Gene therapy in children with mucopolysaccharidosis II (MPSII) consented below the age of 12 months
- Conditions
- Mucopolysaccharidosis type II (MPS II or Hunter Syndrome)Genetic Diseases
- Registration Number
- ISRCTN12458940
- Lead Sponsor
- niversity of Manchester
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- Male
- Target Recruitment
- 5
1. Written informed consent from a legally authorized guardian
2. Male, age at consent =3 months and =12 months
3. Normal cognitive function or mild cognitive dysfunction (patient has a Development Quotient [DQ] score =70 at screening as determined by the Bayley Scale of Infant Development-third edition (BSID-III), cognitive domain), or assessed as normal or only mildly impaired by experienced neuropsychologist
4. Close male relative with known severe (progressive neuronopathic) phenotype of MPSII, or genotype associated with progressive neuronopathic phenotype. This is to be confirmed by the independent expert reviewers.
5. IDS activity =10% of the Lower Limit of Normal as measured in leucocytes or plasma, plus either:
5.1. A normal enzyme activity level of at least one other sulfatase (to rule out multiple sulfatase deficiency) as measured in leucocytes, or
5.2. A documented mutation in the IDS gene
6. Medically stable and able to accommodate the protocol requirements, including travel without placing an undue burden on the patient/patient’s family, as determined by the CI
7. Patients and their parents/legal guardians must be willing and able to comply with study restrictions and to commit to attend clinic for the required duration during the study and follow-up period as specified in the protocol
1. The patient has previously received stem cell or gene therapy
2. The patient has received modified intravenous ERT or intrathecal ERT in a trial setting
3. Patient currently enrolled in another interventional clinical trial
4. The patient has a history of poorly controlled seizures
5. Hemizygous for mutation known to be associated with non-neuropathic phenotype
6. The patient is currently receiving psychotropic or other medications which, in the CI’s opinion, would be likely to substantially confound test results
7. The patient has received any investigational medicinal product (including Genistein) within 30 days prior to the Baseline visit or is scheduled to receive any investigational medicinal product during the course of the study
8. Documented Human Immunodeficiency Virus (HIV) infection (positive HIV RNA and/or anti-p24 antibodies)
9. Malignant neoplasia (except local skin cancer) or a documented history of hereditary cancer syndrome. Patients with a prior successfully treated malignancy and a sufficient follow-up to exclude recurrence (based on oncologist opinion) can be included after discussion and approval by the Medical Monitor
10. Myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndrome and acute myeloid leukaemia, or other serious haematological disorders
11. The patient has a medical condition or extenuating circumstance that, in the opinion of the CI, might compromise the patient’s ability to comply with protocol requirements, the patient’s well-being or safety, or the interpretability of the patient’s clinical data
12. Visual or hearing impairment sufficient to preclude adequate neurodevelopmental testing
13. Severe behavioural disturbances due to reasons other than MPS II and likely to interfere with protocol compliance, as determined by the CI
14. Known sensitivity to Busulfan
15. The receipt of live vaccinations within 30 days prior to treatment start
16. Known sensitivity to DMSO
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety of the IMP, including engraftment, absence of significant regimen-related toxicity, absence of short term infusion reactions and of long term vector related integration events. Safety and tolerability will be assessed throughout the full 2 years of the study from IMP administration by evaluating adverse events (AEs), clinical laboratory test results (haematology, chemistry and urinalysis), vital signs measurements, electrocardiogram (ECG), physical examination results, and concomitant medication usage.
- Secondary Outcome Measures
Name Time Method