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 )

December 11, 2006
December 13, 2006
March 19, 2015
December 2006
March 2009   (Final data collection date for primary outcome measure)
  • 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 ]
  • Immune Response Measure [ Time Frame: Pre-infusion and final visit (Day 28) ]
To evaluate the safety of ascending doses or rhASM administered as a single dose to adults with ASMD.
Complete list of historical versions of study NCT00410566 on Archive Site
PK measurements [ Time Frame: Pre- and Post-infusion up to 72 hrs. ]
To evaluate the single-dose pharmacokinetics (PK) of rhASM.
Not Provided
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Safety Study of rhASM Enzyme Replacement Therapy in Adults With Acid Sphingomyelinase Deficiency (Niemann-Pick Disease)
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.
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.
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Acid Sphingomyelinase Deficiency
  • Niemann-Pick Disease
  • Drug: rhASM
    Single dose of 0.03mg/kg body weight IV
  • Drug: rhASM
    Single dose of 0.1mg/kg body weight IV
  • Drug: rhASM
    Single dose of 0.3mg/kg body weight IV
  • Drug: rhASM
    Single dose of 0.6mg/kg body weight IV
  • Drug: rhASM
    Single dose of 1.0mg/kg body weight IV
  • Experimental: 1
    Intervention: Drug: rhASM
  • Experimental: 2
    Intervention: Drug: rhASM
  • Experimental: 3
    Intervention: Drug: rhASM
  • Experimental: 4
    Intervention: Drug: rhASM
  • Experimental: 5
    Intervention: Drug: rhASM
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
April 2009
March 2009   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years to 65 Years   (Adult)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Not Provided
Sanofi ( Genzyme, a Sanofi Company )
Genzyme, a Sanofi Company
Not Provided
Study Director: Medical Monitor Genzyme, a Sanofi Company
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP