NCT04201405

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

A Phase I-II, Study of Autologous CD34+ Haematopoietic Stem Cells Transduced Ex Vivo with CD11b Lentiviral Vector Encoding for Human SGSH in Patients with Mucopolysaccharidosis Type IIIA (MPS IIIa, Sanfilippo Syndrome Type A)

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 5 (estimated)
• Sponsor: University of Manchester · Academic / Other
• Sex: All
• Age: 3 Months – 24 Months
• Healthy volunteers: Not accepted

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.

Detailed description

MPS IIIA is caused by a deficiency of the heparan-N-sulfatase (SGSH) enzyme, leading to the accumulation of the glycosaminoglycan heparan sulphate in the lysosomes. Untreated patients of MPS IIIA experience rapid and progressive neurologic deterioration. To date, there is no effective disease-modifying treatment for patients suffering from MPS IIIA. This study aims to recruit 3 to 5 patients with MPS IIIA who satisfy the inclusion and exclusion criteria and provide full consent, between 3 months and 24 months of age. The investigational medicinal product (IMP) will be a cell-based gene therapy that uses genetically modified autologous CD34+ haematopoietic stem cells transduced with a lentiviral vector containing the human SGSH gene. Patients will be followed up for a minimum of 3 years after gene therapy.

Conditions

• Mucopolysaccharidosis Type IIIA

Interventions

Type	Name	Description
DRUG	Autologous CD34+ cells transduced with a lentiviral vector containing the human SGSH gene	Autologous CD34+ haematopoietic stem cells from MPS IIIA patients will be genetically modified ex vivo using CD11b.SGSH Lentiviral vector (LV), a self-inactivating LV expressing the SGSH gene codon optimized for human use and regulated by a human CD11b myeloid-specific promoter. Cells will be cryopreserved prior to patient administration.

Timeline

• Start date: 2020-01-07
• Primary completion: 2024-10-30
• Completion: 2026-10-30
• First posted: 2019-12-17
• Last updated: 2025-03-30

Locations

1 site across 1 country: United Kingdom