A Multicenter, Randomized, Double-blind, Placebo-Controlled Phase II Study to Investigate the Efficacy and Safety of CYP-001 in Combination With Corticosteroids vs Corticosteroids Alone for the Treatment of High-Risk Acute Graft Versus Host Disease
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 60
- 试验地点
- 77
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
This study is a prospective randomized placebo-controlled phase 2 study to compare CYP-001 plus corticosteroids (CS) to placebo plus CS in allogeneic hematologic stem cell transplant recipients with HR-aGvHD. Severity of GvHD will be assessed at screening and throughout the study using Mount Sinai Acute GvHD International Consortium (MAGIC) guidelines. Eligible subjects will be randomized to receive either CYP-001 IV infusion on Days 0 and 4 or placebo on the same days. All subjects will receive ongoing CS therapy as appropriate per institutional guidelines. Subjects will have study visits up to Day 100 during the Primary Evaluation Period. During the Follow-Up Period, subjects will have study visits up to 24 months.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Undergone allogeneic hematopoietic stem cell transplant (HSCT)
- •Clinically diagnosed with acute GvHD requiring systemic therapy with corticosteroids.
- •HR-aGvHD must meet one of the following clinical features within 72 hours prior to randomization: (a) high-risk as per Refined Minnesota Criteria; OR (b) One of the following: (i) isolated stage 2 involvement of the lower GI tract; (ii) Stage 1 lower GI tract disease with skin involvement
- •Evidence of myeloid engraftment post allogeneic HSCT
- •Life expectancy of at least one month
排除标准
- •Received any systemic treatment for aGvHD other than corticosteroids +/- calcineurin inhibitors
- •Chronic GvHD or overlap syndrome with both acute and chronic features of GvHD
- •Relapsed primary malignancy since
- •received more than one allogeneic HSCT
- •Clinically significant respiratory, renal or cardiac disease
- •Cholestatic disorders or sinusoidal obstructive syndrome/veno-occlusive disease of the liver
- •Any active uncontrolled infection requiring treatment and likely to impact on the ability of the subject to participate in the trial.
- •Known infection with CMV, EBV, HHV-6, HBV, HCV, HIV or Tuberculosis. If the treatment for CMV, EBV, HHV-6, HBV, HCV has commenced the subject is eligible.
- •Known sensitivity to dimethylsulfoxide (DMSO) or any other component of CYP-
- •Received any investigational treatment agent within 30 days or within 5 half-lives of Screening, whichever is greater.
研究组 & 干预措施
CYP-001 plus corticosteroids
干预措施: Corticosteroids (Drug)
Placebo plus corticosteroids
干预措施: Placebo (Biological)
Placebo plus corticosteroids
干预措施: Corticosteroids (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: 28 days
ORR is defined as the proportion of subjects demonstrating a complete response (CR) or partial response (PR) without requirement for additional systemic therapies for an earlier progression, a mixed response or a nonresponse.
次要结局
- Overall survival(2 years)
- Patient reported outcomes: EuroQol 5-Dimension (EQ-5D) health-related quality of life instrument(2 years)
- Durable Overall response rate (ORR)(100 days)
- Time to non-relapse mortality(2 years)
- Time to malignancy relapse/progression(2 years)
- Patient reported outcomes: Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) instrument(2 years)
- Incidence, severity, duration of treatment-emergent adverse events(2 years)
- Event-free survival(2 years)
- Incidence of chronic GvHD(2 years)
- Weekly cumulative steroid dose(100 days)
- Overall response rate (ORR)(100 days)
- Complete response rate (CRR)(100 days)
- Failure-free survival(2 years)