Cerebroside Lipidosis Syndrome, Gaucher Disease, Non-Neuronopathic Form, Gaucher Disease, Type 1, Glucocerebrosidase Deficiency Disease, Glucosylceramide Beta-Glucosidase Deficiency Disease
Conditions
Keywords
Type 1 Gaucher Disease, Glucocerebrosidase Deficiency Disease
Brief 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.
Interventions
DRUGCerezyme
Cerezyme doses of 20-60U/kg every 2 weeks (Q2 Arm) or 40-120 U/kg every 4 weeks (Q4 Arm).
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Success at Month 24/Discontinuation | Month 24 (or at time of 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Composite Scores of the SF-36 Health Survey at Baseline | 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. |
| Mean Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation. | Month 24 (or at time of 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. |
| Mean Change From Baseline in Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation | Baseline and Month 24 (or at time of 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. |
Countries
Brazil, Canada, Italy, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
Eligible patients were randomized 2:1 to receive Cerezyme either once every 4 weeks (Q4) or once every 2 weeks (Q2) for 24 months. The studied period was from 14 December 2001 through 01 February 2007. There were 26 centers worldwide (18 United States, 1 Canada, 6 Europe, and 1 Brazil); 25 centers randomized patients to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Q2 Cerezyme Patients receiving Cerezyme one infusion every 2 weeks (Q2). | 33 |
| Q4 Cerezyme Patients receiving Cerezyme one infusion every 4 weeks(Q4). | 62 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 5 |
| Overall Study | Clinical baseline issue | 0 | 1 |
| Overall Study | Clinical failure | 2 | 13 |
| Overall Study | Discontinuation at baseline | 1 | 0 |
| Overall Study | Non-compliant | 1 | 0 |
| Overall Study | Pregnancy | 1 | 1 |
| Overall Study | Return to Q2 regimen | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Q2 Cerezyme | Q4 Cerezyme | Total |
|---|---|---|---|
| Age, Continuous | 44.8 years STANDARD_DEVIATION 17.4 | 47.8 years STANDARD_DEVIATION 14.47 | 46.8 years STANDARD_DEVIATION 15.53 |
| Sex: Female, Male Female | 13 Participants | 34 Participants | 47 Participants |
| Sex: Female, Male Male | 20 Participants | 28 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 33 | 51 / 62 | 71 / 95 |
| serious Total, serious adverse events | 7 / 33 | 4 / 62 | 11 / 95 |
Outcome results
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.
Time frame: Month 24 (or at time of discontinuation)
Population: Intent-to-Treat (ITT) Population. All patients who enrolled in the study and received AT LEAST ONE infusion were included in the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Q2 Cerezyme | Number of Participants With Clinical Success at Month 24/Discontinuation | Number of participants with Clinical Success | 21 patients |
| Q2 Cerezyme | Number of Participants With Clinical Success at Month 24/Discontinuation | Proportion of participants with Clinical Success | 0.808 patients |
| Q4 Cerezyme | Number of Participants With Clinical Success at Month 24/Discontinuation | Number of participants with Clinical Success | 36 patients |
| Q4 Cerezyme | Number of Participants With Clinical Success at Month 24/Discontinuation | Proportion of participants with Clinical Success | 0.632 patients |
Comparison: Difference in proportion of Clinical Success = (Proportion of participants with Clinical Success Q4 - Proportion of participants with Clinical Success Q2).95% CI: [-0.357, 0.058]
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.
Time frame: Baseline and Month 24 (or at time of discontinuation)
Population: Quality of life was evaluated and measured by the SF-36 questionnaire.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Q2 Cerezyme | Mean Change From Baseline in Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation | Composite Physical Health | -1.5 Units on a scale | Standard Deviation 7.4 |
| Q2 Cerezyme | Mean Change From Baseline in Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation | Composite Mental Health | 0.6 Units on a scale | Standard Deviation 6.48 |
| Q4 Cerezyme | Mean Change From Baseline in Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation | Composite Physical Health | -0.5 Units on a scale | Standard Deviation 7.33 |
| Q4 Cerezyme | Mean Change From Baseline in Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation | Composite Mental Health | -0.5 Units on a scale | Standard Deviation 7.34 |
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.
Time frame: Baseline
Population: Quality of life was evaluated and measured by the SF-36 questionnaire.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Q2 Cerezyme | Mean Composite Scores of the SF-36 Health Survey at Baseline | Composite Physical Health | 49.8 Units on a scale | Standard Deviation 8.41 |
| Q2 Cerezyme | Mean Composite Scores of the SF-36 Health Survey at Baseline | Composite Mental Health | 52.9 Units on a scale | Standard Deviation 7.6 |
| Q4 Cerezyme | Mean Composite Scores of the SF-36 Health Survey at Baseline | Composite Physical Health | 46.9 Units on a scale | Standard Deviation 10.26 |
| Q4 Cerezyme | Mean Composite Scores of the SF-36 Health Survey at Baseline | Composite Mental Health | 53.0 Units on a scale | Standard Deviation 8.47 |
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.
Time frame: Month 24 (or at time of discontinuation)
Population: Quality of life was evaluated and measured by the SF-36 questionnaire.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Q2 Cerezyme | Mean Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation. | Composite Physical Health | 49.1 Units on a scale | Standard Deviation 7.52 |
| Q2 Cerezyme | Mean Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation. | Composite Mental Health | 53.8 Units on a scale | Standard Deviation 8.47 |
| Q4 Cerezyme | Mean Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation. | Composite Physical Health | 46.2 Units on a scale | Standard Deviation 12.39 |
| Q4 Cerezyme | Mean Composite Scores of the SF-36 Health Survey at Month 24/Discontinuation. | Composite Mental Health | 52.6 Units on a scale | Standard Deviation 7.35 |