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

Sponsor

Gannex Pharma Co., Ltd. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05118360

Collaborator

(none)

180

Enrollment

Arms

13.3

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Nonalcoholic Steatohepatitis (NASH)	Drug: ASC41 2 mg Drug: ASC41 4 mg Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Randomized in 2:1 ratio to receive either oral ASC41 2 mg or oral matching placebo. Randomized in 2:1 ratio to receive either oral ASC41 4 mg or oral matching placebo.Randomized in 2:1 ratio to receive either oral ASC41 2 mg or oral matching placebo. Randomized in 2:1 ratio to receive either oral ASC41 4 mg or oral matching placebo.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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)

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Nov 10, 2023

Anticipated Study Completion Date :

Jan 9, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).