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

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

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.

Study Overview

• Status: Completed
• Conditions: Gaucher Disease, Type 1; Cerebroside Lipidosis Syndrome; Glucocerebrosidase Deficiency Disease; Glucosylceramide Beta-Glucosidase Deficiency Disease; Gaucher Disease, Non-Neuronopathic Form
• Intervention / Treatment: Drug: Cerezyme

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 20211
    • Estadual de Hematologia Arthur de Siqueira Cavalcanti (HEMORIO)
• Canada
  • Ontario
    • Toronto, Ontario, Canada, ON M5G 1X5
      • Mount Sinai Hospital
• Italy
  • Genova, Italy
    • Istituto Giannina Gaslini
  • Naples, Italy, 80131
    • Università degli Studi di Napoli "Federico II"
  • Trieste, Italy, 34137
    • Istituto per l'Infanzia Burlo-Garofolo
• Poland
  • Warsaw, Poland, 04-736
    • Instytut Pomnik Centrum Zdrowia Dzeicka
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d´hebron
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Coral Springs, Florida, United States, 33065
      • University Research Foundation for Lysosomal Storage Disease, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital
    • Skokie, Illinois, United States, 60076
      • Midwest Cancer Research Group, Inc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Institute for Genetics Medicine Saint Peter's University Hospital
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital
  • New York
    • Buffalo, New York, United States, 14215
      • Hemophilia Center of Western New York
    • Latham, New York, United States, 12110
      • New York Oncology/Hematology PC
    • New York, New York, United States, 10016
      • New York University
    • New York, New York, United States, 10029
      • Mt. Sinai Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Children's Hospital Research Foundation
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Q2 Cerezyme; Patients receiving Cerezyme one infusion every 2 weeks (Q2).	Drug: Cerezyme; Cerezyme doses of 20-60U/kg every 2 weeks (Q2 Arm) or 40-120 U/kg every 4 weeks (Q4 Arm).
Other: Q4 Cerezyme; Patients receiving Cerezyme one infusion every 4 weeks (Q4).	Drug: Cerezyme; Cerezyme doses of 20-60U/kg every 2 weeks (Q2 Arm) or 40-120 U/kg every 4 weeks (Q4 Arm).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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)
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)

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company
• Investigators: Study Director: Edward Kaye, M.D., Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start: December 1, 2001
• Study Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: August 15, 2006
• First Submitted That Met QC Criteria: August 15, 2006
• First Posted (Estimate): August 16, 2006

Study Record Updates

• Last Update Posted (Estimate): April 3, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Glucocerebrosidase Deficiency Disease; Type 1 Gaucher Disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Malnutrition; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipid Metabolism, Inborn Errors; Deficiency Diseases; Gaucher Disease; Lipidoses
• Other Study ID Numbers: CZ-011-01