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

Investigating the Effect of an Investigational Medication on Heart Health in Adults with Fabry Disease, a Genetic Disorder Affecting the Heart and Kidneys

Not Recruiting
18 years - 65 years
All
Phase 3
104 participants needed

Study Overview

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.

Study Details

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

Eligibility Criteria

You may be eligible for this study if you meet the following criteria:

  • Conditions: Fabry Disease
  • Age: 18 years - 65 years
  • Gender: All

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.

This study investigates the effect of an investigational medication on the left ventricular mass index (LVMI) in adult participants with Fabry disease, a genetic disorder that affects the heart and kidneys. The purpose of this study is to compare the investigational medication with standard treatments such as agalsidase alfa, agalsidase beta, or migalastat in participants who have left ventricular hypertrophy, a condition where the heart muscle is thickened.

Participants in the study will be randomly assigned to receive either the investigational medication or standard care. During the study, participants will undergo regular heart assessments to measure changes in LVMI. The study includes a long-term extension where participants may continue to receive the investigational medication for additional months. A placebo is not used in this study.

  • Who can participate: Adults aged 18 to 65 with confirmed Fabry disease and left ventricular hypertrophy can participate. Key exclusions include major heart issues, severe depression, and certain infections.
  • Study details: Participants will be randomly assigned to receive the investigational medication or continue with standard care. Regular heart assessments will evaluate the effect on left ventricular mass index.
Updated on 04 Apr 2025. Study ID: NCT05280548