Treatment of Fabry patients greater than 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)

ISRCTN	ISRCTN45178534
DOI	https://doi.org/10.1186/ISRCTN45178534
Protocol serial number	NTR216
Sponsor	Academic Medical Centre (AMC) (The Netherlands)
Funder	The Dutch Health Care Insurance Board (CVZ) (The Netherlands)

Submission date: 20/12/2005
Registration date: 20/12/2005
Last edited: 04/07/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr A C Vedder
Scientific

Academic Medical Centre
Department of Internal Medicine, F4-247
PO Box 22660
Amsterdam
1105 AZ
Netherlands

Phone	+31 (0)20 566 4558
Email	a.c.vedder@amc.uva.nl

Study information

Primary study design	Interventional
Study design	Multicentre, randomised, active controlled, factorial trial
Secondary study design	Randomised controlled trial
Scientific title	Treatment of Fabry patients greater than 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)
Study objectives	Evaluation of efficacy and safety of two different formulas of alfa-Galactosidase A, agalsidase beta (Fabrazyme®) and agalsidase alpha (Replagal®) in an equal dose of 0.2 mg/kg in order to detect any differences between these two drugs.
Ethics approval(s)	Received from the local medical ethics committee
Health condition(s) or problem(s) studied	Fabry disease
Intervention	Patients will receive 0.2 mg/kg Fabrazyme® (agalsidase beta) or 0.2 mg/kg Replagal®(agalsidase alpha), every two weeks for a minumum of 12 months. If there is 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 weeks.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Agalsidase beta (Fabrazyme®), agalsidase alpha (Replagal®)
Primary outcome measure(s)	Wall-thickness (septum and left and right ventricle wall)/end-diastolic volume) on echocardiography.
Key secondary outcome measure(s)	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 (36-item Short Form Health Survey [SF-36])
Completion date	31/12/2005

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	24
Total final enrolment	34
Key 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 alpha-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: Major: 1. Severe acroparesthesias, that cannot satisfactorily be controlled with Carbamazepine 2. Decreased glomerular filtration rate (GFR) less than 80 ml/min 3. Proteinuria greater than 300 mg/ml 4. Documented cerebrovascular accident (CVA) 5. Cardiac infarction 6. Hypertrophic non-obstructive cardiomyopathy resulting in decreased exercise tolerance 7. Rhythm disturbances necessitating a pacemaker 8. Multiple lacunar infarctions on magnetic resonance imaging (MRI) Minor: 1. Documented transient ischaemic attack (TIA) 2. Cardiac hypertrophy on echo or MRI 3. Atrial fibrillation 4. Intraventricular conduction abnormality 5. Sensoric hearing loss as shown on a hearing test 6. Severe vertigo 7. Micro-albuminuria greater than 50 mg/L 8. Mild to moderate acroparesthesias 9. Gastro-intestinal complaints that can not be explained by other medical conditions than Fabry disease
Key exclusion criteria	1. Patient is pregnant or lactating 2. Patient is unwilling to comply to the evaluation program
Date of first enrolment	29/05/2001
Date of final enrolment	31/12/2005

Locations

Countries of recruitment

Netherlands

Study participating centre

Academic Medical Centre

Amsterdam
1105 AZ
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	11/07/2007	04/07/2019	Yes	No

Editorial Notes

04/07/2019: Publication reference and total final enrolment added.