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

NCT05280548 | Active Not Recruiting Phase 3 DMC FDA Drug

• 4 other identifiers: EFC16158U1111-1266-50682023-509715-912021-002320-20
• Study Type: interventional
• Target: 104
• Locations: 19 countries
• Sites: 54

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.

Conditions

Fabry Disease

Outcome Measures

Primary Outcomes (1)

• Slope of left ventricular mass index as measured by cardiac magnetic resonance imaging (MRI) (central reading)

  from baseline to 18 months

Secondary Outcomes (9)

• 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

• Change in T1 relaxation time, measured by cardiac MRI (central reading)

  from baseline to 18 months

• Change in global longitudinal strain, measured by echocardiography (central reading)

  from baseline to 18 months

• Percent Change in tiredness component of FD-PRO

  from baseline to 18 months

• Percent Change in swelling in lower extremities component of FD-PRO

  from baseline to 18 months

Study Arms (2)

Venglustat

EXPERIMENTAL

Participants will receive venglustat once daily, orally

Drug: Venglustat (GZ402671)

Standard of Care Therapy

ACTIVE COMPARATOR

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

Drug: Agalsidase alfa; Drug: Agalsidase beta (GZ419828); Drug: Migalastat

Interventions

Venglustat (GZ402671) DRUG

Tablet; Oral

Venglustat

Agalsidase alfa DRUG

Concentrate for solution for infusion; IV infusion

Also known as: Replagal®

Standard of Care Therapy

Agalsidase beta (GZ419828) DRUG

Powder for concentrate for solution for infusion; IV infusion

Also known as: Fabrazyme®

Standard of Care Therapy

Migalastat DRUG

Hard capsules; Oral

Also known as: Galafold®

Standard of Care Therapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (54)

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

Birmingham, Alabama, 35233, United States

Location

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

Los Angeles, California, 90095, United States

Location

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

Atlanta, Georgia, 30322, United States

Location

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

Chicago, Illinois, 60611, United States

Location

Maryam Banikazemi, MD- Site Number : 8400001

Hawthorne, New York, 10532, United States

Location

Renal Disease Research Institute- Site Number : 8400012

Dallas, Texas, 75204, United States

Location

University of Utah Health Hospital- Site Number : 8400006

Salt Lake City, Utah, 84132, United States

Location

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

Fairfax, Virginia, 22030, United States

Location

Investigational Site Number : 0400001

Graz, 8036, Austria

Location

Investigational Site Number : 1240003

Calgary, Alberta, T2M 0L6, Canada

Location

Investigational Site Number : 1240006

Edmonton, Alberta, T6G 2B7, Canada

Location

Investigational Site Number : 1240002

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Investigational Site Number : 1240005

Toronto, Ontario, M5T 3H7, Canada

Location

Investigational Site Number : 1560002

Beijing, 100034, China

Location

Investigational Site Number : 1560005

Beijing, 100034, China

Location

Investigational Site Number : 1560001

Chengdu, 610041, China

Location

Investigational Site Number : 1560007

Guangzhou, 510080, China

Location

Investigational Site Number : 1560003

Shanghai, 200025, China

Location

Investigational Site Number : 2030001

Prague, 128 08, Czechia

Location

Investigational Site Number : 2080001

Copenhagen, 2100, Denmark

Location

Investigational Site Number : 2500001

Garches, 92380, France

Location

Investigational Site Number : 2760003

Berlin, 10117, Germany

Location

Investigational Site Number : 2760004

Hochheim am Main, 65239, Germany

Location

Investigational Site Number : 2760005

Mainz, 55131, Germany

Location

Investigational Site Number : 2760001

Würzburg, 97080, Germany

Location

Investigational Site Number : 3000002

Athens, 115 27, Greece

Location

Investigational Site Number : 3000003

Athens, 124 62, Greece

Location

Investigational Site Number : 3000001

Heraklion, 711 10, Greece

Location

Investigational Site Number : 3800001

Milan, Lombardy, 20122, Italy

Location

Investigational Site Number : 3800002

Naples, Napoli, 80131, Italy

Location

Investigational Site Number : 3800003

Naples, Napoli, 80131, Italy

Location

Investigational Site Number : 3800004

Bologna, 40138, Italy

Location

Investigational Site Number : 3920004

Fukuoka, Fukuoka, 814-0180, Japan

Location

Investigational Site Number : 3920006

Sapporo, Hokkaido, 060-8648, Japan

Location

Investigational Site Number : 3920007

Kagoshima, Kagoshima-ken, 890-0064, Japan

Location

Investigational Site Number : 3920003

Kagoshima, Kagoshima-ken, 890-8520, Japan

Location

Investigational Site Number : 3920005

Kawasaki, Kanagawa, 215-0026, Japan

Location

Investigational Site Number : 3920002

Sendai, Miyagi, 980-8574, Japan

Location

Investigational Site Number : 3920001

Tokyo, Tokyo, 105-8461, Japan

Location

Investigational Site Number : 5280001

Amsterdam, 1105 AZ, Netherlands

Location

Investigational Site Number : 5780001

Bergen, 5021, Norway

Location

Investigational Site Number : 6160003

Lodz, Lódzkie, 02-213, Poland

Location

Investigational Site Number : 6160001

Krakow, 31-202, Poland

Location

Investigational Site Number : 4100002

Yangsan, Gyeongsangnam-do, 50612, South Korea

Location

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, 03722, South Korea

Location

Investigational Site Number : 7240003

Alicante, Alicante, 03010, Spain

Location

Investigational Site Number : 7240002

Madrid, Madrid, Comunidad de, 28007, Spain

Location

Investigational Site Number : 7240001

Pontevedra, 36312, Spain

Location

Investigational Site Number : 1580003

Taichung, 407, Taiwan

Location

Investigational Site Number : 1580001

Taipei, 104, Taiwan

Location

Investigational Site Number : 7920001

Ankara, 06560, Turkey (Türkiye)

Location

Investigational Site Number : 7920002

Istanbul, 34098, Turkey (Türkiye)

Location

Investigational Site Number : 7920003

İzmit, 41000, Turkey (Türkiye)

Location

Investigational Site Number : 8260001

London, London, City of, NW3 2QG, United Kingdom

Location

MeSH Terms

Conditions

Fabry Disease

Interventions

venglustat; agalsidase alfa; agalsidase beta; migalastat

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Clinical Sciences & Operations Clinical Sciences and Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2022
• First Posted: March 15, 2022
• Study Start: May 3, 2022
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): December 6, 2027
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

GR (3); NL (1); ES (3); GB (1); CN (5); AU (1); KR (2); JP (7); US (8); TW (2); IT (4); DK (1); CZ (1); TU (3); CA (4); FR (1); PL (2); DE (4); NO (1)