"Is it possible for White to gain an advantage due to excellent preparation, or are all uncommon early novelties bad enough to be easy for Black to refute?" Both are possible.
A famous recent example of White getting an advantage due to excellent preparation was Caruana - MVL, Candidates 2021. 16. c3 was essentially a novelty, and the follow-up pieces sacrifices were certainly novel, but Caruana had prepared the entire line until 26. Rd3 where MVL finally made a "mistake" relative to the absolute engine line by choosing to save his knight and not rook. Strictly speaking, 16. c3 is "worse" than the main line (something like +0.3 -> -0.3), but since MVL did not know it, Caruana gained a practical advantage from blitzing out the next 10 moves while MVL used half of his total time and still got a rotten position.
On the other hand, uncommon early novelties usually lead to unclear positions, but positions where the other side should feel reasonably comfortable with their position as long as they understand the main lines. A good example of some games where this occurred were in the 2021 World Chess Championship. In game 2, Carlsen sacrificed a pawn with the novelty 8. Ne5. While he clearly knew the position better than Nepo, Nepo was able to navigate the position well and even won the exchange around 10 moves later once Carlsen mis-stepped. In the infamous game 6, Carlsen sacrificed another pawn with his 8. c4 and 10. Nbd2 novel follow-up. Nepo refused the pawn sacrifice and instead played principled chess, ultimately getting a perfectly respectable position as black. Neither of these games were "refutations" of the novelty, even though Carlsen was certainly going to be the more prepared player in these lines. Still, both games show that with solid play, you should be able to handle whatever White is throwing at you if you're well aware of ideas in the main lines.