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 non-inferiority study is to evaluate the efficacy and safety of GA-GCB (velaglucerase alfa) administered every other week in comparison to imiglucerase in treatment naive 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 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 (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 and safety of GA-GCB (velaglucerase alfa) in comparison to imiglucerase in men, women, and children with Type 1 Gaucher disease.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
34
IV infusion, 60 U/kg every other week for 9 months
IV infusion, 60 U/kg every other week for 9 months
Duke Children's Hospital & Health Center
Durham, North Carolina, United States
Your Health S.A.
Buenos Aires, Argentina
Malabar Institute of Medical Sciences Ltd.
Calicut, Kerala, India
Mean Change From Baseline to Month 9 in Hemoglobin (Hgb) Concentration for Each Treatment Group.
Time frame: Baseline to Month 9
Change From Baseline to Month 9 in Platelet Counts for Each Treatment Group.
Values shown are observed change from Baseline to Month 9.
Time frame: Baseline to Month 9
Change From Baseline to Month 9 in Normalized Liver Volume (Percent (%) Body Weight) for Each Treatment Group.
Values shown are observed change from Baseline to Month 9. Measured by Magnetic resonance imaging (MRI). Liver volume has been normalized for percent (%) body weight for each treatment arm. Liver size relative to body weight = (Liver volume \[cubic centimeter (cc)\]/Body weight \[kg\]\*1000.
Time frame: Baseline to Month 9
Change From Baseline to Month 9 in Normalized Spleen Volume (Percent (%) Body Weight) for Each Treatment Group.
Values shown are observed change from Baseline to month 9. Measured by Magnetic resonance imaging (MRI). Spleen volume was 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: Baseline to Month 9
Change From Baseline to Month 9 in Plasma Chitotriosidase for Each Treatment Group.
Values shown are observed change from Baseline to Month 9. Units of measure is defined as nanomole per milliliter per hour.
Time frame: Baseline to Month 9.
Change From Baseline to Month 9 in Plasma Chemokine (C-C Motif) Ligand 18 (CCL18) for Each Treatment Group.
Values shown are observed change from Baseline to Month 9.
Time frame: Baseline to Month 9
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All India Institute of Medical Sciences
New Delhi, India
KEM Hospital Research Centre
Pune, India
Shaare Zedek Medical Center
Jerusalem, Israel
Sociedad Espanola de Socorros Mutuos
Asunción, Paraguay
National Research Center for Haematology
Moscow, Russia
Hospital Universitario Miguel Servet
Zaragoza, Spain
La Rabta Hospital
Tunis, Tunisia
...and 1 more locations
Number of Participants Who Developed Antibody for Each Treatment Group.
Measure type is actual number of participants who developed antibodies to treatment; GA-GCB or imiglucerase. Antibody detection was based upon serum samples collected at various time points throughout the study. Serum samples were screened using an enzyme-linked immunosorbent assay (ELISA) and positive antibody confirmation was determined using a radioimmunoprecipitation assay (RIP); positive samples were also tested for enzyme neutralizing activity. Participant samples were compared to internal assay controls (positive/negative), positive samples were determined based upon individual assay criteria.
Time frame: Baseline to Month 9
Time to Response- Comparison of GA-GCB and Imiglucerase on the Earliest Time to Respond as Assessed Via Hemoglobin Concentration
Time to response was defined as a ≥ 1 g/dL improvement in hemoglobin levels relative to Baseline. Units (%) correlates to the percentage of participants who had a change of ≥ 1 g/dL improvement in hemoglobin levels relative to Baseline during their participation in the study.
Time frame: Response rate at Month 9 compared to Baseline