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

• Register: JPRN
• Last refreshed on: 17 October 2023
• Main ID: JPRN-jRCT2071220022
• Date of registration: 25/06/2022
• Prospective Registration: Yes
• Primary sponsor: Tanaka Tomoyuki
• Public title: A study to evaluate the effect of venglustat tablets on left ventricular mass index in male and female adult participants with Fabry disease
• Scientific title: 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
• Date of first enrolment: 14/07/2022
• Target sample size: 90
• Recruitment status: Recruiting
• URL: https://jrct.niph.go.jp/latest-detail/jRCT2071220022
• Study type: Interventional
• Study design: randomized controlled trial, open(masking not used), placebo control, parallel assignment, treatment purpose
• Phase: 3

Countries of recruitment

China, Italy, Japan, Republic of Korea

Contacts

• Name: Tomoyuki Tanaka
• Affiliation: Sanofi K.K.

• Name: Unit Study Clinical
• Affiliation: Sanofi K.K.

Key inclusion & exclusion 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.
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.
- Advanced cardiac fibrosis, defined as significant late gadolinium enhancement beyond the basal inferolateral left ventricular wall on cardiac MRI.
- History of ongoing clinically significant cardiac arrythmia, prior or ongoing treatment.
- Estimated glomerular filtration rate <60 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 per Food and
- Drug Administration (FDA) classification 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.

Age minimum: >= 18age old
Age maximum: <= 65age old
Gender: Both

Health Condition(s) or Problem(s) studied

Fabry's disease

Intervention(s)

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

Primary Outcome(s)

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

Secondary Outcome(s)

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. Number of participants with adverse event (AE) and serious adverse event (SAE)
[ Time Frame: from baseline to 18 months ]

5. Change in Beck Depression Inventory-II (BDI-II) score
[ Time Frame: from baseline to 18 months ]

6. Plasma venglustat concentrations at prespecified visits over the study duration
[ Time Frame: from baseline to 18 months ]

Secondary ID(s)

2021-002320-20

NCT05280548