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

NCT ID: NCT00410566

Last Updated: 2015-03-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2009-04-30

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.

Conditions

Acid Sphingomyelinase Deficiency; Niemann-Pick Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

rhASM

Intervention Type: DRUG

Single dose of 0.03mg/kg body weight IV

2

Group Type: EXPERIMENTAL

rhASM

Intervention Type: DRUG

Single dose of 0.1mg/kg body weight IV

3

Group Type: EXPERIMENTAL

rhASM

Intervention Type: DRUG

Single dose of 0.3mg/kg body weight IV

4

Group Type: EXPERIMENTAL

rhASM

Intervention Type: DRUG

Single dose of 0.6mg/kg body weight IV

5

Group Type: EXPERIMENTAL

rhASM

Intervention Type: DRUG

Single dose of 1.0mg/kg body weight IV

Interventions

rhASM

Single dose of 0.03mg/kg body weight IV

Intervention Type: DRUG

rhASM

Single dose of 0.1mg/kg body weight IV

Intervention Type: DRUG

rhASM

Single dose of 0.3mg/kg body weight IV

Intervention Type: DRUG

rhASM

Single dose of 0.6mg/kg body weight IV

Intervention Type: DRUG

rhASM

Single dose of 1.0mg/kg body weight IV

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Genzyme, a Sanofi Company

Locations

New York, New York, United States

Countries

United States

Other Identifiers

SPHINGO00605

Identifier Type: -

Identifier Source: org_study_id