Hemophilia A, Severe

This study longitudinally observes the intergenerational (mother-child) continuum in hemophilia A from pregnancy through early childhood. Because the study follows mother-child pairs, the study includes both a maternal cohort and a pediatric cohort. Each cohort has a primary goal: for the mother with a severe hemophilia genotype, the overarching primary goal is to understand the risks for pregnancy-associated bleeding and postpartum hemorrhage (PPH); for the child, the overarching primary goal is to understand the risks, timing, and circumstances of development of anti-FVIII antibodies. From a longitudinal perspective, risks for both bleeding in the mother and anti-FVIII antibody development in the child are expected to be influenced over time by genetic and environmental factors that begin early in (or before) pregnancy. Enrollment of blood relatives is offered to improve power to better understand inherited contributions to bleeding and inhibitor development in the mother-baby pairs.

To perform a liver biopsy in haemophilia A and B patients with endogenous FVIII:C/FIX:C expression at \>1% any time after gene transfer following AAV mediated gene transfer. This is to obtain tissue for analysis, to understand if FIX/FVIII transgenic protein expression is mediated by AAV proviral DNA that is integrated into the host cell DNA or if stable expression in humans is mediated by episomal maintained AAV genome.

This is a prospective, multicenter, open-label study to assess efficacy, safety, pharmacokinetics (PK), and immunogenicity of human plasma-derived Factor VIII (FVIII) in previously treated patients (PTPs) with severe hemophilia A. Overall, 55 male PTPs aged 12 to 65 years old with a FVIII level of \< 1% and at least 150 treatment exposure days (EDs) with a previous FVIII product will be enrolled. Patients will receive SKP-0141 at a dose of 25 to 50 IU/kg every second day or 3 times per week for at least 50 EDs and/or 6 months from the start of prophylactic treatment. Efficacy of SKP-0141 will be primarily evaluated in bleeding prophylaxis with annualized bleeding rate from start of treatment and until end of treatment (Visit 10).

The goal of this multicentre, prospective, open-label, cross-over clinical study is to determine whether individualized PK-guided dosing of emicizumab is non-inferior to conventional dosing of emicizumab in the prevention of bleeding in congenital haemophilia A patients.