Vonafexor in Patients With Impaired Renal Function and Suspected MASH (Metabolic Dysfunction-associated Steatohepatitis) (MASH)

A Study to Assess the Effect of Vonafexor on Kidney Function in Subjects With Impaired Renal Function and Suspected MASH

This study is designed to establish the effect of 2 doses of vonafexor on the kidney. This will be investigated in subjects with mild or moderate reduced estimated glomerular filtration rate (eGFR) and suspected MASH. In addition, the non-invasive multiparametric magnetic resonance imaging assessment of functional and structural changes in the kidney and in the liver will be investigated.

Study Overview

• Status: Terminated
• Conditions: Chronic Kidney Disease Stage 3; Chronic Kidney Disease Stage 2; Metabolic Dysfunction-Associated Steatohepatitis
• Intervention / Treatment: Drug: Vonafexor low dose; Drug: Vonafexor high dose

Detailed Description

This is a phase 2, open-label, two-dose, randomized, parallel arms, single center study where subjects are participating for up to 32 weeks:

• Screening: 4 weeks
• Treatment: 16 weeks
• Follow-up: 12 weeks

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Profil Institut für Stoffwechselforschung GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed and dated informed consent obtained before any trial-related activities
• Male or female subject.
• Age between 18 and 75 years, both inclusive.
• Overweight or obesity (body mass index BMI ≥ 25.0 kg/m2 and ≤ 45.0 kg/m2) with or without type 2 diabetes mellitus (T2DM with an HbA1c ≤ 9.5%).
• eGFR ≥ 30 and < 90 (mL/min/1.73 m²).
• Presumed mild to higher liver fibrosis as shown by a FIBROTEST score ≥ 0.28 and/or FIB-4 score ≥ 1.3.

Exclusion Criteria:

• Known or suspected hypersensitivity to IMP or any of the excipients or to any component of the IMP formulation.
• Previous participation in this trial. Participation is defined as randomised.
• Receipt of any medicinal product in clinical development within 30 days or at least 5 half-lives of the related substances and their metabolites (whichever is longer) before randomisation in this trial.
• History of multiple and/or severe allergies to drugs including contrast media or foods or a history of severe anaphylactic reaction.
• Known non-MASH liver disease.
• History or presence of cirrhosis (evidenced on imaging or by histology, or liver decompensation, including ascites, hepatic encephalopathy, or presence of esophageal varices).
• Total body weight loss of >5% within 6 months prior to screening.
• If female, pregnancy or breast-feeding.
• Women of childbearing potential who are not using a highly effective contraceptive method and whose male partner is not using a highly effective contraceptive method for the entire study duration and for at least 6 weeks after last dosing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vonafexor low dose; Vonafexor low dose 1 tablet per day	Drug: Vonafexor low dose; Oral tablets
Experimental: Vonafexor high dose; Vonafexor high dose 1 tablet per day	Drug: Vonafexor high dose; Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline of mGFRiohexol at week 16	16 weeks
Change from baseline of eGFRcreatinine at week 16	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vonafexor plasma concentrations	Plasma concentrations pre-dose and post-dose which will be modelled against the MASH PopPK expected values	16 weeks
Change from baseline mGFRiohexol off treatment at week 24		24 weeks
Change from baseline of eGFRcreatinine on treatment at weeks 4, 8, 12 and off treatment at weeks 20, 24 and 28		28 weeks
Correlation of mGFRiohexol with eGFRcreatinine at baseline, on treatment at week 16 and off treatment at week 24		24 weeks
Levels and change in proteinuria in morning urine samples at baseline, on treatment at weeks 4, 8, 12, 16 with off treatment at weeks 20, 24 and 28		28 weeks
Treatment-emergent adverse events and serious adverse events		28 weeks

Other Outcome Measures

Outcome Measure	Time Frame
MRI kidney biomarkers time course from baseline, to on treatment at week 16 and to off treatment at week 24	24 weeks
MRI liver biomarkers time course from baseline, to on treatment at week 16 and to off treatment at week 24	24 weeks
Liver biomarker FIB-4 changes from baseline at on treatment week 8, 16 and off treatment at week 24	24 weeks

Collaborators and Investigators

• Sponsor: Enyo Pharma

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2025
• Primary Completion (Actual): December 22, 2025
• Study Completion (Actual): March 13, 2026

Study Registration Dates

• First Submitted: April 7, 2025
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 23, 2025

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; CKD; eGFR; Kidney function; mGFR; Metabolic Dysfunction-Associated Steatohepatitis; MASH; estimated Glomerular function rate; measured Glomerular function rate
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Renal Insufficiency, Chronic
• Other Study ID Numbers: EYP001-210; 2023-509192-16-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Individual participant data that underline published results might be shared upon request with researchers who provide a methodologically sound proposal and to achieve objectives as set in the approved proposal.

IPD will be shared deidentified and from 3 months and ending 5 years following article publication.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No