Phase 2a Study of HPG1860 in Subjects With NASH

Study Overview
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Brief Summary
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This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel group, multiple arm, multicenter study of 3 different doses of HPG1860 versus placebo in subjects with biopsy-confirmed or phenotypic NASH.

Detailed Description
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This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel group, multiple arm, multicenter study of 3 different doses of HPG1860 versus placebo in subjects with biopsy-confirmed or phenotypic NASH. Screening will occur up to 5 weeks prior to randomization; all eligible subjects will have baseline hepatic imaging during Screening, prior to randomization. Approximately 80 eligible subjects will be randomized 1:1:1:1 on Day 1/Week 0 (T1) to receive either HPG1860 3 mg (n = 20), or 5 mg (n = 20), or 8 mg (n = 20), or placebo (n = 20) for 12 weeks. Following a preplanned interim analysis, a dose cohort may be dropped and/or added.

Official Title
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A Randomized, Double-blind, Placebo-controlled Parallel Group Phase 2a Study to Evaluate the Efficacy and Safety of HPG1860 in Subjects With Nonalcoholic Steatohepatitis

Conditions
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NASH - Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: HPG1860
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written informed consent prior to any study-specific procedure. Males and females between 18 and 75 years of age Nonpregnant, nonlactating women. Male subjects must agree to utilize a highly effective method of contraception. Body mass index (BMI) of ≥25 kg/m2 at Screening. Non-cirrhotic NASH subjects. NASH subjects with hepatic fat assessed by a central reader Willing and able to adhere to study restrictions and agree to comply with study protocol. Exclusion Criteria: Pregnant or lactating females Current significant alcohol consumption Elevated LDL-C with stable dose of statin an or PCSK9 inhibitor Renal dysfunction or nephritic syndrome or a history of nephritis Recent infarction, unstable angina leading to hospitalization, uncontrolled, symptomatic cardiac arrhythmia Uncontrolled hypertension Type 1 diabetes or uncontrolled T2DM Uncontrolled hypothyroidism Liver transplant and/or other significant liver disease or dysfunction HIV antibody positive Known hypersensitivity or formulation excipient Gastrointestinal conditions or procedures that may affect drug absorption Hematologic or coagulation disorders Unstable weight within the last 3 months Active malignancy Unexplained creatine kinase (CK) >3 × ULN Blood donation, blood transfusion Unable to undergo or contraindication to MRI procedure A medical or situational finding that in the investigator's opinion may compromise the subject's safety or ability to complete the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HPG1860 3 mg<br>20 subjects will be treated with HPG1860 3 mg once daily at a similar time with or without food. | Drug: HPG1860<br>* The dosage form for clinical research is a dry-filled capsule for oral administration manufactured as strengths of 3 mg, 5 mg, and 8 mg.<br>|
| Experimental: HPG1860 5 mg<br>20 subjects will be treated with HPG1860 5 mg once daily at a similar time with or without food. | Drug: HPG1860<br>* The dosage form for clinical research is a dry-filled capsule for oral administration manufactured as strengths of 3 mg, 5 mg, and 8 mg.<br>|
| Experimental: HPG1860 8 mg<br>20 subjects will be treated with HPG1860 5 mg once daily at a similar time with or without food. | Drug: HPG1860<br>* The dosage form for clinical research is a dry-filled capsule for oral administration manufactured as strengths of 3 mg, 5 mg, and 8 mg.<br>|
| Placebo Comparator: Placebo<br>20 subjects will be treated with Placebo once daily at a similar time with or without food. | Drug: Placebo<br>* Capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of treatment | Number of participants Treatment-emergent adverse events (TEAEs) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| liver fat content | Change from baseline (CFB) in liver fat content (LFC) measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) at Week 12 | 12 week | 
| Percentage of subjects with ≥30% reduction in LFC from baseline | measured by MRI-PDFF at Week 4 and Week 12 | 4 week and 12 week | 
| Change from baseline (CFB) in liver fat content (LFC) at 4 week | measured by MRI-PDFF at Week 4 | 4 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NASH