An Open-Label Extension Study of GA-GCB ERT in Patients With Type 1 Gaucher Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term safety of every other week dosing of Gene-Activated® human glucocerebrosidase (GA-GCB, velaglucerase alfa) intravenously in patients with type 1 Gaucher disease.

Detailed Description
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Type 1 Gaucher disease, the most common form,accounts for more than 90% of all cases and does not involve the 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 (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 contains terminal mannose residues that target the enzyme to the macrophages-the primary target cells in Gaucher disease. This study was designed to determine the long-term safety of GA-GCB in men, women, and children with Type 1 Gaucher disease.

Official Title
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An Open-Label Extension Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease

Conditions
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Gaucher Disease, Type 1

Intervention / Treatment
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* Biological: VPRIV®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has completed study TKT032 or TKT034, or study HGT-GCB-039. Female patients of child-bearing potential must agree to use a medically acceptable method of contraception at all times during the study and must have negative results to a pregnancy test performed at the time of enrollment and as required throughout their participation in the study. Male patients must agree to use a medically acceptable method of contraception at all times during the study and report a partner's pregnancy to the investigator. The patient, the patient's parent(s) or legal guardian(s) has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC). The patient must be sufficiently cooperative to participate in this clinical study as judged by the Investigator Exclusion Criteria: The patient has received treatment with any non-Gaucher disease-related investigational drug or device within the 30 days prior to study entry; such use during the study is not permitted. The patient is pregnant or lactating. The patient, patient's parent(s), or patient's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study. The patient has a significant comorbidity(ies) that might affect study data or confound the study results (e.g., malignancies, primary biliary cirrhosis, autoimmune liver disease, etc.). The patient is unable to comply with the protocol, e.g., has a clinically relevant medical condition making implementation of the protocol difficult, has an uncooperative attitude, is unable to return for safety evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039)<br>This arm is the Overall velaglucerase alfa (VPRIV) 60 U/kg and includes patients from the following groups: VPRIV 45 U/kg or 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (NCT00430625) and switched to 60 U/kg in HGT-GCB-044 to maintain blindness or 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631) | Biological: VPRIV®<br>* Intravenous infusion, every other week (EOW)<br>* Other names: Gene-Activated® Human Glucocerebrosidase(GA-GCB);|
| Experimental: VPRIV 60 U/kg (Parent study-imiglucerase(60 U/kg) HGT-GCB-039)<br>imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)and switched 60 U/kg VPRIV in HGT-GCB-044 | Biological: VPRIV®<br>* Intravenous infusion, every other week (EOW)<br>* Other names: Gene-Activated® Human Glucocerebrosidase(GA-GCB);|
| Experimental: VPRIV 15-60 U/kg (Parent study VPRIV (15-60 U/kg) TKT034)<br>VPRIV 15- 60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647) and continued in HGT-GCB-044 at the same dose as prescribed in TKT034 | Biological: VPRIV®<br>* Intravenous infusion, every other week (EOW)<br>* Other names: Gene-Activated® Human Glucocerebrosidase(GA-GCB);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Summary of Treatment Emergent Adverse Events | Safety was evaluated by an analysis of adverse events (AEs), concomitant medication use, clinical laboratory tests, vital signs during the infusion of study drug, physical examination, and the development of anti-velaglucerase alfa. No formal comparisons or statistical tests were applied for the safety analyses, including for differences between the groups. | Baseline to termination of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 24 Months in Hemoglobin Concentration for Each Treatment Group |  | Baseline to 24 months | 
| Change From Baseline to 24 Months in Platelet Counts for Each Treatment Group |  | Baseline to 24 months | 
| Change From Baseline to 24 Months in Normalized Liver Volume for Each Treatment Group |  | Baseline to 24 months | 
| Percentage Change From Baseline to 24 Months in Normalized Spleen Volume for Each Treatment Group |  | Baseline to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VPRIV, Enzyme Replacement Therapy, Gaucher disease, glucocerebrosidase, beta-glucocerebrosidase, Acid beta-glucocerebrosidase, glucosylceramidase, D-glucosyl-N-acylsphingosine glucohydrolase, gene activation, human