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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Nonalcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: ASC41 2 mg
* Drug: ASC41 4 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAFLD, Phase 2, Thyroid hormone receptor agonist, NASH, ASC41