Alternative Dosing and Regimen of Replagal to Treat Fabry Disease
The main goal of this study is to assess the pharmacodynamic effects of different or more frequent doses of Replagal compared to the standard dosing regimen. Replagal is a genetically engineered form of alpha-Galactosidase A, an enzyme that normally breaks down a fatty substance called globotriaosylceramide (Gb(3)). In patients with Fabry disease, GB(3) does not function properly and therefore builds up causing problems with the kidneys, heart, nerves, and blood vessels.
Male patients 18 years of age or older with Fabry disease who are not on dialysis and have not received a kidney transplant may be eligible for this study.
Participants are randomly assigned to receive one of the following five regimens of Replagal infusions, given through a vein over 20 to 80 minutes:
0.1 mg/kg body weight every week
0.2 mg/kg body weight every week
0.2 mg/kg body weight every other week
0.4 mg/kg body weight every week
0.4 mg/kg body wieght every other week
In the US, the infusions are given at the NIH Clinical Center. Vital signs are measured before, immediately after, and 1 hour after each infusion.
Baseline evaluations are done on an inpatient or outpatient basis. Baseline tests include a check of vital signs (temperature, respiratory rate, pulse rate, and blood pressure); physical examination; laboratory tests; and review of treatment side effects. Evaluations are also done at every infusion visit, and 1 week and 1 month after the last infusion.
Safety evaluations are done periodically and include vital sign measurements, physical examination, blood and urine tests, review of drug side effects, electrocardiogram (ECG), Holder monitor (2 hour ECG), and QSART (NIH only). The QSART (quantitative sudomotor axon reflex test) measures the amount of sweat in a particular area of skin, mostly the forearm. For this test, a cup partly filled with a liquid is strapped on the arm. A weak electric current is turned on, stimulating the sweat glands, and the amount of sweat produced is measured. There is a tingling sensation when the current is turned on.
Patients who complete the study will be offered the opportunity of receiving Replagal for 6 months in an extension study.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
|Official Title:||A Phase I-II Pharmacokinetic/Pharmacodynamic Study of Replagal to Assess the Effects of Alternative Dose and Regimen in Patients With Fabry Disease|
|Study Start Date:||January 2004|
|Estimated Study Completion Date:||November 2005|
OBJECTIVES: The goal of this study is to assess the pharmacodynamic effects of alternative weekly and every two week dosing regimens of Replagal (agalsidase alfa) in comparison to the current standard Replagal treatment regimen of 0.2 mg/kg given intravenously every two weeks.
STUDY POPULATION: Hemizygous males with Fabry disease who are 18 years of age or older.
DESIGN: This is a randomized, open-label study that will assess the pharmacodynamics and pharmacokinetics of five different dosing regimens of enzyme replacement therapy with Replagal. The effects of dose as well as dosing frequency will be evaluated and compared to the standard Replagal regimen.
OUTCOME MEASURES: The pharmacodynamic parameter to be assessed is plasma globotriaosylceramide (Gb3). The hypothesis to be tested is the role that frequency (weekly) and/or dose (0.1 to 0.4 mg/kg) of Replagal will play in pharmacodynamics as measured by reductions in plasma Gb3 compared to the current dose and frequency of 0.2 mg/kg given every two weeks. Clinical parameters including sweating, heart rate variability, proteinuria, severity of neuropathic pain, pain and anti-diarrheal medication usage, frequency and severity of abdominal pain, and frequency of diarrhea also will be assessed.
|United States, Maryland|
|National Institute of Neurological Disorders and Stroke (NINDS)|
|Bethesda, Maryland, United States, 20892|