
- •Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate rilzabrutinib/placebo absorption.
- •Initiation of prescription moisturizers (with or without additives such as ceramide, hyaluronic acid, urea, or filaggrin), topical anesthetics or antihistamines during the screening period.
- •Use of TCS, topical calcineurin (tacrolimus, and/or pimecrolimus) or topical phosphodiesterase 4 inhibitor within 1 week prior to baseline and as concomitant medication.
- •Use of systemic corticosteroids within 4 weeks prior to baseline and as concomitant medication.
- •Phototherapy for AD or regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks prior to baseline or likely to be required as concomitant procedure during the study.
- •Use of mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, dapsone, intravenous immunoglobulin (IVIG), Kineret (anakinra), Enbrel (etanercept), or any other immunosuppressant not mentioned in this exclusion criterion within 4 weeks prior to baseline.
- •Use of infliximab, adalimumab, golimumab, abatacept, tocilizumab, certolizumab, secukinumab, IFN-γ, JAK inhibitors, dupilumab, and any other biologic or targeted-synthetic disease modifier drug not mentioned in this exclusion criterion or in exclusion criterion, as well as plasmapheresis within 12 weeks prior to baseline.
- •Use of anti-CD20 drugs such as rituximab, ofatumumab, other long-acting biologics within 6 months prior to baseline (or shorter if there is documented B cell reconstitution for anti-CD20 drugs).
- •Use of proton pump inhibitor drugs such as omeprazole and esomeprazole within 3 days of baseline (it is acceptable to change participant to H2 receptor blocking drugs prior to baseline).
- •Concomitant use of known systemic strong-to-moderate inhibitors and inducers of cytochrome P450 3A (CYP3A) within 14 days or 5 half-lives (whichever is longer) prior to baseline.
- •Previous use of a BTK inhibitor.
- •Had received any investigational drug (or is currently using an investigational device) within the 30 days before baseline, or at least 5 times the respective elimination half-life time (whichever is longer).
- •Active TB or a history of incompletely treated TB, Quantiferon positive patients, Clinically significant abnormality consistent with prior/active TB infection based upon chest radiograph with at least posterior-anterior view, Suspected extrapulmonary TB infection, or patients at high risk of contracting TB.
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
BID cohort: Placebo
Participants received placebo matched to rilzabrutinib orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).
干预措施: Placebo (Drug)
TID cohort: Placebo
Participants received placebo matched to rilzabrutinib orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
干预措施: Placebo (Drug)
BID cohort: Rilzabrutinib
Participants received rilzabrutinib 400 milligrams (mg) orally BID from Day 1 up to Week 16. Consecutive doses were ideally administered 12 hours apart (and not less than 8 hours apart).
干预措施: Rilzabrutinib (Drug)
TID cohort: Rilzabrutinib
Participants received rilzabrutinib 400 mg orally TID from Day 1 up to Week 16. Consecutive doses were ideally administered at least 6 hours apart (and not less than 4 hours apart).
干预措施: Rilzabrutinib (Drug)
结局指标
主要结局
Percent Change From Baseline to Week 16 in Eczema Area and Severity Index (EASI) Score
时间窗: Baseline (Day 1) to Week 16
The EASI index is a validated investigator-administered scoring system used to measure the severity of clinical signs in atopic dermatitis (AD). Four AD disease characteristics (erythema, thickness \[induration, papulation, edema\], scratching \[excoriation\], and lichenification) were each assessed for severity by the investigator or designee on a scale of "0" (absent) through "3" (severe). In addition, the area of AD involvement were assessed as a percentage by body area of head, trunk, upper limbs, and lower limbs, and converted to a score of 0 to 6. 0: 0% of body surface area (BSA) involvement with AD; 1: 1-9%; 2: 10-29%; 2: 30-49%; 4: 50-69%; 5: 70-89% and 6: 90-100% of BSA involvement with AD. Total score ranged from 0 (minimum) to 72 (maximum); higher scores indicated greater severity of AD. Baseline was defined as the Day 1 assessment value.
次要结局
- Percentage of Participants Achieving EASI-75 (Reduction of EASI Score By ≥75% From Baseline) At Week 16(Baseline (Day 1) and at Week 16)
- Absolute Change From Baseline to Week 16 In EASI Score(Baseline (Day 1) to Week 16)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and Study intervention Discontinuation(Baseline (Day 1) to 16 weeks)
- Percentage Of Participants With Reduction of Weekly Average of Daily Peak Pruritus Numerical Rating Scale (PP-NRS) of ≥4 Points From Baseline at Week 16(Baseline (Day 1) and at Week 16)
- Change From Baseline to Week 16 in Percent BSA of AD(Baseline (Day 1) to Week 16)
- Percentage of Participants Achieving EASI-50/90 (Reduction of EASI Score by ≥50% or ≥90% From Baseline) at Week 16(Baseline (Day 1) and at Week 16)
- Percent Change From Baseline to Week 16 in Weekly Average of Daily PP-NRS(Baseline (Day 1) to Week 16)
- Percentage of Participants With Investigator's Global Assessment (IGA) of 0 or 1 At Week 16(Week 16)
- Number of Participants With Weekly Average of Daily PP-NRS Reduction ≥4 From Baseline During The 16-Week Treatment Period(Baseline (Day 1) and Week 16)
- Absolute Change From Baseline to Week 16 in Weekly Average of Daily PP-NRS(Baseline (Day 1) to Week 16)
- Percentage of Participants Achieving IGA*BSA-50/75/90 (Reduction of IGA*BSA by ≥50% or 75% or 90% From Baseline) At Week 16(Baseline (Day 1) and at Week 16)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Adverse Events of Special Interest (AESIs) and Study Intervention Discontinuation(Baseline (Day 1) to 16 weeks)