NCT05265767

Hematopoietic Stem Cell Transplantation Gene Therapy for Treatment of Severe Hemophilia A

Gene Therapy for Hemophilia A With a High Expression Factor VIII Transgene in Autologous Hematopoietic Stem Cells

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: Christian Medical College, Vellore, India · Academic / Other
• Sex: Male
• Age: 18 Years – 45 Years
• Healthy volunteers: Not accepted

Summary

Factor VIII (FVIII) is a large plasma glycoprotein that participates in blood coagulation. Loss of circulating FVIII activity due to mutations within the F8 gene results in the X-linked, recessive bleeding disorder hemophilia A. The clinical presentation ranges from a mild to severe bleeding phenotype that correlates with the patient's residual plasma FVIII activity level. Current state of the art treatment entails frequent infusion of FVIII protein. However, several limitations remain to treating hemophilia A, which are 1) access to FVIII-replacement products (currently \<30% of the world population is treated adequately, access is highly restricted in India), 2) high burden of compliance with treatment protocols particularly in children 3) the expense of FVIII-replacement products, 4) the development of humoral anti-FVIII immune responses that block FVIII activity and limit treatment efficacy and 5) morbidity due to crippling musculoskeletal disease when inadequately treated. Several newer hemostasis agents are being developed but like the recombinant Clotting Factor Concentrate (CFC) from the 1990s, these are also not likely to be made available in India for many years. Currently, the only cure for hemophilia A is orthotopic liver transplantation.

Detailed description

Eligible subjects will undergo (Cluster of Differentiation) CD34+ hematopoietic stem cell collection. These cells will be transduced ex vivo with (Cluster of Differentiation) CD68-ET3 lentiviral vector and subsequently, following a conditioning regimen, the transduced cells will be infused to patients. After completion of study treatment, patients are followed up periodically for up to 15 years.

Conditions

• Hemophilia A

Interventions

Type	Name	Description
BIOLOGICAL	Auto CD34+PBSC transduced with a lentiviral vector encoding a novel coagulation factor VIII transgene	Auto CD34+PBSC transduced with a lentiviral vector encoding a novel coagulation factor VIII transgene administered by IV infusion following conditioning regimen.

Timeline

• Start date: 2022-04-01
• Primary completion: 2024-06-28
• Completion: 2024-06-28
• First posted: 2022-03-04
• Last updated: 2024-07-12

Locations

1 site across 1 country: India

Regulatory

• FDA-regulated drug study