AC-003 capsules for adults with steroid-refractory or steroid-dependent acute graft-versus-host disease

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)

This trial will test whether oral AC-003 capsules are safe and show benefit for adults with grade II–IV steroid-refractory or steroid-dependent acute graft-versus-host disease after allogeneic stem cell transplant.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Accro Bioscience (Suzhou) Limited (Industry-sponsored)
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07070674 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm Phase Ib dose-escalation study plans to enroll about 24 adults with grade II–IV steroid-refractory or steroid-dependent aGVHD and is organized in two parts. Part A will escalate AC-003 across four sequential cohorts with 28 days of oral dosing per cohort and a safety follow-up on Day 35, with dose decisions guided by a Safety Review Committee using safety, PK, and PD data. Part B will expand at the recommended dose to gather preliminary efficacy and additional safety, with the same 28-day dosing and Day 35 follow-up. Key outcomes include safety, pharmacokinetics, pharmacodynamics, and signals of clinical efficacy.

Who should consider this trial

Good fit: Adults (≥18 years) who underwent allogeneic hematopoietic stem cell transplantation, developed grade II–IV aGVHD within 100 days per MAGIC criteria, and meet the trial's definitions of steroid-refractory or steroid-dependent disease are the intended candidates.

Not a fit: Patients with relapsed aGVHD, evidence of chronic or overlap GVHD, or who fail to meet the steroid-refractory/steroid-dependent criteria are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, AC-003 could offer a new oral treatment option that reduces GVHD symptoms and lowers reliance on corticosteroids for patients with steroid-refractory or steroid-dependent aGVHD.

How similar studies have performed: Other targeted oral agents, including JAK inhibitors, have shown benefit in steroid-refractory aGVHD, but AC-003 is a novel investigational compound and its efficacy in humans has not yet been established.

Eligibility criteria

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)

Where this trial is running

Tianjin, Tianjin Municipality

• Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences) — Tianjin, Tianjin Municipality, China (Recruiting)

Conditions Acute Graft-versus-Host Disease