Safety and Efficacy of Eliglustat With or Without Imiglucerase in Pediatric Patients With Gaucher Disease (GD) Type 1 and Type 3 (ELIKIDS)
Gaucher's Disease Type I, Gaucher's Disease Type III
About this trial
This is an interventional treatment trial for Gaucher's Disease Type I
Eligibility Criteria
Inclusion criteria :
- The patient is 2 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 2 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, or at the maximum dose locally approved, 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 one 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:
- 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.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Sites / Locations
- Investigational Site Number :0320001
- Investigational Site Number :1240002
- Investigational Site Number :1240003
- Investigational Site Number :1240001
- Investigational Site Number :2500002
- Investigational Site Number :3800002
- Investigational Site Number :3920002
- Investigational Site Number :3920001
- Investigational Site Number :6430001
- Investigational Site Number :6430004
- Investigational Site Number :6430005
- Investigational Site Number :6430002
- Investigational Site Number :7240002
- Investigational Site Number :7240001
- Investigational Site Number :7240003
- Investigational Site Number :7520002
- Investigational Site Number :7520001
- Investigational Site Number :8260002
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Cohort 1: Eliglustat monotherapy
Cohort 2: Eliglustat plus imiglucerase
Eliglustat for at least two years. Cohort 1 patients that experience significant clinical decline will receive rescue treatment. Rescue Treatment Step 1: Switch from eliglustat to imiglucerase monotherapy. Rescue Treatment Step 2: Patients who after 6 months of rescue therapy with imiglucerase monotherapy do not show improvement in the parameter(s) that led to the switch from eliglustat to imiglucerase, will then receive combination therapy with eliglustat + imiglucerase.
Eliglustat plus imiglucerase for two years, at the dose of enzyme replacement therapy received before enrollment. After Week 52, Cohort 2 patients will switch to eliglustat monotherapy for the remainder of the study if the desired clinical response has been achieved.