Gaucher Disease, Type 1Phase 3NCT00635427
An Open-Label Extension Study of GA-GCB ERT in Patients With Type 1 Gaucher Disease
A Phase 3 study testing VPRIV® in people with Gaucher Disease, Type 1, run by Shire at 21 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Gaucher Disease, Type 1
- What is being tested?
- VPRIV®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 21 sitesin 11 countries
- Study dates
- 13 Mar 2008to 28 Dec 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
21 sites in 11 countries.
21 sites in 11 countries
United States10 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
Children's Memorial Hospital
Chicago, Illinois, 60614
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Children's Mercy Hospitals & Clinics
Kansas City, Missouri, 64108
Los Angeles Medical Center
Los Angeles, California, 90027
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, 55404
NYU Medical Center
New York, New York, 10016
Children's Hospital Oakland
Oakland, California, 94609
University of Utah Medical Center
Salt Lake City, Utah, 84132
India2 sites
All India Institute of Medical Sciences
New Delhi, 110 029
KEM Hospital
Pune, 411 011
Russia1 site
State Institution "Hematology Research Centre RAMS"
Moscow, 125167
South Korea1 site
Gyeongsang National University Hospital
Jinju, Gyeongsangnam-do, 660-702
About this study
Official title: An Open-Label Extension Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease
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.
Read the 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
- Being tested
- VPRIV®
- Keywords
- VPRIV, Enzyme Replacement Therapy, Gaucher disease, glucocerebrosidase, beta-glucocerebrosidase, Acid beta-glucocerebrosidase, glucosylceramidase, D-glucosyl-N-acylsphingosine glucohydrolase, gene activation, human
- Medical subject headings
- Gaucher Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VPRIV®Biological
Also called velaglucerase alfa, Gene-Activated® Human Glucocerebrosidase(GA-GCB)
Intravenous infusion, every other week (EOW)
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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 Receives: 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 Receives: Biological: VPRIV® |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to termination of study
Secondary outcomes (4)
Change From Baseline to 24 Months in Hemoglobin Concentration for Each Treatment Group
Measured: Baseline to 24 months
Change From Baseline to 24 Months in Platelet Counts for Each Treatment Group
Measured: Baseline to 24 months
Change From Baseline to 24 Months in Normalized Liver Volume for Each Treatment Group
Measured: Baseline to 24 months
Percentage Change From Baseline to 24 Months in Normalized Spleen Volume for Each Treatment Group
Measured: Baseline to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2008 (estimated)
- Study start13 Mar 2008
- Primary completion28 Dec 2012
- Study completion28 Dec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Gaucher Disease, Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00635427
- Sponsor's protocol ID
- HGT-GCB-044
- Other IDs
- 2008-001965-27, 2008
- Status last verified
- May 2021
- First submitted
- 6 Mar 2008
- Last updated
- 10 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 27839979Smith 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.
PubMed 26043810Hughes 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.
PubMed 25801797
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Extension Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease
- ClinicalTrials.gov ID
- NCT00635427
- Acronym / sponsor ID
- HGT-GCB-044
- Conditions
- Gaucher Disease, Type 1
- Keywords
- VPRIV, Enzyme Replacement Therapy, Gaucher disease, glucocerebrosidase, beta-glucocerebrosidase, Acid beta-glucocerebrosidase, glucosylceramidase, D-glucosyl-N-acylsphingosine glucohydrolase
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 13 Mar 2008 (actual)
- Primary completion
- 28 Dec 2012 (actual)
- Study completion
- 28 Dec 2012 (actual)
- First posted
- 13 Mar 2008 (estimated)
- Results
- Posted 28 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039) | Experimental | Biological: 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) |
| VPRIV 60 U/kg (Parent study-imiglucerase(60 U/kg) HGT-GCB-039) | Experimental | Biological: 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) | Experimental | Biological: 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 |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VPRIV®Also: velaglucerase alfa, Gene-Activated® Human Glucocerebrosidase(GA-GCB)Intravenous infusion, every other week (EOW) | Biological | 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) |
Primary outcome
Overall Summary of Treatment Emergent Adverse Events
Time frame: Baseline 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.
4 secondary outcomes
Change From Baseline to 24 Months in Hemoglobin Concentration for Each Treatment Group
Time frame: Baseline to 24 months
Change From Baseline to 24 Months in Platelet Counts for Each Treatment Group
Time frame: Baseline to 24 months
Change From Baseline to 24 Months in Normalized Liver Volume for Each Treatment Group
Time frame: Baseline to 24 months
Percentage Change From Baseline to 24 Months in Normalized Spleen Volume for Each Treatment Group
Time frame: Baseline to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27839979Zimran 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.
- Derived from this study: PubMed 26043810Smith 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.
- Derived from this study: PubMed 25801797Hughes 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
21 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing VPRIV® in people with Gaucher Disease, Type 1, run by Shire at 21 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, India, Argentina, Israel, Paraguay and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Summary of Treatment Emergent Adverse Events (time frame: Baseline to termination of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00635427, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2021.