Gene Therapy with Modified Autologous Hematopoietic Stem Cells for Patients with Mucopolysacchari… (NCT04201405) | Clinical Trial Compass
Active — Not RecruitingPhase 1/2
Gene Therapy with Modified Autologous Hematopoietic Stem Cells for Patients with Mucopolysaccharidosis Type IIIA
United Kingdom5 participantsStarted 2020-01-07
Plain-language summary
Patients with MPS IIIA have a clinical disorder marked by severe and progressive brain disease and neurological symptoms due to the accumulation of undigested glycosaminoglycans in all cells of the body.
This study will be the first in human clinical trial to explore the safety, tolerability and clinical efficacy of ex vivo gene therapy (autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH gene) in MPSIIIA patients. Following treatment with the gene therapy patients will be followed up for a minimum of 3 years.
Who can participate
Age range3 Months – 24 Months
SexALL
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Inclusion criteria
✓. Written informed consent of a legally authorized guardian(s)
✓. Age at baseline ≥3 months and ≤24 months
✓. Normal cognitive function or mild cognitive deterioration (subject has a Development Quotient (DQ) score ≥80) at baseline as determined by the Bayley Scale of Infant Development-third edition (BSID-III), cognitive domain)
✓. Sibling or relative of known MPS IIIA patients with rapidly progressing phenotype, or genotype associated with rapidly progressing phenotype, or presence of somatic features predictive of rapid progression
✓. SGSH activity ≤10% of the Lower Limit of Normal as measured in leukocytes, plus either (1) a normal enzyme activity level of at least one other sulfatase (to rule out multiple sulfatase deficiency) as measured in leukocytes or (2) two documented mutations in the SGSH 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.
Exclusion criteria
✕. The subject has received stem cell, gene therapy or enzyme replacement therapy (any route of administration)
What they're measuring
1
To evaluate the tolerability of the IMP in MPS IIIA patients: scale
Timeframe: up to 3 years
2
To evaluate the biological efficacy of IMP post-treatment: expression of SGSH in total leukocytes
Timeframe: 12 months post gene therapy
3
To assess the safety of the IMP in MPS IIIA patients
✕. Subject currently enrolled in other interventional clinical trials.
✕. Contraindications for MRI scans.
✕. The subject has a history of poorly controlled seizures.
✕. Homozygous or compound heterozygous for the S298P mutation or any other mutation known to be associated to slow-progressing phenotype.
✕. The subject is currently receiving psychotropic or other medications which, in the CI's opinion, would be likely to substantially confound test results.
✕. The subject 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.
✕. Documented Human Immunodeficiency Virus (HIV) infection (positive HIV RNA and/or anti-p24 antibodies).