A Phase 3, Multicenter, Multinational, Randomized, Double-blind, Double-dummy, Active-comparator Study to Evaluate the Efficacy and Safety of Venglustat in Adult and Pediatric Patients With Gaucher Disease Type 3 (GD3) Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ERT)

Sanofi22 sites in 11 countries43 target enrollmentApril 18, 2022

ConditionsGaucher's Disease Type III

InterventionsVenglustat imiglucerase

DrugsVenglustat imiglucerase

Overview

Phase: Phase 3
Intervention: Venglustat
Conditions: Gaucher's Disease Type III
Sponsor: Sanofi
Enrollment: 43
Locations: 22
Primary Endpoint: Change in Scale for Assessment and Rating of Ataxia (SARA) modified total score
Status: Active, not recruiting
Last Updated: 6 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Detailed Description

Screening period: 45 days Double blind, double-dummy, primary analysis treatment period: 52 weeks Open label extended treatment period: minimum of 52 weeks due to a common study end of treatment date Follow up phone call: 30-37 days after end of treatment

Registry

clinicaltrials.gov

Start Date

April 18, 2022

End Date

October 30, 2026

Last Updated

6 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Sanofi

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.

Exclusion Criteria

•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.

Arms & Interventions

Venglustat

Intervention: Venglustat

Cerezyme

Intervention: imiglucerase

Outcomes

Primary Outcomes

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

Time Frame: From baseline to Week 52

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

Time Frame: From baseline to Week 52

Secondary Outcomes

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)
Percent change in plasma GL-1 and lyso-GL-1 levels(From baseline to Week 52)
Number of patients with treatment emergent adverse events (TEAEs)/ serious adverse events (SAEs)/ adverse events of special interest (AESIs)(From baseline to max of 4.5 years)
Change in score of Beck Depression Inventory II (BDI-II) during the treatment-emergent period (for participants 13 years of age and above at baseline)(From baseline to Week 52)
Change in Patient Health Questionnaire 9 (PHQ-9) during the treatment-emergent period (for participants 12 years of age at baseline)(From baseline to Week 52)