Back to resultsAn Open-Label Extension Study of GA-GCB ERT in Patients With Type 1 Gaucher Disease
Primary Purpose
Gaucher Disease, Type 1
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
VPRIV®
Sponsored by
About this trial
This is an interventional treatment trial for Gaucher Disease, Type 1 focused on measuring VPRIV, Enzyme Replacement Therapy, Gaucher disease, glucocerebrosidase, beta-glucocerebrosidase, Acid beta-glucocerebrosidase, glucosylceramidase, D-glucosyl-N-acylsphingosine glucohydrolase, gene activation, human
Eligibility Criteria
Inclusion Criteria:
- The patient has completed study TKT032 or TKT034, or study HGT-GCB-039.
- 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.
- 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.
- 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).
- The patient must be sufficiently cooperative to participate in this clinical study as judged by the Investigator
Exclusion Criteria:
- 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.
- The patient is pregnant or lactating.
- 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.
- 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.).
- 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
Sites / Locations
- Los Angeles Medical Center
- Children's Hospital Oakland
- Emory University School of Medicine
- Children's Memorial Hospital
- Children's Hospitals and Clinics of Minnesota
- Children's Mercy Hospitals & Clinics
- NYU Medical Center
- Cincinnati Children's Hospital Medical Center
- University of Utah Medical Center
- Children's Hospital of Wisconsin
- Your Health S.A.
- All India Institute of Medical Sciences
- KEM Hospital
- Shaare Zedek Medical Center
- Gyeongsang National University Hospital
- Sociedad Espanola de Socorros Mutuos
- Instytut "Pomnik-Centrum Zdrowia Dziecka"
- State Institution "Hematology Research Centre RAMS"
- Hospital Universitario Miguel Servet
- Hospital de La Rabta
- Royal Free Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039)
VPRIV 60 U/kg (Parent study-imiglucerase(60 U/kg) HGT-GCB-039)
VPRIV 15-60 U/kg (Parent study VPRIV (15-60 U/kg) TKT034)
Arm Description
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)
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, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647) and continued in HGT-GCB-044 at the same dose as prescribed in TKT034
Outcomes
Primary Outcome Measures
Overall Summary of Treatment Emergent Adverse Events
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
Change From Baseline to 24 Months in Hemoglobin Concentration for Each Treatment Group
Change From Baseline to 24 Months in Platelet Counts for Each Treatment Group
Change From Baseline to 24 Months in Normalized Liver Volume for Each Treatment Group
Percentage Change From Baseline to 24 Months in Normalized Spleen Volume for Each Treatment Group
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00635427
Brief Title
An Open-Label Extension Study of GA-GCB ERT in Patients With Type 1 Gaucher Disease
Official Title
An Open-Label Extension Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
March 13, 2008 (Actual)
Primary Completion Date
December 28, 2012 (Actual)
Study Completion Date
December 28, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gaucher Disease, Type 1
Keywords
VPRIV, Enzyme Replacement Therapy, Gaucher disease, glucocerebrosidase, beta-glucocerebrosidase, Acid beta-glucocerebrosidase, glucosylceramidase, D-glucosyl-N-acylsphingosine glucohydrolase, gene activation, human
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
95 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039)
Arm Type
Experimental
Arm Description
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)
Arm Title
VPRIV 60 U/kg (Parent study-imiglucerase(60 U/kg) HGT-GCB-039)
Arm Type
Experimental
Arm Description
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
Arm Title
VPRIV 15-60 U/kg (Parent study VPRIV (15-60 U/kg) TKT034)
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
VPRIV®
Other Intervention Name(s)
velaglucerase alfa, Gene-Activated® Human Glucocerebrosidase(GA-GCB)
Intervention Description
Intravenous infusion, every other week (EOW)
Primary Outcome Measure Information:
Title
Overall Summary of Treatment Emergent Adverse Events
Description
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.
Time Frame
Baseline to termination of study
Secondary Outcome Measure Information:
Title
Change From Baseline to 24 Months in Hemoglobin Concentration for Each Treatment Group
Time Frame
Baseline to 24 months
Title
Change From Baseline to 24 Months in Platelet Counts for Each Treatment Group
Time Frame
Baseline to 24 months
Title
Change From Baseline to 24 Months in Normalized Liver Volume for Each Treatment Group
Time Frame
Baseline to 24 months
Title
Percentage Change From Baseline to 24 Months in Normalized Spleen Volume for Each Treatment Group
Time Frame
Baseline to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The patient has completed study TKT032 or TKT034, or study HGT-GCB-039.
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.
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.
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).
The patient must be sufficiently cooperative to participate in this clinical study as judged by the Investigator
Exclusion Criteria:
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.
The patient is pregnant or lactating.
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.
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.).
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Los Angeles Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's Hospital Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Children's Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Children's Hospitals and Clinics of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Children's Mercy Hospitals & Clinics
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
NYU Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
University of Utah Medical Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Your Health S.A.
City
Buenos Aires
Country
Argentina
Facility Name
All India Institute of Medical Sciences
City
New Delhi
ZIP/Postal Code
110 029
Country
India
Facility Name
KEM Hospital
City
Pune
ZIP/Postal Code
411 011
Country
India
Facility Name
Shaare Zedek Medical Center
City
Jerusalem
ZIP/Postal Code
91031
Country
Israel
Facility Name
Gyeongsang National University Hospital
City
Jinju
State/Province
Gyeongsangnam-do
ZIP/Postal Code
660-702
Country
Korea, Republic of
Facility Name
Sociedad Espanola de Socorros Mutuos
City
Asuncion
Country
Paraguay
Facility Name
Instytut "Pomnik-Centrum Zdrowia Dziecka"
City
Warszawa
Country
Poland
Facility Name
State Institution "Hematology Research Centre RAMS"
City
Moscow
ZIP/Postal Code
125167
Country
Russian Federation
Facility Name
Hospital Universitario Miguel Servet
City
Zaragoza
ZIP/Postal Code
50008
Country
Spain
Facility Name
Hospital de La Rabta
City
Tunis
State/Province
Jebbari
ZIP/Postal Code
1007 BS
Country
Tunisia
Facility Name
Royal Free Hospital
City
London
ZIP/Postal Code
NM3 2QG
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
27839979
Citation
Zimran A, Elstein D, Gonzalez DE, Lukina EA, Qin Y, Dinh Q, Turkia HB. Treatment-naive Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials. Blood Cells Mol Dis. 2018 Feb;68:153-159. doi: 10.1016/j.bcmd.2016.10.007. Epub 2016 Oct 21.
Results Reference
derived
PubMed Identifier
26043810
Citation
Smith L, Rhead W, Charrow J, Shankar SP, Bavdekar A, Longo N, Mardach R, Harmatz P, Hangartner T, Lee HM, Crombez E, Pastores GM. Long-term velaglucerase alfa treatment in children with Gaucher disease type 1 naive to enzyme replacement therapy or previously treated with imiglucerase. Mol Genet Metab. 2016 Feb;117(2):164-71. doi: 10.1016/j.ymgme.2015.05.012. Epub 2015 Jun 1.
Results Reference
derived
PubMed Identifier
25801797
Citation
Hughes DA, Gonzalez DE, Lukina EA, Mehta A, Kabra M, Elstein D, Kisinovsky I, Giraldo P, Bavdekar A, Hangartner TN, Wang N, Crombez E, Zimran A. Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long-term data from phase III clinical trials. Am J Hematol. 2015 Jul;90(7):584-91. doi: 10.1002/ajh.24012.
Results Reference
derived
Learn more about this trial
An Open-Label Extension Study of GA-GCB ERT in Patients With Type 1 Gaucher Disease
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