A Randomized, Double-blind, Placebo-controlled Study of ZSP1601 in Adult Subjects With Nonalcoholic Steatohepatitis (NASH)

Study Overview
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Brief Summary
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The purpose of this research is to evaluate the efficacy and the safety of two doses of ZSP1601 for 48 weeks versus placebo in adult NASH patients.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 2b Study of ZSP1601 in Adult Subjects With Nonalcoholic Steatohepatitis (NASH)

Conditions
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Nonalcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: ZSP1601
* Drug: ZSP1601
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NASH histological diagnosis on a liver biopsy performed ≤ 24 weeks before randomization, and NAS≥4 (at least 1 point each in inflammation and ballooning), and fibrosis score F2 or F3, and no other chronic liver disease Subjects having given her/his written informed consent Good compliance with the protocol and agree to have liver biopsy performed Subjects (including their partners) agreed to use effective contraception throughout the study period and up to 24 weeks after discontinuation Exclusion Criteria: History of cirrhosis or liver biopsy suggestive of cirrhosis Metabolic surgery or new technology treatment for weight loss within 5 years prior to randomization or planned during the study period Type 1 diabetes HIV infection Patients with severe or uncontrollable underlying diseases, unsuitable for treatment with ZSP1601, unable to complete study follow-up, or likely to affect the evaluation of trial results judged by investigator Previous malignancy within 5 years Treatment with hepatoprotective drugs Excessive alcohol consumption for 12 or more consecutive weeks within 1 year prior to screening Pregnant and lactating women or those with a positive serum pregnancy test.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ZSP1601 50mg BID<br> | Drug: ZSP1601<br>* 50mg BID<br>|
| Experimental: ZSP1601 100 mg BID<br> | Drug: ZSP1601<br>* 100mg BID<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of patients with improvement of steatohepatitis and no worsening of liver fibrosis or improvement in liver fibrosis greater than or equal to one stage and no worsening of the steatohepatitis | Percent of patients with improvement of steatohepatitis on overall histopathological reading and no worsening of liver fibrosis on NASH-CRN Fibrosis Score or improvement in liver fibrosis greater than or equal to one stage and no worsening of the steatohepatitis | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of patients with resolution of steatohepatitis and no worsening of fibrosis or improvement of fibrosis by at least 1 stage and no worsening of steatohepatitis |  | 48 weeks | 
| Percent of patients with steatohepatitis improvement and improvement of fibrosis by at least 1 stage |  | 48 weeks | 
| Percent of patients with steatohepatitis resolution and improvement of fibrosis by at least 1 stage |  | 48 weeks | 
| Percent of patients with steatohepatitis resolution and no worsening of fibrosis |  | 48 weeks | 
| Percent of patients with steatohepatitis improvement and no worsening of fibrosis |  | 48 weeks | 
| Change from baseline in liver fat content (LFC) as measured by MRI-PDFF |  | 48 weeks | 
| Change from baseline in liver chemistry（ALT,AST,GGT） |  | 48 weeks |