Chronic Kidney Disease Stage 2, Chronic Kidney Disease Stage 3, Metabolic Dysfunction-Associated Steatohepatitis
Conditions
Keywords
CKD, Chronic Kidney Disease, MASH, Metabolic Dysfunction-Associated Steatohepatitis, Kidney function, eGFR, estimated Glomerular function rate, mGFR, measured Glomerular function rate
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
Interventions
DRUGVonafexor low dose
Oral tablets
DRUGVonafexor high dose
Oral tablets
Sponsors
Enyo Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline of mGFRiohexol at week 16 | 16 weeks |
| Change from baseline of eGFRcreatinine at week 16 | 16 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vonafexor plasma concentrations | 16 weeks | Plasma concentrations pre-dose and post-dose which will be modelled against the MASH PopPK expected values |
| 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 | — |
Countries
Germany
Outcome results
None listed