•  ClinicalTrials.gov Identifier: NCT04418414
• Phase 1, Single Group Assignment, Non-randomized, open label trial *

Not yet recruiting *, Last Update Posted: May 23, 2022

• Male subjects who are >= 18 years of age
• Diagnosis of severe hemophilia A (<1 IU/dL FVIII activity) based on one-stage coagulation assay
• Documented history of more than 150 days of FVIII treatment

• History of spontaneous central nervous system bleeding within the last 5 years
• Subjects who have had prior cellular based therapy or gene editing/ gene therapy including a previous stem cell transplant

Serotype of the lentiviral vector not reported / manufacturing platform unknown

Hybrid human/porcine B-domain deleted FVIII variant (ET3, HP47) ^32-33, 37
    

Lentiviral FVIII gene therapy targeting expression in Macrophages

Hematopoietic Stem Cell Transplantation (HSCT) of CD34+ cells transduced with CD68-ET3 lentiviral vector (encoding human FVIII gene)

Dose for the 7 participants not reported

Not reported

Not reported

Not reported

Not reported

Not reported

Not reported

Not reported

Not reported

Not reported

Not reported

Not reported

Not applicable

Not applicable

Not reported

Not reported

^* ClinicalTrials.gov
32. Brown, H.C., et al., Bioengineered coagulation factor VIII enables long-term correction of murine hemophilia A following liver-directed adeno-associated viral vector delivery.
       Mol Ther Methods Clin Dev, 2014. 1: p. 14036. Bioengineered coagulation factor VIII enables long-term correction of murine hemophilia A following liver-directed adeno-associated
       viral vector delivery - PubMed (nih.gov)
33. Doering, C.B., et al., Identification of porcine coagulation factor VIII domains responsible for high level expression via enhanced secretion. J Biol Chem, 2004. 279(8): p. 6546-52. 37.
       Identification of Porcine Coagulation Factor VIII Domains Responsible for High Level Expression via Enhanced Secretion* - Journal of Biological Chemistry (jbc.org)
37. Doering, C.B., et al., Preclinical Development of a Hematopoietic Stem and Progenitor Cell Bioengineered Factor VIII Lentiviral Vector Gene Therapy for Hemophilia A. Hum Gene Ther,
       2018. 29(10): p. 1183-1201. Preclinical Development of a Hematopoietic Stem and Progenitor Cell Bioengineered Factor VIII Lentiviral Vector Gene Therapy for Hemophilia A - PMC (nih.gov)

CD68, Cluster of Differentiation 68 Marker for monocyte lineage and circulating macrophages; ET3, FVIII variant with porcine A1 and ap-A3 domain sequences; LV; Lentivirus