Vonafexor ALPort Syndrome Efficacy & Safety TRIAl-1 (ALPESTRIA-1)

Alport Syndrome Clinical Trial

— ALPESTRIA-1  

Official title:

Vonafexor Fixed Dose-escalation Safety and Proof-of-concept Study in Patients With at Risk of Progression Alport Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06425055
• Other study ID #: EYP001-208
• Status: Recruiting
• Phase: Phase 2
• Start date: June 6, 2024
• Est. completion date: October 13, 2025

Study information

• Verified date: June 2024
• Source: Enyo Pharma
• Contact: Isabelle Martin
• Phone: +33 4 37 70 02 44
• Email: clinicaltrial[@]enyopharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a proof-of-concept trial of vonafexor safety, its effects on kidney function in subjects with at risk of progression Alport syndrome.

Description:

This is a multicenter study and several clinical sites and countries will be involved. This single arm, fixed dose escalation, open-label, non-randomized study will evaluate three dose levels of vonafexor on safety, tolerability and their effect on kidney function and renal biomarkers in 20 patients with AS at risk of progression. The total duration of study for a participant will be up to 40 weeks and include a screening period, a treatment period of 24 weeks and a follow-up period of 12 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: October 13, 2025
• Est. primary completion date: July 21, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 55 Years

Eligibility

Inclusion Criteria:

• Signed informed consent (also for legal representatives, as applicable in the US for under eighteen patients).
• Has confirmed diagnosis of Alport syndrome: clinical diagnosis (haematuria, family history, hearing loss, ocular change) OR a kidney biopsy showing glomerular basement membrane abnormalities consistent with AS, AND Genetic confirmation of AS.
• Has eGFR between = 30 and < 90 ml/min/1.73m2.
• Has increased albuminuria criteria i.e. UACR = 300 mg/g.
• If on an angiotensin converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB), should be on a stable well tolerated treatment during at least the 60 days prior D1.
• If on Sodium-Glucose Transport Protein 2 (SGLT2), should be on stable well tolerated treatment with SGLT2 during at least 60 days prior D1.
• If patient has a history of arterial hypertension, should be on stable anti-hypertensive therapy for at least 60 days prior to D1 and deemed controlled by the investigator at screening and D1.
• Sexually active female subjects of childbearing potential and sexually mature male subjects must use two acceptable effective methods of contraception for the entire duration of the study and for at least 6 weeks after last dose.
• Has negative results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, and human immunodeficiency virus (HIV).
• Is able to understand all study procedures in the informed consent form (ICF) and willing to comply with all aspects of the protocol.

Exclusion Criteria:

• Is an employee of a site, clinical research organization, vendor, or sponsor involved with this study.
• Is pregnant or breastfeeding.
• Has participated in any investigational drug study within 60 days prior to D1.
• Any clinically significant illness within 30 days before D1 or surgical or medical condition (other than Alport syndrome) that could interfere with the subject's study compliance; confound the study results; impact subject safety.
• Any history of active malignancy within the last 1 year before D1.
• Any other condition or circumstance that, in the opinion of the investigator, may make the subject unlikely to complete the study or comply with study procedures and requirements, or may pose a risk to the subject's safety and well-being.
• Has a history of an allergic condition that required the prescription of an emergency epinephrine injection (such as the EpiPen® Auto-Injector).
• Any prohibited co-medications within 30 days prior D1.
• Has ALT or AST above near normal (>1.5×ULN) at baseline.
• Are at high risk for atherosclerotic cardiovascular disease (ASCVD) risk, with an LDL-C level > 160 mg/dL (4.15 mmol/L) and subjects at intermediate risk for ASCVD risk, with a LDL-C level > 190 mg/dL (4.91 mmol/L).
• Has moderate or severe hepatic impairment (Child-Pugh score B or C).
• Is taking CYP3A4/5 inhibitors or inducers.

Related Conditions & MeSH terms

• Alport Syndrome
• Nephritis, Hereditary
• Syndrome

Intervention

Drug:
• Vonafexor
One tablet of a low dose of vonafexor QD from Day 1 to Week 4 One tablet of a medium dose of vonafexor QD from Week 5 to Week 8 One tablet of a high dose of vonafexor QD from Week 9 to Week 24

Locations

Country	Name	City	State
France	Pr Claire Rigothier - CHU De Bordeaux	Bordeaux
France	Dr Thomas Robert - Hôpital de la Conception	Marseille
France	Dr Moglie Le Quintrec - Hopital Lapeyronie	Montpellier
France	Pr. Bertrand Knebelmann - Necker Enfants Malades	Paris
Germany	Charite Universitatsmedizin Berlin	Berlin
Germany	University Medicine Goettingen	Göttingen
Spain	Fundacio Puigvert	Barcelona
Spain	Hospital Virgen de la Arrixaca	El Palmar
Spain	Fundacion Jimenez Diaz	Madrid
Spain	Hospital De Sagunto	Sagunto
United States	Dr Eric Wallace - University of Alabama	Birmingham	Alabama
United States	Dr Arnold Silva - Boise Kidney & Hypertension	Boise	Idaho
United States	Dr James Simon - Cleveland Clinic Foundation	Cleveland	Ohio
United States	Dr Ankit Mehta - Renal Disease Research Institute	Dallas	Texas
United States	Dr Suneel Udani - NANI Research	Hinsdale	Illinois
United States	Dr Anjay Rastogi - UCLA Health, David Geffen School of Medicine	Los Angeles	California
United States	Dr Andrew Bomback - Columbia University Medical Center	New York	New York
United States	Dr Tingting Li - Washington University	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Enyo Pharma

Countries where clinical trial is conducted

United States,  France,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in albuminuria	To determine the effect of vonafexor on and off treatment on exploratory renal biomarkers	During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline
Other	Change in proteinuria	To determine the effect of vonafexor on and off treatment on exploratory renal biomarkers	During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline
Other	Change in Neutrophil Gelatinase Associated Lipocalin (NGAL)	To determine the effect of vonafexor on and off treatment on exploratory renal biomarkers	During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline
Primary	Number of Treatment-Emergent Adverse Event (TEAE)	To assess the safety and tolerability of vonafexor	From first dose of treatment until 2 weeks after last dose of treatment, i.e assessed up to 26 weeks
Secondary	Change in eGFR	To determine the on with the off-treatment effect of three dose levels of vonafexor on renal function	During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline
Secondary	Vonafexor plasma concentrations	To determine vonafexor plasma concentrations levels	During on-treatment period, assessed up to 24 weeks