The Efficacy and Safety of Venglustat Compared With Cerezyme in Pediatric Participants 2 to 11 Years of Age With Gaucher Disease Type 3 (GD3) (LEAP2KIDS)

A Phase 3, Multicenter, Multinational, Randomized, Open-label, Active-comparator Study to Evaluate the Efficacy and Safety of Venglustat Compared With Cerezyme in Pediatric Participants 2 to 11 Years of Age With Gaucher Disease Type 3 Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy

This is a Phase 3, multi-center, multi-national, randomized, open-label, active-comparator study to evaluate the efficacy and safety of venglustat in pediatric (age ≥2 years to ≤11 years) participants with GD3 who have been treated with ERT for at least 2 years, and have met therapeutic goals. Study details include: Study duration: a 52-week primary analysis period and a 52-week extended treatment period.

Treatment frequency:

• Daily tablets for venglustat for participants randomized to venglustat arm during primary analysis period and for all patients during extended treatment period.
• Cerezyme infusion every 2 weeks for participants randomized to Cerezyme arm during primary analysis period and, if needed, as rescue medication for participants in venglustat treated arm during primary analysis period or for any participant during extended treatment period.

Visit frequency: every 12 to 14 weeks during primary treatment period and 12-26 weeks during extended treatment period.

Study Overview

• Status: Not yet recruiting
• Conditions: Gaucher's Disease Type III
• Intervention / Treatment: Drug: Venglustat; Drug: Imiglucerase

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pediatric participants who are 2 to 11 years of age inclusive, at the time of signing the informed consent.

• The participant has a clinical diagnosis of GD3 and a documented deficiency of acid β-glucosidase activity confirming the diagnosis of Gaucher disease.

• The participant has received ERT (Cerezyme or other ERT; as deemed appropriate by local regulations) for at least 2 years prior to enrollment, on a stable dose for at least 6 months and is within the therapeutic goals defined in I04 and is deemed clinically stable for at least 1 year by the Investigator.

• The participant has reached Gaucher disease therapeutic goals defined as all of the following: • Hemoglobin level of ≥11.0 g/dL

  • Platelet count ≥100 000/mm3
  • Spleen volume <10 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

• 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.

• The participant has been identified to present with gaze palsy, predominantly horizontal, with slow or absent saccades.

• Participants ≥10 kg of weight.

Exclusion Criteria:

• The participant is blood-transfusion dependent.
• The participant has 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 Gaucher disease, 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 (calculated by bedside Schwartz formula).
• The participant has a history of cancer, except for basal cell carcinoma.
• The participant has progressive myoclonic epilepsy.
• 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).
• The participant has a positive result of any of the following tests: anti-hepatitis C virus (anti- HCV) antibodies, anti-human immunodeficiency virus 1 or 2 antibodies (anti-HIV1 or anti-HIV2 Ab).
• With respect to hepatitis B testing, participants are excluded if they have either of the following:
• Positive hepatitis B surface antigen (HBsAg).
• Positive hepatitis B core antibody (HBcAb) and positive hepatitis B virus deoxyribonucleic acid (HBV DNA) test.
• The participant has had a total splenectomy prior to enrollment, or the participant has had a partial splenectomy within 3 years prior to randomization.
• The participant received chaperone therapy within 6 months, substrate reduction therapy other than venglustat within 6 months or venglustat substrate reduction therapy prior to enrollment. Chaperone therapy and substrate reduction therapy other than venglustat will need be discontinued at least 6 months prior to enrollment.
• The participant receives strong or moderate inducers or inhibitors (including food products eg, grapefruit juice double strength) of CYP3A for long term treatment that cannot be replaced.
• The participant has had exposure to any investigational drug within the last 30 days or 5 half-lives from screening, whichever is longer.
• The participant is currently participating in another investigational interventional study.
• The participant used venglustat within 3 months or 5 half-lives, whichever is longer, before study enrollment.
• The participant, in the opinion of the Investigator, is unable to adhere to the requirements of the study or unable to undergo study assessments (eg, contraindication for MRI).
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venglustat; Oral venglustat QD for 52 weeks in an open-label design for Primary Treatment Period followed by oral venglustat QD for 52 weeks in the Extension Treatment Period	Drug: Venglustat; Pharmaceutical form:Tablet-Route of administration:Oral; Other Names: GZ402671
Active Comparator: Cerezyme; Primary Treatment Period: Cerezyme infusion every 2 weeks for 52 weeks	Drug: Imiglucerase; Pharmaceutical form:Sterile lyophilized product vials administered by IV infusion following reconstitution and dilution-Route of administration:IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in magnetic resonance imaging(MRI) spleen volume (in multiples of normal [MN]) at Week 52	at Week 52

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in MRI liver volume (in MN) at Week 52	at Week 52
Change from baseline in hemoglobin level at Week 52	at Week 52
Percent change from baseline in platelet count at Week 52	at Week 52
Changes from baseline in Vineland Adaptive Behavior Scales III Adaptive Behavior Composite (ABC) score at Week 52	at Week 52
Change from baseline in Vineland Adaptive Behavior Scale (VABS) III motor skill score at Week 52	at Week 52
Percent change from baseline in plasma glucosylceramide (GL-1), glucosylsphingosine (lyso-GL-1), and other potential biomarker levels to Week 52	at Week 52
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)	from baseline to week 104
Plasma venglustat Ctrough at prespecified visits	at Week 12, Week 26, Week 40

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Estimated): December 11, 2026
• Primary Completion (Estimated): January 14, 2030
• Study Completion (Estimated): March 3, 2031

Study Registration Dates

• First Submitted: June 24, 2026
• First Submitted That Met QC Criteria: November 4, 2026
• First Posted (Actual): November 10, 2026

Study Record Updates

• Last Update Posted (Actual): November 10, 2026
• Last Update Submitted That Met QC Criteria: November 4, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Sphingolipidoses; Lipidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Gaucher Disease; venglustat; imiglucerase
• Other Study ID Numbers: EFC18362; 2026-525374-19 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No