Overview
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.
Description
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.
Eligibility
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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)