I've had the same issue with a helix I've only had for a short while. I have a complicated multi-amp setup with 4CM, but I began patching everything together piece by piece to try to eliminate previous noise issues since I was rebuilding my whole rig anyway.
I didn't get past step 1. Plugging the helix loop send 1 into the front of my soldano HR100 was incredibly buzzy. I fixed that with either a radial transformer isolator or an ebtech power scrubber (the name escapes me but it basically filters noise out of the ground pin on the power source without disconnecting it completely like on widomakers). I decided to use the power scrubber to avoid using a transformer that affects tone mildly and save it for possible use later once more stuff gets connected. With this problem solved, I flipped to the overdrive channel and that wretched hiss I hated from my pod HD pro was there being amplified to unusable levels by the preamp. My Mesa Roadster has the loud hum too but not nearly to the same extent as the Soldano.
My signal chain at this stage doesn't get any simpler than effect into amp input. I tried all the different outputs, instrument vs line level, guitar connected or not connected, volume knob in and out of the equation, volume pedal/gate in an effects block turned all the way down, the noise stayed steady and didn't fluctuate one bit. It's obviously the noise floor from the DAC stemming from the signal level being set quite low relative to Full Signal in the DAC making the noise floor quite strong relative to the anemic instrument level signal. They've provided an extreme amount of headroom on their outputs that makes no sense to me except....
I have a theory. When I switch the outputs from line to instrument and vice versa, I don't hear any kind of relay clicking inside or anything and the noise level doesn't change at all, leading me to believe they set it up with the extra headroom so that an active guitar signal being sent out line level doesn't clip the DA. The problem seems to lie that instead of having a relay or physical switch step down the signal level to instrument level and take the noise floor down in level with it, it attenuates the signal digitally, utterly decimating the signal to noise ratio on the output in the process. Horrible gain staging practice on Line 6's end. I've used other products that either have a physical pad switch that do not seem to suffer from anything resembling this issue.
In the past, I had used a Digitech GSP1101 with hacked firmeware running "around" my pod HD to both attenuate a boosted signal from my pod back to instrument level to get rid of some of the his as well as act as a gate on the main outputs with it's sidechain input, the signal detector part, in the input section before the pod's input as the noise coming out of the pod would make the gate have to be set way too high to work. It was kind of like having 2 ISP Decimator G-Strings running side by side in stereo. Even with 2 more stages of ADC/DAC (4 total) in the signal, the noise level was much lower this way running a 4 cable method inside of another 4 cable method. Fortunately, this at least also provided means of running a midi controlled volume pedal for each amp that didn't eat up 2 of the limited effects blocks or reset every time i changed patches.
I had really hoped after reading reviews and evaluations that line 6 had figured out how gain staging is supposed to work (look at the Axe FX as an example) and release a product that worked properly for the 4CM without needing to use my GSP1101 again and the extra headache in ground loop control that entailed. I was very disappointed to learn that they had not and I was going to have find a work around again. At least I don't need the GSP for the volume pedals with the Helix.
What I'm going to attempt to do is to jack up the signal on the output either by setting it to instrument or using the send level control or both and then pad the signal back down to go into the amp input at a proper level at unity gain. Fingers crossed that this will work.