A Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Gaucher Disease

A Multicenter, Randomized, Double-Blind, Parallel Group, Two-Dose Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease

Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to this 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 efficacy of every other week dosing of Gene-Activated® Human Glucocerebrosidase (GA-GCB, velaglucerase alfa) at doses of 45 and 60 U/kg in treatment-naïve patients with type 1 Gaucher disease.

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 (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. 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 determine the efficacy, safety and pharmacokinetics of GA-GCB in men, women, and children with Type 1 Gaucher disease. Each patients duration of treatment was 12 months.

Inclusion Criteria:

• Patient 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 is willing and able to provide written informed consent prior to initiating any study-related procedures
• Patient is at least 2 years of age
• Patient has Gaucher disease-related anemia and
• Patient has at least moderate splenomegaly or
• Patient has Gaucher disease-related thrombocytopenia or
• Patient has a readily palpable enlarged liver
• Patient has not received treatment for Gaucher disease within 30 months prior to study entry
• Female patients of child-bearing potential agree to use a medically acceptable method of contraception. Male patients must agree to use a medically acceptable method of birth control.
• Patient must be sufficiently cooperative to participate in the study as judged by the Investigator.

Exclusion Criteria:

Includes:

• Patient has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease
• Patient is antibody-positive to imiglucerase during screening or has experienced an anaphylactic reaction to imiglucerase
• Patient has received treatment with any investigational drug or device within the 30 days prior to study entry
• Patient is Human immunodeficiency virus (HIV) positive
• Patient is hepatitis positive
• Patient presents with iron, folic acid and/or vitamin B12 deficiency sustained anemia during screening
• 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
• Patient has a significant comorbidity(ies)that might affect study data or confound the study results
• Patient is a pregnant and/or lactating female
• Patient is unable to comply with the protocol or is unlikely to complete the study, as determined by the Investigator