Gaucher Disease
Conditions
Keywords
Gaucher Disease, Enzyme replacement therapy
Brief summary
Gaucher disease, the most prevalent lysosomal storage disorder, is caused by mutations in the human glucocerebrosidase gene (GCD) leading to reduced activity of the lysosomal enzyme glucocerebrosidase and thereby to the accumulation of substrate glucocerebroside (GlcCer) in the cells of the monocyte-macrophage system. This is an extension trial to Study NCT00376168 and NCT00712348.
Detailed description
This will be a multi-center, double-blind, parallel group, extension trial to assess the safety and efficacy of prGCD in patients completing NCT00376168. Patients will receive IV infusion of prGCD every two weeks at the selected medical center. The duration of the extension study will be fifteen months. There will be two treatment groups: 30 units/kg every 2 weeks or 60 units/kg every 2 weeks.
Interventions
Intravenous infusion every 2 weeks
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Successful completion of Protocol PB-06-001 * The patient signs informed consent
Exclusion criteria
* Currently taking another experimental drug for any condition * Presence of severe neurological signs and symptoms, defined as complete ocular paralysis, overt myoclonus or history of seizures, characteristic of neuronopathic Gaucher disease * Pregnant or nursing * Presence of any 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 |
|---|---|---|
| Spleen Volume | Spleen Volume at Baseline and Months 12, 24, and 36 | Spleen volume measured by MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin | Hemoglobin at Baseline and Months 12, 24 and 36 | — |
| Liver Volume | Liver volume at Baseline and Months 12, 24 and 36 | Liver volume measured by MRI |
| Platelet Count | Platelet count at Baseline and Months 12, 24 and 36 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Spleen Volume Multiples of Normal (MN) | Baseline and Months 12, 24, and 36 | Spleen volume measured by MRI. Normal spleen volume is 2 mL/kg × body weight (kg) |
| Liver Volume Multiples of Normal (MN) | Baseline and Months 12, 24 and 36 | Liver volume measured by MRI. Normal liver volume is 25 mL/kg × body weight (kg). |
Countries
Australia, Canada, Chile, Israel, South Africa, Spain, United Kingdom, United States
Participant flow
Recruitment details
Patients completing Studies PB-06-001 (NCT00376168) or PB-06-002 (NCT00712348) were offered continued treatment in this study.
Participants by arm
| Arm | Count |
|---|---|
| Naive 30 Units/kg Patients previously naive to enzyme replacement therapy treated in Study PB-06-001 with taliglucerase alfa 30 units/kg | 12 |
| Naive 60 Units/kg Patients previously naive to enzyme replacement therapy from Study PB-06-001 treated with taliglucerase alfa 60 units/kg | 14 |
| Switchover Patients previously treated with imiglucerase in Study PB-06-002 treated with taliglucerase alfa at the same dose as their previous imiglucerase dose | 18 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 3 |
Baseline characteristics
| Characteristic | Naive 30 Units/kg | Naive 60 Units/kg | Switchover | Total |
|---|---|---|---|---|
| Age, Continuous | 39.7 years STANDARD_DEVIATION 11.8 | 36.6 years STANDARD_DEVIATION 12 | 46.5 years STANDARD_DEVIATION 13.7 | 41.6 years STANDARD_DEVIATION 13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 12 Participants | 13 Participants | 18 Participants | 43 Participants |
| Region of Enrollment Australia | 0 participants | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Canada | 1 participants | 1 participants | 1 participants | 3 participants |
| Region of Enrollment Chile | 1 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment Israel | 3 participants | 4 participants | 6 participants | 13 participants |
| Region of Enrollment Italy | 1 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment Mexico | 3 participants | 2 participants | 0 participants | 5 participants |
| Region of Enrollment Serbia | 2 participants | 2 participants | 2 participants | 6 participants |
| Region of Enrollment South Africa | 1 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment Spain | 0 participants | 1 participants | 2 participants | 3 participants |
| Region of Enrollment United Kingdom | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 0 participants | 0 participants | 6 participants | 6 participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 9 Participants | 22 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 9 Participants | 22 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 | 12 / 12 | 12 / 14 | 17 / 18 |
| serious Total, serious adverse events | 2 / 12 | 2 / 14 | 3 / 18 |
Outcome results
Primary
Spleen Volume
Spleen volume measured by MRI
Time frame: Spleen Volume at Baseline and Months 12, 24, and 36
Population: Intent to treat. In the Switchover group, two patients did not have MRI and one patient was splenectomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naive 30 Units/kg | Spleen Volume | Baseline | 2324.0 mL | Standard Deviation 1209 |
| Naive 30 Units/kg | Spleen Volume | Month 12 | 1707.7 mL | Standard Deviation 1069.5 |
| Naive 30 Units/kg | Spleen Volume | Month 24 | 1420.4 mL | Standard Deviation 852.3 |
| Naive 30 Units/kg | Spleen Volume | Month 36 | 1237.2 mL | Standard Deviation 695.7 |
| Naive 60 Units/kg | Spleen Volume | Month 36 | 761.0 mL | Standard Deviation 556 |
| Naive 60 Units/kg | Spleen Volume | Baseline | 2120.0 mL | Standard Deviation 1426.5 |
| Naive 60 Units/kg | Spleen Volume | Month 24 | 946.7 mL | Standard Deviation 699.6 |
| Naive 60 Units/kg | Spleen Volume | Month 12 | 1267.9 mL | Standard Deviation 1114.1 |
| Switchover | Spleen Volume | Month 36 | 548.2 mL | Standard Deviation 433.7 |
| Switchover | Spleen Volume | Month 12 | 883.7 mL | Standard Deviation 760 |
| Switchover | Spleen Volume | Month 24 | 609.1 mL | Standard Deviation 442.7 |
| Switchover | Spleen Volume | Baseline | 778.0 mL | Standard Deviation 666.3 |
Secondary
Hemoglobin
Time frame: Hemoglobin at Baseline and Months 12, 24 and 36
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naive 30 Units/kg | Hemoglobin | Baseline | 12.5 mg/dL | Standard Deviation 1.8 |
| Naive 30 Units/kg | Hemoglobin | Month 12 | 14.2 mg/dL | Standard Deviation 1.7 |
| Naive 30 Units/kg | Hemoglobin | Month 24 | 13.8 mg/dL | Standard Deviation 1.6 |
| Naive 30 Units/kg | Hemoglobin | Month 36 | 14.3 mg/dL | Standard Deviation 1.5 |
| Naive 60 Units/kg | Hemoglobin | Month 36 | 14.1 mg/dL | Standard Deviation 2.2 |
| Naive 60 Units/kg | Hemoglobin | Baseline | 11.4 mg/dL | Standard Deviation 2.7 |
| Naive 60 Units/kg | Hemoglobin | Month 24 | 13.8 mg/dL | Standard Deviation 1.8 |
| Naive 60 Units/kg | Hemoglobin | Month 12 | 13.6 mg/dL | Standard Deviation 2.6 |
| Switchover | Hemoglobin | Month 36 | 13.3 mg/dL | Standard Deviation 1.2 |
| Switchover | Hemoglobin | Month 12 | 13.6 mg/dL | Standard Deviation 1.7 |
| Switchover | Hemoglobin | Month 24 | 13.5 mg/dL | Standard Deviation 1.2 |
| Switchover | Hemoglobin | Baseline | 13.6 mg/dL | Standard Deviation 1.6 |
Secondary
Liver Volume
Liver volume measured by MRI
Time frame: Liver volume at Baseline and Months 12, 24 and 36
Population: Intent to treat. In the Switchover group, two patients did not have MRI .
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naive 30 Units/kg | Liver Volume | Baseline | 2999.7 mL | Standard Deviation 779.4 |
| Naive 30 Units/kg | Liver Volume | Month 24 | 2362.8 mL | Standard Deviation 518.7 |
| Naive 30 Units/kg | Liver Volume | Month 36 | 2341.1 mL | Standard Deviation 553.4 |
| Naive 30 Units/kg | Liver Volume | Month 12 | 2515.6 mL | Standard Deviation 642.1 |
| Naive 60 Units/kg | Liver Volume | Month 24 | 1998.2 mL | Standard Deviation 291.9 |
| Naive 60 Units/kg | Liver Volume | Month 36 | 1971.8 mL | Standard Deviation 404.7 |
| Naive 60 Units/kg | Liver Volume | Baseline | 2470.5 mL | Standard Deviation 484.9 |
| Naive 60 Units/kg | Liver Volume | Month 12 | 2118.7 mL | Standard Deviation 318.1 |
| Switchover | Liver Volume | Baseline | 1775.7 mL | Standard Deviation 434.4 |
| Switchover | Liver Volume | Month 24 | 1757.1 mL | Standard Deviation 357 |
| Switchover | Liver Volume | Month 36 | 1821.2 mL | Standard Deviation 523.6 |
| Switchover | Liver Volume | Month 12 | 1788.9 mL | Standard Deviation 378 |
Secondary
Platelet Count
Time frame: Platelet count at Baseline and Months 12, 24 and 36
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naive 30 Units/kg | Platelet Count | Baseline | 64900 Platelets per cubic millimeter | Standard Deviation 30133 |
| Naive 30 Units/kg | Platelet Count | Month 12 | 80325 Platelets per cubic millimeter | Standard Deviation 41806 |
| Naive 30 Units/kg | Platelet Count | Month 24 | 93333 Platelets per cubic millimeter | Standard Deviation 53328 |
| Naive 30 Units/kg | Platelet Count | Month 36 | 94683 Platelets per cubic millimeter | Standard Deviation 47526 |
| Naive 60 Units/kg | Platelet Count | Month 36 | 144417 Platelets per cubic millimeter | Standard Deviation 55190 |
| Naive 60 Units/kg | Platelet Count | Baseline | 69043 Platelets per cubic millimeter | Standard Deviation 28242 |
| Naive 60 Units/kg | Platelet Count | Month 24 | 141071 Platelets per cubic millimeter | Standard Deviation 73896 |
| Naive 60 Units/kg | Platelet Count | Month 12 | 122857 Platelets per cubic millimeter | Standard Deviation 53857 |
| Switchover | Platelet Count | Month 36 | 172467 Platelets per cubic millimeter | Standard Deviation 89340 |
| Switchover | Platelet Count | Month 12 | 145250 Platelets per cubic millimeter | Standard Deviation 97426 |
| Switchover | Platelet Count | Month 24 | 174200 Platelets per cubic millimeter | Standard Deviation 100483 |
| Switchover | Platelet Count | Baseline | 163833 Platelets per cubic millimeter | Standard Deviation 88882 |
Other Pre-specified
Liver Volume Multiples of Normal (MN)
Liver volume measured by MRI. Normal liver volume is 25 mL/kg × body weight (kg).
Time frame: Baseline and Months 12, 24 and 36
Population: Intent to treat. In the Switchover group, two patients did not have MRI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naive 30 Units/kg | Liver Volume Multiples of Normal (MN) | Baseline | 1.7 Multiples of Normal Liver Volume | Standard Deviation 0.4 |
| Naive 30 Units/kg | Liver Volume Multiples of Normal (MN) | Month 12 | 1.4 Multiples of Normal Liver Volume | Standard Deviation 0.3 |
| Naive 30 Units/kg | Liver Volume Multiples of Normal (MN) | Month 24 | 1.3 Multiples of Normal Liver Volume | Standard Deviation 0.2 |
| Naive 30 Units/kg | Liver Volume Multiples of Normal (MN) | Month 36 | 1.3 Multiples of Normal Liver Volume | Standard Deviation 0.2 |
| Naive 60 Units/kg | Liver Volume Multiples of Normal (MN) | Month 36 | 1.1 Multiples of Normal Liver Volume | Standard Deviation 0.2 |
| Naive 60 Units/kg | Liver Volume Multiples of Normal (MN) | Baseline | 1.5 Multiples of Normal Liver Volume | Standard Deviation 0.4 |
| Naive 60 Units/kg | Liver Volume Multiples of Normal (MN) | Month 24 | 1.1 Multiples of Normal Liver Volume | Standard Deviation 0.2 |
| Naive 60 Units/kg | Liver Volume Multiples of Normal (MN) | Month 12 | 1.2 Multiples of Normal Liver Volume | Standard Deviation 0.2 |
| Switchover | Liver Volume Multiples of Normal (MN) | Month 36 | 1.0 Multiples of Normal Liver Volume | Standard Deviation 0.3 |
| Switchover | Liver Volume Multiples of Normal (MN) | Month 12 | 1.1 Multiples of Normal Liver Volume | Standard Deviation 0.2 |
| Switchover | Liver Volume Multiples of Normal (MN) | Month 24 | 0.9 Multiples of Normal Liver Volume | Standard Deviation 0.2 |
| Switchover | Liver Volume Multiples of Normal (MN) | Baseline | 1.0 Multiples of Normal Liver Volume | Standard Deviation 0.1 |
Other Pre-specified
Spleen Volume Multiples of Normal (MN)
Spleen volume measured by MRI. Normal spleen volume is 2 mL/kg × body weight (kg)
Time frame: Baseline and Months 12, 24, and 36
Population: Intent to treat. In the Switchover group, two patients did not have MRI and one patient was splenectomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Naive 30 Units/kg | Spleen Volume Multiples of Normal (MN) | Month 24 | 9.6 Multiples of Normal Spleen Volume | Standard Deviation 1.6 |
| Naive 30 Units/kg | Spleen Volume Multiples of Normal (MN) | Baseline | 16.4 Multiples of Normal Spleen Volume | Standard Deviation 8.3 |
| Naive 30 Units/kg | Spleen Volume Multiples of Normal (MN) | Month 36 | 8.2 Multiples of Normal Spleen Volume | Standard Deviation 4.4 |
| Naive 30 Units/kg | Spleen Volume Multiples of Normal (MN) | Month 12 | 11.7 Multiples of Normal Spleen Volume | Standard Deviation 7.2 |
| Naive 60 Units/kg | Spleen Volume Multiples of Normal (MN) | Month 24 | 6.6 Multiples of Normal Spleen Volume | Standard Deviation 5.3 |
| Naive 60 Units/kg | Spleen Volume Multiples of Normal (MN) | Month 12 | 9.3 Multiples of Normal Spleen Volume | Standard Deviation 9.4 |
| Naive 60 Units/kg | Spleen Volume Multiples of Normal (MN) | Baseline | 16.8 Multiples of Normal Spleen Volume | Standard Deviation 14.2 |
| Naive 60 Units/kg | Spleen Volume Multiples of Normal (MN) | Month 36 | 5.6 Multiples of Normal Spleen Volume | Standard Deviation 4.5 |
| Switchover | Spleen Volume Multiples of Normal (MN) | Month 12 | 7.0 Multiples of Normal Spleen Volume | Standard Deviation 6.8 |
| Switchover | Spleen Volume Multiples of Normal (MN) | Baseline | 5.5 Multiples of Normal Spleen Volume | Standard Deviation 5.4 |
| Switchover | Spleen Volume Multiples of Normal (MN) | Month 36 | 3.7 Multiples of Normal Spleen Volume | Standard Deviation 2.9 |
| Switchover | Spleen Volume Multiples of Normal (MN) | Month 24 | 4.0 Multiples of Normal Spleen Volume | Standard Deviation 2.7 |