A Multicenter, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HMPL-523, a Syk Inhibitor, in Adult Subjects With Immune Thrombocytopenia
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Hutchmed
- 入组人数
- 48
- 试验地点
- 28
- 主要终点
- Safety and tolerability of HMPL-523 in adult subjects with primary ITP
研究概览
简要总结
This is an open-label, multicenter study to evaluate the safety, tolerability, and efficacy of HMPL-523 in adult subjects with ITP.
详细描述
This study is a Phase 1b, open-label, multicenter, single-arm study to evaluate the safety, tolerability, and preliminary efficacy of HMPL-523 in adult subjects with primary ITP diagnosed at least 3 months prior to enrollment or randomization.
In the dose escalation stage (Part 1), subjects will receive one of 3 dose levels of HMPL-523 to determine the recommended dose of HMPL-523 for the randomized dose optimization- stage (Part 2).
At the end of Part 1, 2 dose levels will be selected to be used in the dose-optimization stage (Part 2) of the study. In Part 2 of the study, subjects will be randomized in a 1:1 ratio between the 2 dose levels to better understand the exposure/efficacy/toxicity relationship.
At the end of Part 2, the Recommended Phase 3 dose (RP3D) of HMPL-523 will be determined based on the safety, efficacy and PK data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Subjects may be enrolled in this study only if they satisfy all the following criteria:
- •Adult male or female subjects ≥18 years of age
- •Diagnosis of ITP, with a duration of disease of at least 3 months prior to randomization or enrollment
- •Intolerance or insufficient response or recurrence after at least 1 prior ITP treatment (excluding splenectomy)
- •Response (defined as achieved a platelet count ≥50 × 109/L) to at least 1 prior ITP therapy (including splenectomy)
- •Adequate hematologic, hepatic and renal function
排除标准
- •Subjects are not eligible for enrollment into this study if any one of the following criteria are met:
- •Evidence of the presence of secondary causes of ITP
- •Clinically serious hemorrhage requiring immediate adjustment of platelets
- •Known history of vital organ transplantation or hematopoietic stem-cell transplantation or chimeric antigen receptor T-cells (CAR-T) therapy
- •Splenectomy within 12 weeks prior to enrollment
- •Presence of active malignancy unless deemed cured by adequate treatment.
- •History of serious cardiovascular disease corrected QT interval (QTcF) ≥450 ms
- •Uncontrolled hypertension
- •Being unsuitable to participate in this study as considered by investigators
研究组 & 干预措施
Dose escalation
Part 1 will consist of the following 3 dose levels: 300, 400, and 500 mg once daily (QD).
干预措施: HMPL-523 (Drug)
Dose optimization stage
In part 2 subjects will be randomized in a 1:1 ratio between the 2 dose levels selected at the end of part 1.
干预措施: HMPL-523 (Drug)
结局指标
主要结局
Safety and tolerability of HMPL-523 in adult subjects with primary ITP
时间窗: week 1 - week 24
Calculated as the number and percent incidence of participants experiencing adverse events (AE).
Dose Limiting Toxicities
时间窗: week 1 - week 4
Defined as an adverse event AE that meets protocol defined Dose Limiting Toxicities (DLT) criteria during the DLT assessment window (first 28 days), unless clearly unrelated to ITP drugs.
次要结局
- Cmax (maximum plasma drug concentration)(week 1 and week 3)
- Tmax (time to reach maximum plasma drug concentration)(week 1 and week 3)
- AUCtau (area under the concentration-time curve over a dosage interval)(week 1 and week 3)
- Cmin (minimum plasma drug concentration)(week 1 - week 20)