A Phase Ib Clinical Study of AC-003 Capsules in Subjects With aGVHD.

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)

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.

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.

Inclusion Criteria:

1. Male or female patients age ≥ 18 years.

2. Patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) from any donor source (including matched unrelated donor, haplo-identical).

3. Diagnosis of grade II-IV aGVHD as per MAGIC criteria within 100 days after HSCT.

4. Diagnosis of steroid-refractory or steroid-dependent aGVHD in at least one of the following criteria:

   1. Progressive Disease, defined as any target organ worsening, after 3 days of initial treatment with methylprednisolone 1~2 mg/kg/day (or equivalent corticosteroid)
   2. Not partial response after 7 days of initial treatment with methylprednisolone 1~2 mg/kg/day (or equivalent corticosteroid)
   3. Not complete response after 14 days of initial treatment with methylprednisolone 1~2 mg/kg/day (or equivalent corticosteroid)
   4. Relapse of aGVHD when corticosteroid tapering.

Exclusion Criteria:

1. Evidence of aGVHD relapsed.
2. Evidence of chronic GVHD or overlap syndrome
3. Receipt of more than one allogeneic HSCT
4. Receipt of more than one systemic treatment for aGVHD in addition to corticosteroid
5. Any corticosteroid therapy for indications other than aGvHD at doses >= 1 mg/kg/day methylprednisolone (or equivalent corticosteroid) within 7 days prior to enrolment
6. Severe organ dysfunction unrelated to aGVHD
7. Uncontrolled active infection (i.e., bacterial, fungal, or viral)