I would simplify the setup to narrow in. Have you tried headphones on the Profiler Headphone Out or connected your powered speakers to the Main out of the Profiler directly? If you don't experience that issue then, this doesn't appear to be a Profiler matter.
Otherwise I would stick to headphones connected to the Profiler, reset all global settings incl. potentially locking by "Init Globals" in the System Settings, reload one of the Factory Rigs in default state, and perhaps test with another guitar and cable.....