Handley, Super League’s top scorer last season, was injured in Sunday’s pre-season friendly with Huddersfield Giants.
Scans have confirmed the 25 year-old - who is in Shaun Wane’s England squad - has damaged medial ligaments and will now miss the opening rounds of the new campaign which starts against Wakefield Trinity on Saturday week.
Agar said: “Ash has been absolutely flying in pre-season.
“He’s highly motivated for the World Cup at the end of the year and it is a big blow to us.
“But he’s in very good shape. Ash is our fittest player, undoubtedly; when you look at the workload, what he does in a game, you’ve got to be fit to do that amount of work.
“That is hopefully going to help him on his recovery and I know Ash will do everything right - eating, sleeping, ticking every box - when he gets the brace off his leg.
“Fingers crossed we can hit all our targets in rehab and get him back early. It is a blow and not something we needed at this stage of the year but that’s what your squad is for.”
Leeds are already without full-back Jack Walker and stand-off Robert Lui and have captain Luke Gale and half-back Callum McLelland battling to be fit for the kick-off.
Given Walker’s injury, Rhinos were contemplating switching Handley to full-back but it is more likely Richie Myler will play there now, as the England scrum-half did for much of last year.
Luke Briscoe is most likely to come in on the wing and Agar said: “Ideally everyone wants to come out of the blocks round one. That’s not going to be the case for us but we’ve every confidence in our squad.”
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