Active — Not RecruitingPhase 1/2

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

United Kingdom5 participantsStarted 2023-06-01

Plain-language summary

MPS II is a genetic disorder that affects boys. Boys with MPS II are missing a working enzyme known as iduronate-2-sulfatase (IDS) which is needed to break down long sugar chains in the body. When this enzyme is missing, these sugars build up to excess causing damage, and stop organs such as the brain from working properly. Children with MPS II often have progressive symptoms such as developmental delay and physical problems. The only approved treatment for MPS II is enzyme replacement therapy. This involves a regular infusion of the missing enzyme into the blood stream. But this treatment only helps some symptoms and cannot help problems in the brain. This study will be the first in human clinical trial to check whether using a gene therapy in children with MPS II is safe and is able to provide enough enzyme to help with disease symptoms. Gene therapy involves changing the genetic information that makes up a person, by taking a correct version of the gene that is needed to make the working IDS enzyme and putting it back into the body. This means that the body can then make the missing enzyme itself. The good thing with this therapy is that the body should be able to make this enzyme forever. To make sure the therapy is safe and working patients will be closely followed for 2 years.

Who can participate

Age range3 Months – 22 Months

SexMALE

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Written informed consent from a legally authorized guardian.
✓. Male, age at consent ≥3 months and ≤22 months.
✓. 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.
✓. 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.
✓. 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.
✓. 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.
✓. 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.

What they're measuring

To evaluate the tolerability of the IMP in MPS II patients

Timeframe: Up to 24 months post-IMP delivery

To assess the safety of the IMP in MPS II patients

Timeframe: Up to 24 months post-IMP delivery

Trial details

NCT IDNCT05665166

SponsorUniversity of Manchester

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2028-07

View on ClinicalTrials.gov More Mucopolysaccharidosis II trials

Plain-language summary

Who can participate

Age range3 Months – 22 Months

SexMALE

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Written informed consent from a legally authorized guardian.
✓. Male, age at consent ≥3 months and ≤22 months.
✓. 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.
✓. 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.
✓. 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.
✓. 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.
✓. 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.

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

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

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

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

Exclusion criteria