A Phase 1b/2 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Efavaleukin Alfa in Adult Subjects With Steroid Refractory Chronic Graft Versus Host Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 32
- 试验地点
- 14
- 主要终点
- Phase 1b: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
研究概览
简要总结
Phase 1b: To evaluate the safety and tolerability of multiple ascending doses of efavaleukin alfa in subjects with steroid refractory chronic graft versus host disease (cGVHD).
Phase 2: To evaluate the efficacy of efavaleukin alfa in subjects with steroid refractory cGVHD as measured by overall response rate (ORR) at 16 weeks according to the 2014 cGVHD NIH Consensus Criteria.
Due to early termination, the Phase 2 portion of this study was not conducted.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase 1: Efavaleukin Alfa Multiple Ascending Doses
Efavaleukin will be administered as multiple ascending doses (MAD) across cohorts 1-5. Each dosing cohort will consist of between 3 and 6 subjects who will receive efavaleukin alfa subcutaneously (SC) either every week or every 2 weeks plus protocol permitted background therapy for 52 weeks. At the discretion of the Sponsor, following discussion and agreement between the principal investigator and medical monitor, subjects responding to efavaleukin alfa (as assessed by the end of week 50), who wish to continue treatment, may continue to receive efavaleukin alfa treatment at their current dosing regimen.
干预措施: Efavaleukin Alfa (Drug)
Phase 2: RP2D Efavaleukin Alfa
The phase 2 portion of this study will be conducted as a single arm, multi-center, open label trial in subjects with steroid refractory chronic graft versus Host Disease (cGVHD). All subjects will receive the recommended phase 2 dose (RP2D) of efavaleukin alfa for up to 52 weeks plus protocol permitted background therapy for cGVHD.
Due to early study termination the Phase 2 portion of the study was never opened.
干预措施: Efavaleukin Alfa (Drug)
结局指标
主要结局
Phase 1b: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
时间窗: Up to 4 weeks after first dose of study drug administration
A DLT was defined as a: * Non-hematological toxicity ≥grade-4(per common terminology criteria for adverse events \[CTCAE\] v4.03) related to efavaleukin alfa. Non-hematological lab abnormalities without clinical significance weren't considered DLTs. * Hematological toxicity ≥grade 4 related to efavaleukin alfa defined as decreases in peripheral counts (absolute neutrophil count or platelets) persisting longer than 72 hrs, as measured by 2 separate results, that were not related to malignant disease relapse, infection, or other etiologies. * Constitutional events (ie, fever, fatigue) ≥grade 3 that were classified as serious adverse events by the investigator and related to efavaleukin alfa. * Infection is considered an expected complication of chronic graft versus host disease (cGVHD) and its treatment. Only grade 4 or 5 infections considered by the investigator to be related to efavaleukin alfa were reviewed by the dose level review meeting to determine whether it was considered a DLT.
Phase 1b: Number of Participants Who Experienced a Treatment-related Adverse Event (AE)
时间窗: Day 1 until the end of study; median (min, max) duration was 38.01 (3.27, 139.81) weeks
A treatment-related AE was any untoward medical occurrence in a clinical study participant deemed to have a possibly causal relationship to the study treatment as determined by the investigator.
Phase 1b: Number of Participants Who Experienced a Treatment-emergent AE
时间窗: Day 1 until the end of study; median (min, max) duration was 38.01 (3.27, 139.81) weeks
A treatment-emergent AE was any untoward medical occurrence in a clinical study participant that occurred after first dose.
Phase 1b: Number of Participants Who Experienced a Treatment-emergent Serious AE
时间窗: Day 1 until the end of study; median (min, max) duration was 38.01 (3.27, 139.81) weeks
A treatment-emergent serious AE was any untoward medical occurrence in a clinical study participant that occurred after first dose that resulted in death, was immediately life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or another medically important serious event.
次要结局
未报告次要终点