Gaucher Disease, Type 3Phase 1/2NCT01685216
Efficacy and Safety Study of Velaglucerase Alfa in Children and Adolescents With Type 3 Gaucher Disease
A Phase 1/2 study testing velaglucerase alfa in people with Gaucher Disease, Type 3, run by Shire at 5 sites in 3 countries.
Trial summary
Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Gaucher disease has been classified into 3 clinical subtypes based on the presence or absence of neurological symptoms and the severity of these neurological symptoms. Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Gaucher Disease, Type 3
- 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
- 7 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 14 Sep 2012to 15 Mar 2015
- Phase
- Phase 1/2
- 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 to 17 years
- All sexes
- No healthy volunteers
- Child
Inclusion Criteria: Each patient must meet the following criteria to be enrolled in this study.
- The patient has a confirmed diagnosis of type 3 Gaucher disease.
- The patient is ≥ 2 and < 18 years of age at the time of enrollment.
- The patient is either näive to treatment or has not received treatment (investigational or approved) for Gaucher disease within 12 months prior to study entry.
- The patient has Gaucher disease-related anemia, defined as hemoglobin concentration below the lower limit of normal for age and sex. AND ONE OR MORE OF THE FOLLOWING THREE CRITERIA
- The patient has at least moderate splenomegaly (2 to 3 cm below the left costal margin) by palpation.
- The patient has Gaucher disease-related thrombocytopenia, defined as platelet count < 120 x 10,000 platelets/cubic mm.
- The patient has a Gaucher disease-related readily palpable enlarged liver.
- Patients who have undergone splenectomy may still be eligible to participate in the study.
- Female patients of child-bearing potential must agree to use a medically acceptable method of contraception at all times during the study. Pregnancy testing will be performed at the time of enrollment and as required throughout 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's parent(s) or the patient's legally authorized representative(s) has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC).
Exclusion Criteria: Patients who meet any of the following criteria will be excluded from this study.
- The patient is suspected of having type 2 or type 1 Gaucher disease.
- The patient is < 2 years of age.
- The patient has experienced a severe (Grade 3 or higher) infusion-related hypersensitivity reaction (anaphylactic or anaphylactoid reaction) to any enzyme replacement therapy for Gaucher disease (approved or investigational).
- The patient has received any non-Gaucher disease-related treatment with an investigational drug within 30 days prior to study entry.
- The patient is a pregnant and/or lactating female.
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
Egypt3 sites
Alexandria University Hospital
Alexandria, 21131
Abu El Rich Hospital, Cairo University Hospital
Cairo
Children's Hospital, Ain Shams University Hospital
Cairo
About this study
Official title: A Multi-center, Open-label, Efficacy and Safety Study of Velaglucerase Alfa Enzyme Replacement Therapy in Children and Adolescents With Type 3 Gaucher Disease
Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Gaucher disease has been classified into 3 clinical subtypes based on the presence or absence of neurological symptoms and the severity of these neurological symptoms. Patients with type 2 Gaucher disease present with acute neurological deterioration, and those with type 3 disease typically display a more sub acute neurological course. Type 1 Gaucher disease, the most common form accounting for more than 90% of all Gaucher disease cases, does not involve the central nervous system.
The purpose of this clinical research study is to investigate the safety and effectiveness of velaglucerase alfa in patients with type 3 Gaucher disease.
Read the detailed description
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 the macrophages leading to cellular engorgement, organomegaly, and organ system dysfunction. Gaucher disease has been classified into 3 clinical subtypes based on the presence or absence of neurological symptoms and severity of neurological symptoms. Patients with type 2 Gaucher disease present with acute neurological deterioration, and those with type 3 Gaucher disease typically display a more sub acute neurological course; type 1 Gaucher disease, the most common form accounting for more than 90% of all cases, does not involve the central nervous system.
Velaglucerase alfa is an approved enzyme replacement therapy (ERT) for pediatric and adult patients with type 1 Gaucher disease. ERTs have been proven to reduce organomegaly, improve hematological parameters and positively impact health-related quality of life; ERTs have not been shown to cross the blood brain barrier and as a result have shown limited ability to improve the neurological (Central Nervous System; CNS) manifestations associated with Gaucher disease.
This study will provide a basis for exploring the efficacy and safety of velaglucerase alfa in patients with type 3 Gaucher disease.
- Conditions
- Gaucher Disease, Type 3
- Being tested
- velaglucerase alfa
- Keywords
- VPRIV, 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 alfaBiological
Also called VPRIV, Gene activated glucocerebrosidase, GA-GCB, Enzyme replacement therapy
lyophilized powder, intravenous infusion, units, Every other week (EOW)
| Study group | Role | What they receive |
|---|---|---|
| velaglucerase alfa | Experimental | IV infusion, 60 U/kg, every other week for 1 year Receives: Biological: velaglucerase alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to 12 Months (Week 53) in Hemoglobin Concentration
Hemoglobin concentration was measured as part of the hematology panel or measured separately when the hematology panel was not scheduled. Samples were measured by a central laboratory. Baseline is the modified baseline hemoglobin concentration, the average of the values from screening, baseline, and Week 1/Day 1. A positive change from baseline indicates that hemoglobin concentration increased.
Measured: Baseline, Week 53 or end of study
Secondary outcomes (6)
Change From Baseline to 12 Months (Week 53) in Platelet Count
Platelet count was measured at a central laboratory as part of the hematology panel. Baseline is the modified baseline platelet count, the average of the values from screening, baseline and Week 1/Day 1. A positive change from baseline indicates that platelet count increased.
Measured: Baseline, Week 53
Percent Change From Baseline to 12 Months (Week 51) in Normalized Liver Volume Measured Using Magnetic Resonance Imaging (MRI)
Quantitative abdominal MRI was used to measure liver volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, liver volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The liver size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in liver volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that liver volume decreased.
Measured: Baseline, Week 51 or end of study
Percent Change From Baseline to 12 Months (Week 51) in Normalized Spleen Volume Measured Using Magnetic Resonance Imaging (MRI)
Quantitative abdominal MRI was used to measure spleen volume. If sedation was necessary to perform an MRI and the investigator deemed that this would be an unwarranted risk to the participant, spleen volume could have been measured by ultrasound. Organ volume was measured by a single independent reviewer who was blinded to the participant identification and time point. The spleen size relative to body weight was determined using the corresponding body weight measured at the same visit. Change in spleen volume is presented as the normalized percentage of body weight. A negative change from baseline indicates that spleen volume decreased.
Measured: Baseline, Week 51
Number of Participants With Abnormal Neurological Status During The Study
Neurological symptoms were evaluated at regular intervals during the study and assessed on an individualized basis by a limited, age- and developmental stage-appropriate neurological examination adapted to suit the status of each participant. It was preferred that each neurological examination be performed by a neurologist with experience in assessment of neurological symptoms in patients with Gaucher disease and, if possible, the same neurologist (or designee) who evaluated a given participant at baseline performed the neurological examinations scheduled for that participant during the treatment phase and at the end of study visit.
Measured: Baseline, Weeks 13, 25, 37, and 53 or end of study
Number of Participants Who Experienced a Treatment-Emergent Adverse Event
Adverse events (AEs) were monitored continuously throughout the study from the time the participant or participants parent/legal guardian signed the informed consent/assent (if applicable) until 30 days after the participant's last dose of study drug or at the end of study visit and/or until the event resolved or stabilized, or an outcome had been reached, whichever came first. Treatment-emergent adverse events (TEAEs) were defined as AEs which occurred on or after the time of the first infusion until 30 days after the participant's last study infusion. An infusion-related reaction is defined as an AE that 1) began either during or within 12 hours after the start of the infusion, and 2) was judged as possibly or probably related to study medication.
Measured: 57 weeks
Number of Participants Who Developed Anti-Velaglucerase Alfa Antibodies During The Study
Participants provided blood samples for measurement of anti-velaglucerase alfa antibodies in serum at baseline and approximately every 12 weeks during the treatment phase. Blood samples collected during the treatment phase were to be drawn prior to infusions. Analysis of anti-velaglucerase antibodies used a validated 3-tier immunoassay method (screening, confirmatory, and titer).
Measured: Baseline, Weeks 13, 25, 37 and 53
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2012 (estimated)
- Study start14 Sep 2012
- Primary completion15 Mar 2015
- Study completion15 Mar 2015
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.
- Other trials for Gaucher Disease, Type 3Studies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 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
- NCT01685216
- Sponsor's protocol ID
- HGT-GCB-068
- Other IDs
- 2012-003427-38
- Status last verified
- May 2021
- First submitted
- 10 Sep 2012
- Last updated
- 11 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Open-label, Efficacy and Safety Study of Velaglucerase Alfa Enzyme Replacement Therapy in Children and Adolescents With Type 3 Gaucher Disease
- ClinicalTrials.gov ID
- NCT01685216
- Acronym / sponsor ID
- HGT-GCB-068
- Conditions
- Gaucher Disease, Type 3
- Keywords
- VPRIV, velaglucerase alfa
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 14 Sep 2012 (actual)
- Primary completion
- 15 Mar 2015 (actual)
- Study completion
- 15 Mar 2015 (actual)
- First posted
- 14 Sep 2012 (estimated)
- Results
- Posted 30 Oct 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 a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Gaucher disease has been classified into 3 clinical subtypes based on the presence or absence of neurological symptoms and the severity of these neurological symptoms. Patients with type 2 Gaucher disease present with acute neurological deterioration, and those with type 3 disease typically display a more sub acute neurological course. Type 1 Gaucher disease, the most common form accounting for more than 90% of all Gaucher disease cases, does not involve the central nervous system.
The purpose of this clinical research study is to investigate the safety and effectiveness of velaglucerase alfa in patients with type 3 Gaucher disease.
Detailed description
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 the macrophages leading to cellular engorgement, organomegaly, and organ system dysfunction. Gaucher disease has been classified into 3 clinical subtypes based on the presence or absence of neurological symptoms and severity of neurological symptoms. Patients with type 2 Gaucher disease present with acute neurological deterioration, and those with type 3 Gaucher disease typically display a more sub acute neurological course; type 1 Gaucher disease, the most common form accounting for more than 90% of all cases, does not involve the central nervous system.
Velaglucerase alfa is an approved enzyme replacement therapy (ERT) for pediatric and adult patients with type 1 Gaucher disease. ERTs have been proven to reduce organomegaly, improve hematological parameters and positively impact health-related quality of life; ERTs have not been shown to cross the blood brain barrier and as a result have shown limited ability to improve the neurological (Central Nervous System; CNS) manifestations associated with Gaucher disease.
This study will provide a basis for exploring the efficacy and safety of velaglucerase alfa in patients with type 3 Gaucher disease.
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 | Biological: velaglucerase alfaIV infusion, 60 U/kg, every other week for 1 year |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
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 glucocerebrosidase, GA-GCB, Enzyme replacement therapylyophilized powder, intravenous infusion, units, Every other week (EOW) | Biological | velaglucerase alfa |
Primary outcome
Change From Baseline to 12 Months (Week 53) in Hemoglobin Concentration
Time frame: Baseline, Week 53 or end of study
Hemoglobin concentration was measured as part of the hematology panel or measured separately when the hematology panel was not scheduled. Samples were measured by a central laboratory. Baseline is the modified baseline hemoglobin concentration, the average of the values from screening, baseline, and Week 1/Day 1. A positive change from baseline indicates that hemoglobin concentration increased.
6 secondary outcomes
Change From Baseline to 12 Months (Week 53) in Platelet Count
Time frame: Baseline, Week 53
Percent Change From Baseline to 12 Months (Week 51) in Normalized Liver Volume Measured Using Magnetic Resonance Imaging (MRI)
Time frame: Baseline, Week 51 or end of study
Percent Change From Baseline to 12 Months (Week 51) in Normalized Spleen Volume Measured Using Magnetic Resonance Imaging (MRI)
Time frame: Baseline, Week 51
Number of Participants With Abnormal Neurological Status During The Study
Time frame: Baseline, Weeks 13, 25, 37, and 53 or end of study
Number of Participants Who Experienced a Treatment-Emergent Adverse Event
Time frame: 57 weeks
Number of Participants Who Developed Anti-Velaglucerase Alfa Antibodies During The Study
Time frame: Baseline, Weeks 13, 25, 37 and 53
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing velaglucerase alfa in people with Gaucher Disease, Type 3, run by Shire at 5 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 11 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 Egypt, India, Tunisia. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 30 Oct 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?
Change From Baseline to 12 Months (Week 53) in Hemoglobin Concentration (time frame: Baseline, Week 53 or end of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Jun 2021.