Efficacy and Safety of Pemvidutide in Subjects With Nonalcoholic Steatohepatitis (NASH) (IMPACT Trial)

Study Overview
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Brief Summary
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Purpose of this study is to assess the effects of pemvidutide on NASH resolution and NASH fibrosis.

Detailed Description
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A Phase 2, multi-center, double-blind, placebo-controlled study to evaluate the efficacy and safety of pemvidutide in NASH.

Official Title
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A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Pemvidutide in Non-Cirrhotic Subjects With Nonalcoholic Steatohepatitis (NASH)

Conditions
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Non-Alcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: Pemvidutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Male or female 18-75 years Histologic diagnosis of NASH and/or histologic confirmation of NASH based on central pathology evaluation of a liver biopsy during screening A histologic NAFLD Activity Score (NAS) ≥ 4 with a score of at least 1 on each subcomponent score based on central pathology evaluation (steatosis [0-3], lobular inflammation [0-3], and hepatocyte ballooning [0-2]) NASH fibrosis stages 2 through 3 according to the NASH CRN fibrosis staging system based on central pathology evaluation Subject agrees to have a liver biopsy performed during the screening period (if no biopsy within the preceding 6 months is available) and at 24 weeks of treatment BMI ≥ 27.0 kg/m2 Subjects with Type 2 diabetes mellitus (T2D) should be on a stable treatment regimen for their T2D for at least 90 days prior to screening Subject meets at least 3 of the 5 criteria of Metabolic Syndrome (American Heart Association 2005) Liver fat content by MRI-PDFF ≥ 8% Exclusion Criteria: Weight gain or loss > 5% in the 3 months prior to randomization or > 10% in the 6 months prior to screening History or clinical evidence of Type 1 diabetes mellitus Hemoglobin A1c (HbA1c) > 9.5% or clinically significant persistent hyperglycemia Liver conditions: History of cirrhosis or complications of cirrhosis, including but not limited to variceal bleeding, encephalopathy, or ascites Documented causes of chronic liver disease other than NASH ALT or AST laboratory values > 5 × ULN

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-blind, Placebo-controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemvidutide 1.2 mg (n=38)<br> | Drug: Pemvidutide<br>* Administered by subcutaneous injection<br>|
| Experimental: Pemvidutide 1.8 mg (n=76)<br> | Drug: Pemvidutide<br>* Administered by subcutaneous injection<br>|
| Placebo Comparator: Placebo (n=76)<br> | Drug: Placebo<br>* Administered by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving NASH resolution (NAFLD activity score [NAS], ballooning = 0; lobular inflammation = 0, 1) with at least a 2-point reduction in NAS without worsening of fibrosis |  | 24 weeks | 
| Proportion of subjects achieving at least 1 stage improvement in liver fibrosis without worsening of NASH (defined as no change in the NAS, ie, the sum score for ballooning, inflammation, and steatosis) |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving the composite of both NASH resolution and at least 1 stage improvement of liver fibrosis at 24 weeks |  | 24 weeks | 
| Relative change (%) in liver fat content by MRI-PDFF |  | 24 weeks and 48 weeks | 
| Absolute change in MRI-based corrected T1 (cT1) imaging |  | 24 weeks and 48 weeks | 
| Absolute change in alanine aminotransferase (ALT) |  | 24 weeks and 48 weeks | 
| Absolute change in Enhanced Liver Fibrosis (ELF) score |  | 24 weeks and 48 weeks | 
| Absolute change in Fibroscan-AST (FAST) score |  | 24 weeks and 48 weeks | 
| Relative (%) change in body weight |  | 24 weeks and 48 weeks | 
| Absolute changes in fasting lipids (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) |  | 24 weeks and 48 weeks | 
| Change in HbA1c (%) |  | 24 weeks and 48 weeks | 
| Change in glucose (mg/dL) |  | 24 weeks and 48 weeks | 
| Change in systolic and diastolic blood pressure (mmHg) |  | 24 weeks and 48 weeks | 
| Change in heart rate (beats per minute) |  | 24 weeks and 48 weeks | 
| The number of subjects with treatment emergent adverse events |  | 48 weeks |