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An Open-Label Extension Study of GA-GCB ERT in Patients With Type 1 Gaucher Disease

Phase 3
Completed
Conditions
Gaucher Disease, Type 1
Interventions
Biological: VPRIV®
Registration Number
NCT00635427
Lead Sponsor
Shire
Brief Summary

The purpose of this study is to evaluate the long-term safety of every other week dosing of Gene-Activated® human glucocerebrosidase (GA-GCB, velaglucerase alfa) intravenously in patients with type 1 Gaucher disease.

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 long-term safety of GA-GCB in men, women, and children with Type 1 Gaucher disease.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
95
Inclusion Criteria
  1. The patient has completed study TKT032 or TKT034, or study HGT-GCB-039.
  2. Female patients of child-bearing potential must agree to use a medically acceptable method of contraception at all times during the study and must have negative results to a pregnancy test performed at the time of enrollment and as required throughout their participation in the study.
  3. Male patients must agree to use a medically acceptable method of contraception at all times during the study and report a partner's pregnancy to the investigator.
  4. The patient, the patient's parent(s) or legal guardian(s) has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC).
  5. The patient must be sufficiently cooperative to participate in this clinical study as judged by the Investigator
Exclusion Criteria
  1. The patient has received treatment with any non-Gaucher disease-related investigational drug or device within the 30 days prior to study entry; such use during the study is not permitted.
  2. The patient is pregnant or lactating.
  3. The 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.
  4. The patient has a significant comorbidity(ies) that might affect study data or confound the study results (e.g., malignancies, primary biliary cirrhosis, autoimmune liver disease, etc.).
  5. The patient is unable to comply with the protocol, e.g., has a clinically relevant medical condition making implementation of the protocol difficult, has an uncooperative attitude, is unable to return for safety evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
VPRIV 60 U/kg (Parent study-imiglucerase(60 U/kg) HGT-GCB-039)VPRIV®imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)and switched 60 U/kg VPRIV in HGT-GCB-044
VPRIV 15-60 U/kg (Parent study VPRIV (15-60 U/kg) TKT034)VPRIV®VPRIV 15- 60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647) and continued in HGT-GCB-044 at the same dose as prescribed in TKT034
VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039)VPRIV®This arm is the Overall velaglucerase alfa (VPRIV) 60 U/kg and includes patients from the following groups: VPRIV 45 U/kg or 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (NCT00430625) and switched to 60 U/kg in HGT-GCB-044 to maintain blindness or 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)
Primary Outcome Measures
NameTimeMethod
Overall Summary of Treatment Emergent Adverse EventsBaseline to termination of study

Safety was evaluated by an analysis of adverse events (AEs), concomitant medication use, clinical laboratory tests, vital signs during the infusion of study drug, physical examination, and the development of anti-velaglucerase alfa. No formal comparisons or statistical tests were applied for the safety analyses, including for differences between the groups.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline to 24 Months in Normalized Liver Volume for Each Treatment GroupBaseline to 24 months
Change From Baseline to 24 Months in Hemoglobin Concentration for Each Treatment GroupBaseline to 24 months
Change From Baseline to 24 Months in Platelet Counts for Each Treatment GroupBaseline to 24 months
Percentage Change From Baseline to 24 Months in Normalized Spleen Volume for Each Treatment GroupBaseline to 24 months

Trial Locations

Locations (21)

Shaare Zedek Medical Center

🇮🇱

Jerusalem, Israel

State Institution "Hematology Research Centre RAMS"

🇷🇺

Moscow, Russian Federation

KEM Hospital

🇮🇳

Pune, India

Los Angeles Medical Center

🇺🇸

Los Angeles, California, United States

Children's Hospital Oakland

🇺🇸

Oakland, California, United States

Emory University School of Medicine

🇺🇸

Atlanta, Georgia, United States

Children's Memorial Hospital

🇺🇸

Chicago, Illinois, United States

Children's Mercy Hospitals & Clinics

🇺🇸

Kansas City, Missouri, United States

NYU Medical Center

🇺🇸

New York, New York, United States

Children's Hospitals and Clinics of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

University of Utah Medical Center

🇺🇸

Salt Lake City, Utah, United States

Children's Hospital of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Your Health S.A.

🇦🇷

Buenos Aires, Argentina

All India Institute of Medical Sciences

🇮🇳

New Delhi, India

Gyeongsang National University Hospital

🇰🇷

Jinju, Gyeongsangnam-do, Korea, Republic of

Sociedad Espanola de Socorros Mutuos

🇵🇾

Asuncion, Paraguay

Instytut "Pomnik-Centrum Zdrowia Dziecka"

🇵🇱

Warszawa, Poland

Hospital Universitario Miguel Servet

🇪🇸

Zaragoza, Spain

Royal Free Hospital

🇬🇧

London, United Kingdom

Hospital de La Rabta

🇹🇳

Tunis, Jebbari, Tunisia

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