Fabry DiseasePhase 4NCT00074984
A Study of the Safety and Efficacy of Fabrazyme (Agalsidase Beta) as Compared to Placebo in Patients With Advanced Fabry Disease
A Phase 4 study testing Fabrazyme (agalsidase beta) in people with Fabry Disease, run by Genzyme, a Sanofi Company at 26 sites in 6 countries.
Trial summary
People with Fabry disease have an alteration in their genetic material (DNA) which causes a deficiency of the a-galactosidase A enzyme. Fabrazyme (agalsidase beta) is a drug that helps to breakdown and remove certain types of fatty substances called "glycolipids." These glycolipids are normally present within the body… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Fabry Disease
- What is being tested?
- Fabrazyme (agalsidase beta)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 26 sitesin 6 countries
- Study dates
- Feb 2001to Jan 2004
- Phase
- Phase 4
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must provide written informed consent
- Patients must be at least 16 years old
- Patients must have a current diagnosis of Fabry disease and have a clinical presentation consistent of Fabry disease (decreased sweating, Fabry pain, angiokeratoma, etc.)
- Patients may not have received enzyme replacement therapy as a treatment for Fabry disease
- Patients must have a documented plasma a-galactosidase A (aGAL) activity of < 1.5 nmol/hr/mL or a documented leukocyte aGAL activity of < 4 nmol/hr/mg
- Patients must have one or more of the following: a serum creatinine measurement of 1.2 to 3 mg/dL (106.1 to 265 umol/L) OR estimated creatinine clearance < 80 mL/min only if the patient's serum creatinine measurement is < 1.2 mg/dL
- Female patients of childbearing potential must have a negative pregnancy test prior to each dosing and all female patients must use a medically accepted form of contraception
Who cannot join
- Patient has undergone or is currently scheduled for kidney transplantation or is currently on dialysis
- Patient has acute renal failure
- Patient has participated in a study employing an investigational drug within 30 days of study entry
- Patient has diabetes mellitus or presence of confounding renal disease
- Patient has a history of transient ischemic attack (TIA) or ischemic stroke within 3 months of study entry documented by mild-to-moderate neurological deficit
- Patient has critical coronary disease
Show all 9Show fewer
- Patient has congestive heart failure
- Patient has severe residual neurological deficit that will confound the detection of new events as determined by an attending neurologist and/or Principal Investigator
- Patient is unwilling to comply with the requirements of the protocol or the patient has a medical condition, serious intercurrent illness, or extenuating circumstances that would significantly decrease study compliance, including prescribed follow-up
Trial locations and contacts
26 sites in 6 countries.
26 sites in 6 countries
United States19 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Massachusetts General Hospital
Boston, Massachusetts, 02114
Children's Hospital
Buffalo, New York, 14209
Children's Memorial Hospital
Chicago, Illinois, 60614
Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Oncology Hematology Association
Coral Springs, Florida, 33065
Duke University Medical Center
Durham, North Carolina, 27710
University of Connecticut Health Partners
Farmington, Connecticut, 06119
Baylor College of Medicine
Houston, Texas, 77030
University of Kansas Medical Center
Kansas City, Kansas, 66160
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Gene Therapy Center - Dept. of Pediatrics and Institute of Human Genetics
Minneapolis, Minnesota, 55455
Mount Sinai School of Medicine
New York, New York, 10029
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
University of Rochester School of Medicine
Rochester, New York, 14642
University of San Francisco
San Francisco, California, 94143
University of Washington School of Medicine
Seattle, Washington, 98195
Canada3 sites
Queen Elizabeth II Health Center
Halifax, Nova Scotia, B3H 1V8
Hopital du Sacre-Coeur de Montreal
Montreal, Quebec, H4J 1C5
North York General Hospital
Toronto, Ontario, M2K 1E1
About this study
Official title: Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Fabrazyme on Progression of Renal Disease and Significant Clinical Events in Patients With Fabry Disease
People with Fabry disease have an alteration in their genetic material (DNA) which causes a deficiency of the a-galactosidase A enzyme. Fabrazyme (agalsidase beta) is a drug that helps to breakdown and remove certain types of fatty substances called "glycolipids." These glycolipids are normally present within the body in most cells. In Fabry disease, glycolipids build up in various tissues such as the liver, kidney, skin, and blood vessels because a-galactosidase A is not present, or is present in small quantities. The build up of glycolipid ("globotriaosylceramide" or "GL-3") levels in these tissues in particular is thought to cause the clinical symptoms that are common to Fabry disease. This study will test the safety and efficacy of Fabrazyme in the treatment of patients with Fabry disease.
- Conditions
- Fabry Disease
- Being tested
- Fabrazyme (agalsidase beta), Placebo
- Keywords
- a-Galactosidase A, aGAL, r-haGAL, Fabry, GL-3, Fabrazyme
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fabrazyme (agalsidase beta)Biological
Also called Fabrazyme
1mg/kg Fabrazyme (agalsidase beta) every 2 weeks
PlaceboBiological
1 mg/kg placebo intravenously every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Patients randomized to placebo Receives: Biological: Placebo |
| Fabrazyme (agalsidase beta) | Active comparator | Patients randomized to Fabrazyme (agalsidase beta). Receives: Biological: Fabrazyme (agalsidase beta) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing a Clinically Significant Renal, Cardiac or Cerebrovascular Event and/or Death in Fabrazyme (Agalsidase Beta) Patients as Compared to Placebo Patients
The primary efficacy endpoint was the time to the first occurrence of a clinically significant renal (33% increase in serum creatinine, dialysis or transplant), cardiac (myocardial infarction, significant change in cardiac status, i.e., angina, congestive heart failure or symptomatic arrhythmia requiring medication or surgery) or cerebrovascular (stroke or transient ischemic attack) event and/or death (due to any cause) in Fabrazyme (agalsidase beta) patients as compared to placebo patients.
Measured: up to 35 months
Secondary outcomes (4)
Number of Participants Experiencing a Renal Event in Fabrazyme (Agalsidase Beta) Patients as Compared to Placebo Patients
Time to a clinically significant renal event (33% increase in serum creatinine, dialysis or transplant) in Fabrazyme (agalsidase beta) patients as compared to placebo patients.
Measured: up to 35 months
Slope of Estimated Glomerular Filtration Rate (eGFR) Comparing Placebo vs Fabrazyme (Agalsidase Beta) Patients
Summary of slopes of eGFR by baseline eGFR subgroups (>60 and <=60 mL/min/1.73m^2/year) comparing Placebo vs Fabrazyme (agalsidase beta) Patients.
Measured: up to 35 months
Slope of Inverse Serum Creatinine Values Comparing Placebo vs Fabrazyme (Agalsidase Beta)Patients
Summary of slopes of inverse serum creatinine by baseline serum creatinine subgroups (> or <= 1.5 mg/dL) comparing Placebo vs Fabrazyme (agalsidase beta) patients.
Measured: up to 35 months
Neuropathic Pain as Assessed by Question 12 of the Brief Pain Inventory (BPI) Questionnaire (Pain at Its Worst)
Neuropathic pain was assessed by Question 12 of the Brief Pain Inventory (BPI) Questionnaire on a scale of 0 (no pain) to 10 (pain as bad as you can imagine)
Measured: at 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2003 (estimated)
- Study startFeb 2001
- Primary completionJan 2004
- Study completionJan 2004
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 Fabry 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Medical Monitor, Study director, Genzyme Coorporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00074984
- Sponsor's protocol ID
- AGAL-008-00
- Status last verified
- Dec 2013
- First submitted
- 24 Dec 2003
- Last updated
- 27 Dec 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M, Finkel R, Packman S, Bichet DG, Warnock DG, Desnick RJ; Fabry Disease Clinical Trial Study Group. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med. 2007 Jan 16;146(2):77-86. doi: 10.7326/0003-4819-146-2-200701160-00148. Epub 2006 Dec 18.
PubMed 17179052
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Fabrazyme on Progression of Renal Disease and Significant Clinical Events in Patients With Fabry Disease
- ClinicalTrials.gov ID
- NCT00074984
- Acronym / sponsor ID
- AGAL-008-00
- Conditions
- Fabry Disease
- Keywords
- a-Galactosidase A, aGAL, r-haGAL, Fabry, GL-3, Fabrazyme
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Feb 2001
- Primary completion
- Jan 2004 (actual)
- Study completion
- Jan 2004 (actual)
- First posted
- 25 Dec 2003 (estimated)
- Results
- Posted 15 Dec 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
People with Fabry disease have an alteration in their genetic material (DNA) which causes a deficiency of the a-galactosidase A enzyme. Fabrazyme (agalsidase beta) is a drug that helps to breakdown and remove certain types of fatty substances called "glycolipids." These glycolipids are normally present within the body in most cells. In Fabry disease, glycolipids build up in various tissues such as the liver, kidney, skin, and blood vessels because a-galactosidase A is not present, or is present in small quantities. The build up of glycolipid ("globotriaosylceramide" or "GL-3") levels in these tissues in particular is thought to cause the clinical symptoms that are common to Fabry disease. This study will test the safety and efficacy of Fabrazyme in the treatment of patients with Fabry 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 |
|---|---|---|
| Placebo | Placebo comparator | Biological: PlaceboPatients randomized to placebo |
| Fabrazyme (agalsidase beta) | Active comparator | Biological: Fabrazyme (agalsidase beta)Patients randomized to Fabrazyme (agalsidase beta). |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must provide written informed consent
- Patients must be at least 16 years old
- Patients must have a current diagnosis of Fabry disease and have a clinical presentation consistent of Fabry disease (decreased sweating, Fabry pain, angiokeratoma, etc.)
- Patients may not have received enzyme replacement therapy as a treatment for Fabry disease
- Patients must have a documented plasma a-galactosidase A (aGAL) activity of < 1.5 nmol/hr/mL or a documented leukocyte aGAL activity of < 4 nmol/hr/mg
Key exclusion criteria (9 listed)
- Patient has undergone or is currently scheduled for kidney transplantation or is currently on dialysis
- Patient has acute renal failure
- Patient has participated in a study employing an investigational drug within 30 days of study entry
- Patient has diabetes mellitus or presence of confounding renal disease
- Patient has a history of transient ischemic attack (TIA) or ischemic stroke within 3 months of study entry documented by mild-to-moderate neurological deficit
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 |
|---|---|---|
| Fabrazyme (agalsidase beta)Also: Fabrazyme1mg/kg Fabrazyme (agalsidase beta) every 2 weeks | Biological | Fabrazyme (agalsidase beta) |
| Placebo1 mg/kg placebo intravenously every 2 weeks | Biological | Placebo |
Primary outcome
Number of Participants Experiencing a Clinically Significant Renal, Cardiac or Cerebrovascular Event and/or Death in Fabrazyme (Agalsidase Beta) Patients as Compared to Placebo Patients
Time frame: up to 35 months
The primary efficacy endpoint was the time to the first occurrence of a clinically significant renal (33% increase in serum creatinine, dialysis or transplant), cardiac (myocardial infarction, significant change in cardiac status, i.e., angina, congestive heart failure or symptomatic arrhythmia requiring medication or surgery) or cerebrovascular (stroke or transient ischemic attack) event and/or death (due to any cause) in Fabrazyme (agalsidase beta) patients as compared to placebo patients.
4 secondary outcomes
Number of Participants Experiencing a Renal Event in Fabrazyme (Agalsidase Beta) Patients as Compared to Placebo Patients
Time frame: up to 35 months
Slope of Estimated Glomerular Filtration Rate (eGFR) Comparing Placebo vs Fabrazyme (Agalsidase Beta) Patients
Time frame: up to 35 months
Slope of Inverse Serum Creatinine Values Comparing Placebo vs Fabrazyme (Agalsidase Beta)Patients
Time frame: up to 35 months
Neuropathic Pain as Assessed by Question 12 of the Brief Pain Inventory (BPI) Questionnaire (Pain at Its Worst)
Time frame: at 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 17179052Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M, Finkel R, Packman S, Bichet DG, Warnock DG, Desnick RJ; Fabry Disease Clinical Trial Study Group. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann Intern Med. 2007 Jan 16;146(2):77-86. doi: 10.7326/0003-4819-146-2-200701160-00148. Epub 2006 Dec 18.
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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.
Medical Monitor study director
Genzyme Coorporation
26 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fabrazyme (agalsidase beta) in people with Fabry Disease, run by Genzyme, a Sanofi Company at 26 sites in 6 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 9 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 27 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, Canada, Czechia, Hungary, Poland and 1 more country. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 15 Dec 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?
Number of Participants Experiencing a Clinically Significant Renal, Cardiac or Cerebrovascular Event and/or Death in Fabrazyme (Agalsidase Beta) Patients as Compared to Placebo Patients (time frame: up to 35 months). 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 NCT00074984, 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 27 Dec 2013.