I think I know who used the Red Rune before Ryze found it.

As we already know, the World Runes come in all shapes and sizes, for example the Green Rune that was featured in the comic. But look closely at the Red one, it has a flat top with a writing, an insignia of some sort, possibly the Rune's original writing. It seems like the outer stone shell remains unaffected by the heat and energy inside, except the very bottom spike, which glows red.

Now, I don't know about you, but one of the first things I thought of that design, flat top and spiked and glowing bottom, is that it looks like a Chisel, a tool used to carve and design statues and other stone objects, and also weapons. Then I thought to myself "well if it was a chisel, the wielder must be someone with some serious power to resist the Rune, plus to wield it so casually to design things, but there's no one in League who can do that... Besides a Demi God". Yep, I believe that this Rune that we see Ryze fight the voidborn for, was actually used By Ornn as a tool of his works. This theory is also supported with some more details, like the destruction of the village in Ornn's lore. Sure, it was caused from the fight between Ornn and Volibear, but who's to say that Ornn didn't use the chisel he had as a weapon, like the way he uses his hammer, to fight his brother and accidentally destroy the village with that sort of power, that we know can level a city? Moreover, there's the location of the Rune. If it was Ornn's chisel and it did cause that destruction, he probably wanted to hide it away from ever being used for evil again, so in his exile he traveled all the way up the Frejlord and into the unknown land, and tried to hide it there, actually using the Voidborn that was stuck there as a final defensive system against people who wanted to take and use it.

Tl:Dr : Ornn was the last user, he used it as a chisel, after the fight with Volibear which killed all of his followers he tried to hide it away in a cave with a Voidborn in it so no one can use that power again.

So what do you think?