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

NCT00635427 | Completed Phase 3 Results

• 2 other identifiers: HGT-GCB-0442008-001965-27
• Study Type: interventional
• Target: 95
• Locations: 11 countries
• Sites: 21

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to termination of study

Secondary Outcomes (4)

• Change From Baseline to 24 Months in Hemoglobin Concentration for Each Treatment Group

  Baseline to 24 months

• Change From Baseline to 24 Months in Platelet Counts for Each Treatment Group

  Baseline to 24 months

• Change From Baseline to 24 Months in Normalized Liver Volume for Each Treatment Group

  Baseline to 24 months

• Percentage Change From Baseline to 24 Months in Normalized Spleen Volume for Each Treatment Group

  Baseline to 24 months

Study Arms (3)

VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039)

EXPERIMENTAL

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)

Biological: VPRIV®

VPRIV 60 U/kg (Parent study-imiglucerase(60 U/kg) HGT-GCB-039)

EXPERIMENTAL

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

Biological: VPRIV®

VPRIV 15-60 U/kg (Parent study VPRIV (15-60 U/kg) TKT034)

EXPERIMENTAL

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

Biological: VPRIV®

Interventions

VPRIV® BIOLOGICAL

Intravenous infusion, every other week (EOW)

Also known as: velaglucerase alfa, Gene-Activated® Human Glucocerebrosidase(GA-GCB)

VPRIV 15-60 U/kg (Parent study VPRIV (15-60 U/kg) TKT034); VPRIV 60 U/kg (Parent study-imiglucerase(60 U/kg) HGT-GCB-039); VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shire: lead

Study Sites (21)

Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Children's Mercy Hospitals & Clinics

Kansas City, Missouri, 64108, United States

Location

NYU Medical Center

New York, New York, 10016, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University of Utah Medical Center

Salt Lake City, Utah, 84132, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Your Health S.A.

Buenos Aires, Argentina

Location

All India Institute of Medical Sciences

New Delhi, 110 029, India

Location

KEM Hospital

Pune, 411 011, India

Location

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

Sociedad Espanola de Socorros Mutuos

Asunción, Paraguay

Location

Instytut "Pomnik-Centrum Zdrowia Dziecka"

Warsaw, Poland

Location

State Institution "Hematology Research Centre RAMS"

Moscow, 125167, Russia

Location

Gyeongsang National University Hospital

Jinju, Gyeongsangnam-do, 660-702, South Korea

Location

Hospital Universitario Miguel Servet

Zaragoza, 50008, Spain

Location

Hospital de La Rabta

Tunis, Jebbari, 1007 BS, Tunisia

Location

Royal Free Hospital

London, NM3 2QG, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 27839979 DERIVED

• 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.

  PMID: 26043810 DERIVED

• 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.

  PMID: 25801797 DERIVED

MeSH Terms

Conditions

Gaucher Disease

Interventions

Glucosylceramidase

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Glucosidases; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2008
• First Posted: March 13, 2008
• Study Start: March 13, 2008
• Primary Completion: December 28, 2012
• Study Completion: December 28, 2012
• Last Updated: June 10, 2021
• Results First Posted: January 28, 2014

Record last verified: 2021-05

Locations

AR (1); ES (1); IN (2); IL (1); PA (1); RU (1); KR (1); PL (1); US (10); TU (1); GB (1)