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

Primary Purpose

Acid Sphingomyelinase Deficiency, Niemann-Pick Disease

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

rhASM

About this trial

This is an interventional treatment trial for Acid Sphingomyelinase Deficiency focused on measuring Acid sphingomyelinase deficiency, Niemann-Pick disease, Lysosomal storage disorder, Enzyme replacement therapy, Treatment

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Arm Description

Outcomes

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

Immune Response Measure

Secondary Outcome Measures

PK measurements

Full Information

NCT ID

NCT00410566

First Posted

December 11, 2006

Last Updated

March 17, 2015

Sponsor

Genzyme, a Sanofi Company

1. Study Identification

Unique Protocol Identification Number

NCT00410566

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2015

Overall Recruitment Status

Terminated

Why Stopped

Terminated by sponsor - Single dose safety objective achieved.

Study Start Date

December 2006 (undefined)

Primary Completion Date

March 2009 (Actual)

Study Completion Date

April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acid Sphingomyelinase Deficiency, Niemann-Pick Disease

Keywords

Acid sphingomyelinase deficiency, Niemann-Pick disease, Lysosomal storage disorder, Enzyme replacement therapy, Treatment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

11 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Title

Arm Type

Experimental

Arm Title

Arm Type

Experimental

Arm Title

Arm Type

Experimental

Arm Title

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

rhASM

Intervention Description

Single dose of 0.03mg/kg body weight IV

Intervention Type

Drug

Intervention Name(s)

rhASM

Intervention Description

Single dose of 0.1mg/kg body weight IV

Intervention Type

Drug

Intervention Name(s)

rhASM

Intervention Description

Single dose of 0.3mg/kg body weight IV

Intervention Type

Drug

Intervention Name(s)

rhASM

Intervention Description

Single dose of 0.6mg/kg body weight IV

Intervention Type

Drug

Intervention Name(s)

rhASM

Intervention Description

Single dose of 1.0mg/kg body weight IV

Primary Outcome Measure Information:

Title

Time Frame

Pre-, During-, and Post-infusion (up to 72 hrs); 14 day and 28 day follow-up visit

Title

Immune Response Measure

Time Frame

Pre-infusion and final visit (Day 28)

Secondary Outcome Measure Information:

Title

PK measurements

Time Frame

Pre- and Post-infusion up to 72 hrs.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Monitor

Organizational Affiliation

Genzyme, a Sanofi Company

Official's Role

Study Director

Facility Information:

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

12. IPD Sharing Statement

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

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