Gaucher disease type 3 MedDRA version: 20.0 Level: PT Classification code 10075699 Term: Gaucher's disease type III System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Venglustat
Product Code: GZ402671
Pharmaceutical Form: Tablet
INN or Proposed INN: Venglustat malate
CAS Number: 1629063-78-0
Current Sponsor code: GZ402671
Concentration unit: mg millig
Sponsors
Genzyme Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - GD3 adult participant =18 years of age. - GD3 pediatric participant is =12 years of age =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Substrate reduction therapy or chaperone therapy for GD within 6 months prior to enrollment. - Participant has had a partial or total splenectomy within 3 years prior to randomization. - 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 patient has a diagnosis of Gilbert Syndrome. - 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. - Participant has renal insufficiency, as defined by an estimated glomerular filtration rate onequarter of the lens circumference (Grade cortical cataract-2) or a posterior subcapsular cataract >2 mm (Grade posterior subcapsular cataract-2). Patients with nuclear cataracts will not be excluded. - Participant requires use of invasive ventilatory support. - Participant requires use of noninvasive ventilator support while awake for longer than 12 hours daily. - Participant is unable to receive treatment with Cerezyme due to a known hypersensitivity or is unwilling to receive Cerezyme treatment to ensure maintenance of Gaucher treatment goals. - Participant is currently receiving potentially cataractogenic medications (corticosteroids, psoralens used in dermatology with ultraviolet light therapy [PUVA], typical antipsychotics, and glaucoma medications) or any medication that may worsen the vision of a patient with cataract (eg, alphaadrenergic glaucoma medications). - Participant has received strong or moderate inducers or inhibitors of CYP3A within 15 days or 5 half-lives from screening, whichever is longer, prior to enrolment in Part 2. This also includes the consumption of grapefruit, grapefruit juice, or grapefruit containing products within 72 hours of starting venglustat administration in Parts 2 and 3. - Participant is scheduled for in-patient hospitalization including elective surgery, during the study. - Participant has had a major organ transplant (e.g., bone marrow or liver). - Participant, in the opinion of the investigator, is unable to adhere to the requirements of the study or unable to undergo study assessments (e.g., contraindications for magnetic resonance imaging).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1, cohort 3: - Evaluate cerebrospinal fluid (CSF) biomarkers in adult Gaucher disease (GD) Type 3 patients that distinguish GD3 from adult Gaucher disease Type 1 (GD1) patients. - Screen adult and pediatric GD3 patients who qualify for treatment with venglustat in Parts 2 and 3. Part 2 and 3, cohort 3: - Evaluate the efficacy of venglustat in combination with Cerezyme in adult and pediatric GD3 patients by assessing: -Ataxia using the Scale for the Assessment and Rating of Ataxia (SARA) -Cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS);Secondary Objective: Parts 2 and 3, cohort 3: -Evaluate the efficacy of venglustat in combination with Cerezyme in adult and pediatric GD3 patients by assessing: -CSF Lyso-GL1 levels -Modified Friedreich´s Ataxia Rating Scale - Activities of Daily Living (FARS-ADL) -Brain resting-state functional Magnetic Resonance Imaging (rs-fMRI) reflecting connectivity between parieto-occipital areas -Bone disease manifestations -Evaluate safety and tolerability of venglustat in combination with Cerezyme in adult and pediatric GD3 patients -Evaluate PK of venglustat in adult and pediatric GD3 patients.;Primary end point(s): - Change in Scale for Assessment and Rating of Ataxia (SARA) modified total score from baseline to Week 52 (Cohort 3 Part 2) - Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score from baseline to Week 52 (Cohort 3 Part 2);Timepoint(s) of evaluation of this end point: Baseline and Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1/ Percent Change in CSF Lyso-GL1 levels from baseline to Baseline and Week 52 Week 52 (Cohort 3 Part 2) 2/ Change in Modified Friedreich´s Ataxia Rating Scale - Activities of Daily Living (FARS-ADL) score from baseline to Week 52 (Cohort 3 Part 2) 3/ Change in connectivity between vision perception (resting state networks 3) and action execution (resting state network 6) areas by task-free blood oxygenation level-dependent (BOLD) fMRI from baseline to Week 52 (Cohort 3 Part 2) 4/ Change in dual-energy X-ray absorptiometry (DXA) lumbar spine bone mineral density (BMD) T-score from baseline to Week 52 (Cohort 3 Part 2) 5/ Change in bone MRI bone marrow burden (BMB) total score from baseline to Week 52 (Cohort 3 Part 2) 6/ Number of participants with TEAEs (Cohort 3 Part 2 and 3) 7/ Growth rate (Cohort 3 Part 2 and 3) 8/ Bone age by hand X-ray (Cohort 3 Part 2 and 3) 9/ Sexual maturation (Tanner stage) (Cohort 3 Part 2 and 3) 10/ Immunogenicity testing to assess possible IAR to Cerezyme (Cohort 3 Part 1) 11/ Beck Depression Inventory-II (BDI-II) (Cohort 3 Part 2 and 3) 12/ Maximum venglustat plasma concentration (Cmax) (Cohort 3 Part 2) 13/ Time to maximum venglustat plasma concentration (tmax) (Cohort 3 Part 2) 14/ Area under the venglustat plasma concentration versus time curve from time 0 to 24 hours (AUC0-24) (Cohort 3 Part 2) 15/ Trough venglustat plasma concentration (Ctrough) (Cohort 3 Part 2 and 3) 16/ Venglustat CSF concentration (Cohort 3 Part 2) (only participants =18 years of age);Timepoint(s) of evaluation of this end point: 1/ to 5/ : Baseline and Week 52 6/ to 9/ ; 11/ : Up to Week 182 10/ : 60 days (Part 1 - screening phase) 12/ to 14/ : Day 1 pre-dose and 1, 2, 4, 8 and 24 hours post-dose 15/ : Pre-dose at Day 2 and Week 4, 52, 78, 104, 156 16/ : Week 52 | — |
Countries
Argentina, Brazil, Canada, China, Egypt, France, Germany, Hungary, Japan, Sweden, Taiwan, Turkey, United States
Outcome results
None listed