Human Acid Sphingomyelinase Deficiency
Conditions
Keywords
Human acid sphingomyelinase deficiency
Brief summary
To evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic profile of rhASM in adult patients with Acid Sphingomyelinase Deficiency (ASMD) following repeated-dose administration.
Interventions
DRUGRecombinant human acid sphingomyelinase
Administered intravenously every 2 weeks for 26 weeks
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Summary of Adverse Events (AEs) | at least 26 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics as measured by peak plasma concentration (Cmax), time to peak concentration (tmax), area under curve (AUC), half life (t1/2), drug clearance (CL), and volume of distribution (Vss) | up to 26 weeks |
| Pharmacodynamics as measured by liver and skin biopsies, plasma, and dried blood spot | up to 26 weeks |
Countries
United Kingdom, United States
Outcome results
None listed