Gene Therapy with Modified Autologous Hematopoietic Stem Cells for Patients with Mucopolysaccharidosis Type II

Launched by UNIVERSITY OF MANCHESTER · Dec 16, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called gene therapy for boys with Mucopolysaccharidosis Type II (MPS II), a genetic disorder that affects how the body breaks down certain sugars. Boys with MPS II lack a specific enzyme called iduronate-2-sulfatase (IDS), which leads to a harmful buildup of sugars that can affect their organs and brain, causing problems like developmental delays. The trial aims to see if this gene therapy can safely help the body produce the missing enzyme on its own, potentially improving symptoms over time.

To participate in the trial, boys between 3 months and 22 months old who have a close male relative with severe MPS II are eligible, as long as they have certain test results showing low levels of the enzyme IDS. The study will follow participants closely for two years to monitor their health and the effects of the treatment. While the only current treatment for MPS II involves regular enzyme infusions, this new therapy could help the body create the enzyme forever, offering hope for better management of the disease. It's important for families to know that participants will need to commit to regular clinic visits and follow specific study guidelines.

Gender

MALE

Eligibility criteria

• Inclusion Criteria:
• • 1. Written informed consent from a legally authorized guardian.
• • 2. Male, age at consent ≥3 months and ≤22 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 (1) a normal enzyme activity level of at least one other sulfatase (to rule out multiple sulfatase deficiency) as measured in leucocytes, or (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.
• Exclusion Criteria:
• • 1. The patient has previously received stem cell or gene therapy
• • 2. The patient has received modified intravenous ERT or intra-thecal 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