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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 )

Tracking Information
First Submitted Date  ICMJE December 11, 2006
First Posted Date  ICMJE December 13, 2006
Last Update Posted Date March 19, 2015
Study Start Date  ICMJE December 2006
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 31, 2007)
  • 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) ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 11, 2006)
To evaluate the safety of ascending doses or rhASM administered as a single dose to adults with ASMD.
Change History Complete list of historical versions of study NCT00410566 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 31, 2007)
PK measurements [ Time Frame: Pre- and Post-infusion up to 72 hrs. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2006)
To evaluate the single-dose pharmacokinetics (PK) of rhASM.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Safety Study of rhASM Enzyme Replacement Therapy in Adults With Acid Sphingomyelinase Deficiency (Niemann-Pick Disease)
Official Title  ICMJE A Phase I, Single-Center, Single Dose, Dose Escalation Study of Recombinant Human Acid Sphingomyelinase (rhASM) in Adults With Acid Sphingomyelinase Deficiency (ASMD)
Brief Summary The purpose of this study is to determine the safe range of single doses of rhASM administered to adults with ASM deficiency.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acid Sphingomyelinase Deficiency
  • Niemann-Pick Disease
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 29, 2009)
Original Enrollment  ICMJE
 (submitted: December 11, 2006)
Actual Study Completion Date  ICMJE April 2009
Actual Primary Completion Date March 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00410566
Other Study ID Numbers  ICMJE SPHINGO00605
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi ( Genzyme, a Sanofi Company )
Study Sponsor  ICMJE Genzyme, a Sanofi Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Genzyme, a Sanofi Company
PRS Account Sanofi
Verification Date March 2015

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