A study to evaluate the effect of venglustat tablets on left ventricular mass index in male and female adult participants with Fabry disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

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

6 May 2022 → ongoing

Decision date (initial)

2024-06-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-509715-91-00

EudraCT number

2021-002320-20

WHO UTN

U1111-1266-5068

ClinicalTrials.gov

NCT05280548

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

To compare the effect of venglustat with standard of care Fabry therapies on left ventricular mass
index over 18 months in participants with Fabry disease and left ventricular hypertrophy

Secondary objectives 5

1. To evaluate the effect of venglustat on renal function
2. To evaluate the effect of venglustat versus standard therapy on measures of cardiac function and cardiac lipid storage
3. To evaluate the effect of venglustat on lower extremities swelling and tiredness
4. To assess the safety and tolerability of venglustat in participants with Fabry disease
5. To evaluate the PK of venglustat in participants with Fabry disease

Conditions and MedDRA coding

Fabry’s disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male and female participants aged 18 to 65 with previously confirmed diagnosis of Fabry disease and a history of clinical symptoms of Fabry disease.
2. Participants may be receiving treatment with agalsidase alfa, agalsidase beta, or migalastat, or may be untreated.
3. Left ventricular hypertrophy.
4. Contraception for male or female participants: not pregnant or breastfeeding; no sperm donating for male participant.
5. A signed informed consent must be provided prior to any study-related procedures.

Exclusion criteria 16

1. History of transient ischemic attack, stroke, myocardial infarction, heart failure, major cardiovascular surgery or kidney transplantation.
2. History of seizures currently requiring treatment.
3. Underlying medical condition that may cause or contribute to left ventricular hypertrophy.
4. Asymmetric hypertrophy by cardiac MRI at screening if considered by central reader to be not related to Fabry disease.
5. Advanced cardiac fibrosis, defined as significant late gadolinium enhancement affecting 3 or more segments involving >50% of myocardial thickness on screening cardiac MRI.
6. History of clinically significant cardiac arrhythmia. Atrial fibrillation that is well controlled on a stable medical regimen for at least 12 months is not an exclusion if the CHA2DS2-VASc score is 0 for males or 1 for females.
7. Estimated glomerular filtration rate <45 mL/min/1.73m2.
8. Presence of severe depression as measured by Beck’s Depression Inventory (BDI)- II >28 and/or a history of an untreated, unstable major affective disorder within 1 year of the screening visit.
9. Patients with hepatitis C, HIV, or hepatitis B infection.
10. Positive SARS-CoV-2 virus test within 2 weeks of enrollment, or COVID-19 requiring hospitalization within 6 months of enrollment.
11. History of drug and/or alcohol abuse.
12. Moderate to severe hepatic impairment.
13. History of or active hepatobiliary disease.
14. Liver enzymes (alanine aminotransferase/aspartate aminotransferase) or total bilirubin >2 times the upper limit of normal.
15. Strong or moderate inducers or inhibitors of cytochrome P450 CYP3A4 within 14 days or 5 half-lives, whichever is longer, prior to randomization.
16. Known contraindication to undergoing MRI or known hypersensitivity to gadoliniumbased contrast agents.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Slope of left ventricular mass index as measured by cardiac magnetic resonance imaging (MRI) (central reading)

Secondary endpoints 9

1. Slope of estimated glomerular filtration rate (eGFR) as assessed by the chronic kidney disease epidemiology collaboration (CKD-EPI) creatinine equation
2. Change in T1 relaxation time, measured by cardiac MRI (central reading)
3. Change in global longitudinal strain, measured by echocardiography (central reading)
4. Percent Change in tiredness component of FDPRO
5. Percent Change in swelling in lower extremities component of FD-PRO
6. Number of participants with adverse event (AE) and serious adverse event (SAE)
7. Change in Beck Depression Inventory-II (BDI-II) score
8. Change in the lens clarity by ophthalmological examination
9. Plasma venglustat concentrations at prespecified visits over the study duration

Investigational products

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

Test 1

Comparator 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

13 Quai Jules Guesde

City

Vitry Sur Seine

Postcode

94400

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 12

Locations

11 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 75 files

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

Application history

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