Clinical trial NCT01722526: Tolerability and Safety Study of Recombinant Human Acid Sphingomyelinase in Acid Sphingomyelinase Deficiency Patients
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Human Acid Sphingomyelinase Deficiency
Keywords: Human acid sphingomyelinase deficiency
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2012-11-07
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Summary of Adverse Events (AEs)
timeFrame: at least 26 weeks
Secondary outcomes:
measure: 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)
timeFrame: up to 26 weeks
measure: Pharmacodynamics as measured by liver and skin biopsies, plasma, and dried blood spot
timeFrame: up to 26 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Manchester
country: United Kingdom
facility: St. Mary's Hospital
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Thurberg BL, Diaz GA, Lachmann RH, Schiano T, Wasserstein MP, Ji AJ, Zaher A, Peterschmitt MJ. Long-term efficacy of olipudase alfa in adults with acid sphingomyelinase deficiency (ASMD): Further clearance of hepatic sphingomyelin is associated with additional improvements in pro- and anti-atherogenic lipid profiles after 42 months of treatment. Mol Genet Metab. 2020 Sep-Oct;131(1-2):245-252. doi: 10.1016/j.ymgme.2020.06.010. Epub 2020 Jun 24.
citation: Thurberg BL, Wasserstein MP, Jones SA, Schiano TD, Cox GF, Puga AC. Clearance of Hepatic Sphingomyelin by Olipudase Alfa Is Associated With Improvement in Lipid Profiles in Acid Sphingomyelinase Deficiency. Am J Surg Pathol. 2016 Sep;40(9):1232-42. doi: 10.1097/PAS.0000000000000659.
citation: Wasserstein MP, Jones SA, Soran H, Diaz GA, Lippa N, Thurberg BL, Culm-Merdek K, Shamiyeh E, Inguilizian H, Cox GF, Puga AC. Successful within-patient dose escalation of olipudase alfa in acid sphingomyelinase deficiency. Mol Genet Metab. 2015 Sep-Oct;116(1-2):88-97. doi: 10.1016/j.ymgme.2015.05.013. Epub 2015 May 30.