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 |
| Secondary identifying numbers | NTR216 |
- 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
Scientific
Academic Medical Centre
Department of Internal Medicine, F4-247
PO Box 22660
Amsterdam
1105 AZ
Netherlands
| Phone | +31 (0)20 566 4558 |
|---|---|
| a.c.vedder@amc.uva.nl |
Study information
| Study design | Multicentre, randomised, active controlled, factorial trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Agalsidase beta (Fabrazyme®), agalsidase alpha (Replagal®) |
| Primary outcome measure | Wall-thickness (septum and left and right ventricle wall)/end-diastolic volume) on echocardiography. |
| Secondary outcome measures | 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]) |
| Overall study start date | 29/05/2001 |
| Completion date | 31/12/2005 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | At least 18 (9 in each group). 24 recruited as of Jan'06 |
| 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
1105 AZ
Netherlands
Sponsor information
Academic Medical Centre (AMC) (The Netherlands)
Hospital/treatment centre
Hospital/treatment centre
Department of Internal Medicine
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
| Website | http://www.amc.uva.nl |
|---|---|
"ROR" |
https://ror.org/03t4gr691 |
Funders
Funder type
Government
The Dutch Health Care Insurance Board (CVZ) (The Netherlands)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | 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.
