Clinical trial NCT03812029: Safety, Tolerability, Pharmacokinetics and Efficacy of EYP001a in Patients With Nonalcoholic Steatohepatitis (NASH)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-alcoholic Steatohepatitis
Keywords: EYP001 (vonafexor)
Liver Diseases
Non-alcoholic Fatty Liver Disease
Non-alcoholic Steatohepatitis
NASH
Lead sponsor: Enyo Pharma
Sponsor class: INDUSTRY
First posted: 2019-01-22
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel assignment
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: 12 weeks
Secondary outcomes:
measure: Analysis of Change From Baseline in Glomerular Filtration rate_Part B
timeFrame: 12 weeks
measure: 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)
timeFrame: 12 weeks
measure: Analysis of Change From Baseline in Corrected T1 (CT1)
timeFrame: 12 weeks
measure: Analysis of Change From Baseline in Alanine Aminotransferase (ALT)
timeFrame: 12 weeks
measure: Analysis of Change From Baseline in Gamma Glutamyltranspeptidase (GT)
timeFrame: 12 weeks
measure: Analysis of Change From Baseline in Body Weight
timeFrame: 12 weeks
measure: Analysis of Change From Baseline in Waist Circumference
timeFrame: 12 weeks
measure: Analysis of Change From Baseline in Waist to Hip ratio_Part B
timeFrame: 12 weeks
measure: Analysis of Change From Baseline in Glomerular Filtration rate_Part A
timeFrame: 12 weeks
Other outcomes:
Locations:
city: North Little Rock
country: United States
facility: ENYO PHARMA Investigative site 0424
state: Arkansas
city: Lakewood Ranch
country: United States
facility: ENYO PHARMA Investigative site 0418
state: Florida
city: Ocoee
country: United States
facility: ENYO PHARMA Investigative site 0402
state: Florida
city: Orlando
country: United States
facility: ENYO PHARMA Investigative site 0420
state: Florida
city: Port Orange
country: United States
facility: ENYO PHARMA Investigative site 0419
state: Florida
city: Athens
country: United States
facility: ENYO PHARMA Investigative site 0403
state: Georgia
city: Savannah
country: United States
facility: ENYO PHARMA Investigative site 0423
state: Georgia
city: Snellville
country: United States
facility: ENYO PHARMA Investigative site 0407
state: Georgia
city: Indianapolis
country: United States
facility: ENYO PHARMA Investigative site 0409
state: Indiana
city: Baton Rouge
country: United States
facility: ENYO PHARMA Investigative site 0413
state: Louisiana
city: Marrero
country: United States
facility: ENYO PHARMA Investigative site 0404
state: Louisiana
city: Baltimore
country: United States
facility: ENYO PHARMA Investigative site 0422
state: Maryland
city: Jackson
country: United States
facility: ENYO PHARMA Investigative site 0412
state: Mississippi
city: Kansas City
country: United States
facility: ENYO PHARMA Investigative site 0414
state: Missouri
city: Durham
country: United States
facility: ENYO PHARMA Investigative site 0406
state: North Carolina
city: Columbus
country: United States
facility: ENYO PHARMA Investigative site 0411
state: Ohio
city: Charleston
country: United States
facility: ENYO PHARMA Investigative site 0401
state: South Carolina
city: Charleston
country: United States
facility: ENYO PHARMA Investigative site 0408
state: South Carolina
city: Rapid City
country: United States
facility: ENYO PHARMA Investigative site 0421
state: South Dakota
city: Arlington
country: United States
facility: ENYO PHARMA Investigative site 0405
state: Texas
city: Austin
country: United States
facility: ENYO PHARMA Investigative site 0416
state: Texas
city: Edinburg
country: United States
facility: ENYO PHARMA Investigative site 0417
state: Texas
city: San Antonio
country: United States
facility: ENYO PHARMA Investigative site 0410
state: Texas
city: San Antonio
country: United States
facility: ENYO PHARMA Investigative site 0415
state: Texas
city: Brussels
country: Belgium
facility: ENYO PHARMA Investigative site 0105
city: Edegem
country: Belgium
facility: ENYO PHARMA Investigative site 0101
city: Gent
country: Belgium
facility: ENYO PHARMA Investigative site 0104
city: Gent
country: Belgium
facility: ENYO PHARMA Investigative site 0103
city: Angers
country: France
facility: ENYO PHARMA Investigative site 0201
city: Créteil
country: France
facility: ENYO PHARMA Investigative site
city: Limoges
country: France
facility: ENYO PHARMA Investigative site 0203
city: Lyon
country: France
facility: ENYO PHARMA Investigative site 0204
city: Paris
country: France
facility: ENYO PHARMA Investigative site 0206
city: Pessac
country: France
facility: ENYO PHARMA Investigative site 0202
city: Toulouse
country: France
facility: ENYO PHARMA Investigative site 0207
city: Villejuif
country: France
facility: ENYO PHARMA Investigative site 0205
city: San Juan
country: Puerto Rico
facility: ENYO PHARMA Investigative site 0429
city: Belfast
country: United Kingdom
facility: ENYO PHARMA Investigative site 0304
city: Cambridge
country: United Kingdom
facility: ENYO PHARMA Investigative site 0302
city: London
country: United Kingdom
facility: ENYO PHARMA Investigative site 0303
city: London
country: United Kingdom
facility: ENYO PHARMA Investigative site 0305
city: Nottingham
country: United Kingdom
facility: ENYO PHARMA Investigative site 0301
Study officials:
affiliation: Pinnacle Clinical Research
name: Harrison Stephen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ratziu V, Harrison SA, Loustaud-Ratti V, Bureau C, Lawitz E, Abdelmalek M, Alkhouri N, Francque S, Girma H, Darteil R, Couchoux H, Wolf M, Sanyal A, Vonderscher J, Scalfaro P. Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH. J Hepatol. 2023 Mar;78(3):479-492. doi: 10.1016/j.jhep.2022.10.023. Epub 2022 Nov 9.