Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency (ASCEND)

This is an interventional treatment trial for Sphingomyelin Lipidosis Read More

Inclusion criteria :

• The participant is willing and able to provide signed written informed consent.
• The participant is male or female aged 18 years or older.
• The participant has documented deficiency of acid sphingomyelinase as measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes; and a clinical diagnosis consistent with Niemann-Pick disease type B (NPD B).
• The participant has diffuse capacity of the lung for carbon monoxide less than or equal to (<=)70% of the predicted normal value.
• The participant has a spleen volume greater than or equal to (>=)6 multiples of normal (MN) measured by MRI; participant who have had partial splenectomy will be allowed if the procedure was performed >=1 year before screening/baseline and the residual spleen volume is >=6 MN.
• The participant has an SRS >=5.
• Female participants of childbearing potential must have a negative serum pregnancy test for beta-human chorionic gonadotropin (β-HCG).
• 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 for up to 15 days following their last dose of study drug.

Exclusion criteria:

• The participant has received an investigational drug within 30 days before study enrollment.
• The participant has a medical condition, including significant intercurrent illness; significant cardiac disease (e.g., clinically significant arrhythmia, moderate or severe pulmonary hypertension or clinically significant valve dysfunction, or less than or equal to (<=)40% left ventricular ejection fraction by echocardiogram); active hepatitis B or hepatitis C, or infection with human immunodeficiency virus (HIV); malignancy diagnosed within the past 5 years (other than non-melanoma skin cancer), or any other serious medical condition that may preclude participation in the study.
• The participant has a platelet count less than (<)60,000/microliters based on the average of 2 samples.
• The participant has an international normalized ratio (INR) greater than (>)1.5.
• The participant has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >250 IU/L or total bilirubin >1.5 mg/dL (except for participant with Gilbert's syndrome).
• The participant has had a major organ transplant (eg, bone marrow or liver).
• The participant is scheduled during the study for in-patient hospitalization including elective surgery and excluding the liver biopsies required per protocol.
• The participant, in the opinion of the investigator, is unable to adhere to the requirements of the study.
• The participant is unwilling or unable to abstain from the use of alcohol for 1 day before and 3 days after each study drug infusion. Testing for blood alcohol levels will not be required.
• The participant is unwilling or unable to avoid 10 days before and 3 days after the protocol scheduled liver biopsies the use of medications or herbal supplements that are potentially hepatotoxic (e.g., 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors, erythromycin, valproic acid, anti-depressants, kava, echinacea) and/or may cause or prolong bleeding (e.g., anti-coagulants, ibuprofen, aspirin, garlic supplements, ginkgo, ginseng).
• The participant requires medications that may decrease olipudase alfa activity (e.g., fluoxetine, chlorpromazine, tricyclic antidepressants [e.g., imipramine, or desipramine]).
• The participant requires use of invasive ventilatory support.
• The participant requires use of noninvasive ventilator support while awake for longer than 12 hours daily.
• The participant is breast-feeding.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.