I'm somewhat concerned about allowing a great plague to happen earlier than 1300. If anything, the great plague had been one of the powerful factors that undermined the basis for the feudalism and played an important role in transition of Europe to post-medieval economy and to the Early Modern Era (which EU4 represented). If the feudalism somehow survived the great plague that broke out earlier than 1300 and go on as if nothing really happened, it would be hugely implausible and immersion-breaking. It have to be a game-changing event.
I would suggest some ways to represent the irreversible change towards post-feudal society / economy or something as result of the great plague.