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Safety, Tolerability, Pharmacokinetics and Efficacy of EYP001a in Patients With Nonalcoholic Steatohepatitis (NASH)

Phase 2
Completed
Conditions
Non-alcoholic Steatohepatitis
Interventions
Other: Placebo
Registration Number
NCT03812029
Lead Sponsor
Enyo Pharma
Brief Summary

The purpose of this study is to assess the effects of EYP001a (Vonafexor) with respect to safety, tolerability, pharmacokinetics and on markers of liver inflammation in patients with NASH

Detailed Description

This is a 2-part, randomized, double-blind, multicenter, placebo-controlled study to evaluate the safety and efficacy of Vonafexor in patients with NASH who likely have stage F2 to F3 fibrosis at approximately 50 global clinical sites. Overall, approximately 114 eligible patients will be enrolled: 24 patients in Part A (Safety Run-in Cohort), followed by 90 patients in Part B.

In Part A, 24 patients will be randomized on Day 1 to 1 of 4 parallel treatment groups: 100 mg Vonafexor twice daily (BID), 200 mg Vonafexor once daily (QD), 400 mg Vonafexor QD, or placebo BID. In Part B, 90 patients will be randomized on Day 1 to 1 of 3 parallel treatment groups: 100 mg Vonafexor QD, 200 mg Vonafexor QD, or placebo QD.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
120
Inclusion Criteria
  • Written informed consent
  • Suspected diagnosis of NASH, evidenced by elevated alanine aminotransferase (ALT), liver stiffness compatible with F2 or F3 fibrosis and Liver Fat Content (LFC) ≥10% as measured by MRI
  • Women of childbearing potential and male patients with female partners must agree to use a dual method of contraception
Exclusion Criteria
  • Evidence of worsening liver injury
  • Previous diagnosis of other forms of non-NASH liver disease
  • Use of Vitamin E, glitazones, glucagon-like Peptide-1 receptor agonists, ursodeoxycholic acid, or obeticholic acid within 90 days prior to screening
  • History of cirrhosis or liver decompensation
  • Known history of alcohol abuse or daily heavy alcohol consumption
  • Pregnant or breastfeeding women
  • Type 1 diabetes mellitus and uncontrolled type 2 diabetes mellitus
  • Patients with contraindications to MRI imaging

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Vonafexor 100 mg QDVonafexorOral dose once daily for 12 weeks (84 days)
Vonafexor 100 mg BIDVonafexorOral dose twice daily for 12 weeks (84 days)
Vonafexor 200 mg QDVonafexorOral dose once daily for 12 weeks (84 days)
Vonafexor 400 mg QDVonafexorOral dose once daily for 12 weeks (84 days)
PlaceboPlaceboOral dose twice daily for 12 weeks (84 days)
Primary Outcome Measures
NameTimeMethod
Analysis of Absolute Change From Baseline in Percentage of Fat in the Liver as Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)12 weeks

The liver fat percentage was assessed by MRI-PDFF, which is an established method that enables the quantification of fat content in the liver; the value of liver fat is expressed in percentage and ranges from 0 to 100% with higher values representing higher liver fat level.

Secondary Outcome Measures
NameTimeMethod
Analysis of Change From Baseline in Body Weight12 weeks
Analysis of Change From Baseline in Glomerular Filtration rate_Part B12 weeks
Analysis of Change From Baseline in Corrected T1 (CT1)12 weeks
Analysis of Percent Change (Relative) From Baseline in Percentage of Fat in the Liver as Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)12 weeks

The liver fat percentage was assessed by MRI-PDFF, which is an established method that enables the quantification of fat content in the liver; the value of liver fat is expressed in percentage and ranges from 0 to 100% with higher values representing higher liver fat level.

Analysis of Change From Baseline in Gamma Glutamyltranspeptidase (GT)12 weeks
Analysis of Change From Baseline in Waist Circumference12 weeks
Analysis of Change From Baseline in Glomerular Filtration rate_Part A12 weeks

For Part A, as per ICH, analysis were performed as defined in the SAP: data from the 3 vonafexor treatment groups were pooled and compared with the placebo group.

Analysis of Change From Baseline in Alanine Aminotransferase (ALT)12 weeks
Analysis of Change From Baseline in Waist to Hip ratio_Part B12 weeks

Trial Locations

Locations (42)

ENYO PHARMA Investigative site 0413

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Baton Rouge, Louisiana, United States

ENYO PHARMA Investigative site 0422

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Baltimore, Maryland, United States

ENYO PHARMA Investigative site 0103

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Gent, Belgium

ENYO PHARMA Investigative site 0407

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Snellville, Georgia, United States

ENYO PHARMA Investigative site 0423

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Savannah, Georgia, United States

ENYO PHARMA Investigative site 0302

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Cambridge, United Kingdom

ENYO PHARMA Investigative site 0205

🇫🇷

Villejuif, France

ENYO PHARMA Investigative site 0418

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Lakewood Ranch, Florida, United States

ENYO PHARMA Investigative site 0404

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Marrero, Louisiana, United States

ENYO PHARMA Investigative site 0421

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Rapid City, South Dakota, United States

ENYO PHARMA Investigative site 0304

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Belfast, United Kingdom

ENYO PHARMA Investigative site 0206

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Paris, France

ENYO PHARMA Investigative site 0101

🇧🇪

Edegem, Belgium

ENYO PHARMA Investigative site 0429

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San Juan, Puerto Rico

ENYO PHARMA Investigative site 0202

🇫🇷

Pessac, France

ENYO PHARMA Investigative site 0305

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London, United Kingdom

ENYO PHARMA Investigative site 0301

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Nottingham, United Kingdom

ENYO PHARMA Investigative site 0207

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Toulouse, France

ENYO PHARMA Investigative site 0411

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Columbus, Ohio, United States

ENYO PHARMA Investigative site 0409

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Indianapolis, Indiana, United States

ENYO PHARMA Investigative site 0105

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Brussels, Belgium

ENYO PHARMA Investigative site 0402

🇺🇸

Ocoee, Florida, United States

ENYO PHARMA Investigative site 0424

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North Little Rock, Arkansas, United States

ENYO PHARMA Investigative site 0403

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Athens, Georgia, United States

ENYO PHARMA Investigative site 0419

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Port Orange, Florida, United States

ENYO PHARMA Investigative site 0203

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Limoges, France

ENYO PHARMA Investigative site 0412

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Jackson, Mississippi, United States

ENYO PHARMA Investigative site 0405

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Arlington, Texas, United States

ENYO PHARMA Investigative site 0201

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Angers, France

ENYO PHARMA Investigative site 0417

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Edinburg, Texas, United States

ENYO PHARMA Investigative site 0104

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Gent, Belgium

ENYO PHARMA Investigative site

🇫🇷

Créteil, France

ENYO PHARMA Investigative site 0204

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Lyon, France

ENYO PHARMA Investigative site 0303

🇬🇧

London, United Kingdom

ENYO PHARMA Investigative site 0420

🇺🇸

Orlando, Florida, United States

ENYO PHARMA Investigative site 0414

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Kansas City, Missouri, United States

ENYO PHARMA Investigative site 0406

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Durham, North Carolina, United States

ENYO PHARMA Investigative site 0416

🇺🇸

Austin, Texas, United States

ENYO PHARMA Investigative site 0410

🇺🇸

San Antonio, Texas, United States

ENYO PHARMA Investigative site 0401

🇺🇸

Charleston, South Carolina, United States

ENYO PHARMA Investigative site 0408

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Charleston, South Carolina, United States

ENYO PHARMA Investigative site 0415

🇺🇸

San Antonio, Texas, United States

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