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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
25
Intravenous (IV) infusion, every other week via intravenous infusion for 12 months
Hipolito Yrigoyen
Buenos Aires, Argentina
Shaare Zedek Medical Center
Jerusalem, Israel
Sociedad Espanola de Socorros Mutuos
Asunción, Paraguay
National Research Center for Haematology
Moscow, Russia
La Rabta Hospital
Change From Baseline to 12 Months in Hemoglobin Concentration for the 60 U/kg Treatment Group.
Efficacy endpoint
Time frame: Week 53
Change From Baseline to 12 Months in Hemoglobin Concentration in 45 U/kg Treatment Group
Time frame: Week 53
Change From Baseline to 12 Months in Platelet Counts for Each Treatment Group.
intent to treat (ITT) Population
Time frame: Week 53
Change From Baseline to 12 Months in Normalized Liver Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI)
Liver Volume has been normalized for percentage of body weight for each treatment arm. Liver size relative to body weight = (Liver volume \[cc\]/Body weight \[kg\])\*100
Time frame: Week 51
Change From Baseline to 12 Months in Normalized Spleen Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI))
12 patients in the 60 U/kg group and 13 patients in the 45 U/kg group were analyzed for efficacy in the intent to treat (ITT) population. Spleen Volume has been normalized for percent of body weight for each treatment arm. Spleen size relative to body weight = (Spleen volume \[cc\]/Body weight \[kg\])\*100
Time frame: Week 51
Percent Change From Baseline to 12 Months in Plasma Chitotriosidase for Each Treatment Group
Percent Change from Baseline to Weeks 53 by Randomized velaglucerase alfa Treatment Group - Subset of intent to treat (ITT) Population who were wild type homozygous for chitotriosidase.
Time frame: Week 53
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Tunis, Tunisia
Percent Change From Baseline to 12 Months in Chemokine (C-C Motif) Ligand 18 (CCL18)
Time frame: Week 53