Clinical trial NCT05118360: Study to Evaluate the Safety, Tolerability, and Efficacy of ASC41 in Adults With NASH
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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Nonalcoholic Steatohepatitis (NASH)
Keywords: NAFLD
Phase 2
Thyroid hormone receptor agonist
NASH
ASC41
Lead sponsor: Ascletis Pharma Inc
Sponsor class: INDUSTRY
First posted: 2021-11-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: 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
timeFrame: Baseline to Week 52
Secondary outcomes:
measure: Safety and tolerability of ASC41 evaluated by incidence of treatment emergent adverse events (TEAEs) in ASC41 treated subjects compared to placebo
timeFrame: Baseline to Week 52
measure: Change in hepatic fat fraction based on MRI-PDFF measurements in ASC41 treated subjects compared to placebo.
timeFrame: Baseline to Week 12 and Week 52
measure: 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
timeFrame: Baseline to Week 52
Other outcomes:
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