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

Study Overview
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Brief Summary
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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.

Official Title
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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

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

Intervention / Treatment
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* Drug: Cerezyme


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Gaucher Disease, Glucocerebrosidase Deficiency Disease