Overview

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.

Eligibility

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