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

Official title

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)

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.

Detailed 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.

Interventions

• Drug AC-003
  AC-003 capsules will be administered orally.

Primary outcome measures

• Incidence and severity of Adverse Events [Time frame: Up to Day 35]

Secondary outcome measures (2)

• Overall Response Rate (ORR) [Time frame: Day 14 and Day 28]
• Complete Response Rate [Time frame: Day 14 and Day 28]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, Chine — Tianjin

Identifiers

NCT: NCT07070674 · AC-003 -CN-PhIb

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗