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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
AC-003 capsules will be administered orally.
Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences)
Tianjin, Tianjin Municipality, China
RECRUITINGIncidence and severity of Adverse Events
An Adverse Event (AE) is defined as any new untoward medical condition or worsening of a pre-existing medical condition following or during exposure to an investigation product, whether or not considered causally related to the product.
Time frame: Up to Day 35
Overall Response Rate (ORR)
ORR is the percentage of patients with complete response (CR) or partial response (PR) as determined by investigator. CR is defined as all target organs evaluated as Mount Sinai Acute GVHD International Consortium (MAGIC) Stage 0 \[Skin - no active GVHD rash; Liver - bilirubin \<2 mg/dL; Upper gastrointestinal (GI) tract - no intermittent nausea, vomiting/anorexia; Lower GI tract - stool output: \< 500 mL/day or \<3 episodes/day (adults)\]. PR is defined as improvement in one or more target organs (skin, liver, upper GI tract, lower GI tract) involved with aGVHD symptoms without worsening in others.
Time frame: Day 14 and Day 28
Complete Response Rate
Complete Response Rate is the percentage of patients with complete response (CR). CR is defined as all target organs evaluated as Mount Sinai Acute GVHD International Consortium (MAGIC) Stage 0 \[Skin - no active GVHD rash; Liver - bilirubin \<2 mg/dL; Upper gastrointestinal (GI) tract - no intermittent nausea, vomiting/anorexia; Lower GI tract - stool output: \< 500 mL/day or \<3 episodes/day (adults)\].
Time frame: Day 14 and Day 28
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