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
Conditions
Sponsors
sanofi-aventis recherche et développement
Eligibility
Sex/Gender
All
Inclusion 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
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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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;Primary end point(s): Slope of left ventricular mass index as measured by cardiac magnetic resonance imaging (MRI) (central reading) ;Timepoint(s) of evaluation of this end point: from baseline to 18 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Austria, Canada, China, Czechia, Czech Republic, Denmark, France, Germany, Greece, Italy, Japan, Korea, Republic of, Netherlands, Norway, Poland, Spain, Taiwan, Türkiye, United Kingdom, United States
Contacts
Public ContactClinical Study Unit
Sanofi AB
Outcome results
None listed