I think I know what you're experiencing. I had a similar problem playing into Logic Pro X on my 2015 MBP when I first got my HX Stomp back in November. I was playing right along in perfect sync, then all of the sudden the audio is delayed about 500 ms. It's like you're using a delay effect with the source audio turned off.
I didn't do enough testing to specifically trace the problem to the root cause; but here are the things I did to stop the problem:
1) Plug the unit into its own USB port on the Mac. Don't plug it into a shared USB hub. The manual actually states this, but I tried to use a hub anyway, 'cause... you can't stop me, I'm controversial. ;-)
2) Install Line 6's driver for MacOS. I didn't want to do this either since it should be able to just use the core audio driver; but audio frequency is not selectable on the core driver.
3) As others have said, make sure the audio frequency on the device and the app are set the same.
Which of these actions fixed my issues? Don't know, but it's been rock solid ever since.
I hope this helps.