To evaluate the safety and tolerability of olipudase alfa administered intravenously in
pediatric patients every 2 weeks for 52 weeks.
To characterize the pharmacokinetic profile and evaluate the pharmacodynamics and exploratory
efficacy of olipudase alfa administered intravenously in pediatric patients every 2 weeks for
The maximum study duration per patient is approximately 18 months (screening period: up to 60
days; treatment period: 64 weeks; post-treatment period: up to 37 days, not applicable if
patient enrolls in a long term extension treatment trial).
Inclusion criteria :
- The patient and/or patient's parent(s)/legal guardian(s) must provide written informed
assent/consent prior to any protocol-related procedures being performed.
- The patient is aged 0 to <18 years of age on the date of informed assent/consent.
- The patient has documented deficiency of acid sphingomyelinase as measured in
peripheral leukocytes, cultured fibroblasts, or lymphocytes.
- The patient has a spleen volume ≥5 multiples of normal (MN) measured by magnetic
resonance imaging (MRI); patients who have had partial splenectomy will be allowed if
the procedure was performed ≥1 year before screening and the residual spleen volume is
- The patient's height is -1 Z-score or lower.
- A negative serum pregnancy test in female patients of childbearing potential.
- Female patients of childbearing potential and male patients must be willing to
practice true abstinence in line with their preferred and usual lifestyle, or use 2
acceptable effective methods of contraception.
- The patient has received an investigational drug within 30 days before study
- The patient has 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% 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 patient has acute or rapidly progressive neurological abnormalities.
- The patients is homozygous for SMPD1 gene mutations R496L, L302P, and fs330 or any
combination of these 3 mutations.
- The patient has a delay of gross motor skills.
- The patient has had a major organ transplant (eg, bone marrow, liver).
- The patient requires use of invasive ventilatory support.
- The patient requires use of noninvasive ventilatory support while awake and for >12
hours a day.
- The patient, in the investigator's opinion, is unable to adhere to the requirements of
- The patient has a platelet count <60 × 10^3/µL (based on the average of 2 screening
samples obtained up to 24 hours apart).
- The patient has alanine aminotransferase or aspartate aminotransferase >250 IU/L or
total bilirubin >1.5 mg/dL.
- The patient has an international normalized ratio (INR) >1.5
- The patient is 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 is not required.
- The patient is scheduled during the study for in-patient hospitalization including
- The patient requires medication(s) that may can decrease olipudase alfa activity (eg,
fluoxetine, chlorpromazine; tricyclic antidepressants [eg, imipramine, or
- The patient is breast-feeding.
The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.