Gaucher Disease
Conditions
Keywords
Gaucher disease, Enzyme Replacement Therapy
Brief summary
Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to the deficiency of functional GCB, glucocerebroside accumulates within macrophages leading to cellular engorgement, organomegaly, and organ system dysfunction. The purpose of this study is to evaluate the long term safety of enzyme replacement therapy with DRX008A (VPRIV®, GA-GCB; velaglucerase alfa) in patients with type 1 Gaucher disease.
Detailed description
Type 1 Gaucher disease, the most common form, accounts for more than 90% of all cases and does not involve the central nervous system (CNS). Typical manifestations of type 1 Gaucher disease include hepatomegaly, splenomegaly, thrombocytopenia, bleeding tendencies, anemia, hypermetabolism, skeletal pathology, growth retardation, pulmonary disease, and decreased quality of life. Gene-Activated® human glucocerebrosidase (the long term safety of enzyme replacement therapy with DRX008A (GA-GCB; velaglucerase alfa) is produced in a continuous human cell line using proprietary gene-activation technology and has an identical amino acid sequence to the naturally occurring human enzyme. GA-GCB (velaglucerase alfa) contains terminal mannose residues that target the enzyme to the macrophages-the primary target cells in Gaucher disease. This study was designed to evaluate the long term safety of GA-GCB (velaglucerase alfa) in patients with Type 1 Gaucher disease
Interventions
DRUGGA-GCB
15-60 U/kg every other week via intravenous infusion
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who have completed through Week 41 visit in the TKT025 study. * Patients must have voluntarily signed an IRB/EC approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient. * Patient must be sufficiently cooperative to participate in this clinical study as judged by the Investigator. * Female and male patients of child bearing potential must agree to use a medically acceptable method of contraception at all times during the study. Female patients must have a negative serum pregnancy test on enrollment.
Exclusion criteria
* Patient has received treatment with non-Gaucher disease related investigational drug or device within the past 30 days prior to study entry; such use during the study is not permitted. * Patient has a clinically relevant medical condition (e.g., HIV, hepatitis B or C) that would make implementation of the protocol difficult and/or confound an assessment of the effects of the experimental therapy and its adverse events. * Patient, patient's parent(s), or patient's legal guardian is unable to understand the nature, scope and possible consequences of the study. * Patient is unable to comply with the protocol, e.g. uncooperative attitude, medical condition, inability to return for safety evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Long Term Safety | Up to 84 months | Overall Summary of Treatment-emergent Adverse Events-Safety Population |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Hemoglobin Concentration | Baseline, then every 12 months |
| Percent Change From Baseline in Platelet Counts | Baseline, then every 12 months |
| Percent Change From Baseline in Liver Volume | Baseline, Month 24, then every 9 or 12 months |
| Percent Change From Baseline in Spleen Size | Baseline, Month 24, then every 9 or 12 months |
Countries
Israel, Romania, Serbia
Participant flow
Recruitment details
The first patient was enrolled on 3 February 2005.
Pre-assignment details
Recruitment of patients was limited to those patient who completed first in man, Phase I/II study TKT025, elected to continue to receive treatment with velaglucerase alfa and met the study inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| GA-GCB 15-60 U/kg every other week via intravenous infusion | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Month 14 | Withdrawal by Subject | 1 |
| Month 50 | Physician Decision | 1 |
Baseline characteristics
| Characteristic | GA-GCB |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 39.8 years STANDARD_DEVIATION 16.34 |
| Region of Enrollment Israel | 8 Participants |
| Region of Enrollment Romania | 1 Participants |
| Region of Enrollment Serbia | 1 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 4 / 10 |
Outcome results
Primary
Evaluation of Long Term Safety
Overall Summary of Treatment-emergent Adverse Events-Safety Population
Time frame: Up to 84 months
Population: ITT patient population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Number (#) Experienced no Adverse Event (AE) | Evaluation of Long Term Safety | 0 Participants |
| # Experienced at Least 1 AE | Evaluation of Long Term Safety | 10 Participants |
| # Experienced at Least 1 Drug-related AE | Evaluation of Long Term Safety | 1 Participants |
| # Experienced at Least 1 Infusion-related AE | Evaluation of Long Term Safety | 1 Participants |
| # Experienced at Least 1 Severe AE | Evaluation of Long Term Safety | 2 Participants |
| # Experienced at Least 1 Drug-related Severe AE | Evaluation of Long Term Safety | 0 Participants |
| # Experienced at Least 1 Life-threatening AE | Evaluation of Long Term Safety | 0 Participants |
| # Experienced at Least 1 Serious AE | Evaluation of Long Term Safety | 4 Participants |
| # Experienced at Least 1 Drug-related Serious AE | Evaluation of Long Term Safety | 0 Participants |
| # Discontinued Due to an AE | Evaluation of Long Term Safety | 0 Participants |
| # Deaths | Evaluation of Long Term Safety | 0 Participants |
Secondary
Percent Change From Baseline in Hemoglobin Concentration
Time frame: Baseline, then every 12 months
Population: Intent to treat (ITT) patient population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Number (#) Experienced no Adverse Event (AE) | Percent Change From Baseline in Hemoglobin Concentration | 20.91 Percent Change from Baseline | Standard Error 1.962 |
| # Experienced at Least 1 AE | Percent Change From Baseline in Hemoglobin Concentration | 20.74 Percent Change from Baseline | Standard Error 2.251 |
| # Experienced at Least 1 Drug-related AE | Percent Change From Baseline in Hemoglobin Concentration | 19.17 Percent Change from Baseline | Standard Error 2.365 |
| # Experienced at Least 1 Infusion-related AE | Percent Change From Baseline in Hemoglobin Concentration | 20.96 Percent Change from Baseline | Standard Error 3.248 |
| # Experienced at Least 1 Severe AE | Percent Change From Baseline in Hemoglobin Concentration | 16.58 Percent Change from Baseline | Standard Error 2.437 |
| # Experienced at Least 1 Drug-related Severe AE | Percent Change From Baseline in Hemoglobin Concentration | 17.48 Percent Change from Baseline | Standard Error 2.317 |
| # Experienced at Least 1 Life-threatening AE | Percent Change From Baseline in Hemoglobin Concentration | 17.97 Percent Change from Baseline | Standard Error 2.46 |
Secondary
Percent Change From Baseline in Liver Volume
Time frame: Baseline, Month 24, then every 9 or 12 months
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Number (#) Experienced no Adverse Event (AE) | Percent Change From Baseline in Liver Volume | -28.00 Percent Change from Baseline | Standard Error 4.835 |
| # Experienced at Least 1 AE | Percent Change From Baseline in Liver Volume | -30.95 Percent Change from Baseline | Standard Error 3.627 |
| # Experienced at Least 1 Drug-related AE | Percent Change From Baseline in Liver Volume | -39.35 Percent Change from Baseline | Standard Error 4.739 |
| # Experienced at Least 1 Infusion-related AE | Percent Change From Baseline in Liver Volume | -38.99 Percent Change from Baseline | Standard Error 4.567 |
| # Experienced at Least 1 Severe AE | Percent Change From Baseline in Liver Volume | -39.78 Percent Change from Baseline | Standard Error 4.821 |
| # Experienced at Least 1 Drug-related Severe AE | Percent Change From Baseline in Liver Volume | -42.07 Percent Change from Baseline | Standard Error 4.705 |
Secondary
Percent Change From Baseline in Platelet Counts
Time frame: Baseline, then every 12 months
Population: ITT patient population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Number (#) Experienced no Adverse Event (AE) | Percent Change From Baseline in Platelet Counts | 78.21 Percent Change from Baseline | Standard Error 15.127 |
| # Experienced at Least 1 AE | Percent Change From Baseline in Platelet Counts | 99.60 Percent Change from Baseline | Standard Error 15.324 |
| # Experienced at Least 1 Drug-related AE | Percent Change From Baseline in Platelet Counts | 111.57 Percent Change from Baseline | Standard Error 13.723 |
| # Experienced at Least 1 Infusion-related AE | Percent Change From Baseline in Platelet Counts | 132.61 Percent Change from Baseline | Standard Error 18.461 |
| # Experienced at Least 1 Severe AE | Percent Change From Baseline in Platelet Counts | 139.73 Percent Change from Baseline | Standard Error 27.89 |
| # Experienced at Least 1 Drug-related Severe AE | Percent Change From Baseline in Platelet Counts | 126.20 Percent Change from Baseline | Standard Error 20.445 |
| # Experienced at Least 1 Life-threatening AE | Percent Change From Baseline in Platelet Counts | 114.93 Percent Change from Baseline | Standard Error 21.783 |
Secondary
Percent Change From Baseline in Spleen Size
Time frame: Baseline, Month 24, then every 9 or 12 months
Population: ITT (One patient was excluded due to an intravascular metallic device that prevented accurate spleen evaluation.)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Number (#) Experienced no Adverse Event (AE) | Percent Change From Baseline in Spleen Size | -66.86 Percent Change from Baseline | Standard Error 6.286 |
| # Experienced at Least 1 AE | Percent Change From Baseline in Spleen Size | -68.09 Percent Change from Baseline | Standard Error 6.204 |
| # Experienced at Least 1 Drug-related AE | Percent Change From Baseline in Spleen Size | -73.56 Percent Change from Baseline | Standard Error 6.717 |
| # Experienced at Least 1 Infusion-related AE | Percent Change From Baseline in Spleen Size | -73.97 Percent Change from Baseline | Standard Error 6.663 |
| # Experienced at Least 1 Severe AE | Percent Change From Baseline in Spleen Size | -75.96 Percent Change from Baseline | Standard Error 6.819 |
| # Experienced at Least 1 Drug-related Severe AE | Percent Change From Baseline in Spleen Size | -77.82 Percent Change from Baseline | Standard Error 7.002 |