A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Oral Brepocitinib in Adults With Dermatomyositis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 241
- 试验地点
- 110
- 主要终点
- Total Improvement Score (TIS) at Week 52
研究概览
简要总结
This is a phase 3, multicenter, randomized, placebo-controlled, double-blind study of treatment with brepocitinib (TYK2/JAK1 inhibitor) in adults with dermatomyositis (DM). The primary objective of this study is to assess the efficacy of two dose levels of brepocitinib in comparison to placebo, as measured by differences in the Total Improvement Score (TIS). After 52 weeks of double-blind treatment, participants have the option to continue therapy in a 52 week open-label extension phase where all participants will receive brepocitinib.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of dermatomyositis according to 2017 EULAR/ACR Classification Criteria for Idiopathic Inflammatory Myopathies
- •Adult subjects (18-75 years old)
- •Active muscle and skin disease at screening and baseline
- •Prior therapy OR current therapy with corticosteroids, hydroxychloroquine, and/or one non-steroid immunosuppressant
- •Weight > 40 kg to < 130 kg, and with a body mass index (BMI) < 40 kg/m2.
排除标准
- •Dermatomyositis with end-stage organ involvement
- •Dermatomyositis with irreversible muscle involvement
- •History of:
- •Any lymphoproliferative disorder
- •Active malignancy;
- •History of cancer within 5 years prior to randomization (exceptions for basal cell carcinoma, squamous cell carcinoma, ductal carcinoma in situ of the breast, carcinoma in situ of the uterine cervix, or thyroid carcinoma.)
- •Cancer-associated dermatomyositis
- •Overlap myositis/connective tissue disease (except for overlap with Sjögren's syndrome)
- •Participants at a risk of thrombosis or cardiovascular disease
- •Participants with a high risk for herpes zoster reactivation
- •Participants with active or recent infections
研究组 & 干预措施
Brepocitinib Dose Level 1 PO QD
干预措施: Brepocitinib (Drug)
Brepocitinib Dose Level 2 PO QD
干预措施: Brepocitinib (Drug)
Placebo PO QD
干预措施: Placebo (Drug)
结局指标
主要结局
Total Improvement Score (TIS) at Week 52
时间窗: 52 weeks
TIS is a composite endpoint based on improvement in the 6 Disease Activity Core Set Measure (CSM) scores and ranges from 0 to 100 (2016 American College of Rheumatology \[ACR\] Myositis Response Criteria/European League Against Rheumatism \[EULAR\]) where a higher score indicates more improvement
次要结局
- Change from baseline in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Activity Score at Week 52(52 weeks)
- Time to achievement of consecutive (≥ 2 visits) TIS ≥ 40 points (moderate improvement) by Week 52(52 weeks)
- Dermatomyositis Outcomes for Muscle and Skin (DMOMS) at Week 52(52 weeks)
- The proportion of participants achieving TIS ≥ 40 points (moderate improvement) at Week 52(52 weeks)
- The proportion of participants, regardless of baseline corticosteroid use, achieving TIS ≥ 40 points (moderate improvement) at Week 52 with 0 to ≤ 2.5 mg/day of oral prednisone (or equivalent) at both Week 48 and Week 52(52 weeks)
- The proportion of participants achieving ≥ 40% improvement with a ≥ 4-point improvement from baseline in CDASI Activity Score at Week 52(52 weeks)
- The proportion of participants achieving TIS ≥ 60 points (major improvement) at Week 52(52 weeks)
- Change from baseline in HAQ Disability Index score at Week 52(52 weeks)
- Change from baseline in CDASI Activity Score at Week 4(4 weeks)