A Phase 2, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of KD025 in Subjects With Chronic Graft Versus Host Disease (cGVHD) After At Least 2 Prior Lines of Systemic Therapy (The ROCKstar Study)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 159
- 试验地点
- 35
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This is a Phase 2, randomized, multicenter study to evaluate the efficacy and safety of KD025 in subjects with Chronic Graft Versus Host Disease (cGVHD) after at least 2 prior lines of systemic therapy
详细描述
Phase 2, open label, randomized, multicenter study in subjects with cGVHD who have previously been treated with at least 2 prior lines of systemic therapy. Approximately 166 subjects with active cGVHD will be randomized (1:1) to receive treatment with one of two belumosudil (formerly known as KD025) regimens:
- Arm A: belumosudil 200 mg QD
- Arm B: belumosudil 200 mg BID
With Amendment 2, the sample size was increased from approximately 126 subjects, with additional subjects to be enrolled as follows:
- 20 adolescents
- 20 adults into a site-specific Companion Study to collect biospecimens
These additional subjects will also be randomized (1:1) to Arm A or Arm B.
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
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female subjects at least 12 years of age who have had allogenic hematopoietic cell transplant (HCT).
- •Previously received at least 2 and not more than 5 lines of systemic therapy for cGVHD
- •Receiving glucocorticoid therapy with a stable dose over the 2 weeks prior to screening
- •Have persistent cGVHD manifestations and systemic therapy is indicated
- •Karnofsky Performance Score of ≥ 60 (if aged 16 years or older); Lansky Performance Score of ≥ 60 (if aged < 16 years)
- •Weight ≥ 40kg
排除标准
- •Subjects has not been on a stable dose / regimen of systemic cGVHD treatments for at least 2 weeks prior to screening. (Note: Concomitant corticosteroids, calcineurin inhibitors, sirolimus, MMF, methotrexate, rituximab, and extracorporeal photophoresis (ECP) are acceptable. Systemic investigational GVHD treatments are not permitted).
- •Histological relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
- •Current treatment with ibrutinib. Prior treatment with ibrutinib is allowed with a washout of at least 28 days prior to randomization.
研究组 & 干预措施
Arm A: belumosudil 200 mg, QD, adult arm
Eligible subjects randomized to arm A will take belumosudil 200 mg once daily
干预措施: Belumosudil (KD025) (Drug)
Arm B: belumosudil 200 mg, BID, adult arm
Eligible subjects randomized to arm B will take belumosudil 200 mg twice daily
干预措施: Belumosudil (KD025) (Drug)
Adolescent arm A: belumosudil 200 mg QD
Eligible subjects randomized to arm A will take belumosudil 200 mg once daily
干预措施: Belumosudil (KD025) (Drug)
Adolescent arm B: belumosudil 200 mg BID
Eligible subjects randomized to arm B will take belumosudil 200 mg twice daily
干预措施: Belumosudil (KD025) (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms)
The ORR was defined as the percentage of participants with a best response meeting the overall response criteria assessment of complete response (CR) or partial response (PR) at any post-baseline response assessment. CR was defined as resolution of all manifestations of cGVHD in each organ or site. PR was defined as the improvement in at least one organ or site without progression in any other organ or site. Responses were assessed by the 2014 National Institutes of Health (NIH) Consensus Development Project on Clinical Trials in cGVHD.
次要结局
- Duration of Response (DOR)(From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms))
- Number of Participants With Best Response by Organ System(From date of randomization until disease progression or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms))
- Number of Participants With Improvement (>=7-Point Reduction [7-PtR] From Baseline) as Assessed by Lee Symptom Scale (LSS) Score(Baseline (Day 1) up to 40.5 months for adult arms; Baseline (Day 1) up to 27.6 months for adolescent arms)
- Percentage of Participants With Best Response of PR and CR(From the date of randomization to the date of first documentation of progression or death due to any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms))
- Percent Change From Baseline in Corticosteroid Dose to Greatest Reduction(Baseline (Day 1) and 40.5 months for adult arms; Baseline (Day 1) and 27.6 months for adolescent arms)
- Percentage of Participants With Reduction and Discontinuation of Calcineurin Inhibitor Dose(Baseline (Day 1) up to 40.5 months for adult arms; Baseline (Day 1) up to 27.6 months for adolescent arms)
- Failure-Free Survival (FFS)(From first dose of study drug to the time of first documentation of response or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms))
- Overall Survival (OS)(From first dose of study drug to date of death from any cause or data cut-off, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms))
- Number of Participants With Best Response of Global Severity Rating Score as Based on the Clinician-Reported Global cGVHD Activity Assessment(Baseline (Day 1) up to 40.5 months for adult arms; Baseline (Day 1) up to 27.6 months for adolescent arms)
- Change From Baseline in Patient Self-Reported Symptom Activity Based on cGVHD Activity Assessment(Baseline (Day 1) and 40.5 months for adult arms; Baseline (Day 1) and 27.6 months for adolescent arms)
- Maximum Concentration Observed (Cmax) of Belumosudil(Cycles 1 and 2: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, and 12 hours post dose on Day 1 for adult arms; Cycles 2 and 4: Pre-dose and 3 and 5 hours post dose on Day 1 for adolescent arms)
- Observed Time to Reach Peak Plasma Concentration (Tmax) of Belumosudil(Cycles 1 and 2: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, and 12 hours post dose on Day 1 for adult arms; Cycles 2 and 4: Pre-dose and 3 and 5 hours post dose on Day 1 for adolescent arms)
- Area Under the Curve Over Time Interval From 0 to 6 Hours (AUC0-6) of Belumosudil(Cycles 1 and 2: Pre-dose and 1, 2, 3, 4, 5, 6, 7, 8, and 12 hours post dose on Day 1 for adult arms; Cycles 2 and 4: Pre-dose and 3 and 5 hours post dose on Day 1 for adolescent arms)
- Time to Response (TTR)(From first dose of study drug to the time of first documentation of response or data cut-off, whichever occurred first(maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms))
- Time to Next Treatment (TTNT)(From first dose of study drug to the time of new treatment or censoring date, whichever occurred first (maximum duration: up to 40.5 months for adult arms and 27.6 months for adolescent arms))