Tolerability and Safety Study of Recombinant Human Acid Sphingomyelinase in Acid Sphingomyelinase Deficiency Patients

An Open-label, Multicenter, Ascending Dose Study of the Tolerability and Safety of Recombinant Human Acid Sphingomyelinase (rhASM) in Patients With Acid Sphingomyelinase Deficiency (ASMD)

To evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic profile of rhASM in adult patients with Acid Sphingomyelinase Deficiency (ASMD) following repeated-dose administration.

Inclusion Criteria:

• Patients with documented non-neuronopathic acid sphingomyelinase deficiency
• The patient has a diffusing capacity of carbon monoxide (DLco) >20% and ≤80% of the predicted normal value.
• The patient has a spleen volume ≥6 multiples of normal(MN). A partial splenectomy will be permitted if performed ≥1 year prior to Screening/Baseline and residual spleen volume is ≥6 MN.
• The patient who is receiving lipid lowering therapy should be on a stable dose and regimen of lipid-lowering therapy(ies) for at least 12 weeks prior to Screening/Baseline, with the patient expected to remain on the same dose and regimen throughout the 26-week treatment period.
• The patient who is female and of childbearing potential must have a negative serum pregnancy test for β-HCG.

Exclusion Criteria:

• The patient is female and pregnant or lactating.
• The patient has a Body Mass Index(BMI)>30.
• The patient has received an investigational drug within 30 days prior to study enrollment
• The patient has a medical condition or any extenuating circumstance that may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities.
• The patient has had a major organ transplant
• ALT or AST >250 IU/L or total bilirubin >1.5 mg/dL.
• The patient is unwilling or unable to abstain from the use of alcohol for 1 day prior to and 3 days after each rhASM infusion for the duration of the study.
• The patient requires medications that may decrease rhASM
• The patient is unwilling or unable to avoid the use of medications or herbal supplements that may cause or prolong bleeding, or have potential hepatotoxicity within 10 days prior to and 3 days after liver biopsy