Gaucher Disease
Conditions
Keywords
Gaucher disease, pediatrics
Brief summary
A protocol to extend the assessment of the safety and efficacy of taliglucerase alfa in pediatric subjects (2 to \<18 years old) with symptoms and clinical manifestations of Gaucher disease who completed treatment in Protocols PB-06-002 (switchover study from imiglucerase) or PB-06-005 (naïve treatment with taliglucerase alfa).
Interventions
Taliglucerase alfa for infusion every two weeks for 24 months
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Successful completion of Protocol PB-06-002 or PB-06-005 * The subject, parent(s) or legal guardian(s) signs an informed consent and/or assent
Exclusion criteria
* Currently taking another investigational drug for any condition. * Presence of neurological signs and symptoms characteristic of Gaucher disease with complex neuronopathic features other than longstanding oculomotor gaze palsy. * Presence of any medical, emotional, behavioral or psychological condition that in the judgment of the Investigator would interfere with the subject's compliance with the requirements of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin | Baseline, months 9, 12 and 24 | Median and interquartile range. Baseline is the value obtained from the parent study: PB-06-005 for 30 and 60 Units/kg arms and PB-06-002 from Switchover arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Chitotriosidase | Baseline, months 9, 12 and 24 | Chitotriosidase. Baseline is the value obtained from the parent study: PB-06-005 for 30 and 60 Units/kg arms and PB-06-002 from Switchover arm. |
| Spleen Volume | Baseline, months 12 and 24 | Spleen volume measured by MRI (or ultrasound). Baseline is the value obtained from the parent study: PB-06-005 for 30 and 60 Units/kg arms and PB-06-002 from Switchover arm. |
| Platelet Count | Baseline, months 9, 12, 24 and 33-36 | Platelet count. Baseline is the value obtained from the parent study: PB-06-005 for 30 and 60 Units/kg arms and PB-06-002 from Switchover arm. |
| Liver Volume | Baseline, months 12 and 24 | Liver volume by MRI or Ultrasound. Baseline is the value obtained from the parent study: PB-06-005 for 30 and 60 Units/kg arms and PB-06-002 from Switchover arm. |
Countries
Israel, Paraguay, South Africa
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 60 Units/kg Taliglucerase alfa: Taliglucerase alfa for infusion every two weeks for 24 months | 5 |
| 30 Units/kg Taliglucerase alfa: Taliglucerase alfa for infusion every two weeks for 24 months | 5 |
| Dose Adjusted Taliglucerase alfa: Dose increased from 30 Units/kg to 45 or 60 Units/kg | 5 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | 60 Units/kg | 30 Units/kg | Dose Adjusted | Total |
|---|---|---|---|---|
| Age, Continuous | 6.6 years STANDARD_DEVIATION 3.1 | 8.6 years STANDARD_DEVIATION 3.8 | 13.0 years STANDARD_DEVIATION 4.1 | 9.4 years STANDARD_DEVIATION 4.4 |
| 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 4 Participants | 13 Participants |
| Region of Enrollment Israel | 2 participants | 1 participants | 0 participants | 3 participants |
| Region of Enrollment Paraguay | 1 participants | 3 participants | 0 participants | 4 participants |
| Region of Enrollment Serbia | 0 participants | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Singapore | 0 participants | 0 participants | 1 participants | 1 participants |
| Region of Enrollment South Africa | 2 participants | 1 participants | 0 participants | 3 participants |
| Region of Enrollment Spain | 0 participants | 0 participants | 2 participants | 2 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 3 Participants | 10 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 | 5 / 5 | 4 / 5 | 5 / 5 |
| serious Total, serious adverse events | 1 / 5 | 0 / 5 | 0 / 5 |
Outcome results
Primary
Hemoglobin
Median and interquartile range. Baseline is the value obtained from the parent study: PB-06-005 for 30 and 60 Units/kg arms and PB-06-002 from Switchover arm.
Time frame: Baseline, months 9, 12 and 24
Population: Two Switchover Patients completed 18 months treatment due to early closure of the study site and continued in a compassionate use program
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 60 Units/kg | Hemoglobin | Month 12 | 12.2 g/dL |
| 60 Units/kg | Hemoglobin | Baseline | 10.6 g/dL |
| 60 Units/kg | Hemoglobin | Month 9 | 11.9 g/dL |
| 60 Units/kg | Hemoglobin | Month 24 | 12.8 g/dL |
| 30 Units/kg | Hemoglobin | Month 24 | 13.1 g/dL |
| 30 Units/kg | Hemoglobin | Month 12 | 12.8 g/dL |
| 30 Units/kg | Hemoglobin | Month 9 | 12.5 g/dL |
| 30 Units/kg | Hemoglobin | Baseline | 11.2 g/dL |
| Switchover | Hemoglobin | Month 24 | 14.2 g/dL |
| Switchover | Hemoglobin | Baseline | 13.5 g/dL |
| Switchover | Hemoglobin | Month 9 | 13.9 g/dL |
| Switchover | Hemoglobin | Month 12 | 13.7 g/dL |
Secondary
Chitotriosidase
Chitotriosidase. Baseline is the value obtained from the parent study: PB-06-005 for 30 and 60 Units/kg arms and PB-06-002 from Switchover arm.
Time frame: Baseline, months 9, 12 and 24
Population: Chitotriosidase was not analyzed for the subjects in the Switchover group
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 60 Units/kg | Chitotriosidase | Baseline | 34968 nmol/mL*h | Standard Deviation 20928 |
| 60 Units/kg | Chitotriosidase | Month 9 | 17416 nmol/mL*h | Standard Deviation 16821 |
| 60 Units/kg | Chitotriosidase | Month 12 | 14677 nmol/mL*h | Standard Deviation 14418 |
| 60 Units/kg | Chitotriosidase | Month 24 | 7449.5 nmol/mL*h | Standard Deviation 6966.5 |
| 30 Units/kg | Chitotriosidase | Month 24 | 10079 nmol/mL*h | Standard Deviation 9452.4 |
| 30 Units/kg | Chitotriosidase | Baseline | 30783 nmol/mL*h | Standard Deviation 17771 |
| 30 Units/kg | Chitotriosidase | Month 12 | 13823 nmol/mL*h | Standard Deviation 11525 |
| 30 Units/kg | Chitotriosidase | Month 9 | 13983 nmol/mL*h | Standard Deviation 10562 |
Secondary
Liver Volume
Liver volume by MRI or Ultrasound. Baseline is the value obtained from the parent study: PB-06-005 for 30 and 60 Units/kg arms and PB-06-002 from Switchover arm.
Time frame: Baseline, months 12 and 24
Population: Two Switchover Patients completed 18 months treatment due to early closure of the study site and continued in a compassionate use program
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 60 Units/kg | Liver Volume | Baseline | 991.7 Milliliters | Standard Error 134.7 |
| 60 Units/kg | Liver Volume | Month 12 | 849.1 Milliliters | Standard Error 121.6 |
| 60 Units/kg | Liver Volume | Month 24 | 865.5 Milliliters | Standard Error 82.4 |
| 60 Units/kg | Liver Volume | Month 33-36 | 890.6 Milliliters | Standard Error 118.2 |
| 30 Units/kg | Liver Volume | Month 33-36 | 1244.8 Milliliters | Standard Error 89.1 |
| 30 Units/kg | Liver Volume | Baseline | 1236.5 Milliliters | Standard Error 210.6 |
| 30 Units/kg | Liver Volume | Month 24 | 1254.4 Milliliters | Standard Error 114.9 |
| 30 Units/kg | Liver Volume | Month 12 | 1140.6 Milliliters | Standard Error 180.9 |
| Switchover | Liver Volume | Month 33-36 | 1274.2 Milliliters | Standard Error 189.7 |
| Switchover | Liver Volume | Month 12 | 1460.7 Milliliters | Standard Error 227.8 |
| Switchover | Liver Volume | Month 24 | 1480.7 Milliliters | Standard Error 253.3 |
| Switchover | Liver Volume | Baseline | 1345.6 Milliliters | Standard Error 193.1 |
Secondary
Platelet Count
Platelet count. Baseline is the value obtained from the parent study: PB-06-005 for 30 and 60 Units/kg arms and PB-06-002 from Switchover arm.
Time frame: Baseline, months 9, 12, 24 and 33-36
Population: Two Switchover Patients completed 18 months treatment due to early closure of the study site and continued in a compassionate use program
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 60 Units/kg | Platelet Count | Month 12 | 172200 Platelets/mm^3 | Standard Error 39932 |
| 60 Units/kg | Platelet Count | Month 9 | 172600 Platelets/mm^3 | Standard Error 38667 |
| 60 Units/kg | Platelet Count | Month 24 | 192800 Platelets/mm^3 | Standard Error 26673 |
| 60 Units/kg | Platelet Count | Baseline | 99600 Platelets/mm^3 | Standard Error 19185 |
| 60 Units/kg | Platelet Count | Month 33-36 | 243750 Platelets/mm^3 | Standard Error 18585 |
| 30 Units/kg | Platelet Count | Month 12 | 233800 Platelets/mm^3 | Standard Error 32759 |
| 30 Units/kg | Platelet Count | Baseline | 182000 Platelets/mm^3 | Standard Error 27009 |
| 30 Units/kg | Platelet Count | Month 9 | 221400 Platelets/mm^3 | Standard Error 30626 |
| 30 Units/kg | Platelet Count | Month 24 | 207600 Platelets/mm^3 | Standard Error 18291 |
| 30 Units/kg | Platelet Count | Month 33-36 | 220200 Platelets/mm^3 | Standard Error 29231 |
| Switchover | Platelet Count | Month 33-36 | 210000 Platelets/mm^3 | Standard Error 10000 |
| Switchover | Platelet Count | Month 24 | 234800 Platelets/mm^3 | Standard Error 14867 |
| Switchover | Platelet Count | Month 12 | 189000 Platelets/mm^3 | Standard Error 7733 |
| Switchover | Platelet Count | Month 9 | 177400 Platelets/mm^3 | Standard Error 16795 |
| Switchover | Platelet Count | Baseline | 164587 Platelets/mm^3 | Standard Error 17321 |
Secondary
Spleen Volume
Spleen volume measured by MRI (or ultrasound). Baseline is the value obtained from the parent study: PB-06-005 for 30 and 60 Units/kg arms and PB-06-002 from Switchover arm.
Time frame: Baseline, months 12 and 24
Population: Two Switchover Patients completed 18 months treatment due to early closure of the study site and continued in a compassionate use program
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 60 Units/kg | Spleen Volume | Baseline | 1023.1 Milliliters | Standard Error 336.9 |
| 60 Units/kg | Spleen Volume | 12 Months | 524.0 Milliliters | Standard Error 125.7 |
| 60 Units/kg | Spleen Volume | 24 Months | 395.8 Milliliters | Standard Error 76.8 |
| 60 Units/kg | Spleen Volume | 33-36 Months | 306.1 Milliliters | Standard Error 55.1 |
| 30 Units/kg | Spleen Volume | 33-36 Months | 673.2 Milliliters | Standard Error 128.7 |
| 30 Units/kg | Spleen Volume | Baseline | 1244.7 Milliliters | Standard Error 317.6 |
| 30 Units/kg | Spleen Volume | 24 Months | 719.0 Milliliters | Standard Error 161.2 |
| 30 Units/kg | Spleen Volume | 12 Months | 759.0 Milliliters | Standard Error 194.4 |
| Switchover | Spleen Volume | 33-36 Months | 185.4 Milliliters | Standard Error 12.6 |
| Switchover | Spleen Volume | 12 Months | 274.1 Milliliters | Standard Error 39.3 |
| Switchover | Spleen Volume | 24 Months | 249.5 Milliliters | Standard Error 69.8 |
| Switchover | Spleen Volume | Baseline | 313.0 Milliliters | Standard Error 69.8 |