Vonafexor ALPort Syndrome Efficacy & Safety TRIAl-1 (ALPESTRIA-1)
ALPESTRIA-1
Vonafexor Fixed Dose-escalation Safety and Proof-of-concept Study in Patients With at Risk of Progression Alport Syndrome
1 other identifier
interventional
26
3 countries
13
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Aug 2024
Shorter than P25 for phase_2
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 14, 2024
CompletedFirst Posted
Study publicly available on registry
May 22, 2024
CompletedStudy Start
First participant enrolled
August 1, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 4, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
November 20, 2025
CompletedFebruary 9, 2026
February 1, 2026
1.1 years
May 14, 2024
February 6, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (2)
Change in eGFR
During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline
Vonafexor plasma concentrations
During on-treatment period, assessed up to 24 weeks
Other Outcomes (3)
Change in albuminuria
During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline
Change in proteinuria
During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline
Change in Neutrophil Gelatinase Associated Lipocalin (NGAL)
During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline
Study Arms (1)
Single arm fixed dose escalation
EXPERIMENTALThis is a single arm fixed dose escalation with three dose levels of vonafexor, all QD.
Interventions
* 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
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Enyo Pharmalead
Study Sites (13)
Dr Eric Wallace - University of Alabama
Birmingham, Alabama, 35294, United States
Dr Anjay Rastogi - UCLA Health, David Geffen School of Medicine
Los Angeles, California, 90095, United States
Dr Arnold Silva - Boise Kidney & Hypertension
Boise, Idaho, 83703, United States
Dr Suneel Udani - NANI Research
Hinsdale, Illinois, 60521, United States
Dr Tingting Li - Washington University
St Louis, Missouri, 63110, United States
Dr James Simon - Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Dr Ankit Mehta - Renal Disease Research Institute
Dallas, Texas, 75126, United States
Pr Claire Rigothier - CHU De Bordeaux
Bordeaux, 33076, France
Dr Moglie Le Quintrec - Hopital Lapeyronie
Montpellier, 34090, France
Pr. Bertrand Knebelmann - Necker Enfants Malades
Paris, 75015, France
Fundacio Puigvert
Barcelona, 08025, Spain
Hospital Virgen de la Arrixaca
El Palmar, 30120, Spain
Fundacion Jimenez Diaz
Madrid, 28040, Spain
Related Publications (1)
Rheault MN. Treatment Approaches for Alport Syndrome. J Am Soc Nephrol. 2026 Jan 1;37(1):172-179. doi: 10.1681/ASN.0000000897. Epub 2025 Sep 12.
PMID: 40938675DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 14, 2024
First Posted
May 22, 2024
Study Start
August 1, 2024
Primary Completion
September 4, 2025
Study Completion
November 20, 2025
Last Updated
February 9, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- From 3 months and ending 5 years following article publication.
Individual participant data that underline published results might be shared upon request with researchers who provide a methodologically sound proposal and to achieve objectives as set in the approved proposal. IPD will be shared deidentified and from 3 months and ending 5 years following article publication.