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

• Register: EUCTR
• Last refreshed on: 10 February 2025
• Main ID: EUCTR2021-002320-20-PL
• Date of registration: 11/01/2022
• Prospective Registration: Yes
• Primary sponsor: sanofi-aventis recherche et développement
• Public title: A study to evaluate the effect of venglustat tablets on left ventricular mass index in male and female adult participants with Fabry disease
• Scientific title: A randomized, open-label, parallel-group, 18-month Phase 3 study to evaluate the effect of venglustat compared with usual standard of care on left ventricular mass index in participants with Fabry disease and left ventricular hypertrophy - CARAT
• Date of first enrolment: 12/04/2022
• Target sample size: 110
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-002320-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Canada, China, Czech Republic, Czechia, Denmark, France, Germany, Greece, Italy, Japan, Korea, Republic of, Netherlands, Norway, Poland, Spain, Taiwan, Türkiye, United Kingdom, United States

Contacts

• Affiliation: Sanofi-Aventis Sp. z o.o.

• Affiliation: Sanofi-Aventis Sp. z o.o.

Key inclusion & exclusion criteria

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


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- History of transient ischemic attack, stroke, myocardial infarction, heart failure, major cardiovascular surgery or kidney transplantation.

- History of seizures currently requiring treatment.

- Underlying medical condition that may cause or contribute to left ventricular hypertrophy.

- Asymmetric hypertrophy by cardiac MRI at screening if considered by central reader to be not related to Fabry disease.

- Advanced cardiac fibrosis, defined as significant late gadolinium enhancement affecting 3 or more segments involving >50% of myocardial thickness on screening cardiac MRI.

- 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.

- Estimated glomerular filtration rate <45 mL/min/1.73m2.

- 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.

- Patients with hepatitis C, HIV, or hepatitis B infection.

- Positive SARS-CoV-2 virus test within 2 weeks of enrollment, or COVID-19 requiring hospitalization within 6 months of enrollment.

- History of drug and/or alcohol abuse.

- Moderate to severe hepatic impairment.

- History of or active hepatobiliary disease.

- Liver enzymes (alanine aminotransferase/aspartate aminotransferase) or total bilirubin >2 times the upper limit of normal.

- Strong or moderate inducers or inhibitors of cytochrome P450 CYP3A4 within 14 days or 5 half lives, whichever is longer, prior to randomization.

-Known contraindication to undergoing MRI or known hypersensitivity
to gadolinium-based contrast agents.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Fabry’s disease
MedDRA version: 24.1 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Venglustat
Product Code: SAR402671, GZ402671 or GZ/SAR402671
Pharmaceutical Form: Tablet
INN or Proposed INN: Venglustat malate
CAS Number: 1629063-78-0
Current Sponsor code: GZ402671
Other descriptive name: GZ/SAR402671
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Trade Name: Replagal
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Agalsidase alfa
CAS Number: 104138-64-9
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Trade Name: Fabrazyme
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Agalsidase beta
CAS Number: 104138-64-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 35-

Trade Name: Galafold
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Migalastat
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 123-

Primary Outcome(s)

Primary end point(s): Slope of left ventricular mass index as measured by cardiac magnetic resonance imaging (MRI) (central reading)

Main Objective: - 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 Objective: - To evaluate the effect of venglustat on renal function
- To evaluate the effect of venglustat versus standard therapy on measures of cardiac function and cardiac lipid storage
- To evaluate the effect of venglustat on lower extremities swelling and tiredness
- To assess the safety and tolerability of venglustat in participants with Fabry disease
- To evaluate the PK of venglustat in participants with Fabry disease

Timepoint(s) of evaluation of this end point: from baseline to 18 months

Secondary Outcome(s)

Secondary end point(s): 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 FD-PRO

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

Timepoint(s) of evaluation of this end point: From 1/ to 9/: from baseline to 18 months

Secondary ID(s)

EFC16158

2021-002320-20-NO

Source(s) of Monetary Support

sanofi-aventis recherche et développement

Ethics review

Status: Approved
Approval date: 12/04/2022
Contact: