A Study to Evaluate the Effect of Venglustat Tablets on Neuropathic and Abdominal Pain in Male and Female Participants ≥16 Years of Age With Fabry Disease

NCT05206773 | Active Not Recruiting Phase 3 DMC FDA Drug

• 4 other identifiers: EFC17045U1111-1256-93102024-511990-312021-002350-90
• Study Type: interventional
• Target: 122
• Locations: 20 countries
• Sites: 57

Brief Summary

This is a 12-month, parallel treatment, Phase 3, double-blind, randomized, placebo-controlled study to evaluate the effect of venglustat on neuropathic and abdominal pain symptoms of Fabry disease in participants ≥16 years of age with Fabry disease who are treatment-naïve or untreated for at least 6 months.

• Study visits will take place approximately every 3 months.
• The double-blind period will be followed by an open-label extension (OLE) during which participants who have completed the double-blind period will be treated with venglustat for an additional 12 months or until the Common Study End of Treatment Day (CSEOTD).

Conditions

Fabry Disease

Outcome Measures

Primary Outcomes (2)

• Percent change from baseline at 6 months in the most bothersome symptom of 3 Fabry Disease Patient-Reported Outcome (FD-PRO) items (neuropathic pain in upper extremities, neuropathic pain in lower extremities, or abdominal pain)

  From baseline to 6 months

• Percent change from baseline at 12 months in the most bothersome symptom of 3 Fabry Disease Patient-Reported Outcome (FD-PRO) items (neuropathic pain in upper extremities, neuropathic pain in lower extremities, or abdominal pain)

  From baseline to 12 months

Secondary Outcomes (12)

• Percent change in plasma globotriaosylsphingosine (lyso-GL-3)

  From baseline to 6 month and 12 months

• Frequency of rescue pain medication use

  From baseline to 6 months and 12 months

• Change in the percentage of days with at least 1 stool reflecting diarrhea (Bristol Stool Form Scale [BSFS] Type 6 or 7)

  From baseline to 6 month and 12 months

• Change in tiredness component of FD-PRO

  From baseline to 6 month and 12 months

• Proportion of responders in neuropathic or abdominal pain, as assessed by FD-PRO

  At 6 months and 12 months

Study Arms (2)

Venglustat

EXPERIMENTAL

Participant will receive venglustat dose once daily for 12 months

Drug: Venglustat (GZ402671)

Placebo

PLACEBO COMPARATOR

Participants will receive placebo once daily for 12 months

Drug: Placebo

Interventions

Venglustat (GZ402671) DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Venglustat

Placebo DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female adult patients 16 year of age or older, who have had a previously confirmed diagnosis of Fabry disease and a history of clinical symptoms of Fabry disease
• Patients who are treatment-naïve or without prior treatment with an approved or experimental therapy for Fabry disease within at least 6 months prior to screening.
• Average score of ≥3 (0=no symptom, 10=symptom as bad as you can imagine) on the participant-defined most-bothersome symptom (among neuropathic pain in upper extremities, neuropathic pain in lower extremities, or abdominal pain), as measured by the Fabry Disease Patient-Reported Outcome (FD-PRO) at screening.
• Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants; no sperm donation for male participants.
• Weight ≥30 Kg
• A signed informed consent must be provided prior to any study-related procedures.

You may not qualify if:

• Any manifestations of Fabry disease that preclude placebo administration.
• History of transient ischemic attack, stroke, myocardial infarction, heart failure, evidence of left ventricular hypertrophy and/or cardiac fibrosis, major cardiovascular surgery, or kidney transplantation.
• Patients with hepatitis C, HIV, or hepatitis B infection.
• Neuropathic pain in upper or lower extremities, or abdominal pain not related to Fabry disease.
• History of seizures currently requiring treatment.
• Uncontrolled hypertension over the past 12 months prior to screening, or systolic BP \>=150 or diastolic BP \>=100 at screening.
• Estimated glomerular filtration rate \<60 mL/min/1.73m².
• Urine protein to creatinine ratio \>= 1 g/g at screening.
• 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.
• Positive SARS-CoV-2 virus test within 2 weeks of enrollment, or COVID 19 requiring hospitalization within 6 months of enrollment.
• Moderate to severe hepatic impairment.
• History of drug and/or alcohol abuse.
• History of or active hepatobiliary disease.
• Liver enzymes (alanine aminotransferase (ALT)/aspartate aminotransferase (AST)) or total bilirubin \>2 times the upper limit of normal (ULN).
• Initiation of chronic treatment for pain, or change in pain medication regimen, within 3 months prior to randomization.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (58)

Nephrology Clinic at Kirklin Clinic of UAB Hospital_Investigational Site Number: 8400011

Birmingham, Alabama, 35233, United States

Location

UCLA Medical Center_Investigational Site Number: 8400006

Los Angeles, California, 90095, United States

Location

University of California Irvine Medical Center- Site Number : 8400019

Orange, California, 92868, United States

Location

Advent Health Orlando_Investigational Site Number: 8400008

Orlando, Florida, 32804, United States

Location

Emory Genetics- Site Number : 8400010

Atlanta, Georgia, 30322, United States

Location

Westchester Medical Center Healthcare Corporation- Site Number : 8400001

Hawthorne, New York, 10532, United States

Location

Cincinnati Children's Hospital Medical Center - PIN- Site Number : 8400013

Cincinnati, Ohio, 45229-3026, United States

Location

Cleveland Clinic Site Number : 8400016

Cleveland, Ohio, 44195, United States

Location

Children's Hospital Of Pittsburgh- Site Number : 8400009

Pittsburgh, Pennsylvania, 15213, United States

Location

Renal Disease Research Institute, An affiliate of: Dallas Nephrology Associates_Investigational Site Number: 8400012

Dallas, Texas, 75235, United States

Location

University Of Utah Health Sciences Center- Site Number : 8400005

Salt Lake City, Utah, 84132, United States

Location

Lysosomal and Rare Disorders Research and Treatment Center_Investigational Site Number: 8400004

Fairfax, Virginia, 22030, United States

Location

Fundacion Cori para la Investigación y Prevención del Cancer_Investigational Site Number: 0320002

La Rioja, F5300, Argentina

Location

Instituto de Investigaciones Clínicas Quilmes (IICQ) SRL_Investigational Site Number: 0320003

Quilmes, B1878GEG, Argentina

Location

Investigational Site Number : 0360001

Parkville, Victoria, 3050, Australia

Location

Investigational Site Number: 0400001

Vienna, 1090, Austria

Location

Hospital de Clínicas de Porto Alegre_Investigational Site Number: 0760001

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Instituto de Genética e Erros Inatos do Metabolismo - IGEIM- Site Number : 0760002

São Paulo, 04020-041, Brazil

Location

M.A.G.I.C Calgary LTD_Investigational Site Number: 1240003

Calgary, Alberta, T2E7Z4, Canada

Location

Medicine Dalhousie University_Investigational Site Number : 1240001

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

University Health Network_Investigational Site Number : 1240005

Toronto, Ontario, M5T 3L9, Canada

Location

No.8, Xishiku Street, Xicheng District_Site Number: 1560001

Beijing, 100034, China

Location

No.197,2nd Ruijin road, Huangpu district_Site Number: 1560003

Shanghai, 200010, China

Location

No.85 South Jiefang road, Yingze District_Site Number: 1560004

Taiyuan, 030001, China

Location

Investigational Site Number : 1560006

Zhengzhou, 450052, China

Location

Investigational Site Number: 2080001

Copenhagen, 2100, Denmark

Location

Investigational Site Number: 2460001

Turku, FI-20520, Finland

Location

Investigational Site Number : 2500001

Garches, 92380, France

Location

ISphinCS GmbH_Investigational Site Number: 2760004

Hochheim am Main, 65239, Germany

Location

Investigational Site Number : 2760005

Mainz, 55131, Germany

Location

Investigational Site Number: 2760003

München, 80336, Germany

Location

Investigational Site Number: 2760001

Würzburg, 97080, Germany

Location

Investigational Site Number : 3000003

Athens, 115 28, Greece

Location

University Hospital of Heraklion_Investigational Site Number: 3000001

Heraklion, 711 10, Greece

Location

University Hospital of Ioannina_Investigational Site Number: 3000002

Ioannina, 455 00, Greece

Location

IRCCS Policlinico di Sant'Orsola_Investigational Site Number : 3800005

Bologna, 40138, Italy

Location

Fondazione IRCCS San Gerardo dei Tintori, S.C. Nefrologia - Clinica Nefrologica_Investigational Site Number: 3800002

Monza, 20052, Italy

Location

Azienda Ospedaliera Universitaria "Federico II", U.O. di Nefrologia- Diparimento di Sanità Pubblica_Investigational Site Number: 3800001

Naples, 80138, Italy

Location

Azienda Ospedaliera Universitaria_Investigational Site Number: 3800003

Palermo, 90127, Italy

Location

Fondazione Policlinico Universitario_Investigational Site Number: 3800004

Roma, 00168, Italy

Location

Investigational Site Number : 3920005

Kawasaki, Kanagawa, 215-0026, Japan

Location

Fukuoka University Hospital_Investigational Site Number: 3920004

Fukuoka-shi, Fukuoka, 814-0180, Japan

Location

The Jikei University Hospital_Investigational Site Number: 3920003

Minato-ku, Tokyo, 105-8471, Japan

Location

Tohoku University Hospital_Investigational Site Number: 3920001

Sendai-shi, Miyagi, 980-8574, Japan

Location

Hospital Universitario "Dr. José Eleuterio González" Departamento de Genética Centro Universitario contra el cáncer_Investigational Site Number: 4840001

Monterrey, Nuevo León, 64460, Mexico

Location

Odette del Carmen DIAZ-AVENDAÑO Clinstile, S.A. de C.V. Durango_Investigational Site Number: 4840002

Mexico City, 06700, Mexico

Location

Investigational Site Number: 5780001

Bergen, 5021, Norway

Location

Investigational Site Number : 6160002

Poznan, Greater Poland Voivodeship, 60-780, Poland

Location

Investigational Site Number : 6160004

Rzeszów, 35-301, Poland

Location

Investigational Site Number: 6160003

Wroclaw, 50-556, Poland

Location

Institutul Clinic Fundeni_Investigational Site Number: 6420001

Bucharest, 22328, Romania

Location

Investigational Site Number : 7560001

Zurich, 8091, Switzerland

Location

Investigational Site Number : 7920001

Ankara, 06560, Turkey (Türkiye)

Location

Investigational Site Number : 7920002

İzmit, 41000, Turkey (Türkiye)

Location

Investigational Site Number : 7920004

Malatya, 44280, Turkey (Türkiye)

Location

Investigational Site Number: 8260001

Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom

Location

Investigational Site Number: 8260002

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

Location

Investigational Site Number : 8260003

Salford, Manchester, M6 8HD, United Kingdom

Location

Related Links

• EFC17045 Plain Language Results Summary

MeSH Terms

Conditions

Fabry Disease

Interventions

venglustat

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

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants enrolled in the open-label extension will be treated with venglustat only.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2021
• First Posted: January 25, 2022
• Study Start: March 11, 2022
• Primary Completion: December 17, 2025
• Study Completion (Estimated): January 4, 2027
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (12); BR (2); GB (3); CH (1); RO (1); AU (1); FI (1); NO (1); PL (3); CA (3); AR (2); DE (4); DK (1); ME (2); JP (4); FR (1); GR (3); IT (5); CN (4); TU (3)