Clinical trial NCT06939816: Vonafexor in Patients With Impaired Renal Function and Suspected MASH (Metabolic Dysfunction-associated Steatohepatitis)
Official title: A Study to Assess the Effect of Vonafexor on Kidney Function in Subjects With Impaired Renal Function and Suspected MASH
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Chronic Kidney Disease Stage 2
Chronic Kidney Disease Stage 3
Metabolic Dysfunction-Associated Steatohepatitis
Keywords: CKD
Chronic Kidney Disease
MASH
Metabolic Dysfunction-Associated Steatohepatitis
Kidney function
eGFR
estimated Glomerular function rate
mGFR
measured Glomerular function rate
Lead sponsor: Enyo Pharma
Sponsor class: INDUSTRY
First posted: 2025-04-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline of mGFRiohexol at week 16
timeFrame: 16 weeks
measure: Change from baseline of eGFRcreatinine at week 16
timeFrame: 16 weeks
Secondary outcomes:
measure: Vonafexor plasma concentrations
timeFrame: 16 weeks
measure: Change from baseline mGFRiohexol off treatment at week 24
timeFrame: 24 weeks
measure: Change from baseline of eGFRcreatinine on treatment at weeks 4, 8, 12 and off treatment at weeks 20, 24 and 28
timeFrame: 28 weeks
measure: Correlation of mGFRiohexol with eGFRcreatinine at baseline, on treatment at week 16 and off treatment at week 24
timeFrame: 24 weeks
measure: 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
timeFrame: 28 weeks
measure: Treatment-emergent adverse events and serious adverse events
timeFrame: 28 weeks
Other outcomes:
measure: MRI kidney biomarkers time course from baseline, to on treatment at week 16 and to off treatment at week 24
timeFrame: 24 weeks
measure: MRI liver biomarkers time course from baseline, to on treatment at week 16 and to off treatment at week 24
timeFrame: 24 weeks
measure: Liver biomarker FIB-4 changes from baseline at on treatment week 8, 16 and off treatment at week 24
timeFrame: 24 weeks
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung GmbH
Study officials:
References: