A phase 2/3, multicenter, randomized, double-blinded, placebo-controlled, repeatdose study to evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of olipudase alfa in patients with acid sphingomyelinase deficiency

The patient is willing and able to provide signed written informed consent.,
The patient is male or female aged 18 years or older., The patient 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 patient has diffuse
capacity of the lung for carbon monoxide <=70% of the predicted normal value.,
The patient has a spleen volume >=6 multiples of normal (MN) measured by MRI;
patients 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., Female patients of childbearing potential must have a negative serum
pregnancy test for beta-human chorionic gonadotropin (β-HCG)., 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
enrollment., The patient has a medical condition, including significant
intercurrent illness; significant cardiac disease (eg, clinically significant
arrhythmia, moderate or severe pulmonary hypertension or valvular dysfunction,
or below 40% left ventricular ejection fraction by echocardiogram); active
hepatitis B or hepatitis C, or infection with human immunodeficiency virus
(HIV); cirrhosis (as determined by clinical evaluation or liver biopsy);
malignancy diagnosed within the past 5 years (other than basal cell carcinoma),
or any other extenuating circumstance that may significantly interfere with
study compliance, including all prescribed evaluations and follow-up
activities., The patient has a platelet count below 60,000/µL (based on the
average of 2 samples obtained at least 12 hours but no longer than 24 hours
apart)., The patient has an international normalized ratio (INR) larger than
1.5., The patient has alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) above 250 IU/L or total bilirubin above1.5 mg/dL (except
for patients with Gilbert's syndrome)., The patient has had a major organ
transplant (eg, bone marrow or liver)., The patient is scheduled during the
study for in-patient hospitalization including elective surgery and excluding
the liver biopsies required per protocol., The patient, in the opinion of the
investigator, is unable to adhere to the requirements of the study., The
patient 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 patient is unwilling or unable to avoid 10
days before and 3 days after the protocol scheduled liver biopsies that are
required at screening/baseline and at week 52, 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 patient requires
medications that may decrease olipudase alfa activity (e.g., fluoxetine,
chlorpromazine, tricyclic antidepressants [e.g., imipramine, or desipramine]).,
The patient requires use of invasive ventilatory support., The patient requires
use of noninvasive ventilator support while awake for longer than 12 hours
daily., The patient is breast-feeding.