Clinical trial NCT06425055: Vonafexor ALPort Syndrome Efficacy & Safety TRIAl-1 (ALPESTRIA-1)
Official title: Vonafexor Fixed Dose-escalation Safety and Proof-of-concept Study in Patients With at Risk of Progression Alport Syndrome
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Alport Syndrome
Lead sponsor: Enyo Pharma
Sponsor class: INDUSTRY
First posted: 2024-05-22
Enrollment: 20
Sex: ALL
Minimum age (years): 16
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm fixed dose escalation
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Treatment-Emergent Adverse Event (TEAE)
timeFrame: From first dose of treatment until 2 weeks after last dose of treatment, i.e assessed up to 26 weeks
Secondary outcomes:
measure: Change in eGFR
timeFrame: During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline
measure: Vonafexor plasma concentrations
timeFrame: During on-treatment period, assessed up to 24 weeks
Other outcomes:
measure: Change in albuminuria
timeFrame: During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline
measure: Change in proteinuria
timeFrame: During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline
measure: Change in Neutrophil Gelatinase Associated Lipocalin (NGAL)
timeFrame: During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline
Locations:
city: Birmingham
country: United States
facility: Dr Eric Wallace - University of Alabama
state: Alabama
city: Los Angeles
country: United States
facility: Dr Anjay Rastogi - UCLA Health, David Geffen School of Medicine
state: California
city: Boise
country: United States
facility: Dr Arnold Silva - Boise Kidney & Hypertension
state: Idaho
city: Hinsdale
country: United States
facility: Dr Suneel Udani - NANI Research
state: Illinois
city: Saint Louis
country: United States
facility: Dr Tingting Li - Washington University
state: Missouri
city: Cleveland
country: United States
facility: Dr James Simon - Cleveland Clinic Foundation
state: Ohio
city: Dallas
country: United States
facility: Dr Ankit Mehta - Renal Disease Research Institute
state: Texas
city: Bordeaux
country: France
facility: Pr Claire Rigothier - CHU De Bordeaux
city: Montpellier
country: France
facility: Dr Moglie Le Quintrec - Hopital Lapeyronie
city: Paris
country: France
facility: Pr. Bertrand Knebelmann - Necker Enfants Malades
city: Barcelona
country: Spain
facility: Fundacio Puigvert
city: El Palmar
country: Spain
facility: Hospital Virgen de la Arrixaca
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
Study officials:
References: