Acid sphingomyelinase deficiency / Niemann Pick B Disease

Full Study Name

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 sphingomyelinas deficiency.

Study ID



Sanofi – Genzyme

Local Principal Investigator

Simon Jones

Study Status


Main Aims

To evaluate the safety and tolerability of olipudase alfa administered intravenously in pediatric patients every 2 weeks for 64 weeks.

Inclusion Criteria
  • The patient is male or female <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 ≥5 MN.
  • 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.
Exclusion Criteria
  • The patient has received an investigational drug within 30 days before study enrollment.
  • 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 study.
  • The patient has a platelet count <60 × 103/μL (based on the average of 2 screening samples obtained greater than 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 elective surgery
  • The patient requires medication(s) that may decrease olipudase alfa activity (eg, fluoxetine, chlorpromazine; tricyclic antidepressants [eg, imipramine, or desipramine]).
  • The patient is breast-feeding.
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