A Phase 2, Uncontrolled, Three-Stage, Dose-Escalation Cohort Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Clinical Activity of OMS721 in Adults With Thrombotic Microangiopathies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 24
- 主要终点
- Number of Participants With HSCT-TMA Who Respond to OMS721
研究概览
简要总结
The purpose of this study is to assess the safety, efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of OMS721 in patients with thrombotic microangiopathies (TMA).
详细描述
This is a Phase 2, uncontrolled, 3-stage, ascending-dose-escalation study in patients with 1 of 3 forms of TMA: atypical hemolytic uremic syndrome (aHUS), thrombotic thrombocytopenia (TTP), and hematopoietic stem cell transplant - associated TMA (HSCT-associated TMA). In Stage 1 of the study, OMS721 was administered to 3 cohorts, with dose escalation by cohort to identify the optimal dosing regimen. In Stage 2, the dose selected in the first stage was administered to expanded cohorts of patients with distinct etiologies (aHUS alone in 1 cohort and TTP or HSCT-TMA in the other cohort). Patients completing Stage 2 were eligible for continued treatment in Stage 3 if they tolerated OMS721 treatment and derived clinical benefit. Enrollment in the study has been completed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Are at least age 18 at screening (Visit 1)
- •Have a diagnosis of primary aHUS, persistent HSCT-associated TMA or TTP
- •No clinically apparent alternative explanation for thrombocytopenia and anemia
排除标准
- •Had eculizumab therapy within three months prior to screening
- •Have STEC-HUS
- •Have a positive direct Coombs test
- •Have an active systemic bacterial or fungal infection requiring antimicrobial therapy (prophylactic antimicrobial therapy administered as standard of care is allowed)
结局指标
主要结局
Number of Participants With HSCT-TMA Who Respond to OMS721
时间窗: Day 1 to up to 2 years following the first dose of OMS721
Response defined as: Improvement in TMA laboratory markers of platelet count and lactate dehydrogenase (LDH) and improvement in clinical status
Assess the Safety and Tolerability of Multiple-dose Administration of OMS721 in Participants With TMA
时间窗: Day 1 to 37 days after end of treatment, approximately up to 31 weeks.
Incidence of treatment-emergent adverse events (AEs): clinically significant changes in vital signs, ECG, and laboratory tests were reported as AEs.
次要结局
- Participants With HSCT-TMA Treated With OMS721: Freedom From Platelet Transfusion(Study Day -14 to 4 weeks following the last platelet transfusion)
- Participants With HSCT-TMA Treated With OMS721: Freedom From Red Blood Cell (RBC) Transfusion(Study Day -14 to 4 weeks following the last RBC transfusion)
- Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Platelet Count(Study Day 1 to Day 97, approximately 13 weeks)
- Participants With HSCT-TMA Treated With OMS721: 100-day Survival(Study Day of HSCT-TMA diagnosis to 100 days later)
- Participants With HSCT-TMA Treated With OMS721: Overall Survival(Study Day of HSCT-TMA diagnosis to up to 2 years following first dose of OMS721)
- Participants With HSCT-TMA Treated With OMS721: Duration of Response(Study Day 1 to up to 2 years following first dose of OMS721)
- Participants With HSCT-TMA (ADA)(Pre-dose and up to 204 days post-dose)
- Participants With HSCT-TMA Treated With OMS721: Change From Baseline in LDH(Study Day 1 to Day 97, approximately 13 weeks)
- Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Creatine(Study Day 1 to Day 97, approximately 13 weeks)
- Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Haptoglobin(Study Day 1 to Day 97, approximately 13 weeks)
- Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Hemoglobin(Study Day 1 to Day 97, approximately 13 weeks)
- Participants With HSCT-TMA: Pharmacodynamics (PD)(Pre-dose and up to 204 days post-dose)
- Participants With HSCT-TMA: Pharmacokinetics (PK) of Multiple-dose Administration of OMS721(Pre-dose and up to 204 days post-dose)