Haemophilia affects approximately half-a-million people worldwide, the vast majority of whom have limited access to treatment. The unique mode of action of SerpinPC may provide safe and convenient prophylaxis for bleeding associated with all forms of haemophilia.
AP-0101 is a phase I/II clinical trial with a single ascending dose study (Part I) followed by a six-month multiple dose study (Part II). Part I began in healthy volunteers (Part IA) and was continued in patients with severe haemophilia at doses predicted to provide clinical benefit (Part IIB). The primary purpose of the trial is to assess the safety, tolerability, and pharmacokinetic profile of SerpinPC, with reduction in bleeding episodes an exploratory endpoint.
Five cohorts of healthy volunteers were successfully dosed in Part IA in the UK, four by IV infusion and one by subcutaneous (SC) injection. The final cohort finished dosing on 5 February 2020. There were no SerpinPC-related adverse events (AEs), no injection site reactions, and no increase in D-dimer levels.
Four cohorts of three patients each were dosed in Part IB in Moldova and Georgia, where all persons with haemophilia (PwH) are treated with replacement factor solely on demand when bleeds occur. Annualised Bleeding Rates (ABR) were calculated for each subject from prospective observation prior to exposure to SerpinPC (median 12 weeks, range 9 to 18 weeks). A total of 97 bleeds occurred in the pre-exposure observation period, with a median ABR of 35 (range 26 to 41).
In the eight weeks following a single SC injection of SerpinPC there was a 55% reduction in all bleeding and a 72% reduction in spontaneous joint and muscle bleeding. Five of the 12 subjects reported no spontaneous bleeds. No dose-dependency of ABR reduction was observed, which is consistent with the mode of action of SerpinPC. A total of 29 bleeds were recorded in the eight-week period following SerpinPC administration. These bleeds were all effectively treated with factor concentrate, as per standard of care, without incident and without increase in D-dimer levels. No SerpinPC-related AEs, injection site reactions, or anti-drug antibodies were observed.
Part II of the study is ongoing. Twenty-three subjects in three dose groups are receiving SerpinPC by monthly SC injection for six months. Results are due to read out in second quarter of this year and will be followed by a year-long, open-label extension study at a flat monthly dose.
ApcinteX’s Chief Medical Officer, Trevor Baglin, presented the results at the 14th Annual Congress of the European Association for Haemophilia and Allied Disorders.