Open-label Gene Therapy Study in p47-CGD

Chronic granulomatous disease (CGD) caused by p47phox deficiency (p47-CGD) is a life-threatening genetic disorder causing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase deficiency in phagocytes. This leads to severe bacterial and fungal infections as well as hyperinflammatory complications that significantly reduces life expectancy. Standard of care includes daily antimicrobial prophylactic treatment by conventional pharmacotherapy. This aims to prevent or reduce the frequency and severity of infections and other disease manifestations. However, the underlying genetic defect in neutrophil cytosolic factor 1 (NCF1) cannot be cured by pharmacotherapy, and many p47-CGD patients suffer from significant morbidity, impaired quality of life, and early mortality. Allogeneic haematopoietic stem cell transplant (HSCT), the only established curative treatment and carries substantial risks when using non-sibling donors. Risks include graft failure and graft-versus-host disease. Treatment with SGX-001 aims to cure the underlying genetic defect using autologous haematopoietic stem and progenitor cells (HSPCs) transduced with a lentiviral self-inactivating vector to express transgenic p47phox protein and restore NADPH oxidase function in phagocytes. This treatment eliminates the need for allogeneic HSCT and could offer a safer alternative to allogeneic transplantation for patients without ideal donors. In this study, safety and efficacy of SGX-001 will be investigated in participants with p47-CGD who have an indication for allogeneic HSCT but lack a human leukocyte antigen-matched suitable sibling donor.