Study to Evaluate the Efficacy and Safety of Venglustat in Adult and Pediatric Patients With Gaucher Disease Type 3

NCT05222906 | Active Not Recruiting Phase 3 DMC FDA Drug

• 4 other identifiers: EFC17215U1111-1265-69302024-514381-392021-005402-10
• Study Type: interventional
• Target: 43
• Locations: 11 countries
• Sites: 22

Brief Summary

This is a parallel arm, Phase 3, double-blind, double-dummy, active-comparator, 2 arm study to evaluate the efficacy and safety of daily oral venglustat versus intravenous Cerezyme infusions every two weeks for improvement or stabilization of the neurological manifestations and maintenance of systemic disease stability in participants aged ≥12 and \<18 years and adult patients with Gaucher disease Type 3 (GD3) who have been treated with Enzyme Replacement Therapy (ERT) for at least 3 years.

Conditions

Gaucher's Disease Type III

Outcome Measures

Primary Outcomes (2)

• Change in Scale for Assessment and Rating of Ataxia (SARA) modified total score

  From baseline to Week 52

• Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score

  From baseline to Week 52

Secondary Outcomes (9)

• Percent change in spleen volume

  From baseline to Week 52

• Percent change in liver volume

  From baseline to Week 52

• Change in hemoglobin level

  From baseline to Week 52

• Percent change in platelet count

  From baseline to Week 52

• Percent change in CSF GL-1 and lyso-GL-1 levels

  From baseline to Week 52

Study Arms (2)

Venglustat

EXPERIMENTAL

Venglustat

Drug: Venglustat

Cerezyme

ACTIVE COMPARATOR

Cerezyme

Drug: imiglucerase

Interventions

Venglustat DRUG

tablet; oral

Venglustat

imiglucerase DRUG

sterile lyophilized product; intravenous

Also known as: Cerezyme®

Cerezyme

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant has received ERT (Cerezyme or other ERT; as deemed appropriate by local regulations) for at least 3 years prior to enrollment, on a stable dose for at least 6 months, is deemed clinically stable for at least 1 year by the Investigator and is within the therapeutic goals as all of the following:
• Hemoglobin level of ≥11.0 g/dL for females and ≥12.0 g/dL for males
• Platelet count ≥100 000/mm3
• Spleen volume \<10 multiples of normal (MN)
• Liver volume \<1.5 MN
• No bone crisis and free of symptomatic bone disease such as bone pain attributable to osteonecrosis and/or pathological fractures within 3 months prior to screening
• Adult participant is ≥18 years of age
• Pediatric participant is ≥12 years \<18 years of age
• The participant has a clinical diagnosis of GD3 and a documented deficiency of acid beta-glucosidase activity confirming this diagnosis.
• The participant has a modified SARA score of 1 or above.
• The presence of gaze palsy, predominantly horizontal, with slow or absent saccades.
• If the participant has a history of seizures, they are well controlled under appropriate medication not identified as a strong or moderate inducer or inhibitor of CYP3A.
• Participants ≥ 30 kg of weight
• Contraception for sexually active male or female participants; not pregnant or breastfeeding; no sperm donating for male participant
• Signed written informed assent/consent

You may not qualify if:

• The participant is blood transfusion-dependent.
• Prior esophageal varices or liver infarction or current liver enzymes (alanine aminotransferase \[ALT\]/ aspartate aminotransferase \[AST\]) or total bilirubin \>2 times the upper limit of normal, unless the participant has a diagnosis of Gilbert Syndrome.
• The participant has any clinically significant disease, other than GD, including cardiovascular (congenital cardiac defect, coronary artery disease, valve disease or left sided heart failure; clinically significant arrhythmias or conduction defect), hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic (eg, hypokalemia, hypomagnesemia) or psychiatric disease, other medical conditions, or serious intercurrent illnesses that may preclude participation in the opinion of the Investigator.
• The participant has renal insufficiency, as defined by an estimated glomerular filtration rate \<30 mL/min/1.73m2 at the screening visit.
• The participant has a history of cancer, except for basal cell carcinoma.
• The participant has progressive myoclonic epilepsy.
• The participant is pregnant (has a positive serum beta-human chronic gonadotropin \[β-hCG\]) or lactating.
• The participant requires use of invasive ventilatory support.
• The participant requires use of noninvasive ventilator support while awake for longer than 12 hours daily.
• The participant is scheduled for in-patient hospitalization including elective surgery, during the study.
• The participant has had a major organ transplant (eg, bone marrow or liver).
• A history of drug and/or alcohol abuse within the past year prior to the screening visit.
• Chaperone therapy within 6 months, substrate reduction therapy other than venglustat within 6 months or venglustat substrate reduction therapy prior to enrollment.
• Exposure to any investigational drug within the last 30 days or 5 half-lives from screening, whichever is longer.
• The participant has received strong or moderate inducers or inhibitors of CYP3A within 14 days or 5 half-lives from screening, whichever is longer, prior to screening. This also includes the consumption of grapefruit, grapefruit juice, or grapefruit containing products within 72 hours of starting venglustat. The participant is unwilling to abstain from consumption of grapefruit, grapefruit juice, or grapefruit containing products for the duration of the treatment period.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (22)

Yale University School of Medicine - Investigational Site Number: 8400003

New Haven, Connecticut, 06511, United States

Location

University of Iowa - Investigational Site Number: 8400002

Iowa City, Iowa, 52242, United States

Location

Texas Oncology - Medical City Dallas Site Number : 8400008

Dallas, Texas, 75230, United States

Location

Lysosomal & Rare Disorders Research & Treatment Center, Inc - Investigational Site Number: 8400001

Fairfax, Virginia, 22030, United States

Location

Hospital de Ninos - Investigational Site Number: 320001

Buenos Aires, 1426, Argentina

Location

Children's Hospital Research Institute of Manitoba - Investigational Site Number: 1240001

Winnipeg, Manitoba, R3E 3P4, Canada

Location

National Taiwan University Hospital-Investigational Site Number: 1580001

Taipei, Taiwan, 10041, China

Location

Peking Union Medical College Hospital - Investigational Site Number: 1560001

Beijing, 100005, China

Location

The First Affiliated Hospital - Investigational Site Number: 1560002

Guangzhou, 510080, China

Location

Xinhua Hospital - Investigational Site Number: 1560004

Shanghai, 200092, China

Location

47-87, boulevard de l'hôpital - Investigational Site Number: 2500003

Paris, 75013, France

Location

Hopital Necker - Investigational Site Number: 2500001

Paris, 75015, France

Location

SphinCS GmbH - Investigational Site Number: 2760001

Hochheim am Main, 65239, Germany

Location

Debreceni Egyetem, Klinikai Központ, Reumatológiai Klinika - Investigational Site Number: 3480001

Debrecen, H-4032, Hungary

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Investigational Site Number : 3800003

Milan, Lombardy, 20122, Italy

Location

Azienda Ospedaliera Universitaria (AOU) "Federico II" - Investigational Site Number: 3800002

Napoli, 80131, Italy

Location

Odawara Municipal Hospital-Investigational Site Number : 3920002

Odawara, Kanagawa, 250-8558, Japan

Location

Tohoku University School of Medicine - Investigational Site Number: 3920001

Sendai, 980-8574, Japan

Location

Cukurova University Medical School Hospital-Investigational Site Number : 7920001

Adana, 01790, Turkey (Türkiye)

Location

Gazi University Medical Hospital-Investigational Site Number : 7920002

Ankara, 06500, Turkey (Türkiye)

Location

Istanbul University Medical Faculty Hospital-Investigational Site Number : 7920004

Istanbul, 34093, Turkey (Türkiye)

Location

Investigational Site Number : 8260001

London, NW3-2PF, United Kingdom

Location

Related Links

• EFC17215 Plain Language Results Summary

MeSH Terms

Conditions

Gaucher Disease

Interventions

venglustat; imiglucerase

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; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; 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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: During the open-label extended treatment period all participants will receive open label venglustat.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double Dummy

Study Record Dates

• First Submitted: January 20, 2022
• First Posted: February 3, 2022
• Study Start: April 18, 2022
• Primary Completion: October 2, 2025
• Study Completion (Estimated): October 30, 2026
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

TU (3); GB (1); CN (4); DE (1); US (4); JP (2); CA (1); AR (1); FR (2); HU (1); IT (2)