Study to Evaluate the Safety, Tolerability, and Efficacy of ASC41 in Adults With NASH

A Seamless Phase 2a/2b, Double-Blind, Randomized, Multicenter, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of ASC41, a Thyroid Hormone Receptor β Agonist, in Adults With Nonalcoholic Steatohepatitis (NASH)

This is a phase 2, randomized, double-blind, placebo controlled study in adults with biopsy confirmed NASH. The study is aimed at evaluating efficacy and tolerability of ASC41 in adults with NASH.

Study Overview

• Status: Withdrawn
• Conditions: Nonalcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: ASC41 2 mg; Drug: Placebo; Drug: ASC41 4 mg

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Presence of ≥ 8% liver fat content on screening MRI-PDFF.
• Histologic evidence of NASH upon central read of a liver biopsy obtained no more than 6 months before Day 1 defined by NASH activity score (NAS) greater than or equal to 4 with at least 1 point each in inflammation and ballooning.
• Diabetes Mellitus well controlled based on laboratory test HbA1c ≤ 9.5%.

Key Exclusion Criteria:

• Evidence of advanced liver disease such as cirrhosis (stage 4 fibrosis) or decompensated liver disease (e.g. ascites, esophageal varices) or liver cancer.
• Evidence of other causes of chronic liver disease.
• Weight change ≥ 5% after qualifying liver biopsy or MRI-PDFF performed.
• Any contraindications to a MRI scan.
• Treatment with vitamin E (unless stable dose of < 400 IU/d), thiazolidinediones (TZD), or glucagon-like peptide-1 receptor agonists (GLP-1 RA), unless subject is on a stable dose for 6 months prior to qualifying liver biopsy.
• Known history of alcohol or other substance abuse within the last year or at any time during the study.
• Use of any investigational drug within 6 months of MRI-PDFF and/or liver biopsy.
• Known positivity for antibody to Human Immunodeficiency Virus (HIV).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1-ASC41 2mg; ASC41 2mg for 52 weeks.	Drug: ASC41 2 mg; 2mg of ASC41 orally once daily for 52 weeks
Placebo Comparator: Part1-placebo; Matching placebo for 52 weeks.	Drug: Placebo; Matching placebo orally once daily for 52 weeks.
Experimental: Part 2-ASC41 4mg; ASC41 4 mg for 52 weeks.	Drug: ASC41 4 mg; 4mg of ASC41 orally once daily for 52 weeks
Placebo Comparator: Part2-placebo; Matching placebo for 52 weeks.	Drug: Placebo; Matching placebo orally once daily for 52 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent of ASC41 subjects compared to placebo with histological reduction in NAS ≥2 points that results from reduction of inflammation or ballooning and no worsening fibrosis assessed by histopathological reading of liver biopsy at Week 52	Baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of ASC41 evaluated by incidence of treatment emergent adverse events (TEAEs) in ASC41 treated subjects compared to placebo	Baseline to Week 52
Change in hepatic fat fraction based on MRI-PDFF measurements in ASC41 treated subjects compared to placebo.	Baseline to Week 12 and Week 52
Resolution of NASH on overall histopathological reading of liver biopsy specimen taken at Week 52 compared to baseline in ASC41 treated subjects compared to placebo treated subjects	Baseline to Week 52

Collaborators and Investigators

• Sponsor: Gannex Pharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): November 10, 2024
• Study Completion (Estimated): January 9, 2025

Study Registration Dates

• First Submitted: November 1, 2021
• First Submitted That Met QC Criteria: November 11, 2021
• First Posted (Actual): November 12, 2021

Study Record Updates

• Last Update Posted (Actual): September 27, 2024
• Last Update Submitted That Met QC Criteria: September 25, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: NAFLD; NASH; Phase 2; Thyroid hormone receptor agonist; ASC41
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: ASC41-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No