Tolerability and Safety Study of Recombinant Human Acid Sphingomyelinase in Acid Sphingomyelinase Deficiency Patients

Human Acid Sphingomyelinase Deficiency Clinical Trial

Official title:

An Open-label, Multicenter, Ascending Dose Study of the Tolerability and Safety of Recombinant Human Acid Sphingomyelinase (rhASM) in Patients With Acid Sphingomyelinase Deficiency (ASMD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01722526
• Other study ID #: DFI13412
• Secondary ID: 2012-003542-32SP
• Status: Completed
• Phase: Phase 1
• First received: November 5, 2012
• Last updated: July 29, 2015
• Start date: March 2013
• Est. completion date: January 2014

Study information

• Verified date: July 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

To evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic profile of rhASM in adult patients with Acid Sphingomyelinase Deficiency (ASMD) following repeated-dose administration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patients with documented non-neuronopathic acid sphingomyelinase deficiency

• The patient has a diffusing capacity of carbon monoxide (DLco) >20% and =80% of the predicted normal value.

• The patient has a spleen volume =6 multiples of normal(MN). A partial splenectomy will be permitted if performed =1 year prior to Screening/Baseline and residual spleen volume is =6 MN.

• The patient who is receiving lipid lowering therapy should be on a stable dose and regimen of lipid-lowering therapy(ies) for at least 12 weeks prior to Screening/Baseline, with the patient expected to remain on the same dose and regimen throughout the 26-week treatment period.

• The patient who is female and of childbearing potential must have a negative serum pregnancy test for ß-HCG.

Exclusion Criteria:

• The patient is female and pregnant or lactating.

• The patient has a Body Mass Index(BMI)>30.

• The patient has received an investigational drug within 30 days prior to study enrollment

• The patient has a medical condition or any extenuating circumstance that may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities.

• The patient has had a major organ transplant

• ALT or AST >250 IU/L or total bilirubin >1.5 mg/dL.

• The patient is unwilling or unable to abstain from the use of alcohol for 1 day prior to and 3 days after each rhASM infusion for the duration of the study.

• The patient requires medications that may decrease rhASM

• The patient is unwilling or unable to avoid the use of medications or herbal supplements that may cause or prolong bleeding, or have potential hepatotoxicity within 10 days prior to and 3 days after liver biopsy

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Human Acid Sphingomyelinase Deficiency
• Niemann-Pick Disease, Type C
• Niemann-Pick Diseases

Intervention

Drug:
• Recombinant human acid sphingomyelinase
Administered intravenously every 2 weeks for 26 weeks

Locations

Country	Name	City	State
United Kingdom	St. Mary's Hospital	Manchester
United States	Mount Sinai School of Medicine	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Summary of Adverse Events (AEs)		at least 26 weeks	Yes
Secondary	Pharmacokinetics as measured by peak plasma concentration (Cmax), time to peak concentration (tmax), area under curve (AUC), half life (t1/2), drug clearance (CL), and volume of distribution (Vss)		up to 26 weeks	No
Secondary	Pharmacodynamics as measured by liver and skin biopsies, plasma, and dried blood spot		up to 26 weeks	No