|- candidate number||1381|
|- NTR Number||NTR216|
|- Date ISRCTN created||20-dec-2005|
|- date ISRCTN requested||18-okt-2005|
|- Date Registered NTR||5-sep-2005|
|- Secondary IDs||N/A |
|- Public Title||Treatment of Fabry patients > 18 years with enzyme supplementation therapy: comparison of efficacy and toxicity of low dose (0,2 mg/kg) fabrazyme (agalsidase beta) or replagal (agalsidase alfa).|
|- Scientific Title||Treatment of Fabry patients > 18 years with enzyme supplementation therapy: comparison of efficacy and toxicity of low dose (0,2 mg/kg) fabrazyme (agalsidase beta) or replagal (agalsidase alfa).|
|- hypothesis||Evaluation of efficacy and safety of two different formulas of alfa-Galactosidase A, agalsidase beta (FabrazymeTM) and agalsidase alpha (ReplagalTM) in an equal dose of 0,2 mg/kg in order to detect any differences between these two drugs.|
|- Healt Condition(s) or Problem(s) studied||Fabry disease|
|- Inclusion criteria||1. The patient must have given written informed consent;|
2. Patients must be 18 years or older;
3. Patient must have a current diagnosis of Fabry disease;
4. Patients must have a decreased á-Gal activity or proven alfa-Gal A mutation;
5. Female patients must have a negative pregnancy test, and must use a medically accepted method of contraception;
6. Patients must be willing to comply to the evaluation program;
7. Patients must have a clinical presentation consistent with either typical or atypical Fabry disease. Patients must have at least one major or two minor objective criteria:
a. Severe acroparesthesias, that cannot satisfactorily be controlled with Carbamazepine;
b. Decreased GFR < 80 ml/min;
c. Proteinuria > 300 mg/ml;
d. Documented CVA;
e. Cardiac infarction;
f. Hypertrophic Non-obstructive Cardiomyopathy resulting in decreased exercise tolerance;
g. Rhythm disturbances necessitating a pacemaker;
h. Multiple lacunar infarctions on MRI;
i. Documented TIA;
j. Cardiac hypertrophy on echo or MRI;
k. Atrial fibrillation;
l. Intraventricular conduction abnormality;
m. Sensoric hearing loss as shown on a hearing test;
n. Severe vertigo;
o. Micro-albuminuria > 50 mg/L;
p. Mild to moderate acroparesthesias;br>
q. Gastro-intestinal complaints that can not be explained by other medical conditions than Fabry disease.
|- Exclusion criteria||1. Patient is pregnant or lactating;|
2. Patient is unwilling to comply to the evaluation program.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||6-mei-2002|
|- planned closingdate||31-dec-2005|
|- Target number of participants||24|
|- Interventions||Patients will receive 0,2mg/kg Fabrazyme (agalsidase beta) or 0,2 mg/kg Replagal (agalsidase alpha), every two weeks for a minumum of 12 months. If there's treatment failure (progression of renal disease, cardiac disease and/or a new cerebral stroke or TIA) during or after this period, patients will be advised to switch to Fabrazyme 1,0 mg/kg/2 wks.|
|- Primary outcome||Wall-thickness (septum and left and right ventricle wall) / end-diastolic volume) on echocardiography.|
|- Secondary outcome||1. Improvement of renal function as measured by GFR;|
2. Reduction of glycolipid accumulation in skin tissue (LM and biochemistry);
3. Reduction in pain as measured by the BPI;
4. Reduction in glycosphingolipid in plasma and 24-hr urine;
5. Quality of life scores (SF-36).
|- Trial web site||N/A|
|- status||stopped: trial finished|
|- CONTACT FOR PUBLIC QUERIES|| A.C. Vedder|
|- CONTACT for SCIENTIFIC QUERIES||Dr. C.E.M. Hollak|
|- Sponsor/Initiator ||Academic Medical Center (AMC), Department of Internal Medicine|
(Source(s) of Monetary or Material Support)
|Dutch Health Care Insurance Board (CVZ, independent governement organisation)|
|- Publications||PLoS ONE. 2007 Jul 11;2(7):e598.|
|- Brief summary||Fabry disease is an X-linked disorder caused by the deficiency of the lysosomal enzyme alfa-Galactosidase A (alfa-Gal). Patients with this disorder suffer in childhood from severe pains in hands and feet and develop severe complications later in life such as renal failure, CVA¡¦s and cardiac complications. |
Patients with Fabry disease have a reduced life expectancy. Recently two differently alfa-Galactosidase enzyme preparations have received marketing authorization in the EU (orphan drug).
Conclusions on the differences between these products with regard to safety and efficacy cannot be drawn because of the different dosage and evaluation methods performed.
Therefore treatment should be performed according to a standardized treatment approach which allows comparison of both drugs.
To monitor and evaluate the efficacy and safety of two different formulas of alfa-Galactosidase A, agalsidase alpha (FabrazymeTM) and agalsidase beta (ReplagalTM) in an equal dose of 0,2 mg/kg in adults with Fabry disease.
Investigational plan: Symptomatic Fabry patients (aged 18 or older) who fulfil the criteria will receive enzyme therapy for at least 12 months and will be evaluated every 3 months.
|- Main changes (audit trail)|
|- RECORD||5-sep-2005 - 9-okt-2008|