erfelijke lysosomale stofwisselingsziekte (Gaucher) Gaucher disease
Conditions
Interventions
- Cohort 1: Eliglustat monotherapy: Eliglustat for two years. Cohort 1 patients
that experience significant clinical decline will receive rescue treatment.
Rescue Treatment Step 1: Switch from eligl
Sponsors
Sanofi-aventis
Eligibility
Age
2 Years to 17 Years
Inclusion criteria
Inclusion criteria: -The patient is 6 to <18 years old at the time of informed consent. -Male and female patients with a clinical diagnosis of Gaucher disease (GD) type 1 or type 3 with documented deficiency of acid beta-glucosidase activity by enzyme assay and glucocerebrosidase (GBA) genotype. -Postmenarchal female patients must have a documented negative pregnancy test prior to enrollment and throughout the study. Patients must be willing to practice true abstinence in line with their preferred and usual lifestyle, or use a medically accepted form of contraception throughout the study.;Cohort 1 (Eliglustat monotherapy): -Patients must have been receiving an enzyme replacement therapy (ERT) for a minimum of 24 months at a monthly dose equivalent to 30 U/kg to 130 U/kg of Cerezyme® (imiglucerase) with treatment ongoing at the time of enrollment. Patients must be at pre-specified treatment goals, as defined by: -Hemoglobin level for ages 6 to <12 years: >=11.0 g/dL; for ages 12 to <18 years: >=11.0 g/dL for females and >=12.0 g/dL for males; -Platelet count >=100,000/mm3; -Spleen volume <10.0 multiples of normal (MN); -Liver volume <1.5 MN; -Absence of GD related pulmonary disease, and severe bone disease, as defined below for Cohort 2.;Cohort 2 (Eliglustat plus imiglucerase): -Patients must have been receiving an ERT for a minimum of 36 months at a dose equivalent to at least 60 U/kg of imiglucerase every 2 weeks at the time of enrollment with treatment ongoing at the time of enrollment and the dose stable for at least the 6 months preceding enrollment. Patients must have severe clinical manifestations of GD, as defined by the presence of at least of the following: -GD related pulmonary disease such as interstitial lung disease (ILD). The diagnosis of ILD must be confirmed by the presence of reticulonodular densities on chest X-ray. AND/OR -Symptomatic bone disease characterized by pathological fracture, osteonecrosis, osteopenia/osteoporosis, or bone crisis occurring in the 12 months prior to enrollment. AND/OR -Persistent thrombocytopenia (<80,000/mm3) related to GD.
Exclusion criteria
Exclusion criteria: -Substrate reduction therapy for GD within 6 months prior to enrollment -Partial or total splenectomy if performed within 2 years prior to enrollment -The patient is transfusion dependent, a history of esophageal varices or liver infarction, elevated liver enzymes, significant congenital cardiac defect, coronary artery disease or left sided heart failure; clinically significant arrhythmias or conduction defect such as Type 2 second degree or third degree atrioventricular (AV) block, complete bundle branch block, prolonged QTc interval, or sustained ventricular tachycardia (VT). -The patient has any clinically significant disease other than GD. -The patient has neurological symptoms other than oculomotor apraxia at study entry. -The patient has received an investigational product within 30 days prior to enrollment. -The patient is unable to receive treatment with imiglucerase due to a known hypersensitivity or is unwilling to receive imiglucerase treatment every 2 weeks. -The patient has a known hereditary galactose intolerance, Lapp lactase deficiency or glucose galactose malabsorption, or is a CYP2D6 ultra-rapid metabolizer or indeterminate metabolizer.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluate the safety and pharmacokinetics of eliglustat in pediatric patients (2 to 18 years old). | — |
Secondary
| Measure | Time frame |
|---|---|
| Evaluate the efficacy of eliglustat and quality of life in pediatric patients (2 to 18 years old). | — |
Countries
Netherlands
Outcome results
None listed