Study of GA-GCB Enzyme Replacement Therapy in Type 1 Gaucher Disease Patients Previously Treated With Imiglucerase

Study Overview
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Brief Summary
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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 safety and efficacy of every other week dosing of GA-GCB (velaglucerase alfa) in participants with type 1 Gaucher disease who were previously treated with imiglucerase.

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 safety of GA-GCB in men, women, and children with Type 1 Gaucher disease who were previously treated with imiglucerase. Each participant's duration of treatment will be 12 months.

Official Title
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A Multicenter Open-Label Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease Previously Treated With Imiglucerase

Conditions
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Gaucher Disease

Intervention / Treatment
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* Biological: GA-GCB (velaglucerase alfa)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Includes: The participant has a documented diagnosis of type 1 Gaucher disease, as determined by deficient glucocerebrosidase (GCB) activity relative to normal as measured in leukocytes or by genotype analysis and the participant/legal guardian is willing and able to provide written informed consent prior to initiating any study-related procedures The participant has received consistent treatment with imiglucerase at a dose ≤ 60 U/kg and ≥ 15 U/kg every other week for a minimum of 30 consecutive months. Participants who are anti-imiglucerase antibody positive will be allowed to enter this study The participant is at least 2 years of age Female participants of child-bearing potential agree to use a medically acceptable method of contraception. Male participants must agree to use a medically acceptable method of birth control Participant must be sufficiently co-operative to participate in the study as judged by the Investigator. Exclusion Criteria: Includes: The participant has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease The participant has received treatment with any investigational drug or device within the 30 days prior to study entry; such use during the study is not permitted Participant is HIV positive Participant is hepatitis B/C positive The participant presents with sustained iron, folic acid and/or vitamin B12 deficiency-related anemia during Screening The participant, participant's parent(s), or participant's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study The participant has a significant comorbidity that might affect study data or confound the study results The participant is unable to comply with the protocol or is otherwise unlikely to complete the study, as determined by the Investigator The participant has experienced an anaphylactic/anaphylactoid reaction during treatment with imiglucerase The participant has received miglustat during the 6 months prior to study enrollment The participant has an active, clinically significant spleen infarction The participant has active, progressive bone necrosis The participant is a pregnant and/or lactating female

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GA-GCB (velaglucerase alfa)<br>15-60 U/kg, every other week via intravenous infusion | Biological: GA-GCB (velaglucerase alfa)<br>* 15-60 U/kg, every other week via intravenous infusion<br>* Other names: GA-GCB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants Who Experienced at Least One Adverse Event | Safety was assessed throughout the study by assessments including adverse events, concomitant medication use, and vital signs. Additional safety assessments, including 12-lead ECGs, physical examinations, clinical laboratory tests and determination of the presence of anti-velaglucerase alfa antibodies. Refer to Adverse event section for further details. | Week 53 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 53 in Hemoglobin Concentration |  | Week 53 | 
| Percent Change From Baseline to Week 53 in Platelet Count |  | Week 53 | 
| Percent Change From Baseline to Week 51 in Normalized Liver Volume | Liver volume has been normalized for percentage (%) of body weight. Liver size relative to body weight= (Liver volume [cc]/Body weight [kg])*100 | Week 51 | 
| Percent Change From Baseline to Week 51 in Normalized Spleen Volume | Spleen volume has been normalized for percentage (%) of body weight. Spleen size relative to body weight= (Spleen volume [cc]/Body weight [kg])*100 | Week 51 | 

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