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
Protocol serial number	NL331 (NTR369)
Sponsor	Erasmus Medical Centre (The Netherlands)
Funder	Dutch Health Care Insurance Board (College Voor Zorgverzekeringen [CVZ]) (The Netherlands)

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

Erasmus Medical Centre Rotterdam
Department of Internal Medicine
P.O. Box 2040
Rotterdam
3000 CA
Netherlands

Email	a.zandbergen@erasmusmc.nl

Study information

Primary study design	Interventional
Study design	Non-randomised, non-controlled, parallel group, multicentre clinical trial
Secondary study design	Multi-centre
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
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Recombinant human a-L-iduronidase (Aldurazyme™)
Primary outcome measure(s)	1. Improvement of joint mobility 2. Improvement of quality of life
Key secondary outcome measure(s)	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
Completion date	31/12/2005

Eligibility

Participant type(s)	Patient
Age group	Child
Sex	All
Target sample size at registration	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

Results and Publications

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

Editorial Notes

20/08/2021: Proactive update review. No publications found. Search options exhausted.