FASCINATE-2 Phase IIb clinical trial for NASH patients
FASCINATE-2 Phase IIb clinical trial for non-alcoholic steatohepatitis (NASH).cFASCINATE-2 is a randomized, double-blind, placebo-controlled Phase IIb clinical trial of approximately 330 NASH patients with moderate to advanced fibrosis (F2-F3). This trial will evaluate the impact of oral, once-daily doses of TVB-2640 (ASC40) for 52 weeks as assessed by biopsy. Patients will initially be randomized to receive placebo or 50 mg of TVB-2640 (ASC40). A 75 mg dose level of TVB-2640 (ASC40) is planned to be added to FASCINATE-2 following an open-label cohort in the FASCINATE-1 Phase IIa clinical trial.
Primary efficacy endpoints are:
- ≥ 2-point improvement in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) that results from reduction of necro-inflammation (inflammation or ballooning) ; or
- improvement in fibrosis.
The U.S. Food and Drug Administration (FDA) accepted these two endpoints for Phase IIb studies in NASH. Liver biopsy data will also be evaluated to assess NASH resolution without worsening of fibrosis and/or improvement in fibrosis without worsening of NASH, both of which are endpoints accepted by the FDA for accelerated approval following Phase III studies. The study will also measure liver fat, assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF), and other serum biomarkers of inflammation, fibrosis, and liver injury in a portion of patients at 26 weeks of treatment in an interim analysis.
In March 2021, Gannex Pharma Co., Ltd., a wholly-owned company of the Company., and Sagimet jointly announced positive topline results from the China cohort of a Phase II randomized, placebo-controlled clinical trial of oral, once-daily fatty acid synthase (FASN) inhibitor ASC40, known as TVB-2640 outside of China. The preliminary data showed that ASC40 meaningfully reduced liver fat, the primary efficacy endpoint of this trial, with a 50% responder rate (patients achieving ≥30% liver fat reduction). Participants also showed robust improvement in ALT, a liver enzyme associated with inflammation. These data from the China cohort are consistent with those of the U.S. cohort.
Ascletis has obtained an exclusive rights from Sagimet to develop, manufacture and commercialize FASN inhibitors including ASC40 (TVB-2640) and all related compounds in Greater China for all indications such as NASH and oncology.