When a profile stops working in the middle of a game, there are two possible causes. Either the profile is:
Not associated with the correct .exe file
The profile is detected in the game launcher or menu, but stops working while playing the game. This happens when the profile isn't associated with the correct .exe file. You can fix this by assigning the game's .exe file to the profile and not the launcher's .exe file. See answer 360023245494 for instructions.
Reverted to the Default Profile
Another application running on your computer may come to the foreground, causing the active profile to revert to the Default Profile. You can fix this by locking the profile assigned to the game. See answer 360023245494 for instructions.