A Phase 2/3, Multicenter, Randomized, Double-blinded, Placebo-controlled, Repeat-dose Study to Evaluate the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency

DFI12712

Primary Objective: The primary objective of this phase 2/3 study is to evaluate the efficacy of olipudase alfa (recombinant human acid sphingomyelinase) administered intravenously once every 2 weeks for 52 weeks in adult participants with acid sphingomyelinase deficiency (ASMD) by assessing changes in: 1) spleen volume as measured by abdominal magnetic resonance imaging (MRI) (and, for the United States \[US\] only, in association with participant perception related to spleen volume as measured by splenomegaly-related score \[SRS\]); and 2) infiltrative lung disease as measured by the pulmonary function test, diffusing capacity of the lung for carbon monoxide (DLCO). Secondary Objectives: * To confirm the safety of olipudase alfa administered intravenously once every 2 weeks for 52 weeks. * To characterize the effect of olipudase alfa on the participant perception related to spleen volume as measured by the SRS after 52 weeks of study drug administration. (For the US, the effect of olipudase alfa on the SRS is part of the primary objective). * To characterize the effect of olipudase alfa after 52 weeks of study drug administration on the following outcome measures assessed sequentially: * The effect of olipudase alfa on liver volume; * The effect of olipudase alfa on platelet count; * The effect of olipudase alfa on fatigue; * The effect of olipudase alfa on pain; * The effect of olipudase alfa on dyspnea.

2015-12-18

2021-03-15

2023-10-19

Completed

Early phase I

36

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.

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2023-12-04