Safety Study of rhASM Enzyme Replacement Therapy in Adults With Acid Sphingomyelinase Deficiency (Niemann-Pick Disease)
This study has been terminated.
(Terminated by sponsor - Single dose safety objective achieved.)
Sponsor:
Genzyme
Information provided by:
Genzyme
ClinicalTrials.gov Identifier:
NCT00410566
First received: December 11, 2006
Last updated: August 3, 2009
Last verified: April 2009
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Purpose
The purpose of this study is to determine the safe range of single doses of rhASM administered to adults with ASM deficiency.
| Condition | Intervention | Phase |
|---|---|---|
|
Acid Sphingomyelinase Deficiency Niemann-Pick Disease |
Drug: rhASM |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I, Single-Center, Single Dose, Dose Escalation Study of Recombinant Human Acid Sphingomyelinase (rhASM) in Adults With Acid Sphingomyelinase Deficiency (ASMD) |
Resource links provided by NLM:
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U.S. FDA Resources
Further study details as provided by Genzyme:
Primary Outcome Measures:
- 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 ] [ Designated as safety issue: Yes ]
- Immune Response Measure [ Time Frame: Pre-infusion and final visit (Day 28) ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- PK measurements [ Time Frame: Pre- and Post-infusion up to 72 hrs. ] [ Designated as safety issue: No ]
| Enrollment: | 11 |
| Study Start Date: | December 2006 |
| Study Completion Date: | April 2009 |
| Primary Completion Date: | March 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: 1 |
Drug: rhASM
Single dose of 0.03mg/kg body weight IV
|
| Experimental: 2 |
Drug: rhASM
Single dose of 0.1mg/kg body weight IV
|
| Experimental: 3 |
Drug: rhASM
Single dose of 0.3mg/kg body weight IV
|
| Experimental: 4 |
Drug: rhASM
Single dose of 0.6mg/kg body weight IV
|
| Experimental: 5 |
Drug: rhASM
Single dose of 1.0mg/kg body weight IV
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Contacts and Locations More Information
Additional Information:
No publications provided
| Responsible Party: | Medical Monitor, Genzyme Corporation |
| ClinicalTrials.gov Identifier: | NCT00410566 History of Changes |
| Other Study ID Numbers: | SPHINGO00605 |
| Study First Received: | December 11, 2006 |
| Last Updated: | August 3, 2009 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Genzyme:
|
Acid sphingomyelinase deficiency Niemann-Pick disease Lysosomal storage disorder Enzyme replacement therapy Treatment |
Additional relevant MeSH terms:
|
Niemann-Pick Diseases Niemann-Pick Disease, Type A Niemann-Pick Disease, Type C Aphasia, Primary Progressive Pick Disease of the Brain Frontotemporal Dementia Sphingolipidoses Lysosomal Storage Diseases, Nervous System Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Histiocytosis, Non-Langerhans-Cell Histiocytosis |
Lymphatic Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn Lipidoses Lipid Metabolism, Inborn Errors Lysosomal Storage Diseases Metabolic Diseases Lipid Metabolism Disorders Dementia Aphasia Speech Disorders Language Disorders Communication Disorders Neurobehavioral Manifestations Neurologic Manifestations |
ClinicalTrials.gov processed this record on May 16, 2013