Gaucher DiseasePhase 3NCT01842841
Multicenter Extension Study of Velaglucerase Alfa in Japanese Patients With Gaucher Disease
A Phase 3 study testing velaglucerase alfa in people with Gaucher Disease, run by Shire at 5 sites in Japan.
Trial summary
Gaucher disease is an inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCB) that leads to progressive accumulation of glucocerebroside within macrophages and subsequent tissue and organ damage; typically of the liver, spleen, bone marrow, and brain. 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?
- velaglucerase alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 5 sitesJapan
- Study dates
- 13 Mar 2013to 8 Oct 2014
- 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 treatment with EOW velaglucerase alfa through Week 51 of study HGT-GCB-087.
- Female patients of child bearing potential must agree to use a medically acceptable method of contraception at all times during the study.
- 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 investigational drug, other than velaglucerase alfa, or investigational device within 30 days prior to study entry; such use during the study is not permitted.
- 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, as determined by the Investigator that might affect study data or confound the study results.
- The patient is unable to comply with the protocol as determined by the Investigator.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Japan5 sites
Chiba Children's Hospital
Chiba, 266-0007
Hamamatsu University School of Medicine
Hamamatsu, Shizuoka, 431-3192
The Jikei University School of Medicine
Minato-ku, Tokyo, 105-8471
Iwata City Hospital
Ōkubo, Shizuoka, 438-8550
Osaka City University Hospital
Osaka, 545-8586
About this study
Official title: A Multicenter, Open-label Extension Study of Velaglucerase Alfa Enzyme Replacement Therapy in Japanese Patients With Gaucher Disease
Gaucher disease is an inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCB) that leads to progressive accumulation of glucocerebroside within macrophages and subsequent tissue and organ damage; typically of the liver, spleen, bone marrow, and brain. Type 1 Gaucher disease affects an estimated 30,000 persons worldwide and is the most common. Type 1 Gaucher disease does not involve the central nervous system. Patients with Type 2 Gaucher disease present with acute neurological deterioration, which leads to early death. Those with Type 3 disease typically display a more sub-acute neurological course, with later onset and slower progression.
The primary objective of this study is to evaluate the long-term safety of every other week (EOW) dosing of velaglucerase alfa in Japanese patients with Gaucher disease who completed study HGT-GCB-087 and elected to continue treatment with velaglucerase alfa.
Velaglucerase alfa has been developed and approved as an enzyme replacement therapy for Type 1 Gaucher disease.
Read the detailed description
Gaucher disease is an inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCB) that leads to progressive accumulation of glucocerebroside within macrophages and subsequent tissue and organ damage; typically of the liver, spleen, bone marrow, and brain.
Gaucher disease has been designated in the list of Specified Rare and Intractable Diseases by Specified Disease Treatment Research Program of Ministry of Health, Labor and Welfare (MHLW) as one of "lysosomal storage diseases" since 2001. Gaucher disease is also designated in the Medical Aid Program for Specified Categories of Chronic Pediatric Diseases.
The prevalence of mutations and the phenotype of patients with Gaucher disease in Japan differs from that in non-Japanese populations. Some patients with type 1 Gaucher disease in Japan have more severe and progressive disease compared to non-Japanese patients and the disease is characterized by an earlier onset of symptoms.
Velaglucerase alfa, a highly-purified form of the naturally occurring enzyme glucocerebrosidase, has been developed as an enzyme replacement therapy for Gaucher disease for the symptoms (anemia, thrombocytopenia, hepatomegaly, splenomegaly, and bone manifestation).
The primary objective of this study is to evaluate the long-term safety of every other week (EOW) dosing of velaglucerase alfa in Japanese patients with Gaucher disease who completed study HGT-GCB-087 and elected to continue treatment with velaglucerase alfa.
- Conditions
- Gaucher Disease
- Being tested
- velaglucerase alfa
- 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 alfaDrug
Also called VPRIV
15-60 U/kg, EOW
| Study group | Role | What they receive |
|---|---|---|
| velaglucerase alfa | Experimental | 15 to 60 U/kg, EOW via intravenous infusion Receives: Drug: velaglucerase alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Drug-related Adverse Events (AEs), Infusion-related AEs, and Serious AEs (SAEs)
An AE was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered related to investigational product. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An infusion-related AE was defined as an AE that started either during or within 12 hours after the start of the infusion and that was judged as possibly or probably related to investigational product.
Measured: From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
Number of Participants Using Concomitant Medication
Measured: From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
Number of Participants With Abnormal and Clinically Significant Laboratory Test Results
Laboratory test results were considered abnormal and clinically significant at the discretion of the investigator.
Measured: From Week 65 until the end of study (Week 155)
Number of Participants With Positive Anti-Velaglucerase Alfa Antibodies
Serum samples were collected for all participants for determination of anti-velaglucerase alfa antibodies every 12 weeks.
Measured: From Week 65 until the end of study (Week 155)
Secondary outcomes (12)
Change From Baseline in Hemoglobin Concentration at Week 101
Baseline was the modified baseline hemoglobin concentration, the average of the values from screening, baseline, and Week 1 Day 1 from Study HGT-GCB-087 (NCT01614574).
Measured: Baseline, Week 101
Change From Baseline in Platelet Count at Week 101
Baseline was the modified baseline platelet count, the average of the values from screening, baseline, and Week 1 Day 1 from Study HGT-GCB-087 (NCT01614574).
Measured: Baseline, Week 101
Change From Baseline in Liver Volume Normalized to Body Weight at Week 103
Liver volume was measured using magnetic resonance imaging (MRI). Liver volume measurements were normalized to the percentage of body weight. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Measured: Baseline, Week 103
Change From Baseline in Spleen Volume Normalized to Body Weight at Week 103
Spleen volume was measured using MRI. Spleen volume measurements were normalized to the percentage of body weight. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Measured: Baseline, Week 103
Change From Baseline in Bone Mineral Density (BMD) at Week 103: Z Score
BMD was measured by dual energy x-ray absorptiometry (DXA) for lumbar spine and femurs. To ensure standardization and allow for comparisons of BMD, results were converted to standardized Z-scores (matched for age and gender). Z-scores express the BMD as the number of standard deviations (SDs) above or below the average BMD of a healthy participant of the same age and gender. Statistical analysis plan only required summarization if greater than (>) 50 percent (%) of participants had evaluable data. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Measured: Baseline, Week 103
Change From Baseline in Bone Mineral Density (BMD) at Week 103: T-Score
BMD was measured by DXA for lumbar spine and femurs. To ensure standardization and allow for comparisons of BMD, results were converted to standardized T-scores; normal values were used from databases from Hologic based on standard criteria. T-scores are the number of SDs above or below the average for a young adult at peak BMD. Statistical analysis plan only required summarization if >50% of participants had evaluable data. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Measured: Baseline, Week 103
Change From Baseline in Bone Marrow Burden (BMB) Score at Week 103
BMB Score was measured using MRI, range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0-16 points. A higher BMB score signified more severe bone marrow involvement. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Measured: Baseline, Week 103
Change From Baseline in Growth Velocity at Week 101 : Height Z-Score
The Z-score, or Standard Deviation Score, is a measure of number of SDs above or below the average BMD of a healthy participant of the same age and gender. World Health Organization 2007 growth reference data were used for Z-score calculation. Statistical analysis plan only required summarization if >50% of participants had evaluable data. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Measured: Baseline, Week 101
Change From Baseline in Skeletal Age at Week 103: Z-Score
Skeletal age was measured via radiography (X-ray) of the left hand and wrist by the method of Greulich and Pyle. The Z-score, or Standard Deviation Score, is a measure of number of SDs above or below the average BMD of a healthy participant of the same age and gender. Statistical analysis plan only required summarization if >50% of participants had evaluable data. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Measured: Baseline, Week 103
Change From Baseline in Plasma Chitotriosidase Levels at Week 101
Plasma chitotriosidase activity levels were measured using an enzymatic assay with 4-methylumbelliferyl-deoxychitobiose as a substrate. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Measured: Baseline, Week 101
Number of Participants With Change From Baseline in Neurological Status at Week 103
Neurological status was considered normal or abnormal based on investigator's discretion. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Measured: Baseline, Week 103
Change From Baseline in Chemokine [C-C Motif] Ligand 18 (CCL18) Levels at Week 101
Plasma CCL18 concentrations were measured using a time-resolved fluorescence assay. Week 51 of Study HGT-GCB-087 (NCT01614574) was considered as baseline for this endpoint.
Measured: Baseline, Week 101
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2013 (estimated)
- Study start13 Mar 2013
- Primary completion8 Oct 2014
- Study completion8 Oct 2014
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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01842841
- Sponsor's protocol ID
- HGT-GCB-091
- Status last verified
- May 2021
- First submitted
- 11 Apr 2013
- Last updated
- 14 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ida H, Tanaka A, Matsubayashi T, Murayama K, Hongo T, Lee HM, Mellgard B. A multicenter, open-label extension study of velaglucerase alfa in Japanese patients with Gaucher disease: Results after a cumulative treatment period of 24months. Blood Cells Mol Dis. 2016 Jul;59:140-7. doi: 10.1016/j.bcmd.2015.10.002. Epub 2015 Oct 16.
PubMed 27241455
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label Extension Study of Velaglucerase Alfa Enzyme Replacement Therapy in Japanese Patients With Gaucher Disease
- ClinicalTrials.gov ID
- NCT01842841
- Acronym / sponsor ID
- HGT-GCB-091
- Conditions
- Gaucher Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Study start
- 13 Mar 2013 (actual)
- Primary completion
- 8 Oct 2014 (actual)
- Study completion
- 8 Oct 2014 (actual)
- First posted
- 30 Apr 2013 (estimated)
- Results
- Posted 14 Dec 2015
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 an inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCB) that leads to progressive accumulation of glucocerebroside within macrophages and subsequent tissue and organ damage; typically of the liver, spleen, bone marrow, and brain. Type 1 Gaucher disease affects an estimated 30,000 persons worldwide and is the most common. Type 1 Gaucher disease does not involve the central nervous system. Patients with Type 2 Gaucher disease present with acute neurological deterioration, which leads to early death. Those with Type 3 disease typically display a more sub-acute neurological course, with later onset and slower progression.
The primary objective of this study is to evaluate the long-term safety of every other week (EOW) dosing of velaglucerase alfa in Japanese patients with Gaucher disease who completed study HGT-GCB-087 and elected to continue treatment with velaglucerase alfa.
Velaglucerase alfa has been developed and approved as an enzyme replacement therapy for Type 1 Gaucher disease.
Detailed description
Gaucher disease is an inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCB) that leads to progressive accumulation of glucocerebroside within macrophages and subsequent tissue and organ damage; typically of the liver, spleen, bone marrow, and brain.
Gaucher disease has been designated in the list of Specified Rare and Intractable Diseases by Specified Disease Treatment Research Program of Ministry of Health, Labor and Welfare (MHLW) as one of "lysosomal storage diseases" since 2001. Gaucher disease is also designated in the Medical Aid Program for Specified Categories of Chronic Pediatric Diseases.
The prevalence of mutations and the phenotype of patients with Gaucher disease in Japan differs from that in non-Japanese populations. Some patients with type 1 Gaucher disease in Japan have more severe and progressive disease compared to non-Japanese patients and the disease is characterized by an earlier onset of symptoms.
Velaglucerase alfa, a highly-purified form of the naturally occurring enzyme glucocerebrosidase, has been developed as an enzyme replacement therapy for Gaucher disease for the symptoms (anemia, thrombocytopenia, hepatomegaly, splenomegaly, and bone manifestation).
The primary objective of this study is to evaluate the long-term safety of every other week (EOW) dosing of velaglucerase alfa in Japanese patients with Gaucher disease who completed study HGT-GCB-087 and elected to continue treatment with velaglucerase alfa.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| velaglucerase alfa | Experimental | Drug: velaglucerase alfa15 to 60 U/kg, EOW 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 (4 listed)
- The patient has completed treatment with EOW velaglucerase alfa through Week 51 of study HGT-GCB-087.
- Female patients of child bearing potential must agree to use a medically acceptable method of contraception at all times during the study.
- 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 (4 listed)
- The patient has received treatment with any investigational drug, other than velaglucerase alfa, or investigational device within 30 days prior to study entry; such use during the study is not permitted.
- 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, as determined by the Investigator that might affect study data or confound the study results.
- The patient is unable to comply with the protocol 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 |
|---|---|---|
| velaglucerase alfaAlso: VPRIV15-60 U/kg, EOW | Drug | velaglucerase alfa |
Primary outcome
Number of Participants With Drug-related Adverse Events (AEs), Infusion-related AEs, and Serious AEs (SAEs)
Time frame: From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
An AE was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered related to investigational product. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An infusion-related AE was defined as an AE that started either during or within 12 hours after the start of the infusion and that was judged as possibly or probably related to investigational product.
Number of Participants Using Concomitant Medication
Time frame: From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)
Number of Participants With Abnormal and Clinically Significant Laboratory Test Results
Time frame: From Week 65 until the end of study (Week 155)
Laboratory test results were considered abnormal and clinically significant at the discretion of the investigator.
Number of Participants With Positive Anti-Velaglucerase Alfa Antibodies
Time frame: From Week 65 until the end of study (Week 155)
Serum samples were collected for all participants for determination of anti-velaglucerase alfa antibodies every 12 weeks.
12 secondary outcomes
Change From Baseline in Hemoglobin Concentration at Week 101
Time frame: Baseline, Week 101
Change From Baseline in Platelet Count at Week 101
Time frame: Baseline, Week 101
Change From Baseline in Liver Volume Normalized to Body Weight at Week 103
Time frame: Baseline, Week 103
Change From Baseline in Spleen Volume Normalized to Body Weight at Week 103
Time frame: Baseline, Week 103
Change From Baseline in Bone Mineral Density (BMD) at Week 103: Z Score
Time frame: Baseline, Week 103
Change From Baseline in Bone Mineral Density (BMD) at Week 103: T-Score
Time frame: Baseline, Week 103
Change From Baseline in Bone Marrow Burden (BMB) Score at Week 103
Time frame: Baseline, Week 103
Change From Baseline in Growth Velocity at Week 101 : Height Z-Score
Time frame: Baseline, Week 101
Change From Baseline in Skeletal Age at Week 103: Z-Score
Time frame: Baseline, Week 103
Change From Baseline in Plasma Chitotriosidase Levels at Week 101
Time frame: Baseline, Week 101
Number of Participants With Change From Baseline in Neurological Status at Week 103
Time frame: Baseline, Week 103
Change From Baseline in Chemokine [C-C Motif] Ligand 18 (CCL18) Levels at Week 101
Time frame: Baseline, Week 101
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27241455Ida H, Tanaka A, Matsubayashi T, Murayama K, Hongo T, Lee HM, Mellgard B. A multicenter, open-label extension study of velaglucerase alfa in Japanese patients with Gaucher disease: Results after a cumulative treatment period of 24months. Blood Cells Mol Dis. 2016 Jul;59:140-7. doi: 10.1016/j.bcmd.2015.10.002. Epub 2015 Oct 16.
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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
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing velaglucerase alfa in people with Gaucher Disease, run by Shire at 5 sites in Japan.
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 4 inclusion and 4 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 14 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 5 sites in Japan. 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 14 Dec 2015). 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?
Number of Participants With Drug-related Adverse Events (AEs), Infusion-related AEs, and Serious AEs (SAEs) (time frame: From the day of first infusion (Week 53) up to 30 days after last infusion (approximately 107 weeks)). The study lists 4 primary outcomes in all. 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 NCT01842841, 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 14 Jun 2021.