NCT02701634终止2 期
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Tolerability of Entospletinib, a Selective SYK Inhibitor, in Combination With Systemic Corticosteroids as First-Line Therapy in Subjects With Chronic Graft Versus Host Disease (cGVHD)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 66
- 试验地点
- 30
- 主要终点
- Best Overall Response Rate
研究概览
简要总结
The primary objective of this study is to evaluate the effect of entospletinib (ENTO) on the best overall response rate in adults with chronic graft versus host disease (cGVHD) who are currently receiving systemic corticosteroids as part of first-line therapy for cGVHD.
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
- •Willing and able to provide written informed consent
- •Male or non-pregnant, non-lactating, females
- •Newly diagnosed cGVHD defined by:
- •At least 100 days after receiving any allogeneic hematopoietic stem cell transplant AND
- •Receiving a new course of systemic corticosteroids (≥ 0.5 mg/kg/day) as first-line cGVHD therapy at least 1 day and no more than 21 days prior to first dose of ENTO/Placebo AND
- •Moderate to severe cGVHD as assessed by NIH cGVHD Diagnosis and Staging Criteria (NCDSC) with at least three organ systems involved OR one organ system with a score of 2 OR lung organ score = 1
- •Individuals who have undergone transplant for hematologic malignancy are required to be in complete remission.
- •Have either a normal ECG or one with abnormalities that are considered clinically insignificant by the investigator in consultation with the Sponsor
排除标准
- •Inability to begin systemic corticosteroids therapy at a dose of ≥ 0.5 mg/kg/day (or equivalent)
- •Uncontrolled infection within 4 weeks prior to randomization
- •History of the following therapies in the post-transplant period:
- •B cell depleting biologic agents
- •CD19 CAR-T cells based therapies
- •BTK/SYK/JAK/PI3K inhibitors
- •Phototherapy-unless administered for acute GVHD
- •Treatment of cGVHD with anti-thymocyte globulins (ATG), or campath within 60 days of screening visit unless used for treatment of acute GVHD
- •Severe organ dysfunction manifested during screening period:
- •Requiring supplemental oxygen at more than 2 L/min
- •Uncontrolled arrhythmia or heart failure
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
ENTO
Experimental
ENTO 400 mg or 200 mg tablet twice daily for 48 weeks
干预措施: ENTO (Drug)
Placebo
Placebo Comparator
Placebo to match tablet twice daily for 48 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Best Overall Response Rate
时间窗: Up to 24 weeks
Best overall response rate by 24 weeks was defined as the proportion of participants who achieved a complete or partial overall response as assessed by the NIH cGVHD Activity Assessment (NCAA) within 24 weeks, in the setting of add-on therapy to systemic corticosteroids as part of first-line therapy for cGVHD.
次要结局
- Percentage of Participants Who Achieve at Least 50% Reduction in Systemic Corticosteroid Dose Relative to Baseline(Baseline; Up to 48 weeks)
- Percentage of Participants Who Initiate Second-Line Therapy for cGVHD(Up to 48 weeks)
- Failure-Free Survival(Up to 48 weeks)
- Percentage of Participants Who Experience Any Treatment-Emergent Adverse Events (AEs)(Up to 48 weeks plus 30 days)
- Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event(Up to 48 weeks plus 30 days)
- Percentage of Participants Who Experienced Treatment-Emergent Graded Laboratory Abnormalities(Up to 48 weeks plus 30 days)
- Change From Baseline in the Skin Domain of the Lee Symptom Scale (LSS) at 24 Weeks(Baseline; Week 24)
- Change From Baseline in the Mouth Domain of the LSS at 24 Weeks(Baseline; Week 24)
- Change From Baseline in the Eyes Domain of the LSS at 24 Weeks(Baseline; Week 24)
- Change From Baseline in the Total Score of the LSS at 24 Weeks(Baseline; Week 24)
- Duration of Response(Up to 48 weeks)
研究者
研究点 (30)
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