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

The study included a screening period of up to 60 days (Day -60 to -1), a primary analysis treatment period (Day 1 to Week 52), a long-term treatment period (Week 53 to Week 104), and an extension period continuing up to Week 364 (for patients who continue to demonstrate the clinical benefit from eliglustat monotherapy at Week 104). After study completion, participants were encouraged to enroll in the International Collaborative Gaucher Group (ICGG) Gaucher Registry.

Inclusion criteria

• 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.

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 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 any clinically significant disease other than GD.
• The participant had neurological symptoms other than oculomotor apraxia at study entry.
• 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.
• 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.