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

Fabry Disease Clinical Trial

— CARAT  

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05280548
• Other study ID #: EFC16158
• Secondary ID: U1111-1266-50682
• Status: Recruiting
• Phase: Phase 3
• Start date: May 3, 2022
• Est. completion date: July 15, 2027

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free for US & Canada)
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 34 months with the total study duration up to 4.4 years maximum.

Description:

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 35 months (34 months of treatment and 1 month of follow-up period). The maximum total study duration is approximately 4.4 years

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: July 15, 2027
• Est. primary completion date: December 29, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fabry Disease

Intervention

Drug:
• Venglustat (GZ402671)
Tablet; Oral
• Agalsidase alfa
Concentrate for solution for infusion; IV infusion
• Agalsidase beta (GZ419828)
Powder for concentrate for solution for infusion; IV infusion
• Migalastat
Hard capsules; Oral

Locations

Country	Name	City	State
Austria	Investigational Site Number : 0400001	Graz
Canada	Investigational Site Number : 1240006	Edmonton	Alberta
Canada	Investigational Site Number : 1240005	Toronto	Ontario
Canada	Investigational Site Number : 1240002	Vancouver	British Columbia
China	Investigational Site Number : 1560002	Beijing
China	Investigational Site Number : 1560005	Beijing
China	Investigational Site Number : 1560001	Chengdu
China	Investigational Site Number : 1560007	Guangzhou
China	Investigational Site Number : 1560003	Shanghai
Czechia	Investigational Site Number : 2030001	Praha 2
Denmark	Investigational Site Number : 2080001	Copenhagen
France	Investigational Site Number : 2500001	Garches
Germany	Investigational Site Number : 2760003	Berlin
Germany	Investigational Site Number : 2760004	Hochheim am Main
Germany	Investigational Site Number : 2760001	Würzburg
Greece	Investigational Site Number : 3000002	Athens
Greece	Investigational Site Number : 3000003	Athens
Greece	Investigational Site Number : 3000001	Heraklion
Italy	Investigational Site Number : 3800001	Milano	Lombardia
Italy	Investigational Site Number : 3800002	Napoli
Italy	Investigational Site Number : 3800003	Napoli
Japan	Investigational Site Number : 3920004	Fukuoka-shi	Fukuoka
Japan	Investigational Site Number : 3920003	Kagoshima-shi	Kagoshima
Japan	Investigational Site Number : 3920005	Kawasaki-shi	Kanagawa
Japan	Investigational Site Number : 3920001	Minato-ku	Tokyo
Japan	Investigational Site Number : 3920002	Sendai-shi	Miyagi
Korea, Republic of	Investigational Site Number : 4100001	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100002	Yangsan-si	Gyeongsangnam-do
Netherlands	Investigational Site Number : 5280001	Amsterdam
Norway	Investigational Site Number : 5780001	Bergen
Poland	Investigational Site Number : 6160001	Krakow
Spain	Investigational Site Number : 7240003	Alicante
Spain	Investigational Site Number : 7240002	Madrid / Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240001	Vigo
Taiwan	Investigational Site Number : 1580003	Taichung
Taiwan	Investigational Site Number : 1580001	Taipei 104
Turkey	Investigational Site Number : 7920001	Ankara
Turkey	Investigational Site Number : 7920002	Istanbul
Turkey	Investigational Site Number : 7920003	Kocaeli
United Kingdom	Investigational Site Number : 8260001	London	London, City Of
United States	Emory Clinic Site Number : 8400009	Atlanta	Georgia
United States	University of Alabama at Birmingham (UAB) - The Kirklin Clin Site Number : 8400010	Birmingham	Alabama
United States	Lurie Childrens Hospital Site Number : 8400005	Chicago	Illinois
United States	Renal Disease Research Institute Site Number : 8400012	Dallas	Texas
United States	Lysosomal and Rare Disorders Research and Treatment Center, Inc Site Number : 8400004	Fairfax	Virginia
United States	Maryam Banikazemi, MD Site Number : 8400001	Hawthorne	New York
United States	UCLA Medical Center Site Number : 8400008	Los Angeles	California
United States	University of Utah Medical Center Site Number : 8400006	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Austria,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Greece,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Norway,  Poland,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Slope of left ventricular mass index as measured by cardiac magnetic resonance imaging (MRI) (central reading)		from baseline to 18 months
Secondary	Slope of estimated glomerular filtration rate (eGFR) as assessed by the chronic kidney disease epidemiology collaboration (CKD-EPI) creatinine equation		from baseline to 18 months
Secondary	Change in T1 relaxation time, measured by cardiac MRI (central reading)		from baseline to 18 months
Secondary	Change in global longitudinal strain, measured by echocardiography (central reading)		from baseline to 18 months
Secondary	Percent Change in tiredness component of FD-PRO		from baseline to 18 months
Secondary	Percent Change in swelling in lower extremities component of FD-PRO		from baseline to 18 months
Secondary	Number of participants with adverse event (AE) and serious adverse event (SAE)		from baseline to 18 months
Secondary	Change in Beck Depression Inventory-II (BDI-II) score		from baseline to 18 months
Secondary	Change in the lens clarity by ophthalmological examination		from baseline to 18 months
Secondary	Plasma venglustat concentrations at prespecified visits over the study duration		from baseline to 18 months