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

-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.

-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 <60 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.