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

NCT ID: NCT00635427

Last Updated: 2021-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-13
• Study Completion Date: 2012-12-28

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.

Conditions

Gaucher Disease, Type 1

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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)

Group Type: EXPERIMENTAL

VPRIV®

Intervention Type: BIOLOGICAL

Intravenous infusion, every other week (EOW)

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

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

Group Type: EXPERIMENTAL

VPRIV®

Intervention Type: BIOLOGICAL

Intravenous infusion, every other week (EOW)

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

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

Group Type: EXPERIMENTAL

VPRIV®

Intervention Type: BIOLOGICAL

Intravenous infusion, every other week (EOW)

Interventions

VPRIV®

Intravenous infusion, every other week (EOW)

Intervention Type: BIOLOGICAL

Other Intervention Names

velaglucerase alfa; Gene-Activated® Human Glucocerebrosidase(GA-GCB)

Eligibility Criteria

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

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

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 Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, United States

Children's Mercy Hospitals & Clinics

Kansas City, Missouri, United States

NYU Medical Center

New York, New York, 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

KEM Hospital

Pune, , India

Shaare Zedek Medical Center

Jerusalem, , Israel

Sociedad Espanola de Socorros Mutuos

Asunción, , Paraguay

Instytut "Pomnik-Centrum Zdrowia Dziecka"

Warsaw, , Poland

State Institution "Hematology Research Centre RAMS"

Moscow, , Russia

Gyeongsang National University Hospital

Jinju, Gyeongsangnam-do, South Korea

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Hospital de La Rabta

Tunis, Jebbari, Tunisia

Royal Free Hospital

London, , United Kingdom

Countries

United States; Argentina; India; Israel; Paraguay; Poland; Russia; South Korea; Spain; Tunisia; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 27839979 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26043810 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25801797 (View on PubMed)

Other Identifiers

2008-001965-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HGT-GCB-044

Identifier Type: -

Identifier Source: org_study_id