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

Accro Bioscience (Suzhou) Limited

Status and phase: Enrolling; Phase 1

Conditions: Acute Graft-versus-Host Disease

Treatments: Drug: AC-003

Study type: Interventional

Funder types: Industry

Identifiers

NCT07070674

AC-003 -CN-PhIb

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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24 participants in 4 patient groups

AC-003 cohort 1

Experimental group

Description:

Specified dose of AC-003 will be administered orally twice daily (BID) for 28 days.

Treatment:

Drug: AC-003

AC-003 cohort 2

Experimental group

Description:

Specified dose of AC-003 will be administered orally once daily (QD) for 28 days.

Treatment:

Drug: AC-003

AC-003 cohort 3

Experimental group

Description:

Specified dose of AC-003 will be administered orally twice daily (BID) for 28 days.

Treatment:

Drug: AC-003

AC-003 cohort 4

Experimental group

Description:

Specified dose of AC-003 will be administered orally twice daily (BID) for 28 days.

Treatment:

Drug: AC-003