Vonafexor in Impaired Renal Function and Suspected MASH

Phase 1

Conditions: Impaired renal function and suspected MASH
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: CTIS2023-509192-16-00

Lead Sponsor: ENYO Pharma

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 50

Inclusion Criteria

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., 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., Proteinuria in the nephrotic range with a protein-to-creatinine ratio > 3.5 g protein/g creatinine (350 mg/mmol).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the effect of vonafexor on renal function in a population with suspected MASH and mild to moderately reduced GFR.;Secondary Objective: To determine the PK profile of vonafexor 25 mg and 100 mg QD, To compare the on-treatment with the off-treatment effect of two dose levels of vonafexor on renal function and proteinuria, To determine the safety and tolerability profile of two dose levels of vonafexor;Primary end point(s): Change from baseline of mGFRiohexol and eGFRcreat at W16

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Plasma concentrations pre-dose (0h) and post-dose (2h, 5h, and 7h) on Day 1 (W0) and D113 (W16), which will be modelled against the MASH PopPK expected values.;Secondary end point(s):Change from baseline mGFRiohexol off treatment at W24.;Secondary end point(s):Change from baseline of eGFRcreat on treatment at W4, W8, W12 and off treatment at W20, W24 and W28;Secondary end point(s):Correlation of mGFRiohexol with eGFRcreat at baseline, on treatment at W16 and off treatment at W24;Secondary end point(s):Levels and change in albuminuria (Urinary Albumin to Creatinine Ratio (UACR) and proteinuria (Urinary Protein to Creatinine ratio (UPCR)) in morning urine samples at baseline, on treatment at W4, W8, W12, W16 with off treatment at W20, W24 and W28.;Secondary end point(s):AEs, SAEs;Secondary end point(s):Changes from baseline at W16 in laboratory safety parameters, physical examination, vital signs and ECGs