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.)
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company ) Identifier:
First received: December 11, 2006
Last updated: March 17, 2015
Last verified: March 2015
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:

Further study details as provided by Sanofi:

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.

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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.
  Contacts and Locations
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Please refer to this study by its identifier: NCT00410566

United States, New York
New York, New York, United States, 10029
Sponsors and Collaborators
Genzyme, a Sanofi Company
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

Additional Information:
Responsible Party: Sanofi ( Genzyme, a Sanofi Company ) Identifier: NCT00410566     History of Changes
Other Study ID Numbers: SPHINGO00605 
Study First Received: December 11, 2006
Last Updated: March 17, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Acid sphingomyelinase deficiency
Niemann-Pick disease
Lysosomal storage disorder
Enzyme replacement therapy

Additional relevant MeSH terms:
Aphasia, Primary Progressive
Frontotemporal Dementia
Niemann-Pick Disease, Type A
Niemann-Pick Disease, Type C
Niemann-Pick Diseases
Pick Disease of the Brain
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Communication Disorders
Frontotemporal Lobar Degeneration
Genetic Diseases, Inborn
Histiocytosis, Non-Langerhans-Cell
Language Disorders
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lymphatic Diseases
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Mental Disorders
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Neurobehavioral Manifestations
Neurocognitive Disorders processed this record on May 26, 2016