My buddy has this exact same problem as you last year, after loaning out his .50 T/C Encore ML here and there, after previously shooting it himself preparing for ML season. This year he got out the gun and had all the same thoughts you did, and tried same fixes to no avail. Good shooter formerly, now shooting 6-8" groups at 100!
Shooting was with Triple 7 pellets and Win 209 muzzleloader primers (weaker 209s that will set off Triple 7 but with less crud resulting -- sure seems to me that suggests these primers work enough to ignite, but push the pelllets forward a bit during that slightly slower burn, resulting in pretty good accuracy while reducing the critical buildup of crud in the tiny touch-hole dowm inside the breechplug.)
I took his gun apart and also researched about the breech plugs. Even with prior thread paste on the plus threads, it was now very hard to break it loose and get it out.
After soaking in typical water-based ML cleaner (for BP, Pyrodex, Triple 7, etc. except 209), it was not very difficult to use a 1/8" drill bit by hand, as you should, to properly clean out the larger rearward portion of the plug. But OMG, you could barely see any light thru the tiny .032" D. touch-hole. It is best cleaned out properly with machinist's number drills, starting at .029 or .030", then .031 and .032. .032" is the "new" size of T/C Encore plugs.These drills are tumed only by hand as well, and with great care. If you can get welder's gas-tip pins in those sizes they would be stronger. A broken-off drill in that tiny hole is very likely to mean buying a new breechplug.
Once I had the plug's rear hole and touch-hole properly cleaned out., plus the front of the plug, taking about half an hour (!) the rifle went right back to accuracy. So yes, the proper plug touch-hole is critical.
By researching your Win. .45 , or calling Winchester C.S. and asking for the right person, you will be able to find out just what size the critical touch-hole should be. You can bet that if a bigger hole worked better they would always go with that, but they want powder ignition and as little blowback of fouling crud into the action area. For that you also need proper "headspace" between rear of primer and breech face, (minimum for closure of action) and also tightest primer fit possible in the primer's hole That's what using the base end of machinist's drills are for to size the primer hole in thousandths of an inch, and cheap digital calipers is for to measure the depth of the primer hole and then measure in thousandths and sort your primers -- to find the best primer fit to your gun. Oh yes, primer brands and the primers themselves vary in length and diameter.
All that said, the CVA .50 inline (Omega or Wolf) takes a .033 touch-hole as new and should be replaced, as with the T/C, when it burns out to .002-3 larger. That's how critical hole size is, and the reason you need the stiff wires or better the tiny drills, to measure your well cleaned touch-hole. Same with a competition traditional ML nipple hole. They are often platinum-lined (very high melting point) for such guns shooting 85 gr or more with a heavy bullet. Even platinum will burn out in a season or less with heavy loads. And heavy loads (higher breech pressure) are often the case in inlines.
Lastly, if shooting Blackhorn 209 in the CVA Wolf, order their BH209 breechplug and never look back. Awesome design for the loose BH 209 powder which has very low "extreme spread" of velocity to die for, just like BP. But only use Smokeless type cleaner to soak and clean with BH 209 use.
Aloha, Ka'imiloa