Fabry DiseasePhase 2NCT00068107
Dosing Study of Replagal in Patients With Fabry Disease
A Phase 2 study testing Replagal in people with Fabry Disease, run by Baylor Research Institute at 1 site in United States.
Trial summary
This study will determine the safety and effectiveness of increasing Replagal infusions in certain patients with Fabry disease. Replagal is a genetically engineered form of Alpha-galactosidase A, an enzyme that normally breaks down a fatty substance called globotriaosylceramide (Gb3). Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Fabry Disease
- What is being tested?
- Replagal
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2003to Dec 2013
- Phase
- Phase 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 Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with Fabry disease participating in 00-N-0185/TKT011 or 02-N-0220/TKT015 may be eligible. No other Fabry patients will be eligible.
- Patients losing GFR at a rate greater than 5 ml/min/year despite ERT with agalsidase alfa for greater than or equal to 2.5 years in 00-N-0185/TKT/003/006/011 Study or ERT over greater than or equal to 1.0 years in 02-N-0220/TKT/010/015 Study.
- Patients who at least twice demonstrated significant improvement or normalization of sweat function (by QSART or thermoregulatory sweat test) or reduction in serum creatinine by at least 10% but return to the pre-infusion state before the subsequent biweekly enzyme infusion.
- Patients who freely agree to participate in this study and understand the nature, risks and benefits of this study and give their written informed consent.
Who cannot join
- Patients with Fabry disease, who are not already part of 00-N-0185/TKT011 or 02-N-0220/TKT015.
- Patients on these protocols who have stable serum creatinine (or a lesser rise in serum creatinine than stipulated in the inclusion criteria), and do not show other objective evidence of incomplete clinical response between biweekly infusions (e.g. sweat function).
- Patients who have begun dialysis or who have received a renal transplant.
- Patients who cannot tolerate the study procedures or who are unable or unwilling to travel to the study center as required by this protocol.
- Patients with an intercurrent medical condition that would render them unsuitable for mthe study e.g. HIV, diabetes. The reason is that the pathologies of these conditions will be significant confounders in assessing the effect of the experimental therapy and its adverse events.
- Patients who in the opinion of the investigator (for whatever reason) are thought to be unsuitable for the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Study of Weekly Dosing Regimens of Replagal in Patients With Fabry Disease With Incomplete Clinical Response to Long-Term Therapy
This study will determine the safety and effectiveness of increasing Replagal infusions in certain patients with Fabry disease. Replagal is a genetically engineered form of Alpha-galactosidase A, an enzyme that normally breaks down a fatty substance called globotriaosylceramide (Gb3). In patients with Fabry disease, Alpha-galactosidase A does not function properly and, therefore, Gb3 builds up, causing problems with the kidneys, heart, nerves, and blood vessels.
Patients with Fabry disease who are participating in NIH protocol 00-N-0185 or 02-N-0220 may be eligible for this study. This includes patients who are currently taking Replagal but whose kidney function continues to worsen, or patients who have certain test results that are much improved after Replagal infusion.
Read more
Participants will receive Replagal infusions (0.2 mg/kg body weight) through a vein once a week (as opposed to the previous dosage of once every 2 weeks) for up to 2 years. The first infusion, and some others, are given at the NIH Clinical Center, but most are administered by the patient's local doctor. Vital signs are measured before, immediately after, and 1 hour after each infusion.
Baseline evaluations are done on an inpatient basis at the NIH Clinical Center over a 1-week period before and after the first Replagal infusion and at 6-month intervals during the study. Tests include a check of vital signs (temperature, respiratory rate, pulse rate, and blood pressure); weight measurement; physical and neurological examinations; routine blood and urine tests; 24-hour urine collection; electrocardiogram; and review of treatment side effects. In addition, the following tests are done:
- Quantitative sensory testing: This is a non-invasive test to measure the ability to sense warm, cold and vibration in the hand and foot.
- QSART: This test measures the amount of sweat in a particular area of skin that did not sweat enough. A small amount of a medicine called acetylcholine is put on the skin and made to enter the skin using a very small electric current.
- Doppler skin blood flow: This test measures blood flow to the blood vessels of the skin. A machine takes pictures of blood flow in the skin of the forearm using a laser beam. Pictures are taken before and during application of medicines that cause blood vessels to dilate. Acetylcholine is used on one forearm and nitroprusside is used on the other. The medication is made to enter the skin using a small el...
Read the detailed description
Objectives: The goal of this study is to determine whether higher frequency of dosing of enzyme replacement therapy (ERT) can either significantly slow the decline of renal function or continuously sustain the normalization of other objective functions in patients with Fabry disease who have been receiving intravenous infusions of Replagal (agalsidase alfa) at a dose of 0.2 mg/kg of body weight administered every 2 weeks.
Study Population: Patients with Fabry disease who are currently on clinical research protocols 00-N-0185/TKT011 or 02-N-0220/TKT015 and who have demonstrated progressive decline in calculated glomerular filtration rate (GFR) of at least 5 ml/min/year on ERT or who consistently show transient improvement in objective functions (such as sweating) in the few days post-infusion.
Design: This is an open label study comparing one dosing regimen with a previous less intensive dosing regimen. Patients will receive a dose of 0.2 mg/kg of body weight every week.
Outcome Measures: The main outcome measure will be a change in the mean linear rate of decline of the estimated calculated GFR. The main hypothesis is that a more frequent administration of the previous dose of Replagal will significantly reduce the mean slope of the decline of the calculated glomerular filtration rate GFR compared with the currently observed slope on a dose of 0.2 mg/kg administered every 2 weeks. At the 2-year time point, the dose will be increased to 0.4 mg/kg only in the patients whose GFR continues to significantly decline. Secondary outcome measures will be globotriaosylceramide (Gb(3)) in plasma and urinary sediment, quantitative sudomotor axon reflex test, quantitative sensory testing. Study duration is 2 years with a possibility of additional one-year extensions.
- Conditions
- Fabry Disease
- Being tested
- Replagal
- Keywords
- Lysosomal Storage, Renal Insufficiency, Stroke, Hypohidrosis, Peripheral Neuropathy, Fabry Disease
- Medical subject headings
- Fabry Disease, Renal Insufficiency, Stroke, Hypohidrosis, Peripheral Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ReplagalDrug
Also called agalsidase alfa
enzyme replacement therapy
| Study group | Role | What they receive |
|---|---|---|
| Relagal | Experimental | All participants received Relagal administered weekly Receives: Drug: Replagal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimated Glomerular Filtration Rate (eGFR)
The rate of decline in renal function, as measured by estimation of glomerular filtration rate at baseline when participants were receiving agalsidase alfa (Relagal) every 2 weeks and when participants were receiving weekly infusion of Relagal.
Measured: Relagal was administered every 2 weeks for 2-4 years pre-study, Relagal was administred weekly during the study (approx. 4.5-10 years)
Secondary outcomes (5)
Globotriaosylceramide (Gb(3)) in Plasma
Measured: Baseline and last observation (up to 10 years)
Globotriaosylceramide (Gb(3)) in Urine Sediment
Measured: Baseline and last observation (up to 10 years)
Number of Participants With a Change in Quantitative Sudomotor Axon Reflex Test
Quantitative sudomotor axon reflex test (QSART) is a measure of sweat function
Measured: Baseline and last observation (up to 10 years)
Quantitative Sensory Testing
For quantitative sensory testing, the outcome variable (detection threshold score) was analyzed for all combinations of location (foot, hand, and thigh) and test (cold, vibration, and warm). Possible threshold scores may range from 1-25. Score values of ">25" were set to 25. Higher scores indicate higher sensory detection threshold. Therefore, lower score is better. Time, measured in years, was centered at the date in which patients switched treatment regimen. All available measurements were used. A linear mixed model analysis was used to test for differences in the linear association between time and detection threshold score pre-and-post ERT regiment change while accounting for the correlation among observations from the same individual. Specifically, the model contained a subject specific random intercept with year as a fixed effect and knot at time of the treatment change.
Measured: pre-study was 2-4 years, during study sensory testing measured for approx. 4.5-5 years
Doppler Skin Blood Flow
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2003 (estimated)
- Study startSep 2003
- Primary completionDec 2013
- Study completionDec 2013
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 (3)Papers the sponsor has linked to this study.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- More trials run by Baylor Research InstituteThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00068107
- Sponsor's protocol ID
- 030286
- Other IDs
- 03-N-0286
- Status last verified
- Mar 2015
- First submitted
- 6 Sep 2003
- Last updated
- 31 Mar 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Altarescu G, Schiffmann R, Parker CC, Moore DF, Kreps C, Brady RO, Barton NW. Comparative efficacy of dose regimens in enzyme replacement therapy of type I Gaucher disease. Blood Cells Mol Dis. 2000 Aug;26(4):285-90. doi: 10.1006/bcmd.2000.0310.
PubMed 11042029Brady RO. Enzymatic abnormalities in diseases of sphingolipid metabolism. Clin Chem. 1967 Jul;13(7):565-77. No abstract available.
PubMed 5006481Brady RO, Schiffmann R. Clinical features of and recent advances in therapy for Fabry disease. JAMA. 2000 Dec 6;284(21):2771-5. doi: 10.1001/jama.284.21.2771.
PubMed 11105184
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Weekly Dosing Regimens of Replagal in Patients With Fabry Disease With Incomplete Clinical Response to Long-Term Therapy
- ClinicalTrials.gov ID
- NCT00068107
- Acronym / sponsor ID
- 030286
- Conditions
- Fabry Disease
- Keywords
- Lysosomal Storage, Renal Insufficiency, Stroke, Hypohidrosis, Peripheral Neuropathy, Fabry Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Baylor Research InstituteUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Sep 2003
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 8 Sep 2003 (estimated)
- Results
- Posted 31 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will determine the safety and effectiveness of increasing Replagal infusions in certain patients with Fabry disease. Replagal is a genetically engineered form of Alpha-galactosidase A, an enzyme that normally breaks down a fatty substance called globotriaosylceramide (Gb3). In patients with Fabry disease, Alpha-galactosidase A does not function properly and, therefore, Gb3 builds up, causing problems with the kidneys, heart, nerves, and blood vessels.
Patients with Fabry disease who are participating in NIH protocol 00-N-0185 or 02-N-0220 may be eligible for this study. This includes patients who are currently taking Replagal but whose kidney function continues to worsen, or patients who have certain test results that are much improved after Replagal infusion.
Participants will receive Replagal infusions (0.2 mg/kg body weight) through a vein once a week (as opposed to the previous dosage of once every 2 weeks) for up to 2 years. The first infusion, and some others, are given at the NIH Clinical Center, but most are administered by the patient's local doctor. Vital signs are measured before, immediately after, and 1 hour after each infusion.
Baseline evaluations are done on an inpatient basis at the NIH Clinical Center over a 1-week period before and after the first Replagal infusion and at 6-month intervals during the study. Tests include a check of vital signs (temperature, respiratory rate, pulse rate, and blood pressure); weight measurement; physical and neurological examinations; routine blood and urine tests; 24-hour urine collection; electrocardiogram; and review of treatment side effects. In addition, the following tests are done:
- Quantitative sensory testing: This is a non-invasive test to measure the ability to sense warm, cold and vibration in the hand and foot.
- QSART: This test measures the amount of sweat in a particular area of skin that did not sweat enough. A small amount of a medicine called acetylcholine is put on the skin and made to enter the skin using a very small electric current.
- Doppler skin blood flow: This test measures blood flow to the blood vessels of the skin. A machine takes pictures of blood flow in the skin of the forearm using a laser beam. Pictures are taken before and during application of medicines that cause blood vessels to dilate. Acetylcholine is used on one forearm and nitroprusside is used on the other. The medication is made to enter the skin using a small el...
Detailed description
Objectives: The goal of this study is to determine whether higher frequency of dosing of enzyme replacement therapy (ERT) can either significantly slow the decline of renal function or continuously sustain the normalization of other objective functions in patients with Fabry disease who have been receiving intravenous infusions of Replagal (agalsidase alfa) at a dose of 0.2 mg/kg of body weight administered every 2 weeks.
Study Population: Patients with Fabry disease who are currently on clinical research protocols 00-N-0185/TKT011 or 02-N-0220/TKT015 and who have demonstrated progressive decline in calculated glomerular filtration rate (GFR) of at least 5 ml/min/year on ERT or who consistently show transient improvement in objective functions (such as sweating) in the few days post-infusion.
Design: This is an open label study comparing one dosing regimen with a previous less intensive dosing regimen. Patients will receive a dose of 0.2 mg/kg of body weight every week.
Outcome Measures: The main outcome measure will be a change in the mean linear rate of decline of the estimated calculated GFR. The main hypothesis is that a more frequent administration of the previous dose of Replagal will significantly reduce the mean slope of the decline of the calculated glomerular filtration rate GFR compared with the currently observed slope on a dose of 0.2 mg/kg administered every 2 weeks. At the 2-year time point, the dose will be increased to 0.4 mg/kg only in the patients whose GFR continues to significantly decline. Secondary outcome measures will be globotriaosylceramide (Gb(3)) in plasma and urinary sediment, quantitative sudomotor axon reflex test, quantitative sensory testing. Study duration is 2 years with a possibility of additional one-year extensions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Relagal | Experimental | Drug: ReplagalAll participants received Relagal administered weekly |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with Fabry disease participating in 00-N-0185/TKT011 or 02-N-0220/TKT015 may be eligible. No other Fabry patients will be eligible.
- Patients losing GFR at a rate greater than 5 ml/min/year despite ERT with agalsidase alfa for greater than or equal to 2.5 years in 00-N-0185/TKT/003/006/011 Study or ERT over greater than or equal to 1.0 years in 02-N-0220/TKT/010/015 Study.
- Patients who at least twice demonstrated significant improvement or normalization of sweat function (by QSART or thermoregulatory sweat test) or reduction in serum creatinine by at least 10% but return to the pre-infusion state before the subsequent biweekly enzyme infusion.
- Patients who freely agree to participate in this study and understand the nature, risks and benefits of this study and give their written informed consent.
Key exclusion criteria (6 listed)
- Patients with Fabry disease, who are not already part of 00-N-0185/TKT011 or 02-N-0220/TKT015.
- Patients on these protocols who have stable serum creatinine (or a lesser rise in serum creatinine than stipulated in the inclusion criteria), and do not show other objective evidence of incomplete clinical response between biweekly infusions (e.g. sweat function).
- Patients who have begun dialysis or who have received a renal transplant.
- Patients who cannot tolerate the study procedures or who are unable or unwilling to travel to the study center as required by this protocol.
- Patients with an intercurrent medical condition that would render them unsuitable for mthe study e.g. HIV, diabetes. The reason is that the pathologies of these conditions will be significant confounders in assessing the effect of the experimental therapy and its adverse events.
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 |
|---|---|---|
| ReplagalAlso: agalsidase alfaenzyme replacement therapy | Drug | Relagal |
Primary outcome
Estimated Glomerular Filtration Rate (eGFR)
Time frame: Relagal was administered every 2 weeks for 2-4 years pre-study, Relagal was administred weekly during the study (approx. 4.5-10 years)
The rate of decline in renal function, as measured by estimation of glomerular filtration rate at baseline when participants were receiving agalsidase alfa (Relagal) every 2 weeks and when participants were receiving weekly infusion of Relagal.
5 secondary outcomes
Globotriaosylceramide (Gb(3)) in Plasma
Time frame: Baseline and last observation (up to 10 years)
Globotriaosylceramide (Gb(3)) in Urine Sediment
Time frame: Baseline and last observation (up to 10 years)
Number of Participants With a Change in Quantitative Sudomotor Axon Reflex Test
Time frame: Baseline and last observation (up to 10 years)
Quantitative Sensory Testing
Time frame: pre-study was 2-4 years, during study sensory testing measured for approx. 4.5-5 years
Doppler Skin Blood Flow
Time frame: 10 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11042029Altarescu G, Schiffmann R, Parker CC, Moore DF, Kreps C, Brady RO, Barton NW. Comparative efficacy of dose regimens in enzyme replacement therapy of type I Gaucher disease. Blood Cells Mol Dis. 2000 Aug;26(4):285-90. doi: 10.1006/bcmd.2000.0310.
- Background: PubMed 5006481Brady RO. Enzymatic abnormalities in diseases of sphingolipid metabolism. Clin Chem. 1967 Jul;13(7):565-77. No abstract available.
- Background: PubMed 11105184Brady RO, Schiffmann R. Clinical features of and recent advances in therapy for Fabry disease. JAMA. 2000 Dec 6;284(21):2771-5. doi: 10.1001/jama.284.21.2771.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Replagal in people with Fabry Disease, run by Baylor Research Institute at 1 site in United States.
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 6 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 31 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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 31 Mar 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?
Estimated Glomerular Filtration Rate (eGFR) (time frame: Relagal was administered every 2 weeks for 2-4 years pre-study, Relagal was administred weekly during the study (approx. 4.5-10 years)). 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 NCT00068107, which also lists 3 linked publications.
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 31 Mar 2015.