Gaucher DiseasePhase 2/3NCT00478647
Study of GA-GCB Enzyme Replacement Therapy in Type 1 Gaucher Disease Patients Previously Treated With Imiglucerase
A Phase 2/3 study testing GA-GCB (velaglucerase alfa) in people with Gaucher Disease, run by Shire at 15 sites in 5 countries.
Trial summary
Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to the deficiency of functional GCB, glucocerebroside accumulates within macrophages leading to cellular engorgement, organomegaly, and organ system dysfunction. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Gaucher Disease
- What is being tested?
- GA-GCB (velaglucerase alfa)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 15 sitesin 5 countries
- Study dates
- 25 Jul 2007to 26 Jun 2009
- Phase
- Phase 2/3
- 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
- Includes:
- The participant has a documented diagnosis of type 1 Gaucher disease, as determined by deficient glucocerebrosidase (GCB) activity relative to normal as measured in leukocytes or by genotype analysis and the participant/legal guardian is willing and able to provide written informed consent prior to initiating any study-related procedures
- The participant has received consistent treatment with imiglucerase at a dose ≤ 60 U/kg and ≥ 15 U/kg every other week for a minimum of 30 consecutive months. Participants who are anti-imiglucerase antibody positive will be allowed to enter this study
- The participant is at least 2 years of age
- Female participants of child-bearing potential agree to use a medically acceptable method of contraception. Male participants must agree to use a medically acceptable method of birth control
- Participant must be sufficiently co-operative to participate in the study as judged by the Investigator.
Who cannot join
- Includes:
- The participant has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease
- The participant has received treatment with any investigational drug or device within the 30 days prior to study entry; such use during the study is not permitted
- Participant is HIV positive
- Participant is hepatitis B/C positive
- The participant presents with sustained iron, folic acid and/or vitamin B12 deficiency-related anemia during Screening
Show all 14Show fewer
- The participant, participant's parent(s), or participant's legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study
- The participant has a significant comorbidity that might affect study data or confound the study results
- The participant is unable to comply with the protocol or is otherwise unlikely to complete the study, as determined by the Investigator
- The participant has experienced an anaphylactic/anaphylactoid reaction during treatment with imiglucerase
- The participant has received miglustat during the 6 months prior to study enrollment
- The participant has an active, clinically significant spleen infarction
- The participant has active, progressive bone necrosis
- The participant is a pregnant and/or lactating female
Trial locations and contacts
15 sites in 5 countries.
15 sites in 5 countries
United States11 sites
Feinberg School of Medicine
Chicago, Illinois, 60614
Cincinatti Children's Hospital
Cincinnati, Ohio, 45229
Emory University
Decatur, Georgia, 30033
Texas Children's Hospital
Houston, Texas, 77030
Children's Mercy Hospital and Clinic
Kansas City, Missouri, 64108
Regional Metabolic Center
Los Angeles, California, 90027
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Children's of Minnesota
Minneapolis, Minnesota, 55404
NYU School of Medicine
New York, New York, 10016
Children's Hospital Oakland
Oakland, California, 94609
Medical Genetics/Pediatrics
Salt Lake City, Utah, 84132
About this study
Official title: A Multicenter Open-Label Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease Previously Treated With Imiglucerase
Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to the deficiency of functional GCB, glucocerebroside accumulates within macrophages leading to cellular engorgement, organomegaly, and organ system dysfunction. The purpose of this study is to evaluate the safety and efficacy of every other week dosing of GA-GCB (velaglucerase alfa) in participants with type 1 Gaucher disease who were previously treated with imiglucerase.
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 safety of GA-GCB in men, women, and children with Type 1 Gaucher disease who were previously treated with imiglucerase. Each participant's duration of treatment will be 12 months.
- Conditions
- Gaucher Disease
- Being tested
- GA-GCB (velaglucerase alfa)
- Keywords
- Acid beta-glucocerebrosidase, human, glucocerebrosidase, Gaucher disease, Enzyme Replacement Therapy, D-glucosyl-N-acylsphingosine glucohydrolase, glucosylceramidase, gene activation, beta-glucocerebrosidase
- Medical subject headings
- Gaucher Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GA-GCB (velaglucerase alfa)Biological
Also called gene-activated® human glucocerebrosidase, VPRIV®, GA-GCB
15-60 U/kg, every other week via intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| GA-GCB (velaglucerase alfa) | Experimental | 15-60 U/kg, every other week via intravenous infusion Receives: Biological: GA-GCB (velaglucerase alfa) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants Who Experienced at Least One Adverse Event
Safety was assessed throughout the study by assessments including adverse events, concomitant medication use, and vital signs. Additional safety assessments, including 12-lead ECGs, physical examinations, clinical laboratory tests and determination of the presence of anti-velaglucerase alfa antibodies. Refer to Adverse event section for further details.
Measured: Week 53
Secondary outcomes (4)
Change From Baseline to Week 53 in Hemoglobin Concentration
Measured: Week 53
Percent Change From Baseline to Week 53 in Platelet Count
Measured: Week 53
Percent Change From Baseline to Week 51 in Normalized Liver Volume
Liver volume has been normalized for percentage (%) of body weight. Liver size relative to body weight= (Liver volume [cc]/Body weight [kg])*100
Measured: Week 51
Percent Change From Baseline to Week 51 in Normalized Spleen Volume
Spleen volume has been normalized for percentage (%) of body weight. Spleen size relative to body weight= (Spleen volume [cc]/Body weight [kg])*100
Measured: Week 51
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2007 (estimated)
- Study start25 Jul 2007
- Primary completion26 Jun 2009
- Study completion26 Jun 2009
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 (1)Papers the sponsor has linked to this study.
- Other trials for Gaucher DiseaseStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 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
- NCT00478647
- Sponsor's protocol ID
- TKT034
- Other IDs
- 2006-006304-11
- Status last verified
- May 2021
- First submitted
- 23 May 2007
- Last updated
- 10 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Zimran A, Pastores GM, Tylki-Szymanska A, Hughes DA, Elstein D, Mardach R, Eng C, Smith L, Heisel-Kurth M, Charrow J, Harmatz P, Fernhoff P, Rhead W, Longo N, Giraldo P, Ruiz JA, Zahrieh D, Crombez E, Grabowski GA. Safety and efficacy of velaglucerase alfa in Gaucher disease type 1 patients previously treated with imiglucerase. Am J Hematol. 2013 Mar;88(3):172-8. doi: 10.1002/ajh.23383. Epub 2013 Jan 22.
PubMed 23339116
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
- A Multicenter Open-Label Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease Previously Treated With Imiglucerase
- ClinicalTrials.gov ID
- NCT00478647
- Acronym / sponsor ID
- TKT034
- Conditions
- Gaucher Disease
- Keywords
- Acid beta-glucocerebrosidase, human, glucocerebrosidase, Gaucher disease, Enzyme Replacement Therapy, D-glucosyl-N-acylsphingosine glucohydrolase, glucosylceramidase, gene activation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 25 Jul 2007 (actual)
- Primary completion
- 26 Jun 2009 (actual)
- Study completion
- 26 Jun 2009 (actual)
- First posted
- 25 May 2007 (estimated)
- Results
- Posted 2 Sep 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to the deficiency of functional GCB, glucocerebroside accumulates within macrophages leading to cellular engorgement, organomegaly, and organ system dysfunction. The purpose of this study is to evaluate the safety and efficacy of every other week dosing of GA-GCB (velaglucerase alfa) in participants with type 1 Gaucher disease who were previously treated with imiglucerase.
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 safety of GA-GCB in men, women, and children with Type 1 Gaucher disease who were previously treated with imiglucerase. Each participant's duration of treatment will be 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GA-GCB (velaglucerase alfa) | Experimental | Biological: GA-GCB (velaglucerase alfa)15-60 U/kg, every other week via intravenous infusion |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- The participant has a documented diagnosis of type 1 Gaucher disease, as determined by deficient glucocerebrosidase (GCB) activity relative to normal as measured in leukocytes or by genotype analysis and the participant/legal guardian is willing and able to provide written informed consent prior to initiating any study-related procedures
- The participant has received consistent treatment with imiglucerase at a dose ≤ 60 U/kg and ≥ 15 U/kg every other week for a minimum of 30 consecutive months. Participants who are anti-imiglucerase antibody positive will be allowed to enter this study
- The participant is at least 2 years of age
- Female participants of child-bearing potential agree to use a medically acceptable method of contraception. Male participants must agree to use a medically acceptable method of birth control
- Participant must be sufficiently co-operative to participate in the study as judged by the Investigator.
Key exclusion criteria (14 listed)
- The participant has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease
- The participant has received treatment with any investigational drug or device within the 30 days prior to study entry; such use during the study is not permitted
- Participant is HIV positive
- Participant is hepatitis B/C positive
- The participant presents with sustained iron, folic acid and/or vitamin B12 deficiency-related anemia during Screening
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 |
|---|---|---|
| GA-GCB (velaglucerase alfa)Also: gene-activated® human glucocerebrosidase, VPRIV®, GA-GCB15-60 U/kg, every other week via intravenous infusion | Biological | GA-GCB (velaglucerase alfa) |
Primary outcome
Participants Who Experienced at Least One Adverse Event
Time frame: Week 53
Safety was assessed throughout the study by assessments including adverse events, concomitant medication use, and vital signs. Additional safety assessments, including 12-lead ECGs, physical examinations, clinical laboratory tests and determination of the presence of anti-velaglucerase alfa antibodies. Refer to Adverse event section for further details.
4 secondary outcomes
Change From Baseline to Week 53 in Hemoglobin Concentration
Time frame: Week 53
Percent Change From Baseline to Week 53 in Platelet Count
Time frame: Week 53
Percent Change From Baseline to Week 51 in Normalized Liver Volume
Time frame: Week 51
Percent Change From Baseline to Week 51 in Normalized Spleen Volume
Time frame: Week 51
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.
- Results publication: PubMed 23339116Zimran A, Pastores GM, Tylki-Szymanska A, Hughes DA, Elstein D, Mardach R, Eng C, Smith L, Heisel-Kurth M, Charrow J, Harmatz P, Fernhoff P, Rhead W, Longo N, Giraldo P, Ruiz JA, Zahrieh D, Crombez E, Grabowski GA. Safety and efficacy of velaglucerase alfa in Gaucher disease type 1 patients previously treated with imiglucerase. Am J Hematol. 2013 Mar;88(3):172-8. doi: 10.1002/ajh.23383. Epub 2013 Jan 22.
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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
15 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing GA-GCB (velaglucerase alfa) in people with Gaucher Disease, run by Shire at 15 sites in 5 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 6 inclusion and 14 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 15 sites in United States, Israel, Poland, Spain, United Kingdom. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 2 Sep 2010). 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?
Participants Who Experienced at Least One Adverse Event (time frame: Week 53). 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 NCT00478647, which also lists 1 linked publication.
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.