- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01722526
Tolerability and Safety Study of Recombinant Human Acid Sphingomyelinase in Acid Sphingomyelinase Deficiency Patients
July 29, 2015 updated by: Genzyme, a Sanofi Company
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
5
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Manchester, United Kingdom
- St. Mary's Hospital
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New York
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New York, New York, United States
- Mount Sinai School of Medicine
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Recombinant human acid sphingomyelinase
Participants will receive rhASM of an initial dose of 0.1 mg/kg, followed by several dose escalations, as tolerated, up to 3.0 mg/kg.
All doses are given 2 weeks apart.
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Administered intravenously every 2 weeks for 26 weeks
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Summary of Adverse Events (AEs)
Time Frame: at least 26 weeks
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at least 26 weeks
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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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)
Time Frame: up to 26 weeks
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up to 26 weeks
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Pharmacodynamics as measured by liver and skin biopsies, plasma, and dried blood spot
Time Frame: up to 26 weeks
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up to 26 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2013
Primary Completion (Actual)
January 1, 2014
Study Completion (Actual)
January 1, 2014
Study Registration Dates
First Submitted
November 5, 2012
First Submitted That Met QC Criteria
November 5, 2012
First Posted (Estimate)
November 7, 2012
Study Record Updates
Last Update Posted (Estimate)
July 30, 2015
Last Update Submitted That Met QC Criteria
July 29, 2015
Last Verified
July 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Lymphatic Diseases
- Genetic Diseases, Inborn
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Lipid Metabolism Disorders
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Sphingolipidoses
- Lysosomal Storage Diseases, Nervous System
- Lipidoses
- Lipid Metabolism, Inborn Errors
- Histiocytosis, Non-Langerhans-Cell
- Histiocytosis
- Niemann-Pick Diseases
- Niemann-Pick Disease, Type A
- Niemann-Pick Disease, Type C
Other Study ID Numbers
- DFI13412
- 2012-003542-32 (EudraCT Number)
- SPHINGO00812 (Other Identifier: Genzyme)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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