OK. Did more testing last night. I initially chalked it up to phase cancellation, but it's definitely not.
-It's not the cables (used different ones)
-It's not the PowerStage (I tried a Quilter we have)
-Power sources were different
-We can see the volume gradually dropping 15-20 db on the meter in the mixing board when I crank the amp all the way.
I ran my in-ear module straight from the XLR out of the Helix, and the issue was definitely occurring. At this point, I have to say it's the Helix. I'm going to backup/factory reset after my next round of shows. We'll see if that fixes the issue, but I'm not hopeful. Still going to experiment with a couple of small things, such as the power cord I'm using from the Helix to my SKB PS-45 power supply (it's in a 120v socket, NOT the pedalboard onboard pedal power connections which obviously don't have juice to power a Helix). Definitely going to test the sockets with a multimeter though, just to rule that out too. Even with that, I still can't see how the issue would be caused by it. I also forgot to try the synth patch mentioned above. I will try that as well if the reset doesn't resolve it.
Thanks again, everyone. I'll keep the thread updated.