Vonafexor fixed dose-escalation safety and proof-of-concept study in patients with at risk of progression Alport syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ENYO Pharma

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

30 Sep 2024 → 5 Mar 2026

Decision date (initial)

2024-08-26

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the safety and tolerability of vonafexor (on and off treatment) in at risk of progression Alport syndrome patients.

Secondary objectives 2

1. To determine the on with the off-treatment effect of three dose levels of vonafexor on renal function.
2. To determine vonafexor plasma concentrations levels.

Conditions and MedDRA coding

Alport Syndrome

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

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. Study Protocol and Statistical Analysis Plan might be shared as supporting documentation.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Subject signed informed consent and legal representatives signed informed consent as applicable for United States (US) under eighteen patients.
2. Has negative results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, and human immunodeficiency virus (HIV)
3. Male and female patients ≥ 18 years (in US accepted lower limit age is ≥ 16 years) and ≤ 55 years.
4. Has confirmed diagnosis of Alport syndrome: A. Clinical diagnosis (haematuria, family history, hearing loss, ocular change), OR a kidney biopsy showing glomerular basement membrane abnormalities (e.g., significant thinning, thickening, irregularity or lucencies) consistent with AS, AND B. Genetic confirmation of AS (medical history or genotyped during screening)
5. Has eGFR between ≥ 30 and < 90 ml/min/1.73m2.
6. Has increased albuminuria criteria i.e. UACR ≥ 300 mg/g
7. 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.
8. If on Sodium-Glucose Transport Protein 2 (SGLT2), should be on stable well tolerated treatment with SGLT2 during at least 60 days prior D1.
9. 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
10. Sexually active female subjects of childbearing potential and sexually mature male subjects must agree to use two acceptable effective methods of contraception for the entire duration of the study and for at least 6 weeks after last dose.

Exclusion criteria 11

1. Is pregnant or breastfeeding.
2. Has participated in any investigational drug study within 60 days prior to D1.
3. 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.
4. Any history of active malignancy within the last 1 year before D1 (history of localized basal cell or squamous cell carcinoma and cervical carcinoma in situ that has been excised/appropriately treated or a fully excised malignant lesion with a low probability of recurrence will not be considered exclusionary).
5. 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.
6. Has a history of an allergic condition that required the prescription of an emergency epinephrine injection (such as the EpiPen® Auto-Injector).
7. Any prohibited co-medications as per section 5.2.3 within 30 days prior D1.
8. Has ALT or AST above near normal (>1.5×ULN) at baseline.
9. 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) (Lloyd-Jones DM et al., 2019)23.
10. Has moderate or severe hepatic impairment (Child-Pugh score B or C).
11. Is taking CYP3A4/5 inhibitors or inducers.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Number of Treatment-Emergent Adverse Event (TEAE) from first dose of treatment until 2 weeks after last dose of treatment
2. Change in physical examinations, vital signs, laboratory variables and lipid profile at on-treatment and off-treatment periods compared to baseline.

Secondary endpoints 2

1. Change in eGFR response at applicable visits during on-treatment and off-treatment periods compared to baseline
2. Vonafexor plasma concentrations levels at on-treatment applicable visits compared to expected concentrations based on a vonafexor Population Pharmacokinetic (PK) model.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ENYO Pharma

Sponsor organisation

ENYO Pharma

Address

60 Avenue Rockefeller

City

Lyon

Postcode

69008

Country

France

Scientific contact point

Organisation

ENYO Pharma

Contact name

Clinical Operation Department

Public contact point

Organisation

ENYO Pharma

Contact name

Clinical Operation Department

Third parties 6

Locations

3 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 42 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications