Hepion Pharmaceuticals (NASDAQ:HEPA) screened the first subject in its ASCEND-NASH clinical trial being conducted at up to 121 sites in seven countries, including 85 sites in the U.S.
The Phase 2b, randomized, multi-center, double-blinded study is designed to evaluate the safety and efficacy of rencofilstat in 336 subjects dosed for 12 months.
Subjects included in the trial will be either F2 or F3 biopsy-confirmed, with enrollment of F3 subjects of at least 60%, to focus on NASH subjects with more advanced fibrosis. Subjects will receive either placebo or rencofilstat, administered orally, once daily at doses of 75 mg, 150 mg, or 225 mg, with 84 subjects per cohort.
Endpoints will evaluate improvements in both fibrosis and steatosis, with the overall study primary endpoint being an improvement of fibrosis score by one point without a worsening of steatosis, or an improvement of steatosis without worsening of fibrosis.
Although the main trial endpoint is histologic and determined by changes in biopsy, numerous other non-invasive markers will be assessed, including NASH efficacy biomarkers, magnetic resonance elastography (MRE), and multiomics, for example, proteomics and transcriptomics.
In a statement, Todd Hobbs, M.D. and CMO of Hepion, said ASCEND-NASH represents the first time that rencofilstat is being studied in a biopsy-confirmed trial.
“We anticipate full enrollment in 12-to-14 months, as this is a large and rigorously controlled trial with a 60-day screening period, including multiple laboratory analyses, Fibroscan evaluation, liver biopsy, and MRE. We also will be following the FDA-recommended utilization of a three-panel consensus to read all liver biopsies,” he added.
As the study advances, the independent Data and Safety Monitoring Board will conduct two interim analyses. The first review will occur when one-third of study subjects have passed the six-month evaluation, and the second DSMB review will occur when one-third of subjects have completed the study and have had a final biopsy.
In addition, Dr. Hobbs said, “we received Fast Track designation from the FDA in November 2021, which allows for the submission of study reports as they are obtained, as well as more frequent engagement with the agency, which should provide for smoother transition from Phase 2b to Phase 3.”
Robert Foster, PharmD, Ph.D., and CEO of Hepion, said initiation of screening in the Phase 2b ASCEND-NASH clinical trial represents a significant step forward for the company.
“For quite some time, our team has been busy setting the stage for this major clinical trial,” he said. “Our efforts have focussed on ongoing optimization of drug manufacturing and product formulation; packaging; qualification of trial sites; and engagement with contract research organizations and regulatory agencies around the world. While these activities are time- and resource-intensive, it is gratifying to now see them culminate in the initiation of subject screening.”
Dr. Foster said Hepion’s goal is to create an ecosystem built around rencofilstat as the core asset.
“To that end, we are utilizing our proprietary AI-POWR tools to explore ways to create companion diagnostics to help identify which subjects may best respond to rencofilstat,” he added. “We anticipate this approach of bundling rencofilstat with companion diagnostics will be advantageous when conducting future clinical trials, and developing a commercial strategy.”