A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Efficacy and Safety of Abiprubart in Participants With Sjögren's Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 15
- 主要终点
- Change From Baseline in European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) at Week 24
研究概览
简要总结
Primary objective of the study is to evaluate the effect of abiprubart on an established systemic disease activity measure for Sjögren's Disease.
详细描述
This is a 56-week (24-week randomized double-blind period, 24-week active treatment period, and 8-week safety follow-up period) multicenter, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of abiprubart in participants with Sjögren's Disease with moderate or high systemic disease activity according to the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI). The objectives of the study are to evaluate efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of abiprubart compared with placebo across the estimated therapeutic range using different dosing regimens of abiprubart.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a diagnosis of Sjögren's Disease according to 2016 American College or Rheumatology (ACR)-EULAR Classification Criteria.
- •Has ESSDAI value ≥ 5, counting only the biological, hematological, articular, cutaneous, glandular, lymphadenopathy, and constitutional organ domains at Screening.
- •Is seropositive at Screening for anti-Sjögren's-syndrome-related antigen A autoantibodies (SSA) antibodies tested at a central laboratory.
- •Has stimulated whole salivary flow rate at Screening of ≥ 0.05 mL/min
- •Weighs at least 40 kg and no more than 150 kg and has a body mass index (BMI) within the range of 18-40 kg/m2.
排除标准
- •Prior exposure to any other anti-CD40/CD154 agent.
- •Diagnosis of Sjögren's Disease overlap syndromes where another autoimmune rheumatic disease constitutes the principal illness, including fibromyalgia with currently active, inadequately controlled symptoms.
- •Has received cataract surgery, Lasik, or other ophthalmologic surgery procedure (e.g., lachrymal plug) in the 6 months prior to Screening.
- •Injectable corticosteroids (including intra-articular) within 8 weeks prior to randomization.
- •Has started, stopped or adjusted dose/regimen of medications for treatment of, or known to cause dry mouth/eyes within the 30 days prior to screening or is anticipating change to these treatment regimens during the study.
- •Has history of immunodeficiency (e.g., immune disorders or disorders that result in decreased immunity), including human immunodeficiency virus (HIV).
- •History of thromboembolic event or a significant risk of future thromboembolic events.
- •Has a known high risk of infection; Has a history of chronic or recurrent infectious disease; Has any known or suspected active infection, or has had a serious infection requiring hospitalization, or has been treated with IV/IM antibiotics for an infection within 8 weeks prior to first dose of study drug or treatment with oral antibiotics for an infection within 2 weeks prior to first dose of study drug.
研究组 & 干预措施
Abiprubart 400mg SC q2wk
Part A: Loading dose of abiprubart 800 mg subcutaneous (SC) followed by abiprubart 400 mg SC every 2 weeks (q2wk) through Week 22.
Part B: Abiprubart 400 mg SC q2wk: abiprubart 400 mg SC q2wk up to and including Week 46.
干预措施: Abiprubart (Drug)
Abiprubart 400mg SC q4wk
Part A: Loading dose of abiprubart 800 mg SC followed by abiprubart 400 mg SC q2wk through Week 22 which will alternately administer placebo or abiprubart to provide active drug every 4 weeks (q4wk) while maintaining treatment concealment.
Part B: Abiprubart 400 mg SC q4wk: abiprubart 400 mg SC q2wk up to and including Week 46 which will alternately administer placebo or abiprubart to provide active drug q4wk while maintaining treatment concealment.
干预措施: Abiprubart (Drug)
Abiprubart 400mg SC q4wk
Part A: Loading dose of abiprubart 800 mg SC followed by abiprubart 400 mg SC q2wk through Week 22 which will alternately administer placebo or abiprubart to provide active drug every 4 weeks (q4wk) while maintaining treatment concealment.
Part B: Abiprubart 400 mg SC q4wk: abiprubart 400 mg SC q2wk up to and including Week 46 which will alternately administer placebo or abiprubart to provide active drug q4wk while maintaining treatment concealment.
干预措施: Placebo (Drug)
Placebo
Part A: A matched volume placebo loading dose followed by placebo SC injections q2wk through Week 22.
Part B: Participants assigned to placebo in Part A will transition to active abiprubart treatment, according to randomized assignment, with either abiprubart 400 mg SC q2wk or abiprubart 400 mg SC q4wk.
干预措施: Abiprubart (Drug)
Placebo
Part A: A matched volume placebo loading dose followed by placebo SC injections q2wk through Week 22.
Part B: Participants assigned to placebo in Part A will transition to active abiprubart treatment, according to randomized assignment, with either abiprubart 400 mg SC q2wk or abiprubart 400 mg SC q4wk.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) at Week 24
时间窗: Baseline, Week 24
次要结局
- Proportion of Sjögren's Tool for Assessing Response (STAR) Responders (≥ 5 points) at Week 24(Week 24)
- Change From Baseline in Stimulated Salivary Flow Rate (mL/min) at Week 24(Baseline, Week 24)
- Change From Baseline in Unstimulated Salivary Flow Rate (mL/min) at Week 24(Baseline, Week 24)
- Change From Baseline in Unstimulated Salivary Flow Rate (mL/min) Over Time(Baseline, Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 52, 56)
- Change From Baseline in EULAR Sjögren's Syndrome Disease Patient Reported Index (ESSPRI) at Week 24(Baseline, Week 24)
- Change From Baseline in ESSPRI Over Time(Baseline, Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 52, 56)
- Change From Baseline in Schirmer's Test at Week 24(Baseline, Week 24)
- Change From Baseline in Clinical EULAR Sjögren's Syndrome Disease Activity Index (clinESSDAI) at Week 24(Baseline, Week 24)
- Change From Baseline in FACIT-Fatigue Over Time(Baseline, Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 52, 56)
- Change From Baseline in clinESSDAI Over Time(Baseline, Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 52, 56)
- Proportion of STAR Responders (≥ 5 points) Over Time(Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 52, 56)
- Change From Baseline in Stimulated Salivary Flow Rate (mL/min) Over Time(Baseline, Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 52, 56)
- Change From Baseline in Schirmer's Test Over Time(Baseline, Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 52, 56)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) at Week 24(Baseline, Week 24)
- Change From Baseline in EQ-5D 5L Over Time(Baseline, Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 52, 56)
- Change From Baseline in EuroQol 5 Dimension 5 Level (EQ-5D 5L) at Week 24(Baseline, Week 24)