Gaucher Disease, Type 1Phase 3NCT00553631
Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) ERT Compared With Imiglucerase in Type I Gaucher Disease
A Phase 3 study testing velaglucerase alfa and imiglucerase in people with Gaucher Disease, Type 1, run by Shire at 11 sites in 9 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, Type 1
- What is being tested?
- velaglucerase alfa and imiglucerase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 11 sitesin 9 countries
- Study dates
- 29 Jan 2008to 5 May 2009
- 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
- Includes:
- The patient has a documented diagnosis and clinical manifestation of type 1 Gaucher disease
- The patient is at least 2 years of age.
- The patient has not received treatment for Gaucher disease (investigational products, miglustat, or imiglucerase) within 12 months prior to study entry, as documented in the patient's medical history.
- 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 use a medically acceptable method of birth control throughout their participation in the study and must report their partner's pregnancy.
- 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
- Includes:
- The patient has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease.
- 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 known to be positive for human immunodeficiency virus (HIV).
- The patient is known to be positive for hepatitis B and/or C.
- 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
11 sites in 9 countries.
11 sites in 9 countries
India3 sites
Malabar Institute of Medical Sciences Ltd.
Calicut, Kerala, 673 016
All India Institute of Medical Sciences
New Delhi, 110 029
KEM Hospital Research Centre
Pune
United States1 site
Duke Children's Hospital & Health Center
Durham, North Carolina, 27710
About this study
Official title: A Multicenter, Randomized, Double-Blind, Parallel-Group Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy Compared With Imiglucerase in Patients With Type I Gaucher Disease
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 non-inferiority study is to evaluate the efficacy and safety of GA-GCB (velaglucerase alfa) administered every other week in comparison to imiglucerase in treatment naive 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 (velaglucerase alfa) 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 efficacy and safety of GA-GCB (velaglucerase alfa) in comparison to imiglucerase in men, women, and children with Type 1 Gaucher disease.
- Conditions
- Gaucher Disease, Type 1
- Being tested
- velaglucerase alfa, imiglucerase
- Keywords
- 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.
velaglucerase alfaBiological
Also called VPRIV™, gene-activated human glucocerebrosidase
IV infusion, 60 U/kg every other week for 9 months
imigluceraseBiological
Also called Cerezyme®
IV infusion, 60 U/kg every other week for 9 months
| Study group | Role | What they receive |
|---|---|---|
| GA-GCB | Experimental | VPRIV™ ,velaglucerase alfa Receives: Biological: velaglucerase alfa |
| imiglucerase | Active comparator | Not described Receives: Biological: imiglucerase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change From Baseline to Month 9 in Hemoglobin (Hgb) Concentration for Each Treatment Group.
Measured: Baseline to Month 9
Secondary outcomes (7)
Change From Baseline to Month 9 in Platelet Counts for Each Treatment Group.
Values shown are observed change from Baseline to Month 9.
Measured: Baseline to Month 9
Change From Baseline to Month 9 in Normalized Liver Volume (Percent (%) Body Weight) for Each Treatment Group.
Values shown are observed change from Baseline to Month 9. Measured by Magnetic resonance imaging (MRI). Liver volume has been normalized for percent (%) body weight for each treatment arm. Liver size relative to body weight = (Liver volume [cubic centimeter (cc)]/Body weight [kg]*1000.
Measured: Baseline to Month 9
Change From Baseline to Month 9 in Normalized Spleen Volume (Percent (%) Body Weight) for Each Treatment Group.
Values shown are observed change from Baseline to month 9. Measured by Magnetic resonance imaging (MRI). Spleen volume was normalized for percent (%) of body weight for each treatment arm. Spleen size relative to body weight=(Spleen volume [cc]/Body weight [kg])*100.
Measured: Baseline to Month 9
Change From Baseline to Month 9 in Plasma Chitotriosidase for Each Treatment Group.
Values shown are observed change from Baseline to Month 9. Units of measure is defined as nanomole per milliliter per hour.
Measured: Baseline to Month 9.
Change From Baseline to Month 9 in Plasma Chemokine (C-C Motif) Ligand 18 (CCL18) for Each Treatment Group.
Values shown are observed change from Baseline to Month 9.
Measured: Baseline to Month 9
Number of Participants Who Developed Antibody for Each Treatment Group.
Measure type is actual number of participants who developed antibodies to treatment; GA-GCB or imiglucerase. Antibody detection was based upon serum samples collected at various time points throughout the study. Serum samples were screened using an enzyme-linked immunosorbent assay (ELISA) and positive antibody confirmation was determined using a radioimmunoprecipitation assay (RIP); positive samples were also tested for enzyme neutralizing activity. Participant samples were compared to internal assay controls (positive/negative), positive samples were determined based upon individual assay criteria.
Measured: Baseline to Month 9
Time to Response- Comparison of GA-GCB and Imiglucerase on the Earliest Time to Respond as Assessed Via Hemoglobin Concentration
Time to response was defined as a ≥ 1 g/dL improvement in hemoglobin levels relative to Baseline. Units (%) correlates to the percentage of participants who had a change of ≥ 1 g/dL improvement in hemoglobin levels relative to Baseline during their participation in the study.
Measured: Response rate at Month 9 compared to Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2007 (estimated)
- Study start29 Jan 2008
- Primary completion5 May 2009
- Study completion5 May 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 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 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
- NCT00553631
- Sponsor's protocol ID
- HGT-GCB-039
- Other IDs
- 2007-002840-21
- Status last verified
- May 2021
- First submitted
- 1 Nov 2007
- Last updated
- 8 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 27839979
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Parallel-Group Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy Compared With Imiglucerase in Patients With Type I Gaucher Disease
- ClinicalTrials.gov ID
- NCT00553631
- Acronym / sponsor ID
- HGT-GCB-039
- Conditions
- Gaucher Disease, Type 1
- Keywords
- Enzyme Replacement Therapy, Gaucher disease, glucocerebrosidase, beta-glucocerebrosidase, Acid beta-glucocerebrosidase, glucosylceramidase, D-glucosyl-N-acylsphingosine glucohydrolase, gene activation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 29 Jan 2008 (actual)
- Primary completion
- 5 May 2009 (actual)
- Study completion
- 5 May 2009 (actual)
- First posted
- 5 Nov 2007 (estimated)
- Results
- Posted 4 Jan 2011
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 non-inferiority study is to evaluate the efficacy and safety of GA-GCB (velaglucerase alfa) administered every other week in comparison to imiglucerase in treatment naive 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 (velaglucerase alfa) 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 efficacy and safety of GA-GCB (velaglucerase alfa) in comparison to imiglucerase in men, women, and children with Type 1 Gaucher disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GA-GCB | Experimental | Biological: velaglucerase alfaVPRIV™ ,velaglucerase alfa |
| imiglucerase | Active comparator | Biological: imiglucerase |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- The patient has a documented diagnosis and clinical manifestation of type 1 Gaucher disease
- The patient is at least 2 years of age.
- The patient has not received treatment for Gaucher disease (investigational products, miglustat, or imiglucerase) within 12 months prior to study entry, as documented in the patient's medical history.
- 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 use a medically acceptable method of birth control throughout their participation in the study and must report their partner's pregnancy.
- 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).
Key exclusion criteria (8 listed)
- The patient has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease.
- 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 known to be positive for human immunodeficiency virus (HIV).
- The patient is known to be positive for hepatitis B and/or C.
- 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.
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 |
|---|---|---|
| velaglucerase alfaAlso: VPRIV™, gene-activated human glucocerebrosidaseIV infusion, 60 U/kg every other week for 9 months | Biological | GA-GCB |
| imigluceraseAlso: Cerezyme®IV infusion, 60 U/kg every other week for 9 months | Biological | imiglucerase |
Primary outcome
Mean Change From Baseline to Month 9 in Hemoglobin (Hgb) Concentration for Each Treatment Group.
Time frame: Baseline to Month 9
7 secondary outcomes
Change From Baseline to Month 9 in Platelet Counts for Each Treatment Group.
Time frame: Baseline to Month 9
Change From Baseline to Month 9 in Normalized Liver Volume (Percent (%) Body Weight) for Each Treatment Group.
Time frame: Baseline to Month 9
Change From Baseline to Month 9 in Normalized Spleen Volume (Percent (%) Body Weight) for Each Treatment Group.
Time frame: Baseline to Month 9
Change From Baseline to Month 9 in Plasma Chitotriosidase for Each Treatment Group.
Time frame: Baseline to Month 9.
Change From Baseline to Month 9 in Plasma Chemokine (C-C Motif) Ligand 18 (CCL18) for Each Treatment Group.
Time frame: Baseline to Month 9
Number of Participants Who Developed Antibody for Each Treatment Group.
Time frame: Baseline to Month 9
Time to Response- Comparison of GA-GCB and Imiglucerase on the Earliest Time to Respond as Assessed Via Hemoglobin Concentration
Time frame: Response rate at Month 9 compared to Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 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.
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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
11 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing velaglucerase alfa and imiglucerase in people with Gaucher Disease, Type 1, run by Shire at 11 sites in 9 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 7 inclusion and 8 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 8 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 11 sites in India, United States, Argentina, Israel, Paraguay and 4 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 4 Jan 2011). 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?
Mean Change From Baseline to Month 9 in Hemoglobin (Hgb) Concentration for Each Treatment Group. (time frame: Baseline to Month 9). 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 NCT00553631, 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 8 Jun 2021.