Ignite Creation Date:
2024-05-05 @ 11:31 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00068107
Status:
COMPLETED
Last Update Posted:
2015-03-31
First Post:
2003-09-06
Brief Title:
Dosing Study of Replagal in Patients With Fabry Disease
Sponsor:
Baylor Research Institute
Organization:
Baylor Research Institute
Study Overview
Official Title:
Study of Weekly Dosing Regimens of Replagal in Patients With Fabry Disease With Incomplete Clinical Response to Long-Term Therapy
Status:
COMPLETED
Status Verified Date:
2015-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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 02 mgkg 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 patients 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
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 02 mgkg 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 patients 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 02 mgkg of body weight administered every 2 weeks
Study Population Patients with Fabry disease who are currently on clinical research protocols 00-N-0185TKT011 or 02-N-0220TKT015 and who have demonstrated progressive decline in calculated glomerular filtration rate GFR of at least 5 mlminyear 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 02 mgkg 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 02 mgkg administered every 2 weeks At the 2-year time point the dose will be increased to 04 mgkg only in the patients whose GFR continues to significantly decline Secondary outcome measures will be globotriaosylceramide Gb3 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 Population Patients with Fabry disease who are currently on clinical research protocols 00-N-0185TKT011 or 02-N-0220TKT015 and who have demonstrated progressive decline in calculated glomerular filtration rate GFR of at least 5 mlminyear 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 02 mgkg 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 02 mgkg administered every 2 weeks At the 2-year time point the dose will be increased to 04 mgkg only in the patients whose GFR continues to significantly decline Secondary outcome measures will be globotriaosylceramide Gb3 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 03-N-0286 | None | None | None |