Non-alcoholic SteatohepatitisPhase 2NCT03812029

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

A Phase 2 study testing Vonafexor in people with Non-alcoholic Steatohepatitis, run by Enyo Pharma at 42 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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 Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Non-alcoholic Steatohepatitis
What is being tested?: Vonafexor
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 120 participants
Where: 42 sitesin 5 countries
Study dates: 30 Jan 2019to 6 Jul 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

42 sites in 5 countries.

Country

City, postcode or hospital

42 sites in 5 countries

United States24 sites

ENYO PHARMA Investigative site 0405
Arlington, Texas, 76012
ENYO PHARMA Investigative site 0403
Athens, Georgia, 30607
ENYO PHARMA Investigative site 0416
Austin, Texas, 78746
ENYO PHARMA Investigative site 0422
Baltimore, Maryland, 21202
ENYO PHARMA Investigative site 0413
Baton Rouge, Louisiana, 70809
ENYO PHARMA Investigative site 0401
Charleston, South Carolina, 29401
ENYO PHARMA Investigative site 0408
Charleston, South Carolina, 29407
ENYO PHARMA Investigative site 0411
Columbus, Ohio, 43213
ENYO PHARMA Investigative site 0406
Durham, North Carolina, 27710
ENYO PHARMA Investigative site 0417
Edinburg, Texas, 78539
ENYO PHARMA Investigative site 0409
Indianapolis, Indiana, 46260
ENYO PHARMA Investigative site 0412
Jackson, Mississippi, 39216
ENYO PHARMA Investigative site 0414
Kansas City, Missouri, 64131
ENYO PHARMA Investigative site 0418
Lakewood Rch, Florida, 34211
ENYO PHARMA Investigative site 0404
Marrero, Louisiana, 70072
ENYO PHARMA Investigative site 0424
North Little Rock, Arkansas, 72117
ENYO PHARMA Investigative site 0402
Ocoee, Florida, 34761
ENYO PHARMA Investigative site 0420
Orlando, Florida, 32806
ENYO PHARMA Investigative site 0419
Port Orange, Florida, 32127
ENYO PHARMA Investigative site 0421
Rapid City, South Dakota, 57701
ENYO PHARMA Investigative site 0410
San Antonio, Texas, 78215
ENYO PHARMA Investigative site 0415
San Antonio, Texas, 78229
ENYO PHARMA Investigative site 0423
Savannah, Georgia, 31406
ENYO PHARMA Investigative site 0407
Snellville, Georgia, 30078

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France8 sites

ENYO PHARMA Investigative site 0201
Angers, 49933
ENYO PHARMA Investigative site
Créteil, 94010
ENYO PHARMA Investigative site 0203
Limoges, 87000
ENYO PHARMA Investigative site 0204
Lyon, 69004
ENYO PHARMA Investigative site 0206
Paris, 75013
ENYO PHARMA Investigative site 0202
Pessac, 33600
ENYO PHARMA Investigative site 0207
Toulouse, 31059
ENYO PHARMA Investigative site 0205
Villejuif, 94800

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United Kingdom5 sites

ENYO PHARMA Investigative site 0304
Belfast, BT12 6BA
ENYO PHARMA Investigative site 0302
Cambridge, CB2 0QQ
ENYO PHARMA Investigative site 0303
London, E1 1BB
ENYO PHARMA Investigative site 0305
London, SE5 9RS
ENYO PHARMA Investigative site 0301
Nottingham, NG7 2UH

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Belgium4 sites

ENYO PHARMA Investigative site 0105
Brussels, 1070
ENYO PHARMA Investigative site 0101
Edegem, 2650
ENYO PHARMA Investigative site 0104
Ghent, 3000
ENYO PHARMA Investigative site 0103
Ghent, 9000

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Puerto Rico1 site

ENYO PHARMA Investigative site 0429
San Juan

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About this study

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

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

Read the 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.

Conditions: Non-alcoholic Steatohepatitis
Being tested: Vonafexor, Placebo
Keywords: EYP001 (vonafexor), Liver Diseases, Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, NASH
Medical subject headings: Non-alcoholic Fatty Liver Disease, Liver Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VonafexorDrug
Oral tablets
PlaceboOther
Oral tablets

Study groups in NCT03812029
Study group	Role	What they receive
Vonafexor 100 mg BID	Experimental	Oral dose twice daily for 12 weeks (84 days) Receives: Drug: Vonafexor
Vonafexor 200 mg QD	Experimental	Oral dose once daily for 12 weeks (84 days) Receives: Drug: Vonafexor
Vonafexor 400 mg QD	Experimental	Oral dose once daily for 12 weeks (84 days) Receives: Drug: Vonafexor
Placebo	Placebo comparator	Oral dose twice daily for 12 weeks (84 days) Receives: Other: Placebo
Vonafexor 100 mg QD	Experimental	Oral dose once daily for 12 weeks (84 days) Receives: Drug: Vonafexor

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 12 weeks

Secondary outcomes (9)

Analysis of Change From Baseline in Glomerular Filtration rate_Part B
Measured: 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.
Measured: 12 weeks
Analysis of Change From Baseline in Corrected T1 (CT1)
Measured: 12 weeks
Analysis of Change From Baseline in Alanine Aminotransferase (ALT)
Measured: 12 weeks
Analysis of Change From Baseline in Gamma Glutamyltranspeptidase (GT)
Measured: 12 weeks
Analysis of Change From Baseline in Body Weight
Measured: 12 weeks
Analysis of Change From Baseline in Waist Circumference
Measured: 12 weeks
Analysis of Change From Baseline in Waist to Hip ratio_Part B
Measured: 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.
Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Jan 20196 Jul 2021

First posted22 Jan 2019
Study start30 Jan 2019
Primary completion16 Jun 2021
Study completion6 Jul 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Non-alcoholic SteatohepatitisStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Parallel assignment
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 120 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03812029
Sponsor's protocol ID: EYP001-202
Other IDs: 2018-003119-22, 2018
Status last verified: Apr 2023
First submitted: 17 Jan 2019
Last updated: 6 May 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 36334688

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 6 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03812029
Acronym / sponsor ID: EYP001-202
Conditions: Non-alcoholic Steatohepatitis
Keywords: EYP001 (vonafexor), Liver Diseases, Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, NASH
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 120 participants (actual)
Lead sponsor: Enyo PharmaIndustry (pharma, biotech, devices)
Study start: 30 Jan 2019 (actual)
Primary completion: 16 Jun 2021 (actual)
Study completion: 6 Jul 2021 (actual)
First posted: 22 Jan 2019 (actual)
Results: Posted 6 May 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 5
Model description: Parallel assignment

Arm	Type	Receives
Vonafexor 100 mg BID	Experimental	Drug: VonafexorOral dose twice daily for 12 weeks (84 days)
Vonafexor 200 mg QD	Experimental	Drug: VonafexorOral dose once daily for 12 weeks (84 days)
Vonafexor 400 mg QD	Experimental	Drug: VonafexorOral dose once daily for 12 weeks (84 days)
Placebo	Placebo comparator	Other: PlaceboOral dose twice daily for 12 weeks (84 days)
Vonafexor 100 mg QD	Experimental	Drug: VonafexorOral dose once daily for 12 weeks (84 days)

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VonafexorOral tablets	Drug	Vonafexor 100 mg BID, Vonafexor 100 mg QD, Vonafexor 200 mg QD, Vonafexor 400 mg QD
PlaceboOral tablets	Other	Placebo

Primary outcome

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)
Time frame: 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.

9 secondary outcomes

Analysis of Change From Baseline in Glomerular Filtration rate_Part B
Time frame: 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)
Time frame: 12 weeks
Analysis of Change From Baseline in Corrected T1 (CT1)
Time frame: 12 weeks
Analysis of Change From Baseline in Alanine Aminotransferase (ALT)
Time frame: 12 weeks
Analysis of Change From Baseline in Gamma Glutamyltranspeptidase (GT)
Time frame: 12 weeks
Analysis of Change From Baseline in Body Weight
Time frame: 12 weeks
Analysis of Change From Baseline in Waist Circumference
Time frame: 12 weeks
Analysis of Change From Baseline in Waist to Hip ratio_Part B
Time frame: 12 weeks
Analysis of Change From Baseline in Glomerular Filtration rate_Part A
Time frame: 12 weeks

Results and safety

Results posted to the registry on 6 May 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo Part A	7	5
Vonafexor Pooled Part A	17	7
Placebo Part B	32	32
Vonafexor 100 mg QD Part B	31	25
Vonafexor 200 mg QD Part B	33	23

Primary outcome: 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)

Time frame: 12 weeks. Least squares mean (95% Confidence Interval). Unit: Percentage of liver fat change

Measure	Placebo Part B n = 32	Vonafexor 100 mg QD Part B n = 28	Vonafexor 200 mg QD Part B n = 28	Placebo Part A n = 5	Vonafexor Pooled Part A n = 12
Value	-2.3 (-4.0 to -0.6)	-6.3 (-8.1 to -4.5)	-5.4 (-7.2 to -3.6)	3.9 (-2.5 to 10.4)	-4.7 (-8.5 to 0.9)

Placebo Part B vs Vonafexor 100 mg QD Part B: p = 0.0015, ANCOVA
Placebo Part B vs Vonafexor 200 mg QD Part B: p = 0.0121, ANCOVA
Placebo Part A vs Vonafexor Pooled Part A: p = 0.0371, ANCOVA

Population analysed: 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. The modified ITT (mITT) Population which was defined as patients from the ITT Population who have valid baseline and Week 12/Early Termination (ET) MRI-PDFF measurements of Liver Fat Content (LFC) has been used to analyse this endpoint.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: After dose the first dose of study drug until D96. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo Part A	0 of 7 (0%)	4 of 7 (57.1%)	0 of 7
Vonafexor 100 mg BID Part A	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Vonafexor 200 mg QD Part A	0 of 5 (0%)	4 of 5 (80%)	0 of 5
Vonafexor 400 mg QD Part A	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Placebo Part B	1 of 32 (3.1%)	22 of 32 (68.8%)	0 of 32
Vonafexor 100 mg QD Part B	1 of 31 (3.2%)	25 of 31 (80.6%)	0 of 31
Vonafexor 200 mg QD Part B	2 of 33 (6.1%)	30 of 33 (90.9%)	0 of 33

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36334688Ratziu 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Harrison Stephen, MD principal investigator

Pinnacle Clinical Research

42 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vonafexor in people with Non-alcoholic Steatohepatitis, run by Enyo Pharma at 42 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in United States, France, United Kingdom, Belgium, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03812029, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2023.