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

Phase 2

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
GA-GCB (velaglucerase alfa)	GA-GCB (velaglucerase alfa)	15-60 U/kg, every other week via intravenous infusion

Primary Outcome Measures

Name	Time	Method
Participants Who Experienced at Least One Adverse Event	Week 53	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.

Secondary Outcome Measures

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

Locations (15): Feinberg School of Medicine
🇺🇸
Chicago, Illinois, United States
NYU School of Medicine
🇺🇸
New York, New York, United States
Children's Memorial Health Institute
🇵🇱
Warszawa, Poland
Emory University
🇺🇸
Decatur, Georgia, United States
Regional Metabolic Center
🇺🇸
Los Angeles, California, United States
Children's Mercy Hospital and Clinic
🇺🇸
Kansas City, Missouri, United States
Shaare Zedek Medical Center
🇮🇱
Jerusalem, Israel
Hospital Universitario Miguel Servet
🇪🇸
Zaragoza, Spain
The Royal Free Hospital
🇬🇧
London, United Kingdom
Children's of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Cincinatti Children's Hospital
🇺🇸
Cincinnati, Ohio, United States
Texas Children's Hospital
🇺🇸
Houston, Texas, United States
Medical Genetics/Pediatrics
🇺🇸
Salt Lake City, Utah, United States
Children's Hospital of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Children's Hospital Oakland
🇺🇸
Oakland, California, United States