safety, tolerability, pk, and efficacy evaluation of repeat ascending doses of olipudase alfa in pediatric patients <18 years of age with acid sphingomyelinase deficiency

Conditions: Sphingomyelin Lipidosis

Summary: primary objective: to evaluate the safety and tolerability of olipudase alfa administered intravenously in pediatric participants every 2 weeks for 64 weeks. secondary objective: to characterize the pharmacokinetic profile and evaluate the pharmacodynamics and exploratory efficacy of olipudase alfa administered intravenously in pediatric participants every 2 weeks for 64 weeks.

the maximum study duration per participant was approximately 18 months (screening period: up to 60 days; treatment period: 64 weeks; post-treatment period: up to 37 days, not applicable if participants enrolled in a long-term extension treatment trial).

Eligibility criteria:
inclusion criteria : * the participant and/or participant's parent(s)/legal guardian(s) must provide written informed assent/consent prior to any protocol-related procedures being performed. * the participant was \<18 years of age on the date of informed assent/consent. * the participant had documented deficiency of acid sphingomyelinase as measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes. * the participant had a spleen volume greater than or equal to (\>=) 5 multiples of normal (mn) measured by magnetic resonance imaging (mri); participants who had partial splenectomy were allowed if the procedure was performed \>=1 year before screening and the residual spleen volume was \>=5 mn. * the participant's height was -1 z-score or lower. * a negative serum pregnancy test in female participants of childbearing potential. * female participants of childbearing potential and male participants must be willing to practice true abstinence in line with their preferred and usual lifestyle or use 2 acceptable effective methods of contraception. exclusion criteria: * the participant had received an investigational drug within 30 days before study enrollment. * the participant had any of the following medical conditions: * an active, serious, intercurrent illness. * active hepatitis b or hepatitis c infection. * infection with human immunodeficiency virus (hiv). * cirrhosis (determined by clinical evaluation). * significant cardiac disease (eg, clinically significant arrhythmia, moderate or severe pulmonary hypertension or valvular dysfunction, or \<40 percent (%) left ventricular ejection fraction by echocardiogram). * malignancy diagnosed within the previous 5 years (except basal cell carcinoma). * any other extenuating circumstance that can significantly interfere with study compliance, including all prescribed evaluations and follow-up activities. * the participant had acute or rapidly progressive neurological abnormalities. * the participant was homozygous for smpd1 gene mutations r496l, l302p, and fs330 or any combination of these 3 mutations. * the participant had a delay of gross motor skills. * the participant had a major organ transplant (eg, bone marrow, liver). * the participant required use of invasive ventilatory support. * the participant required use of noninvasive ventilatory support while awake and for greater than (\>)12 hours a day. * the participant in the investigator's opinion, was unable to adhere to the requirements of the study. * the participant had a platelet count \<60 × 10\^3/µl (based on the average of 2 screening samples obtained up to 24 hours apart). * the participant had alanine aminotransferase or aspartate aminotransferase \>250 iu/l or total bilirubin \>1.5 mg/dl. * the participant had an international normalized ratio (inr) \>1.5. * the participant was unwilling or unable to abstain from ingesting alcohol the day before through 3 days after each infusion of olipudase alfa during the treatment period. measuring alcohol concentration in blood was not required. * the participant was scheduled during the study for in-patient hospitalization including elective surgery. * the participant required medication(s) that may can decrease olipudase alfa activity (eg, fluoxetine, chlorpromazine; tricyclic antidepressants \[eg, imipramine, or desipramine\]). * the participant was breast-feeding. the above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.