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

JRCT ID: jRCT2071220022

Registered date:25/06/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Fabry's disease
• Date of first enrollment: 14/07/2022
• Target sample size: 90
• Countries of recruitment: China,Japan,Italy,Japan,Republic of Korea,Japan
• Study type: Interventional

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

Outcome(s)

Primary Outcome

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

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 ]

Key inclusion & exclusion criteria

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

Include 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.

Exclude 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.

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT05280548,2021-002320-20