A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Sibeprenlimab Administered Subcutaneously in Participants With Sjögren's
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 83
- 试验地点
- 125
- 主要终点
- Change from baseline in European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) score
研究概览
简要总结
This is a phase 2 study to evaluate the effects of sibeprenlimab 400 mg administered subcutaneously (SC) every 4 (Q4) weeks as an add-on to background treatment in participants with Sjögren's disease.
详细描述
This is a multicenter, randomized, double-blind, placebo-controlled, proof-of-concept study followed by an optional open-label extension to evaluate the efficacy and safety of sibeprenlimab 400 mg administered SC Q4 weeks as an add-on to background treatment in participants with Sjögren's disease.
The primary objective is to compare the effect of sibeprenlimab versus placebo added to background treatment on European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) scores at 28 weeks.
The key secondary objective is to compare the effect of sibeprenlimab versus placebo added to background treatment on European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index (ESSPRI) at 28 weeks.
Approximately 80 participants who have a diagnosis of Sjögren's disease according to the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria will be randomized with approximately 40 participants in the sibeprenlimab group and 40 participants in the placebo group.
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
- Double (Participant, Investigator)
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
- •Diagnosed with Sjögren's disease.
- •ESSDAI score (which measures disease activity) must be 5 or higher.
- •Salivary flow rate must be at least 0.05 mL/min.
- •Serum IgG level must be higher than 900 mg/dL.
- •Must be able to communicate well with the investigator and agree to follow the trial requirements.
- •Participants can continue certain medications (hydroxychloroquine, methotrexate, leflunomide, or azathioprine) if they have been on a stable dose for at least 30 days.
- •Corticosteroid dose must be stable and no more than 10 mg/day for at least 30 days.
- •Test positive for anti-Ro52 and/or anti-Ro60 antibodies.
排除标准
- •Another active autoimmune rheumatic disease.
- •Prior use of B-cell depleting therapy or prohibited immunosuppressants.
- •Significant comorbidities including uncontrolled type 2 diabetes, malignancy, and chronic and/or acute infections.
- •Suicidal ideation or behavior based on the Patient Health Questionnaire-9 (PHQ-9).
研究组 & 干预措施
400 mg Sibeprenlimab
干预措施: Sibeprenlimab (Biological)
Placebo
干预措施: Placebo (Other)
结局指标
主要结局
Change from baseline in European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) score
时间窗: 28 weeks
Higher scores on the ESSDAI indicate a worse outcome, as they reflect higher disease activity. Minimum value is 0 and the maximum value is 123.
次要结局
- Tmax of sibeprenlimab(28 weeks)
- Cmax of sibeprenlimab(28 weeks)
- Percent change from baseline in total serum IgM(Week 28)
- Percent change from baseline in total serum free APRIL (a proliferation-inducing ligand) concentrations(Week 28)
- Area Under the Curve (AUC) of sibeprenlimab(28 weeks)
- Serum concentration of sibeprenlimab(28 weeks)
- Presence or absence of serum antidrug antibody (ADA) to sibeprenlimiab(28 weeks)
- Proportion of participants with minimal clinical improvement, defined as Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) score increase of ≥ 4 from baseline(At 28 weeks)
- Time to the first occurrence of minimal clinical improvement in ESSDAI(Week 28)
- Time to the first occurrence of minimal clinical improvement in ESSPRI(Week 28)
- Percent change from baseline in total serum IgA(Week 28)
- Percent change from baseline in total serum IgG(Week 28)
- Change from baseline in patient-reported Sjögren's disease diary score(At 28 weeks)
- Change from baseline in European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index (ESSPRI) score(28 weeks)
- Incidence of treatment-emergent adverse events (TEAEs)(28 weeks)
- Incidence of treatment-emergent adverse events (TEAEs) by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade(28 weeks)
- Incidence of treatment-emergent adverse events (TEAEs) with an outcome of death(28 weeks)
- Incidence of serious treatment-emergent adverse events (TEAEs)(28 weeks)
- Incidence of treatment-emergent adverse events (TEAEs) leading to discontinuation of the investigational medicinal product (IMP)(28 weeks)
- Proportion of participants with minimal clinical improvement defined as European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) reduction ≥ 3 points from baseline(At 28 weeks)
- Proportion of participants with minimal clinical improvement defined as European League Against Rheumatism Sjögren's Syndrome Patient-Reported Index (ESSPRI) reduction ≥ 1 point from baseline(At 28 weeks)
- Change from baseline in individual European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) domains(At 28 weeks)
- Change from baseline in salivary flow rate(At 28 weeks)
- Change from baseline in tear flow rate(At 28 weeks)
- Change from baseline in Clinical European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ClinESSDAI) score(At 28 weeks)
- Change from baseline in Physician Global Assessment (PhGA) score(At 28 weeks)
- Change from baseline in Patient Global Assessment (PaGA) score of participant outcomes(At 28 weeks)
- Change from baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) score(At 28 weeks)
- Change from baseline in 36 Item Short-Form Survey Version 2 (SF-36v2) Physical Component Summary Scale score and Mental Component Summary Scale score(At 28 weeks)