COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Safety Study of rhASM Enzyme Replacement Therapy in Adults With Acid Sphingomyelinase Deficiency (Niemann-Pick Disease)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00410566
Recruitment Status : Terminated (Terminated by sponsor - Single dose safety objective achieved.)
First Posted : December 13, 2006
Last Update Posted : March 19, 2015
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Brief Summary:
The purpose of this study is to determine the safe range of single doses of rhASM administered to adults with ASM deficiency.

Condition or disease Intervention/treatment Phase
Acid Sphingomyelinase Deficiency Niemann-Pick Disease Drug: rhASM Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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)
Study Start Date : December 2006
Actual Primary Completion Date : March 2009
Actual Study Completion Date : April 2009

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 ]
  2. Immune Response Measure [ Time Frame: Pre-infusion and final visit (Day 28) ]

Secondary Outcome Measures :
  1. PK measurements [ Time Frame: Pre- and Post-infusion up to 72 hrs. ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00410566

Layout table for location information
United States, New York
New York, New York, United States, 10029
Sponsors and Collaborators
Genzyme, a Sanofi Company
Layout table for investigator information
Study Director: Medical Monitor Genzyme, a Sanofi Company
Layout table for additonal information
Responsible Party: Genzyme, a Sanofi Company Identifier: NCT00410566    
Other Study ID Numbers: SPHINGO00605
First Posted: December 13, 2006    Key Record Dates
Last Update Posted: March 19, 2015
Last Verified: March 2015
Keywords provided by Sanofi ( Genzyme, a Sanofi Company ):
Acid sphingomyelinase deficiency
Niemann-Pick disease
Lysosomal storage disorder
Enzyme replacement therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Pick Disease of the Brain
Aphasia, Primary Progressive
Frontotemporal Dementia
Niemann-Pick Diseases
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Frontotemporal Lobar Degeneration
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Histiocytosis, Non-Langerhans-Cell
Lymphatic Diseases