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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2a, Randomized, Double-Blind, Multicenter, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of EYP001a in Patients With Nonalcoholic Steatohepatitis

Conditions
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Non-alcoholic Steatohepatitis

Intervention / Treatment
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* Drug: Vonafexor
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

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: Parallel assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vonafexor 100 mg BID<br>Oral dose twice daily for 12 weeks (84 days) | Drug: Vonafexor<br>* Oral tablets<br>|
| Experimental: Vonafexor 200 mg QD<br>Oral dose once daily for 12 weeks (84 days) | Drug: Vonafexor<br>* Oral tablets<br>|
| Experimental: Vonafexor 400 mg QD<br>Oral dose once daily for 12 weeks (84 days) | Drug: Vonafexor<br>* Oral tablets<br>|
| Placebo Comparator: Placebo<br>Oral dose twice daily for 12 weeks (84 days) | Other: Placebo<br>* Oral tablets<br>|
| Experimental: Vonafexor 100 mg QD<br>Oral dose once daily for 12 weeks (84 days) | Drug: Vonafexor<br>* Oral tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of Change From Baseline in Glomerular Filtration rate_Part B |  | 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) | 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. | 12 weeks | 
| Analysis of Change From Baseline in Corrected T1 (CT1) |  | 12 weeks | 
| Analysis of Change From Baseline in Alanine Aminotransferase (ALT) |  | 12 weeks | 
| Analysis of Change From Baseline in Gamma Glutamyltranspeptidase (GT) |  | 12 weeks | 
| Analysis of Change From Baseline in Body Weight |  | 12 weeks | 
| Analysis of Change From Baseline in Waist Circumference |  | 12 weeks | 
| Analysis of Change From Baseline in Waist to Hip ratio_Part B |  | 12 weeks | 
| Analysis of Change From Baseline in Glomerular Filtration rate_Part A | 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. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EYP001 (vonafexor), Liver Diseases, Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, NASH