Cara Therapeutics, a biopharmaceutical company focused on developing and commercializing new chemical entities designed to alleviate pruritus and pain by selectively targeting peripheral kappa opioid receptors, announced the initiation of its first pivotal phase 3 efficacy trial of Korsuva (CR845/difelikefalin) injection in hemodialysis patients suffering from moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP) in the United States (US). The US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to Korsuva injection for this indication, for which there are currently no approved therapies in the US.

"The initiation of the first phase 3 efficacy trial in dialysis patients with CKD-aP is a key milestone in the development of Korsuva injection as a potential novel treatment option for a significant unmet medical need in this patient population," said Derek Chalmers, Ph.D., D.Sc., President and Chief Executive Officer of Cara Therapeutics. "Additionally, through the rest of this year, we will be working to expand our clinical development activities with Korsuva beyond hemodialysis patients into additional renal, hepatic and dermatological patient populations."

The phase 3 US study is a multicenter, randomized, double-blind, placebo-controlled 12-week treatment trial (with a 52-week open label extension phase) in the US designed to evaluate the safety and efficacy of 0.5 mcg/kg of Korsuva injection in 350 hemodialysis patients with moderate-to-severe pruritus.

The primary efficacy endpoint is the proportion of patients achieving at least a 3 point improvement from baseline with respect to the weekly mean of the daily 24 hour worst itching intensity numeric rating scale (NRS) score at week 12. In a completed phase 2 trial, the proportion of patients with an improvement from baseline in the weekly mean worst itching intensity NRS score of =3 points at week eight was statistically significantly higher in the Korsuva 0.5 mcg/kg group compared to the placebo group (64% vs. 29%; p < 0.01)1.

Secondary endpoints of the phase 3 trial include assessment of itch-related quality of life changes measured using validated self-assessment 5-D Itch and Skindex-10 scales, as well as the proportion of patients achieving > 4-point improvement from baseline in weekly mean of the daily 24-hour worst itching NRS score at week 12.

The FDA has conditionally accepted Korsuva as the trade name for difelikefalin injection. CR845/difelikefalin is an investigational drug product and its safety and efficacy have not been fully evaluated by any regulatory authority.