Gaucher Disease
Conditions
Keywords
gaucher disease, pediatric
Brief summary
This is a multi-center, double-blind trial to assess the safety and efficacy of taliglucerase alfa in untreated subjects (2 to \<18 years old) with Gaucher disease randomly assigned to treatment with one of two doses, 30 or 60 units/kg. Subjects will receive an intravenous (IV) infusion of taliglucerase alfa every two weeks. The total duration of treatment will be 12 months. At the end of the 12-month treatment period eligible subjects will be offered enrollment in an open-label extension study if taliglucerase alfa is not commercially available.
Interventions
Taliglucerase alfa for infusion every two weeks for 12 months
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Males and females 2 to \<18 years old. * Diagnosis of Gaucher disease with leukocyte acid β-glucosidase activity ≤30% of the mean of the reference range for healthy subjects. * Subjects who have not received enzyme replacement therapy (ERT) in the past or who have not received ERT in the past 12 months and have a negative anti-glucocerebrosidase antibody assay. * Subjects who have not received substrate reduction therapy (SRT) in the past 12 months. * Subjects whose clinical condition, in the opinion of the investigator, requires treatment with enzyme replacement therapy (ERT).
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 unresolved anemia due to iron, folic acid, or vitamin B12 deficiency * Previous hypersensitivity reaction to Cerezyme® (imiglucerase) or Ceredase® (alglucerase). * History of allergy to carrots. * Presence of HIV, HBsAg or hepatitis C infections. * Subject's parent(s) or legal guardian(s) are unable to understand the nature, scope and possible consequences of the study. * 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 | Every 3 months for 12 months | median and interquartile range for change from baseline in haemoglobin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Chitotriosidase | Every 3 months for 12 months | Percent change from baseline in chitotriosidase |
| Spleen Volume | Baseline and Month 12 | Spleen volume measured by MRI |
| Platelet Count | Baseline and 12 months | Mean and standard deviation of platelet count per cubic mm |
| Chemokine (C-C Motif) Ligand 18 (CCL18) | Every 3 months for 12 months | Percent change from baseline in CCL18 |
| Liver Volume | Baseline and Month 12 | Liver volume measured by MRI |
Countries
Israel, Paraguay, South Africa
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 30 Units/kg Taliglucerase alfa: Taliglucerase alfa for infusion every two weeks for 12 months | 6 |
| 60 Units/kg Taliglucerase alfa: Taliglucerase alfa for infusion every two weeks for 12 months | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | 30 Units/kg | 60 Units/kg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 6 Participants | 5 Participants | 11 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 9.5 years STANDARD_DEVIATION 4 | 6.6 years STANDARD_DEVIATION 3.1 | 8.2 years STANDARD_DEVIATION 3.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 6 Participants | 4 Participants | 10 Participants |
| Region of Enrollment Israel | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Paraguay | 3 participants | 1 participants | 4 participants |
| Region of Enrollment South Africa | 1 participants | 2 participants | 3 participants |
| Religion Jewish - Ashkenazi | 0 participants | 2 participants | 2 participants |
| Religion Jewish - Non-Ashkenazi | 0 participants | 0 participants | 0 participants |
| Religion Non Jewish | 6 participants | 3 participants | 9 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 2 / 5 |
| serious Total, serious adverse events | 0 / 6 | 1 / 5 |
Outcome results
Primary
Hemoglobin
median and interquartile range for change from baseline in haemoglobin
Time frame: Every 3 months for 12 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 30 Units/kg | Hemoglobin | Month 3 | 1.2 g/dL |
| 30 Units/kg | Hemoglobin | Month 6 | 1.1 g/dL |
| 30 Units/kg | Hemoglobin | Month 9 | 0.9 g/dL |
| 30 Units/kg | Hemoglobin | Month 12 | 1.4 g/dL |
| 60 Units/kg | Hemoglobin | Month 12 | 1.6 g/dL |
| 60 Units/kg | Hemoglobin | Month 3 | 0.4 g/dL |
| 60 Units/kg | Hemoglobin | Month 9 | 1.5 g/dL |
| 60 Units/kg | Hemoglobin | Month 6 | 1.5 g/dL |
Secondary
Chemokine (C-C Motif) Ligand 18 (CCL18)
Percent change from baseline in CCL18
Time frame: Every 3 months for 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 30 Units/kg | Chemokine (C-C Motif) Ligand 18 (CCL18) | Month 3 | -31.4 Percent Change from Baseline | Standard Deviation 15.3 |
| 30 Units/kg | Chemokine (C-C Motif) Ligand 18 (CCL18) | Month 6 | -45.7 Percent Change from Baseline | Standard Deviation 11.9 |
| 30 Units/kg | Chemokine (C-C Motif) Ligand 18 (CCL18) | Month 9 | -49.9 Percent Change from Baseline | Standard Deviation 13 |
| 30 Units/kg | Chemokine (C-C Motif) Ligand 18 (CCL18) | Month 12 | -50.6 Percent Change from Baseline | Standard Deviation 19.4 |
| 60 Units/kg | Chemokine (C-C Motif) Ligand 18 (CCL18) | Month 12 | -52.6 Percent Change from Baseline | Standard Deviation 22.5 |
| 60 Units/kg | Chemokine (C-C Motif) Ligand 18 (CCL18) | Month 3 | -18.3 Percent Change from Baseline | Standard Deviation 16.3 |
| 60 Units/kg | Chemokine (C-C Motif) Ligand 18 (CCL18) | Month 9 | -46.5 Percent Change from Baseline | Standard Deviation 22.4 |
| 60 Units/kg | Chemokine (C-C Motif) Ligand 18 (CCL18) | Month 6 | -37.3 Percent Change from Baseline | Standard Deviation 28.8 |
Secondary
Chitotriosidase
Percent change from baseline in chitotriosidase
Time frame: Every 3 months for 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 30 Units/kg | Chitotriosidase | Month 3 | -32.4 Percent Change from Baseline | Standard Deviation 23.5 |
| 30 Units/kg | Chitotriosidase | Month 6 | -49.6 Percent Change from Baseline | Standard Deviation 19.8 |
| 30 Units/kg | Chitotriosidase | Month 9 | -57.2 Percent Change from Baseline | Standard Deviation 18.7 |
| 30 Units/kg | Chitotriosidase | Month 12 | -58.5 Percent Change from Baseline | Standard Deviation 17.5 |
| 60 Units/kg | Chitotriosidase | Month 12 | -66.1 Percent Change from Baseline | Standard Deviation 20.1 |
| 60 Units/kg | Chitotriosidase | Month 3 | -32.7 Percent Change from Baseline | Standard Deviation 15.1 |
| 60 Units/kg | Chitotriosidase | Month 9 | -58.9 Percent Change from Baseline | Standard Deviation 21.8 |
| 60 Units/kg | Chitotriosidase | Month 6 | -50.2 Percent Change from Baseline | Standard Deviation 23.7 |
Secondary
Liver Volume
Liver volume measured by MRI
Time frame: Baseline and Month 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 30 Units/kg | Liver Volume | Baseline | 1214 mL | Standard Deviation 424.7 |
| 30 Units/kg | Liver Volume | Month 12 | 1116 mL | Standard Deviation 366.9 |
| 60 Units/kg | Liver Volume | Baseline | 991.7 mL | Standard Deviation 301.3 |
| 60 Units/kg | Liver Volume | Month 12 | 849.1 mL | Standard Deviation 271.9 |
Secondary
Platelet Count
Mean and standard deviation of platelet count per cubic mm
Time frame: Baseline and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 30 Units/kg | Platelet Count | Baseline | 162667 platelets per cubic mm | Standard Deviation 71838 |
| 30 Units/kg | Platelet Count | Month 12 | 208167 platelets per cubic mm | Standard Deviation 90747 |
| 60 Units/kg | Platelet Count | Baseline | 99600 platelets per cubic mm | Standard Deviation 42899 |
| 60 Units/kg | Platelet Count | Month 12 | 172200 platelets per cubic mm | Standard Deviation 89290 |
Secondary
Spleen Volume
Spleen volume measured by MRI
Time frame: Baseline and Month 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 30 Units/kg | Spleen Volume | Baseline | 1218 mL | Standard Deviation 638.4 |
| 30 Units/kg | Spleen Volume | Month 12 | 811.6 mL | Standard Deviation 409.6 |
| 60 Units/kg | Spleen Volume | Baseline | 1023 mL | Standard Deviation 753.4 |
| 60 Units/kg | Spleen Volume | Month 12 | 524.0 mL | Standard Deviation 281.1 |