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

Primary Purpose

Non-alcoholic Steatohepatitis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Vonafexor
Placebo
Sponsored by
Enyo Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-alcoholic Steatohepatitis focused on measuring EYP001 (vonafexor), Liver Diseases, Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, NASH

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Written informed consent
  • Suspected diagnosis of NASH, evidenced by elevated alanine aminotransferase (ALT), liver stiffness compatible with F2 or F3 fibrosis and 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

Sites / Locations

  • ENYO PHARMA Investigative site 0424
  • ENYO PHARMA Investigative site 0418
  • ENYO PHARMA Investigative site 0402
  • ENYO PHARMA Investigative site 0420
  • ENYO PHARMA Investigative site 0419
  • ENYO PHARMA Investigative site 0403
  • ENYO PHARMA Investigative site 0423
  • ENYO PHARMA Investigative site 0407
  • ENYO PHARMA Investigative site 0409
  • ENYO PHARMA Investigative site 0413
  • ENYO PHARMA Investigative site 0404
  • ENYO PHARMA Investigative site 0422
  • ENYO PHARMA Investigative site 0412
  • ENYO PHARMA Investigative site 0414
  • ENYO PHARMA Investigative site 0406
  • ENYO PHARMA Investigative site 0411
  • ENYO PHARMA Investigative site 0401
  • ENYO PHARMA Investigative site 0408
  • ENYO PHARMA Investigative site 0421
  • ENYO PHARMA Investigative site 0405
  • ENYO PHARMA Investigative site 0416
  • ENYO PHARMA Investigative site 0417
  • ENYO PHARMA Investigative site 0410
  • ENYO PHARMA Investigative site 0415
  • ENYO PHARMA Investigative site 0105
  • ENYO PHARMA Investigative site 0101
  • ENYO PHARMA Investigative site 0104
  • ENYO PHARMA Investigative site 0103
  • ENYO PHARMA Investigative site 0201
  • ENYO PHARMA Investigative site
  • ENYO PHARMA Investigative site 0203
  • ENYO PHARMA Investigative site 0204
  • ENYO PHARMA Investigative site 0206
  • ENYO PHARMA Investigative site 0202
  • ENYO PHARMA Investigative site 0207
  • ENYO PHARMA Investigative site 0205
  • ENYO PHARMA Investigative site 0429
  • ENYO PHARMA Investigative site 0304
  • ENYO PHARMA Investigative site 0302
  • ENYO PHARMA Investigative site 0303
  • ENYO PHARMA Investigative site 0305
  • ENYO PHARMA Investigative site 0301

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Experimental

Arm Label

Vonafexor 100 mg BID

Vonafexor 200 mg QD

Vonafexor 400 mg QD

Placebo

Vonafexor 100 mg QD

Arm Description

Oral dose twice daily for 12 weeks (84 days)

Oral dose once daily for 12 weeks (84 days)

Oral dose once daily for 12 weeks (84 days)

Oral dose twice daily for 12 weeks (84 days)

Oral dose once daily for 12 weeks (84 days)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Analysis of Change From Baseline in Glomerular Filtration rate_Part B
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.
Analysis of Change From Baseline in Corrected T1 (CT1)
Analysis of Change From Baseline in Alanine Aminotransferase (ALT)
Analysis of Change From Baseline in Gamma Glutamyltranspeptidase (GT)
Analysis of Change From Baseline in Body Weight
Analysis of Change From Baseline in Waist Circumference
Analysis of Change From Baseline in Waist to Hip ratio_Part B
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.

Full Information

First Posted
January 17, 2019
Last Updated
April 13, 2023
Sponsor
Enyo Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT03812029
Brief Title
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
January 30, 2019 (Actual)
Primary Completion Date
June 16, 2021 (Actual)
Study Completion Date
July 6, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Enyo Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-alcoholic Steatohepatitis
Keywords
EYP001 (vonafexor), Liver Diseases, Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, NASH

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Parallel assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Triple (Participant, Care Provider, Investigator)
Allocation
Randomized
Enrollment
120 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vonafexor 100 mg BID
Arm Type
Experimental
Arm Description
Oral dose twice daily for 12 weeks (84 days)
Arm Title
Vonafexor 200 mg QD
Arm Type
Experimental
Arm Description
Oral dose once daily for 12 weeks (84 days)
Arm Title
Vonafexor 400 mg QD
Arm Type
Experimental
Arm Description
Oral dose once daily for 12 weeks (84 days)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral dose twice daily for 12 weeks (84 days)
Arm Title
Vonafexor 100 mg QD
Arm Type
Experimental
Arm Description
Oral dose once daily for 12 weeks (84 days)
Intervention Type
Drug
Intervention Name(s)
Vonafexor
Intervention Description
Oral tablets
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Oral tablets
Primary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Analysis of Change From Baseline in Glomerular Filtration rate_Part B
Time Frame
12 weeks
Title
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)
Description
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.
Time Frame
12 weeks
Title
Analysis of Change From Baseline in Corrected T1 (CT1)
Time Frame
12 weeks
Title
Analysis of Change From Baseline in Alanine Aminotransferase (ALT)
Time Frame
12 weeks
Title
Analysis of Change From Baseline in Gamma Glutamyltranspeptidase (GT)
Time Frame
12 weeks
Title
Analysis of Change From Baseline in Body Weight
Time Frame
12 weeks
Title
Analysis of Change From Baseline in Waist Circumference
Time Frame
12 weeks
Title
Analysis of Change From Baseline in Waist to Hip ratio_Part B
Time Frame
12 weeks
Title
Analysis of Change From Baseline in Glomerular Filtration rate_Part A
Description
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.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harrison Stephen, MD
Organizational Affiliation
Pinnacle Clinical Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
ENYO PHARMA Investigative site 0424
City
North Little Rock
State/Province
Arkansas
ZIP/Postal Code
72117
Country
United States
Facility Name
ENYO PHARMA Investigative site 0418
City
Lakewood Ranch
State/Province
Florida
ZIP/Postal Code
34211
Country
United States
Facility Name
ENYO PHARMA Investigative site 0402
City
Ocoee
State/Province
Florida
ZIP/Postal Code
34761
Country
United States
Facility Name
ENYO PHARMA Investigative site 0420
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
ENYO PHARMA Investigative site 0419
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
Facility Name
ENYO PHARMA Investigative site 0403
City
Athens
State/Province
Georgia
ZIP/Postal Code
30607
Country
United States
Facility Name
ENYO PHARMA Investigative site 0423
City
Savannah
State/Province
Georgia
ZIP/Postal Code
31406
Country
United States
Facility Name
ENYO PHARMA Investigative site 0407
City
Snellville
State/Province
Georgia
ZIP/Postal Code
30078
Country
United States
Facility Name
ENYO PHARMA Investigative site 0409
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
ENYO PHARMA Investigative site 0413
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70809
Country
United States
Facility Name
ENYO PHARMA Investigative site 0404
City
Marrero
State/Province
Louisiana
ZIP/Postal Code
70072
Country
United States
Facility Name
ENYO PHARMA Investigative site 0422
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21202
Country
United States
Facility Name
ENYO PHARMA Investigative site 0412
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
ENYO PHARMA Investigative site 0414
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64131
Country
United States
Facility Name
ENYO PHARMA Investigative site 0406
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
ENYO PHARMA Investigative site 0411
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43213
Country
United States
Facility Name
ENYO PHARMA Investigative site 0401
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29401
Country
United States
Facility Name
ENYO PHARMA Investigative site 0408
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29407
Country
United States
Facility Name
ENYO PHARMA Investigative site 0421
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57701
Country
United States
Facility Name
ENYO PHARMA Investigative site 0405
City
Arlington
State/Province
Texas
ZIP/Postal Code
76012
Country
United States
Facility Name
ENYO PHARMA Investigative site 0416
City
Austin
State/Province
Texas
ZIP/Postal Code
78746
Country
United States
Facility Name
ENYO PHARMA Investigative site 0417
City
Edinburg
State/Province
Texas
ZIP/Postal Code
78539
Country
United States
Facility Name
ENYO PHARMA Investigative site 0410
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
ENYO PHARMA Investigative site 0415
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
ENYO PHARMA Investigative site 0105
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
ENYO PHARMA Investigative site 0101
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
ENYO PHARMA Investigative site 0104
City
Gent
ZIP/Postal Code
3000
Country
Belgium
Facility Name
ENYO PHARMA Investigative site 0103
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
ENYO PHARMA Investigative site 0201
City
Angers
ZIP/Postal Code
49933
Country
France
Facility Name
ENYO PHARMA Investigative site
City
Créteil
ZIP/Postal Code
94010
Country
France
Facility Name
ENYO PHARMA Investigative site 0203
City
Limoges
ZIP/Postal Code
87000
Country
France
Facility Name
ENYO PHARMA Investigative site 0204
City
Lyon
ZIP/Postal Code
69004
Country
France
Facility Name
ENYO PHARMA Investigative site 0206
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
ENYO PHARMA Investigative site 0202
City
Pessac
ZIP/Postal Code
33600
Country
France
Facility Name
ENYO PHARMA Investigative site 0207
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
ENYO PHARMA Investigative site 0205
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
ENYO PHARMA Investigative site 0429
City
San Juan
Country
Puerto Rico
Facility Name
ENYO PHARMA Investigative site 0304
City
Belfast
ZIP/Postal Code
BT12 6BA
Country
United Kingdom
Facility Name
ENYO PHARMA Investigative site 0302
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
ENYO PHARMA Investigative site 0303
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Facility Name
ENYO PHARMA Investigative site 0305
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
ENYO PHARMA Investigative site 0301
City
Nottingham
ZIP/Postal Code
NG7 2UH
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
36334688
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.
Results Reference
derived

Learn more about this trial

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

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