A Safety, Tolerability, Efficacy, and Pharmacokinetics Study of HEC96719 in Subjects With Non-Cirrhotic Non-Alcoholic Steatohepatitis

Study Overview
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Brief Summary
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This is a Phase 2, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics of HEC96719 in non-cirrhotic NASH patients.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Orally Administered HEC96719 Tablets in Adult Patients With Presumed Non-Cirrhotic Non-Alcoholic Steatohepatitis

Conditions
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Non-Alcoholic Steatohepatitis

Intervention / Treatment
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* Drug: HEC96719
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An informed consent document must be signed and dated by the subject Male or female, 18 to 65 years of age Body mass index (BMI)≥18.0 and≤35.0 kg/m2, and Weight≥40 kg; Presumed NASH based on clinical characteristics or prior liver biopsy MRI PDFF liver fat content ≥ 10 % Exclusion Criteria: previous diagnosis of other forms of chronic liver disease Laboratory Screening Results: AST > 5 x ULN ALP > 3 x ULN Total bilirubin > 1.5 x ULN Albumin < 3.2 g/dL INR > 1.3 Platelet count < 100,000 /mm3 creatinine clearance <60 ml/min (based on Cockroft Gault method) previous exposure to OCA uncontrolled diabetes mellitus presence of cirrhosis patients with contraindications to MRI imaging

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HEC96719 0.25 mg<br>Oral dose once daily for 12 weeks | Drug: HEC96719<br>* Oral tablets<br>|
| Experimental: HEC96719 0.35 mg<br>Oral dose once daily for 12 weeks | Drug: HEC96719<br>* Oral tablets<br>|
| Experimental: HEC96719 0.5 mg<br>Oral dose once daily for 12 weeks | Drug: HEC96719<br>* Oral tablets<br>|
| Experimental: HEC96719 0.25 mg bid<br>Oral dose twice daily for 12 weeks | Drug: HEC96719<br>* Oral tablets<br>|
| Placebo Comparator: Placebo<br>Oral dose once or twice daily for 12 weeks | Drug: Placebo<br>* Comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Percentage of Fat in the Liver as Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 12 |  | Baseline and Week 12 | 
| Plasma concentration of HEC96719 - AUC | Area under the curve | 4 weeks | 
| Plasma concentration of HEC96719 - Cmax | Maximum observed concentration | 4 weeks | 
| Plasma concentration of HEC96719 - Tmax | Time to reach maximum measured plasma concentration | 4 weeks | 
| Plasma concentration of HEC96719 - t1/2 | Determination of half-life | 4 weeks |