A Phase Ib Clinical Trial to Investigate the Safety, Tolerability, Preliminary Efficacy, and Pharmacokinetic Profile of AC-003 Capsules in Patients With Acute GraftVersus-Host Disease (aGVHD)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Incidence and severity of Adverse Events
研究概览
简要总结
The study was an open-label, single-arm, dose-escalation, Phase Ib, multi-center study to investigate safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of AC-003 in patients with grade II-IV SR-aGVHD.
详细描述
The study will enroll approximately 24 subjects in 2 parts:
Part A is a dose-escalation stage to investigate 4 cohorts of AC-003 in adult patients with grade II-IV SR-aGVHD who have undergone allogeneic hematopoietic stem cell transplantation.
The dose escalation will start with cohort 1, in which patients will receive specified dose of AC-003 capsules orally for 28 days and escalate to cohort 2, 3 and 4 sequentially when the previous cohort is deemed to be safe by Safety Review Committee (SRC). Safety follow-up will occur on Day 35. Decision of recommended dose will be made depend on the safety, PK and PD assessments across cohorts.
Part B is a dose-expansion stage to investigate the preliminary efficacy of recommended dose. Patient will receive recommended dose of AC-003 capsules orally for 28 days. Safety follow-up will occur on Day 35.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Male or female patients age ≥ 18 years.
- •Patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) from any donor source (including matched unrelated donor, haplo-identical).
- •Diagnosis of grade II-IV aGVHD as per MAGIC criteria within 100 days after HSCT.
- •Diagnosis of steroid-refractory or steroid-dependent aGVHD in at least one of the following criteria:
- •Progressive Disease, defined as any target organ worsening, after 3 days of initial treatment with methylprednisolone 1~2 mg/kg/day (or equivalent corticosteroid)
- •Not partial response after 7 days of initial treatment with methylprednisolone 1~2 mg/kg/day (or equivalent corticosteroid)
- •Not complete response after 14 days of initial treatment with methylprednisolone 1~2 mg/kg/day (or equivalent corticosteroid)
- •Relapse of aGVHD when corticosteroid tapering.
排除标准
- •Evidence of aGVHD relapsed.
- •Evidence of chronic GVHD or overlap syndrome
- •Receipt of more than one allogeneic HSCT
- •Receipt of more than one systemic treatment for aGVHD in addition to corticosteroid
- •Any corticosteroid therapy for indications other than aGvHD at doses >= 1 mg/kg/day methylprednisolone (or equivalent corticosteroid) within 7 days prior to enrolment
- •Severe organ dysfunction unrelated to aGVHD
- •Uncontrolled active infection (i.e., bacterial, fungal, or viral)
研究组 & 干预措施
AC-003 cohort 1
Specified dose of AC-003 will be administered orally twice daily (BID) for 28 days.
干预措施: AC-003 (Drug)
AC-003 cohort 2
Specified dose of AC-003 will be administered orally once daily (QD) for 28 days.
干预措施: AC-003 (Drug)
AC-003 cohort 3
Specified dose of AC-003 will be administered orally twice daily (BID) for 28 days.
干预措施: AC-003 (Drug)
AC-003 cohort 4
Specified dose of AC-003 will be administered orally twice daily (BID) for 28 days.
干预措施: AC-003 (Drug)
结局指标
主要结局
Incidence and severity of Adverse Events
时间窗: Up to Day 35
An Adverse Event (AE) is defined as any new untoward medical condition or worsening of a pre-existing medical condition following or during exposure to an investigation product, whether or not considered causally related to the product.
次要结局
- Overall Response Rate (ORR)(Day 14 and Day 28)
- Complete Response Rate(Day 14 and Day 28)