A clinical review will be held after each clinically significant bleed on phase 3 of the study. If a participant experiences more than 4 bleeds during phase 3 of the study, this will be classed as an adverse event and the participant will be withdrawn from the study. If more than 5 participants have more than 1 spontaneous clinically significant bleed in a 4 month period after the dose escalation to 3%, the study will be reviewed by the IDMC and if confirmed all participants will be reverted back to standard care and the study terminated.