Gene therapy for boys with Mucopolysaccharidosis Type II

A Phase I-II Study of Cryopreserved Autologous CD34+ Haematopoietic Stem Cells Transduced Ex Vivo with CD11b Lentiviral Vector Encoding Human IDS Tagged with ApoEII in Patients with Neuronopathic Mucopolysaccharidosis Type II (nMPS II, Hunters Syndrome)

This study is testing a new gene therapy for young boys with Mucopolysaccharidosis Type II to see if it can help them by using their own modified stem cells to fix the missing enzyme that causes their symptoms.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 3 Months to 22 Months
• Sex: Male
• Sponsor: University of Manchester (other)
• Locations: 1 site (Manchester)
• Trial ID: NCT05665166 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and efficacy of a novel gene therapy using modified autologous hematopoietic stem cells in children diagnosed with Mucopolysaccharidosis Type II (MPS II). The therapy involves extracting the child's own stem cells, genetically modifying them to produce the missing enzyme, and then reintroducing these cells back into the patient. The study will recruit a small cohort of male patients aged between 3 months and 22 months, who will be monitored for at least two years post-treatment to assess the therapy's impact on disease symptoms. This approach seeks to address the underlying cause of MPS II rather than just alleviating symptoms.

Who should consider this trial

Good fit: Ideal candidates for this study are male children aged 3 to 22 months with a confirmed diagnosis of MPS II and specific genetic criteria.

Not a fit: Patients who are not male, older than 22 months, or do not meet the genetic and health criteria for MPS II may not benefit from this study.

Why it matters

Potential benefit: If successful, this gene therapy could provide a long-term solution for boys with MPS II by potentially restoring enzyme function and improving overall health outcomes.

How similar studies have performed: While gene therapy for other genetic disorders has shown promise, this specific approach for MPS II is novel and has not been previously tested in humans.

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

Where this trial is running

Manchester

• Manchester University Foundation Trust — Manchester, United Kingdom (RECRUITING)

Study contacts

• Principal investigator: Robert Wynn — Manchester Foundation Trust
• Study coordinator: Robert Wynn, Prof

Conditions: Mucopolysaccharidosis II