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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

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

Tanaka Tomoyuki

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

clinical-trials-jp@sanofi.com

Clinical Study Unit

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

+81-3-6301-3670

clinical-trials-jp@sanofi.com

Not Recruiting

July. 14, 2022

Interventional

randomized controlled trial

open(masking not used)

placebo control

parallel assignment

treatment purpose

- 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 <45 mL/min/1.73m^2.
- 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.

Both

Fabry disease

Drug: Venglustat (GZ402671)
Pharmaceutical form: Tablet, Route of administration: Oral
Drug: Agalsidase alfa
Pharmaceutical form: Concentrate for solution for infusion, Route of administration: IV infusion
Drug: Agalsidase beta (GZ419828)
Pharmaceutical form: Powder for concentrate for solution for infusion, Route of administration: IV infusion
Drug: Migalastat
Pharmaceutical form: Hard capsules, Route of administration: Oral

1. Slope of left ventricular mass index as measured by cardiac magnetic resonance imaging (MRI) (central reading)
[ Time Frame: from baseline to 18 months ]

1. Slope of estimated glomerular filtration rate (eGFR) as assessed by the chronic kidney disease epidemiology collaboration (CKD-EPI) creatinine equation
[ Time Frame: from baseline to 18 months ]
2. Change in T1 relaxation time, measured by cardiac MRI (central reading)
[ Time Frame: from baseline to 18 months ]
3. Change in global longitudinal strain, measured by echocardiography (central reading)
[ Time Frame: from baseline to 18 months ]
4. Percent Change in tiredness component of Fabry disease patient-reported outcome (FD-PRO)
[ Time Frame: from baseline to 18 months ]
5. Percent Change in swelling in lower extremities component of FD-PRO
[ Time Frame: from baseline to 18 months ]
6. Number of participants with adverse event (AE) and serious adverse event (SAE)
[ Time Frame: from baseline to 18 months ]
7. Change in Beck Depression Inventory-II (BDI-II) score
[ Time Frame: from baseline to 18 months ]
8. Change in the lens clarity by ophthalmological examination
[ Time Frame: from baseline to 18 months ]
9. Plasma venglustat concentrations at prespecified visits over the study duration
[ Time Frame: from baseline to 18 months ]

+81-99-275-5553

May. 31, 2022

Yes

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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