Safety and Efficacy of Cerezyme® Infusions Every 4 Weeks Versus Every 2 Weeks in Type 1 Gaucher Disease

Gaucher Disease, Type 1 Clinical Trial

Official title:

A Phase IV, Multicenter, Randomized, Dose Frequency Study of the Safety and Efficacy of Cerezyme® Infusions Every Four Weeks Versus Every Two Weeks in the Maintenance Therapy of Patients With Type 1 Gaucher Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00364858
• Other study ID #: CZ-011-01
• Status: Completed
• Phase: Phase 4
• First received: August 15, 2006
• Last updated: March 17, 2015
• Start date: December 2001
• Est. completion date: February 2007

Study information

• Verified date: March 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, randomized trial to compare the safety and efficacy of two dosing frequencies of Cerezyme® in patients with Gaucher disease who are currently being treated with Cerezyme®.

Approximately 90 patients will be randomized in a 2:1 (q4 : q2) ratio to one of two treatment arms at up to 26 study centers worldwide. Patients will continue to receive the same total 4-week dose that they were receiving prior to study enrollment, however, they will be randomized to receive either their total 4-week dose in two infusions, one infusion every 2 weeks or their total 4-week dose in one infusion every 4 weeks. The randomization scheme will ensure a 2:1 balance between the every 4-week versus every 2-week infusion groups, respectively.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• The patient must provide written informed consent prior to undergoing any study-related procedures.

• The patient has a confirmed diagnosis of Gaucher disease with a documented deficiency of glucocerebrosidase by enzyme assay

• The patient has been genotyped or will have genotyping performed within 3 months of study enrollment.

• The patient has been treated with Cerezyme for at least 2 years prior to study enrollment.

• The patient has been on a stable dose of between 20-60 U/kg every 2 weeks for at least 6 months prior to study enrollment.

• The patient is at least 18 years old.

• The patient has a hemoglobin value of = 11.0 g/dL for women and = 12.0 g/dL for men and a platelet count of = 100,000 mm^3.

• The patient's liver volume is = 1.8 x normal confirmed by MRI or CT within 6 months of randomization.

• The patient's spleen volume is = 10 x normal confirmed by MRI or CT within 6 months of randomization.

• The patient has a serum creatinine < 2.0 mg/dL, an ASTand ALT < 2 x upper limit of normal and a total bilirubin < 2.0 x upper limit of normal.

• Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to randomization into the study.

Exclusion Criteria:

• The patient is pregnant.

• The patient has evidence of neurologic or pulmonary involvement with Gaucher disease confirmed by medical history.

• The patient has evidence of current or prior bleeding varices or liver infarction requiring hospitalization confirmed by medical history.

• The patient has evidence of pathologic bone fractures, medullary infarctions, lytic lesions or avascular necrosis secondary to Gaucher disease confirmed by skeletal evaluation within 6 months of randomization.

• The patient has had a bone crisis (defined as pain with acute onset which requires immobilization of the affected area, narcotics for relief of pain and may be accompanied by periosteal elevation, increased white cell count, fever or debilitation of > 3 days) within 12 months of randomization.

• Patient has received an investigational drug within 30 days of the start of their participation in this trial. Patients may not receive any other investigational product throughout the course of the study.

• The patient has a clinically significant disease (with the exception of symptoms relating to Gaucher disease), including clinically significant cardiovascular, hepatic, immunologic, pulmonary, neurologic, or renal disease, or other medical condition, serious intercurrent illness, or extenuating circumstances that, in the opinion of the Investigator, would preclude participation in the trial or potentially decrease survival

• Patient has a medical, emotional, behavioral or psychological condition that in the judgment of the Investigator would interfere with the patient's compliance with the requirements of the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebroside Lipidosis Syndrome
• Deficiency Diseases
• Gaucher Disease
• Gaucher Disease, Non-Neuronopathic Form
• Gaucher Disease, Type 1
• Glucocerebrosidase Deficiency Disease
• Glucosylceramide Beta-Glucosidase Deficiency Disease

Intervention

Drug:
• Cerezyme
Cerezyme doses of 20-60U/kg every 2 weeks (Q2 Arm) or 40-120 U/kg every 4 weeks (Q4 Arm).

Locations

Country	Name	City	State
Brazil	Estadual de Hematologia Arthur de Siqueira Cavalcanti (HEMORIO)	Rio de Janeiro
Canada	Mount Sinai Hospital	Toronto	Ontario
Italy	Istituto Giannina Gaslini	Genova
Italy	Universita degli Studi di Napoli "Federico II"	Naples
Italy	Istituto per l'Infanzia Burlo-Garofolo	Trieste
Poland	Instytut Pomnik Centrum Zdrowia Dzeicka	Warsaw
Spain	Hospital Vall d´Hebrón	Barcelona
United Kingdom	Royal Free Hospital	London
United States	Emory University	Atlanta	Georgia
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Hemophilia Center of Western New York	Buffalo	New York
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Children's Hospital Research Foundation	Cincinnati	Ohio
United States	University Research Foundation for Lysosomal Storage Disease, Inc.	Coral Springs	Florida
United States	Duke University Medical Center	Durham	North Carolina
United States	New York Oncology/Hematology PC	Latham	New York
United States	Institute for Genetics Medicine Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Mt. Sinai Medical Center	New York	New York
United States	New York University	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	University of Utah	Salt Lake City	Utah
United States	Midwest Cancer Research Group, Inc.	Skokie	Illinois
United States	Holy Name Hospital	Teaneck	New Jersey
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Clinical Success at Month 24/Discontinuation	Patients are considered to be a clinical success if ALL of the following are met: The patient's hemoglobin does not fall more than 1.25g/dL for women or 1.5 g/dL for men below the patient's baseline value, platelet count does not fall more than 25% below the patient's baseline value or does not fall below 80,000 mm3, liver and spleen volumes are not greater than 20% above the patient's baseline value, no evidence of bone disease progression, including no incidence of pathologic fractures, medullary infarctions, lytic lesions or avascular necrosis and has had no bone crises during the study.	Month 24 (or at time of discontinuation)	No
Secondary	Mean Composite Scores of the SF-36 Health Survey at Baseline	The mean composite scores (0 being worst and 100 being best) for both treatment groups at Baseline. Composite scores for both treatment groups approximated those of the general population at baseline and at Month 24.	Baseline	No
Secondary	Mean Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation.	The mean composite scores (0 being worst and 100 being best) for both treatment groups at Month 24/Discontinuation. The mean composite scores for both treatment groups approximated those of the general population at baseline and at Month 24.	Month 24 (or at time of discontinuation)	No
Secondary	Mean Change From Baseline in Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation	The mean composite scores (0 being worst and 100 being best) for both treatment groups approximated those of the general population at baseline. Composite score - The overall composite scores were comprised of a standardized physical and mental component score.	Baseline and Month 24 (or at time of discontinuation)	No

External Links

•   US FDA Approved Full Prescribing Information for Cerezyme®