Efficacy and safety of enzyme replacement therapy for Mucopolysaccharidosis type I with 100 IU/Kg recombinant human a-L-iduronidase (Aldurazyme™)
| ISRCTN | ISRCTN22324060 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN22324060 |
| Secondary identifying numbers | NL331 (NTR369) |
- Submission date
- 06/03/2007
- Registration date
- 06/03/2007
- Last edited
- 20/08/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr A A M Zandbergen
Scientific
Scientific
Erasmus Medical Centre Rotterdam
Department of Internal Medicine
P.O. Box 2040
Rotterdam
3000 CA
Netherlands
| a.zandbergen@erasmusmc.nl |
Study information
| Study design | Non-randomised, non-controlled, parallel group, multicentre clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Multi-centre |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | Efficacy and safety of enzyme replacement therapy for MPS I with 100 I.U./Kg recombinant human a-L-iduronidase (ALDURAZYME™). |
| Study objectives | Mucopolysaccharidosis type I (MPS I) is caused by the deficiency of the lysosomal enzyme a-L-Iduronidase. Due to this deficiency heparan sulphate and dermatan sulphate (Glycosaminoglycans [GAGs]) accumulate in the lysosomes of all cells, but predominantly in the connective tissue. Clinical features encompass a spectrum of disease manifestations. Three phenotypes are recognised: 1. The neuronopathic (Hurler) type at one end of the spectrum 2. An intermediate (Hurler-Scheie) phenotype 3. A non-neuronopathic (Scheie) phenotype at the far end of the spectrum In both the non-neuronopathic and neuronopathic forms, visceral complications occur, such as joint abnormalities, hepatomegaly, cardiac valve abnormalities, skeletal abnormalities and corneal clouding. The most severe expression of the disease is found in the neuronopathic form; here visceral symptoms occur very early in life, with concomitant devastating, irreversible central nervous system involvement, giving rise to considerable morbidity from a very early age onwards and death on average around the fifth year of age. In the Scheie phenotype psychomotor development is normal. Skeletal and joint manifestations form the important disease burden in these patients. Recently, trials with weekly a-L-Iduronidase (Aldurazyme™, Genzyme/Biomarin) infusions showed improvement in joint mobility, lung function and exercise tolerance, as determined by the six minute walk test. Aldurazyme™ received marketing approval as an orphan drug from the European Medicines Agency (EMEA) in April 2003. However, there are still many open issues regarding the efficacy of treatment, making uniform evaluation of treatment in selected groups of MPS I patients mandatory. Hypothesis: MPS I patients can be treated with Aldurazyme safely and effectively. |
| Ethics approval(s) | Ethics approval received from the local medical ethics committee |
| Health condition(s) or problem(s) studied | Mucopolysaccharidosis type I |
| Intervention | Enzyme replacement therapy with Aldurazyme™. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Recombinant human a-L-iduronidase (Aldurazyme™) |
| Primary outcome measure | 1. Improvement of joint mobility 2. Improvement of quality of life |
| Secondary outcome measures | 1. Improvement of sleep apnea registration 2. Improvement in six-minute walk test 3. Improvement of cardiac geometry and function 4. Improvement in lung function 5. Improved motor performance (handicap status) 6. Evaluation of visual acuity/performance 7. Evaluation of mental condition and social performance 8. Decrease of liver and/or spleen size as measured by ultrasound 9. Effect of dose and infusion rate on plasma enzyme levels and enzyme availability |
| Overall study start date | 01/01/2004 |
| Completion date | 31/12/2005 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Sex | Both |
| Target number of participants | 35 |
| Key inclusion criteria | 1. The patient must give written informed consent 2. If the patient is younger than 12 years, informed consent from his/her parents or his/her legal representative is necessary 3. If the patient is below 18 years, but older than 12 years, informed consent from the child is necessary if the patient is mentally and physically able to do so 4. The patients can be included in this protocol, and not in any of the two other MPS I treatment protocols 5. The patient must have a current diagnosis of MPS I, as documented by a decreased a-L-iduronidase activity in leukocytes or fibroblasts 6. Patients must be willing and able to comply with the study protocol 7. Female patients must have a negative pregnancy test, and must use a medically accepted method of contraception during the study |
| Key exclusion criteria | 1. Patient is unable or unwilling to comply with the study protocol 2. Parent(s) or legal representatives are unable or unwilling to comply with the evaluation program 3. Patient is pregnant or lactating 4. Life expectancy less than six months 5. Very severe neurological involvement as evidenced by: a. total or subtotal absence of cortical activity (vegetative state) b. untreatable seizures c. loss of (almost) all abilities to communicate |
| Date of first enrolment | 01/01/2004 |
| Date of final enrolment | 31/12/2005 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Erasmus Medical Centre Rotterdam
Rotterdam
3000 CA
Netherlands
3000 CA
Netherlands
Sponsor information
Erasmus Medical Centre (The Netherlands)
Hospital/treatment centre
Hospital/treatment centre
Sophia Children's Hospital
Department of Metabolic Diseases
P.O. Box 2040
Rotterdam
3015 GJ
Netherlands
| Website | http://www.erasmusmc.nl/ |
|---|---|
"ROR" |
https://ror.org/018906e22 |
Funders
Funder type
Government
Dutch Health Care Insurance Board (College Voor Zorgverzekeringen [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 |
Editorial Notes
20/08/2021: Proactive update review. No publications found. Search options exhausted.
