SPHINGO00605: Safety Study of rhASM Enzyme Replacement Therapy in Adults With Acid Sphingomyelinase Deficiency (Niemann-Pick Disease)

This study is currently recruiting patients.

Sponsored By:	Genzyme
Information Provided By:	Genzyme
ClinicalTrials.gov Identifier:	NCT00410566

Purpose

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 I

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety Study

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)

Further Study Details:

Primary Outcome Measures:
To evaluate the safety of ascending doses of rhASM administered as a single dose to adults with ASMD as determined by safety monitoring during the in-patient visit at selected time points pre- and post-infusion and during the two follow-up visits.

Secondary Outcome Measures:
To evaluate the single-dose pharmacokinetics (PK) of rhASM as determined by blood draws pre- and post-infusion.

Expected Total Enrollment: 30

Study start: 2006-11
Expected Completion: 2008-02

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 15 and a maximum of 30 eligible adults patients with ASMD. The study will last approximately 1.5 years, with each patient participating for approximately 7 weeks.

Eligibility

Ages Eligible for Study: 18 Years – 65 Years, Genders Eligible for Study: Both

Criteria

Inclusion Criteria:
-Signed, informed consent by the patient or legal guardian prior to performing any study-related procedures;
-Have < 30% of the lower limit of normal ASM activity of the reference laboratory, as measured in peripheral leukocytes or in cultured fibroblasts or lymphocytes;
-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 < 60,000x 10^3/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.

Location and Contact Information

New York
New York, New York, 10029, United States; Recruiting

More Information

Study ID Numbers: SPHINGO00605
ClinicalTrials.gov Identifier: NCT00410566
Health Authority: United States: Food and Drug Administration