Gaucher disease MedDRA version: 24.1 Level: PT Classification code 10075699 Term: Gaucher's disease type III System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 24.1 Level: PT Classification code 10075697 Term: Gaucher's disease type I System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Venglustat
Product Code: GZ402671
Pharmaceutical Form: Capsule
CAS Number: 1401090-53-6
Current Sponsor code: SAR402671A / GZ402671
Other descriptive name: Genz-682452-AU
Concentration u
Sponsors
Genzyme Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -The patient must provide written informed consent prior to any studyrelated procedures being performed. -Has a clinical diagnosis of Gaucher Disease Type 1 (GD1) or Gaucher Disease Type 3 GD3 and documented deficiency of acid beta-glucosidase activity. -The patient has received treatment with enzyme repalcement therapy for at least 3 years. For at least 6 months prior to enrollment, the Patient has received Cerezyme at a stable monthly dose and must continue at the same monthly dose during the study. -The patient has reached Gaucher disease therapeutic goals defined as all of the following to be eligible for this study: -Hemoglobin level of =11.0 g/dL for females and =12.0 g/dL for males. -Platelet count =100 000/mm^3. -Spleen volume 3 years prior to randomization). -Liver volume =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. -The patient has had a partial or total splenectomy within 3 years Prior to randomization. -The patient 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. -Clinically significant congenital cardiac defect, coronary artery disease, valve disease or left sided heart failure; clinically significant arrhythmias or conduction defect. -The patient has any clinically significant disease, other than GD, including cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic (eg, hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses that may preclude participation. -The patient has received an investigational product within 30 days Prior to enrollment. -The patient has a history of cancer, with the exception of basal cell carcinoma. -The patient has myoclonic seizures. -The patient is pregnant or lactating. -The patient has, according to World Health Organization (WHO) Grading, a cortical cataract >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. -The patient requires use of invasive ventilatory support. -The patient requires use of noninvasive ventilator support while awake for longer than 12 hours daily. -The patient is unable to receive treatment with Cerezyme due to a known hypersensitivity or is unwilling to receive Cerezyme Treatment every 2 weeks. -The patient is currently receiving potentially cataractogenic medications as listed in Section 8.8.2. -The patient has received strong or moderate inducers or inhibitors of Cytochrome p450 Isoform 3A within 30 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 GZ/SAR402671 administration in Parts 2 and 3. -The patient is scheduled for in-patient hospitalization including elective surgery, during the study. -Has had a major organ transplant (eg, bone marrow or liver). -The patient, 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: -Evaluate central nervous system (CNS) biomarkers in adult Gaucher disease (GD) type 3 that distinguish GD3 from adult Gaucher disease type 1 (GD1) patients. -Screen adult GD3 patients who qualify for treatment with venglustat in Parts 2,3 and Part 4 Part 2 and 3: Combination treatment phases -Evaluate short-term (Part 2) and long-term (Part 3) safety and tolerability of GZ/SAR402671 in combination with Cerezyme in adult GD3 patients. -Evaluate the change in cerebrospinal fluid (CSF) CNS biomarkers (glucosylceramide [GL-1] and lyso-glucosylceramide [lyso-GL1]) from adult GD3 patients receiving GZ/SAR402671 in combination with Cerezyme (Part 2 only). Part 4: Extended treatment phase with monotherapy - Evaluate safety and tolerability of venglustat monotherapy in adult GD3 patients who have remained systemically stable on venglustat in combination with Cerezyme;Secondary Objective: Parts 2 and 3: Combination treatment phases -Evaluate the pharmacokinetics of GZ/SAR402671 in adult GD3 patients (Part2). -Explore the efficacy of GZ/SAR402671 in combination with Cerezyme in infiltrative lung disease (IDL) in adult GD3 patients (Part 2 and 3). -Explore the efficacy of GZ/SAR402671 in combination with Cerezyme in systemic disease in adult GD3 patients (Part 2 and 3). -Explore the efficacy of GZ/SAR402671 in combination with Cerezyme in neurological function and on exploratory CSF biomarkers in adult GD3 patients (Part 2 and 3). - Explore plasma biomarkers (lyso-GL-1 and GL-1) in adult GD3 patients - Explore CSF biomarkers other than lyso-GL-1 and GL-1 in adult GD3 patients (Part 2 only) Part 4: Extended treatment phase with monotherapy - Explore the efficacy of venglustat in systemic disease in adult GD3 patients - Explore the efficacy of venglustat on neurological function in adult GD3 patients - Explore plasma biomarkers (lyso-GL-1 and GL-1) in adult GD3 patients;Primary end point(s): 1) Number of patients with adverse events 2) Assessment of phar | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - Assessment of pharmacodynamic (PD) parameter: Lysoglucosylceramide (lyso-GL1) and glucosylceramide (GL-1) in plasma ; Change from baseline in plasma lyso-GL1 and GL1 2 - Assessment of plasma pharmacokinetic parameter: Cmax ; Plasma maximum concentration (Cmax) 3 - Assessment of plasma pharmacokinetic parameter: Tmax ; Plasma time at Cmax (Tmax) 4 - Assessment of plasma pharmacokinetic parameter: AUC ;Plasma area under the curve (AUC) 5 - Assessment of plasma pharmacokinetic parameter: Ctrough ; Plasma trough concentration (Ctrough) 6 - Assessment of CSF pharmacokinetic parameter: Cmax ; CSF maximum concentration (Cmax) 7 - Assessment of pharmacokinetic parameter: CSF time at Cmax (Tmax) 8 - Assessment of pharmacokinetic parameter: CSF area under the curve (AUC);Timepoint(s) of evaluation of this end point: 1 - From screening up to end of study, up to approximately 8.7 years 2, 3, 4, 6, 7, 8 - Day 1, Week 4, Week 26, and Week 52 5 - Weeks 12 and 39 (Part 2), and on Weeks 78, 104, and 156 (for Part 3) | — |
Countries
Germany, Japan, United Kingdom, United States
Outcome results
None listed