A Study to Evaluate the Effect of Venglustat Tablets on Left Ventricular Mass Index in Male and Female Adult Participants With Fabry Disease (CARAT)

Sanofi

Status and phase: Active, not recruiting; Phase 3

Conditions: Fabry Disease

Treatments: Drug: Venglustat (GZ402671); Drug: Agalsidase alfa; Drug: Agalsidase beta (GZ419828); Drug: Migalastat

Study type: Interventional

Funder types: Industry

Identifiers

NCT05280548

EFC16158

2021-002320-20 (EudraCT Number)

U1111-1266-5068 (Registry Identifier)

2023-509715-91 (Registry Identifier)

Details and patient eligibility

About

This is an 18-month, multicenter, randomized, active-control, parallel-group Phase 3 study, in which participants will be randomized to venglustat versus standard of care therapy (agalsidase alfa, agalsidase beta, or migalastat) to evaluate the effect of venglustat on left ventricular mass index (LVMI) in adult participants with Fabry disease and left ventricular hypertrophy.

• Study visits will take place approximately every 3 to 6 months
• Participants who complete the randomized period may continue to the long-term extension (LTE) to receive venglustat for up to additional 45 months with the total study duration up to 5.3 years maximum.

Full description

Randomized period: the total duration will be up to approximately of 20 months (1 month screening 18 months of treatment and a possible follow-up period of 1 month if no participation in the long-term extension period)

Long-term extension period: the total duration will be from minimum 19 months (18 months of treatment and 1 month of follow-up period) to maximum 46 months (45 months of treatment and 1 month of follow-up period). The maximum total study duration is approximately 5.3 years

Enrollment: 104 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

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.

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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104 participants in 2 patient groups

Venglustat

Experimental group

Description:

Participants will receive venglustat once daily, orally

Treatment:

Drug: Venglustat (GZ402671)

Standard of Care Therapy

Active Comparator group

Description:

Participants will receive a locally approved Fabry therapy at the standard dose and schedule (in accordance with the locally approved prescribing information)

Treatment:

Drug: Migalastat

Drug: Agalsidase beta (GZ419828)

Drug: Agalsidase alfa