- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00410566
Safety Study of rhASM Enzyme Replacement Therapy in Adults With Acid Sphingomyelinase Deficiency (Niemann-Pick Disease)
March 17, 2015 updated by: Genzyme, a Sanofi Company
A Phase I, Single-Center, Single Dose, Dose Escalation Study of Recombinant Human Acid Sphingomyelinase (rhASM) in Adults With Acid Sphingomyelinase Deficiency (ASMD)
The purpose of this study is to determine the safe range of single doses of rhASM administered to adults with ASM deficiency.
Study Overview
Status
Terminated
Intervention / Treatment
Detailed Description
ASM deficiency (ASMD), also known as Niemann-Pick A and B disease, is a rare genetic disorder in which reduced activity of the lysosomal enzyme, ASM, leads to the accumulation of sphingomyelin primarily in macrophages throughout the body.
This deficiency results in characteristic features such as hepatosplenomegaly, thrombocytopenia, interstitial lung disease, growth retardation, coronary artery disease, fatigue, and in severe cases, neurodegeneration with death in early childhood.
There is no specific treatment for this disease.
This Phase 1 safety study will seek to enroll a minimum of 12 and a maximum of 30 eligible adults patients with ASMD with each patient participating for approximately 7 weeks.
Study Type
Interventional
Enrollment (Actual)
11
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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New York
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New York, New York, United States, 10029
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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:
- Signed, informed consent by the patient or legal guardian prior to performing any study-related procedures;
- Have ≤ 0.2 nmol/hr/mg protein ASM activity in peripheral leukocytes, as measured by the reference laboratory;
- Have a diffusing capacity (DLco) > 30% of the predicted normal value;
- Have a spleen volume ≥ 2x normal
- Female patients of childbearing potential must have a serum pregnancy test negative for β-hCG and agree to use a reliable birth control method for the duration of the study.
Exclusion Criteria:
- Is pregnant or lactating;
- Has received an investigational drug within 30 days prior to study enrollment;
- Has a medical condition, including serious intercurrent illness, active hepatitis B or C or human immunodeficiency virus (HIV) infection, cirrhosis, > stage 3 liver fibrosis, INR >1.5, platelet count < 60.0x10^3/µL, significant cardiac disease (e.g. pulmonary artery pressure > 40 mm Hg, moderate or severe valvular dysfunction, or < 40% left ventricular ejection fraction by echocardiography (ECHO)), or any other extenuating circumstances that may significantly interfere with study compliance including all prescribed evaluations and follow-up activities;
- Has had a major organ transplant (e.g. bone marrow or liver);
- Has had a total splenectomy;
- Has an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value >250 IU/L or a total bilirubin >3.6 mg/dL;
- Is unwilling or unable to avoid the use of alcohol, medications that may decrease rhASM activity, medications or herbal supplements that may cause or prolong bleeding, and the use of medications or herbal supplements with potential hepatoxicity within 14 days prior to and 28 days afte the rhASM infusion.
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: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
|
Single dose of 0.03mg/kg body weight IV
Single dose of 0.1mg/kg body weight IV
Single dose of 0.3mg/kg body weight IV
Single dose of 0.6mg/kg body weight IV
Single dose of 1.0mg/kg body weight IV
|
Experimental: 2
|
Single dose of 0.03mg/kg body weight IV
Single dose of 0.1mg/kg body weight IV
Single dose of 0.3mg/kg body weight IV
Single dose of 0.6mg/kg body weight IV
Single dose of 1.0mg/kg body weight IV
|
Experimental: 3
|
Single dose of 0.03mg/kg body weight IV
Single dose of 0.1mg/kg body weight IV
Single dose of 0.3mg/kg body weight IV
Single dose of 0.6mg/kg body weight IV
Single dose of 1.0mg/kg body weight IV
|
Experimental: 4
|
Single dose of 0.03mg/kg body weight IV
Single dose of 0.1mg/kg body weight IV
Single dose of 0.3mg/kg body weight IV
Single dose of 0.6mg/kg body weight IV
Single dose of 1.0mg/kg body weight IV
|
Experimental: 5
|
Single dose of 0.03mg/kg body weight IV
Single dose of 0.1mg/kg body weight IV
Single dose of 0.3mg/kg body weight IV
Single dose of 0.6mg/kg body weight IV
Single dose of 1.0mg/kg body weight IV
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Safety assessments via physical exam,AE reporting,telemetry heartrate monitoring,ECG,ECHO,clinical lab evaluations,liver and adrenal function tests,cytokine testing,adrenal hormone levels,lipid profile,chest Xrays,liver biopsies,MRI of internal
Time Frame: Pre-, During-, and Post-infusion (up to 72 hrs); 14 day and 28 day follow-up visit
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Pre-, During-, and Post-infusion (up to 72 hrs); 14 day and 28 day follow-up visit
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Immune Response Measure
Time Frame: Pre-infusion and final visit (Day 28)
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Pre-infusion and final visit (Day 28)
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
PK measurements
Time Frame: Pre- and Post-infusion up to 72 hrs.
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Pre- and Post-infusion up to 72 hrs.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
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
December 1, 2006
Primary Completion (Actual)
March 1, 2009
Study Completion (Actual)
April 1, 2009
Study Registration Dates
First Submitted
December 11, 2006
First Submitted That Met QC Criteria
December 11, 2006
First Posted (Estimate)
December 13, 2006
Study Record Updates
Last Update Posted (Estimate)
March 19, 2015
Last Update Submitted That Met QC Criteria
March 17, 2015
Last Verified
March 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Lymphatic Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Neurocognitive Disorders
- Genetic Diseases, Inborn
- Neurodegenerative Diseases
- TDP-43 Proteinopathies
- Proteostasis Deficiencies
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Lipid Metabolism Disorders
- Dementia
- Brain Diseases, Metabolic
- Brain Diseases, Metabolic, Inborn
- Language Disorders
- Communication Disorders
- Sphingolipidoses
- Lysosomal Storage Diseases, Nervous System
- Lipidoses
- Lipid Metabolism, Inborn Errors
- Speech Disorders
- Frontotemporal Lobar Degeneration
- Aphasia
- Histiocytosis, Non-Langerhans-Cell
- Histiocytosis
- Frontotemporal Dementia
- Aphasia, Primary Progressive
- Pick Disease of the Brain
- Niemann-Pick Diseases
- Niemann-Pick Disease, Type A
- Niemann-Pick Disease, Type C
Other Study ID Numbers
- SPHINGO00605
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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