Gaucher Disease, Type 1Phase 3NCT00430625
A Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Gaucher Disease
A Phase 3 study testing VPRIV ®, in people with Gaucher Disease, Type 1, run by Shire at 5 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 this 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?
- VPRIV ®,
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 5 sitesin 5 countries
- Study dates
- 15 Feb 2007to 1 Apr 2009
- Phase
- Phase 3
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
- Patient 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 is willing and able to provide written informed consent prior to initiating any study-related procedures
- Patient is at least 2 years of age
- Patient has Gaucher disease-related anemia and
- Patient has at least moderate splenomegaly or
- Patient has Gaucher disease-related thrombocytopenia or
- Patient has a readily palpable enlarged liver
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- Patient has not received treatment for Gaucher disease within 30 months prior to study entry
- Female patients of child-bearing potential agree to use a medically acceptable method of contraception. Male patients must agree to use a medically acceptable method of birth control.
- Patient must be sufficiently cooperative to participate in the study as judged by the Investigator.
Who cannot join
- Includes:
- Patient has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease
- Patient is antibody-positive to imiglucerase during screening or has experienced an anaphylactic reaction to imiglucerase
- Patient has received treatment with any investigational drug or device within the 30 days prior to study entry
- Patient is Human immunodeficiency virus (HIV) positive
- Patient is hepatitis positive
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- Patient presents with iron, folic acid and/or vitamin B12 deficiency sustained anemia during screening
- 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
- Patient has a significant comorbidity(ies)that might affect study data or confound the study results
- Patient is a pregnant and/or lactating female
- Patient is unable to comply with the protocol or is unlikely to complete the study, as determined by the Investigator
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
About this study
Official title: A Multicenter, Randomized, Double-Blind, Parallel Group, Two-Dose Study of Gene-Activated® Human Glucocerebrosidase (GA-GCB) Enzyme Replacement Therapy in Patients With Type 1 Gaucher Disease
Gaucher disease is a rare lysosomal storage disorder caused by the deficiency of the enzyme glucocerebrosidase (GCB). Due to this 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 efficacy of every other week dosing of Gene-Activated® Human Glucocerebrosidase (GA-GCB, velaglucerase alfa) at doses of 45 and 60 U/kg in treatment-naïve 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 Central Nervous System (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. 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, safety and pharmacokinetics of GA-GCB in men, women, and children with Type 1 Gaucher disease. Each patients duration of treatment was 12 months.
- 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 VPRIV®, velaglucerase alfa, GA-GCB, Gene-activated® human glucocerebrosidase
Intravenous (IV) infusion, every other week via intravenous infusion for 12 months
| Study group | Role | What they receive |
|---|---|---|
| VPRIV®-45 U/kg, IV, every other week | Experimental | VPRIV® (velaglucerase alfa, Gene Activated® human glucocerebrosidase, GA-GCB) Receives: Biological: VPRIV ®, |
| VPRIV®-60 U/kg, IV, every other week | Experimental | VPRIV® (velaglucerase alfa, Gene Activated® human glucocerebrosidase,GA-GCB) Receives: Biological: VPRIV ®, |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to 12 Months in Hemoglobin Concentration for the 60 U/kg Treatment Group.
Efficacy endpoint
Measured: Week 53
Secondary outcomes (6)
Change From Baseline to 12 Months in Hemoglobin Concentration in 45 U/kg Treatment Group
Measured: Week 53
Change From Baseline to 12 Months in Platelet Counts for Each Treatment Group.
intent to treat (ITT) Population
Measured: Week 53
Change From Baseline to 12 Months in Normalized Liver Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI)
Liver Volume has been normalized for percentage of body weight for each treatment arm. Liver size relative to body weight = (Liver volume [cc]/Body weight [kg])*100
Measured: Week 51
Change From Baseline to 12 Months in Normalized Spleen Volume (Percent Body Weight) for Each Treatment Group (Measured by Magnetic Resonance Imaging (MRI))
12 patients in the 60 U/kg group and 13 patients in the 45 U/kg group were analyzed for efficacy in the intent to treat (ITT) population. Spleen Volume has been normalized for percent of body weight for each treatment arm. Spleen size relative to body weight = (Spleen volume [cc]/Body weight [kg])*100
Measured: Week 51
Percent Change From Baseline to 12 Months in Plasma Chitotriosidase for Each Treatment Group
Percent Change from Baseline to Weeks 53 by Randomized velaglucerase alfa Treatment Group - Subset of intent to treat (ITT) Population who were wild type homozygous for chitotriosidase.
Measured: Week 53
Percent Change From Baseline to 12 Months in Chemokine (C-C Motif) Ligand 18 (CCL18)
Measured: Week 53
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2007 (estimated)
- Study start15 Feb 2007
- Primary completion1 Apr 2009
- Study completion1 Apr 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 25 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
- NCT00430625
- Sponsor's protocol ID
- TKT032
- Status last verified
- Jun 2021
- First submitted
- 1 Feb 2007
- Last updated
- 29 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