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

NCT ID: NCT05280548

Last Updated: 2025-01-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-03
• Study Completion Date: 2027-12-06

Brief 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 45 months with the total study duration up to 5.3 years maximum.

Detailed 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 46 months (45 months of treatment and 1 month of follow-up period). The maximum total study duration is approximately 5.3 years

Conditions

Fabry Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Venglustat

Participants will receive venglustat once daily, orally

Group Type: EXPERIMENTAL

Venglustat (GZ402671)

Intervention Type: DRUG

Tablet; Oral

Standard of Care Therapy

Participants will receive a locally approved Fabry therapy at the standard dose and schedule (in accordance with the locally approved prescribing information)

Group Type: ACTIVE_COMPARATOR

Agalsidase alfa

Intervention Type: DRUG

Concentrate for solution for infusion; IV infusion

Agalsidase beta (GZ419828)

Intervention Type: DRUG

Powder for concentrate for solution for infusion; IV infusion

Migalastat

Intervention Type: DRUG

Hard capsules; Oral

Interventions

Venglustat (GZ402671)

Tablet; Oral

Intervention Type: DRUG

Agalsidase alfa

Concentrate for solution for infusion; IV infusion

Intervention Type: DRUG

Agalsidase beta (GZ419828)

Powder for concentrate for solution for infusion; IV infusion

Intervention Type: DRUG

Migalastat

Hard capsules; Oral

Intervention Type: DRUG

Other Intervention Names

Replagal®; Fabrazyme®; Galafold®

Eligibility 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 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations Clinical Sciences and Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

University of Alabama -The Kirklin Clinic- Site Number : 8400010

Birmingham, Alabama, United States

University of California Los Angeles Medical Center- Site Number : 8400008

Los Angeles, California, United States

Emory University School of Medicine - Atlanta- Site Number : 8400009

Atlanta, Georgia, United States

Ann & Robert H. Lurie Children's Hospital of Chicago- Site Number : 8400005

Chicago, Illinois, United States

Maryam Banikazemi, MD- Site Number : 8400001

Hawthorne, New York, United States

Renal Disease Research Institute- Site Number : 8400012

Dallas, Texas, United States

University of Utah Health Hospital- Site Number : 8400006

Salt Lake City, Utah, United States

Lysosomal and Rare Disorders Research and Treatment Center (LDRTC)- Site Number : 8400004

Fairfax, Virginia, United States

Investigational Site Number : 0400001

Graz, , Austria

Investigational Site Number : 1240003

Calgary, Alberta, Canada

Investigational Site Number : 1240006

Edmonton, Alberta, Canada

Investigational Site Number : 1240002

Vancouver, British Columbia, Canada

Investigational Site Number : 1240005

Toronto, Ontario, Canada

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, , China

Investigational Site Number : 2030001

Prague, , Czechia

Investigational Site Number : 2080001

Copenhagen, , Denmark

Investigational Site Number : 2500001

Garches, , France

Investigational Site Number : 2760003

Berlin, , Germany

Investigational Site Number : 2760004

Hochheim am Main, , Germany

Investigational Site Number : 2760005

Mainz, , Germany

Investigational Site Number : 2760001

Würzburg, , Germany

Investigational Site Number : 3000002

Athens, , Greece

Investigational Site Number : 3000003

Athens, , Greece

Investigational Site Number : 3000001

Heraklion, , Greece

Investigational Site Number : 3800001

Milan, Lombardy, Italy

Investigational Site Number : 3800002

Naples, Napoli, Italy

Investigational Site Number : 3800003

Naples, Napoli, Italy

Investigational Site Number : 3800004

Bologna, , Italy

Investigational Site Number : 3920006

Sapporo, Hokkaido, Japan

Investigational Site Number : 3920007

Kagoshima, Kagoshima-ken, Japan

Investigational Site Number : 3920003

Kagoshima, Kagoshima-ken, Japan

Investigational Site Number : 3920005

Kawasaki, Kanagawa, Japan

Investigational Site Number : 3920002

Sendai, Miyagi, Japan

Investigational Site Number : 3920004

Fukuoka, , Japan

Investigational Site Number : 3920001

Tokyo, , Japan

Investigational Site Number : 5280001

Amsterdam, , Netherlands

Investigational Site Number : 5780001

Bergen, , Norway

Investigational Site Number : 6160003

Lodz, Lódzkie, Poland

Investigational Site Number : 6160001

Krakow, , Poland

Investigational Site Number : 4100002

Yangsan, Gyeongsangnam-do, South Korea

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number : 7240002

Madrid, Madrid, Comunidad de, Spain

Investigational Site Number : 7240003

Alicante, , Spain

Investigational Site Number : 7240001

Pontevedra, , Spain

Investigational Site Number : 1580003

Taichung, , Taiwan

Investigational Site Number : 1580001

Taipei, , Taiwan

Investigational Site Number : 7920001

Ankara, , Turkey (Türkiye)

Investigational Site Number : 7920002

Istanbul, , Turkey (Türkiye)

Investigational Site Number : 7920003

İzmit, , Turkey (Türkiye)

Investigational Site Number : 8260001

London, London, City of, United Kingdom

Countries

United States; Austria; Canada; China; Czechia; Denmark; France; Germany; Greece; Italy; Japan; Netherlands; Norway; Poland; South Korea; Spain; Taiwan; Turkey (Türkiye); United Kingdom

Other Identifiers

U1111-1266-5068

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-509715-91

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-002320-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC16158

Identifier Type: -

Identifier Source: org_study_id