Study to Evaluate the Safety, Tolerability, and Efficacy of ASC41 Tablets in Adult Patients With NASH

Study Overview
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Brief Summary
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This is a Phase 2, Double-Blind, Randomized, Multicenter, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of ASC41 in Adults with Nonalcoholic Steatohepatitis (NASH).

Official Title
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A Phase II, Double-Blind, Randomized, Multicenter, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of ASC41 in Subjects With Nonalcoholic Steatohepatitis (NASH)

Conditions
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Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis

Intervention / Treatment
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* Drug: 2mg of ASC41
* Drug: 4mg of ASC41 (2 tablets of 2 mg ASC41)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 and ≤ 80 years old at screening. Presence of ≥ 7.5% steatosis on screening MRI-PDFF read centrally by a radiologist and performed either during the screening period or within 6 months prior to the first visit. HbA1c ≤ 9.5%. Normal or minimally abnormal renal function as defined by estimated glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73 m^2 Exclusion Criteria: Presence or history of cirrhosis or evidence of decompensated liver disease (e.g., ascites, variceal bleeding) or hepatocellular carcinoma. History or presence of other concomitant liver disease as assessed by the investigator or determined by laboratory findings. Uncontrolled Type 2 diabetes mellitus (T2DM) defined as HbA1c of > 9.5% within 60 days prior to enrollment. Change in anti-diabetic therapy within 6 months prior to qualifying liver biopsy.

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 Low Dose<br>1 tablet of ASC41 (2 mg) for 52 weeks | Drug: 2mg of ASC41<br>* ASC41 tablet administered orally once daily.<br>Drug: Placebo<br>* Placebo tablets administered orally once daily.<br>|
| Experimental: Cohort 2 High Dose<br>2 tablet of ASC41 (4 mg) for 52 weeks | Drug: 4mg of ASC41 (2 tablets of 2 mg ASC41)<br>* ASC41 tablets administered orally once daily.<br>|
| Placebo Comparator: Placebo tablet<br>Placebo tablet for 52 weeks | Drug: Placebo<br>* Placebo tablets administered orally once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of ASC41 compared with placebo in noncirrhotic subjects with NASH by a histological change. | A histological change in NAFLD (nonalcoholic fatty liver disease) Activity Score (NAS) ≥ 2 points that results from reduction of necroinflammation (inflammation or ballooning) without worsening fibrosis. (The NAFLD Activity Score including steatosis, inflammation and ballooning. The maximum score of steatosis was 3 and the minimum score was 0, the maximum score of inflammation was 3 and the minimum score was 0, and the maximum score of ballooning was 2 and the minimum score was 0. The higher scores mean a worse outcome. ） | Baseline and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence, type and severity of AEs/SAEs were assessed by CTCAE v5.0 to assess the safety and tolerability of ASC41 compared to placebo |  | 24 and 52 weeks | 
| Change from baseline in hepatic fat fraction assessed by MRI-PDFF |  | 24 and 52 weeks | 
| To evaluate the effect of ASC41 compared with placebo on serum lipids (cholesterol, HDL-C, LDL-C, triglycerides, Lp(a), VLDL) |  | 12, 24 and 52 weeks | 
| Plasma pharmacokinetics - Peak Plasma Concentration (Cmax) | Measured after administration | 1 and 15 Days | 
| Plasma pharmacokinetics - Area under the plasma drug concentration versus time curve( AUC0-t_, AUC0-∞) |  | 1 and 15 Days | 
| Plasma pharmacokinetics - The amount of time that a drug is present at the maximum concentration in serum(Tmax) |  | 1 and 15 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-alcoholic Fatty Liver Disease, NASH, ASC41, Phase II, THR-β