Double-Blind, Placebo-Controlled Study of Two Doses of EPA-E in Patients With Non Alcoholic Steatohepatitis (NASH)

Study Overview
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Brief Summary
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This is a controlled study to determine the effectiveness and safety of ethyl icosapentate (EPA-E) in the treatment of adult patients with non-alcoholic steatohepatitis (NASH).

Detailed Description
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This is a phase II, double-blinded, placebo-controlled study to investigate the safety, efficacy, and pharmacokinetic profile of two doses of EPA-E in adult subjects with NASH. Subjects are required to have a liver biopsy with proven NASH in the 6 month period prior to screening. Up to 70 subjects will be enrolled into each treatment arm in a 1:1:1 ratio, for a total of 210 subjects. Subjects will be stratified at randomization by presence or absence of diabetes. Duration of treatment is 12 months.

Official Title
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A Phase II Double-Blind, Placebo-Controlled Study of Two Doses of EPA-E in Patients With NASH

Conditions
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Steatohepatitis

Intervention / Treatment
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* Drug: Placebo capsule
* Drug: EPA-E 300 mg capsule
* Drug: EPA-E 300 mg capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of definite NASH Patients with diabetes taking stable doses of anti-diabetic agents are eligible No significant concomitant medical illness Exclusion Criteria: Diagnosis of cirrhosis. Serum ALT > 300 U/L Use of drugs associated with steatohepatitis Use of the following anit-NASH agents: Vitamin E > 60 IU per day Omega-3-acid ethyl esters or omega-3-polyunsaturated fatty acid (PUFA)-containing supplements > 200 mg per day Thiazolidinediones (e.g. pioglitazone) Use of non-stable doses of the following anti-NASH agents: HMGCoA reductase inhibitors (statins), fibrates, probucol, ezetimibe, ursodiol (UDCA), taurine, betaine, N-acetylcysteine, s-adenosylmethionine (SAM-E), milk thistle, anti-TNF therapies, or probiotics. Other liver disease

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>3x placebo capsules TID | Drug: Placebo capsule<br>* 3x Placebo capsules three times a day (TID) for 365 days<br>|
| Experimental: EPA-E 1800 mg/day<br>2x EPA-E 300 mg capsules + 1placebo capsule TID | Drug: EPA-E 300 mg capsule<br>* 2x 300 mg capsules + placebo capsule TID for 365 days<br>|
| Experimental: EPA-E 2700 mg/day<br>3x EPA-E 300 mg capsules TID | Drug: EPA-E 300 mg capsule<br>* 3x 300 mg capsules TID for 365 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological Response Defined by Change From Baseline in Standardized Scoring of Liver Biopsies | Patient is considered a responder if histological examination shows: Composite NAS of <=3 AND no worsening in Fibrosis OR Improvement in NAS by >=2 across at least 2 of the NAS components AND no worsening in fibrosis A priori threshold for statistical significance is p<0.05, 1-sided | 12 months | 
| Alanine Transaminase (ALT) Levels | Mean change from baseline at month 3 analyzed by Analysis of Covariance (ANCOVA) in the efficacy evaluable analysis set with treatment group as a factor and baseline ALT as a covariate. Principal comparisons were the response between; EPA-E 2700 mg and Placebo groups EPA-E 1800 mg and Placebo groups | 3 month endpoint | 
| Alanine Transaminase (ALT) Levels | Mean change from baseline at month 6 analyzed by Analysis of Covariance (ANCOVA) in the efficacy analysis set with treatment group as a factor and baseline ALT as a covariate. Principal comparisons were the response between; EPA-E 2700 mg and Placebo groups EPA-E 1800 mg and Placebo groups | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lipids, omega-3 fatty acids, alanine transaminase, triglycerides, EPA, ethyl-EPA, ethyl icosapentate, Non Alcoholic steatohepatitis, Non Alcoholic fatty liver disease, fatty acids