Safety and Efficacy of Eliglustat With or Without Imiglucerase in Pediatric Patients With Gaucher Disease (GD) Type 1 and Type 3

Prior treatment

• Substrate reduction therapy for GD within 6 months prior to enrollment.
• Partial or total splenectomy if performed within 2 years prior to enrollment
• The participant had received an investigational product within 30 days prior to enrollment.
• The participant was unable to receive treatment with imiglucerase due to a known hypersensitivity or was unwilling to receive imiglucerase treatment every 2 weeks.

Other illness

• The participant had any clinically significant disease other than GD.

Lab values

• The participant was 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 participant had 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.

Other

• The participant had neurological symptoms other than oculomotor apraxia at study entry.

• The participant were 2 to \<18 years old at the time of informed consent.
• Male and female participants 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 participants had a documented negative pregnancy test prior to enrollment and throughout the study. Participants had to be willing to practice true abstinence in line with their preferred and usual lifestyle, or used a medically accepted form of contraception throughout the study.
  • Cohort 1 (Eliglustat monotherapy):
• Participants must had 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. Participants had to 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):
• Participants must had 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. Participants must had 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 had to 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.