A Phase 2b Study of Icosabutate in Fatty Liver Disease

Study Overview
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Brief Summary
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A Phase 2b study to evaluate the efficacy of different doses of NST-4016 on the resolution of NASH without worsening of fibrosis

Detailed Description
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This is a 62 week (including screening and follow-up), multicenter, randomized, double blind, placebo-controlled, parallel group study in male and female patients with a histological diagnosis of NASH. The study includes a screening period, double blind treatment period, and post-treatment follow up

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of NST-4016 in Patients With Nonalcoholic Steatohepatitis (NASH)

Conditions
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Non Alcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: Icosabutate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provides signed written informed consent and agrees to comply with the study protocol. Is a male or female aged 18 to 75 years, inclusive. Has a histological diagnosis of NASH prior to study entry Has (NAS) greater than or equal to 4, with a score of at least 1 in each component (steatosis, lobular inflammation, and ballooning), Has a fibrosis score F1 to F3, inclusive (F1 capped at 30%), Has a Proton Density Fat Fraction (PDFF) greater than or equal to 10% on MRI at screening Exclusion Criteria: Has a known history of alcohol abuse or daily heavy alcohol consumption Has had bariatric surgery within the past 5 years Has significant systemic or major illnesses other than liver disease Has a recent (within 6 months) history of cardiac dysrhythmias and/or cardiovascular disease Has uncontrolled arterial hypertension Positive for Hep B, Hepatitis C Virus (HCV) or HCV Polymerase Chain Reaction (PCR) Has type 1 diabetes mellitus Has diabetic ketoacidosis Has a history of liver decompensation

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo oral capsules taken one daily for 52 weeks | Drug: Placebo<br>* Matching placebo oral capsule<br>|
| Experimental: Icosabutate 300mg<br>Icosabutate 300mg oral capsule taken once daily for 52 weeks | Drug: Icosabutate<br>* Icosabutate oral capsule once daily<br>* Other names: NST-4016;|
| Experimental: Icosabutate 600mg<br>Icosabutate 600mg oral capsules taken once daily for 52 weeks | Drug: Icosabutate<br>* Icosabutate oral capsule once daily<br>* Other names: NST-4016;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of patients with resolution of NASH, defined as disappearance of ballooning (score = 0) with lobular inflammation score 0 or 1, with no worsening of fibrosis. |  | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Nonalcoholic fatty liver disease (NAFLD) activity score (NAS) | A histological scoring system that assesses a liver biopsy and gives scores for steatosis (0-3), lobular inflammation (0-3), and hepatocyte ballooning (0-2) giving a total score of (0-8). The higher the score the more severe the disease | 52 weeks | 
| Changes in individual histological scores for steatosis, ballooning, inflammation, and fibrosis from baseline | Changes in scores for the individual component parts of the Nonalcoholic fatty liver disease (NAFLD) activity score (NAS) as judged by a pathologist examining sections from a liver biopsy; steatosis (range 0-3), lobular inflammation (range 0-3), and hepatocyte ballooning (range 0-2) In all cases a higher number denotes more severe disease activity | 52 weeks | 
| Changes in the liver enzymes Aspartate Aminotransferase (AST)U/L, Alanine Aminotransferase ( ALT)U/L and Gamma Glutamyl Transferase (GGT) U/L from baseline |  | 52 weeks | 
| Change in bilirubin mg/dL from baseline |  | 52 weeks |