Safety, Tolerability, PK, and Efficacy Evaluation of Repeat Ascending Doses of Olipudase Alfa in Pediatric Patients <18 Years of Age With Acid Sphingomyelinase Deficiency

A Phase 1/2, Multi-Center, Open-Label, Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Exploratory Efficacy of Olipudase Alfa in Pediatric Patients Aged <18 Years With Acid Sphingomyelinase Deficiency

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).

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.