Wayne sustained a torn ACL in his side's win over the Denver Broncos two weeks ago and has been ruled out for the season, leaving the Colts without a veteran presence on the offensive side of the ball.
"Reggie was the leader of that offense and Andrew plays the position that requires, obviously, great leadership," Pagano told reporters. "He's always been a leader and he's going to be the same guy he's always been.
"He's got great command. He's got great respect, not only in the offense but in this entire building and that locker room. He's just going to continue to do what he's done."
The Colts face the Houston Texans on Sunday.