Cara Therapeutics announced positive topline results from its Phase 2 dose-ranging trial of Oral KORSUVA™ (CR845/difelikefalin) for the treatment of pruritus in patients with stage III-V (moderate-to-severe) chronic kidney disease (CKD).
"CKD-associated pruritus remains a significant unmet need for approximately one-third of diagnosed CKD patients in the U.S.," said Derek Chalmers, Ph.D., D.Sc., President and Chief Executive Officer of Cara Therapeutics. "We are pleased that this Phase 2 study has successfully identified an appropriate tablet strength of Oral KORSUVA to carry forward into a pivotal Phase 3 registration program which we expect to initiate next year."
"These exciting results underscore Oral KORSUVA’s potential to be the first approved therapy in the U.S. for CKD patients suffering from moderate-to-severe pruritus," said Gil Yosipovitch, M.D., Professor, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery and Director of the Miami Itch Center. "There is an unmet medical need for an effective long-term therapy for treating intractable pruritus and the results from this trial suggest Oral KORSUVA holds great promise for CKD patients."
The Phase 2, multicenter, randomized, double-blind, placebo-controlled 12-week trial was designed to evaluate the safety and efficacy of three dose levels (0.25 mg, 0.5 mg and 1 mg, once daily) of Oral KORSUVA vs. placebo (randomized 1:1:1:1) in approximately 240 stage III-V CKD patients with moderate-to-severe pruritus.
The primary efficacy endpoint was the change from baseline in the weekly mean of the daily 24-hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) score at Week 12 of the treatment period for any of the three tablet strengths vs. placebo. Secondary endpoints included change from baseline in itch-related quality of life scores at the end of Week 12, as assessed by the total Skindex-10 and 5-D itch scales, as well as the proportion of patients achieving an improvement from baseline of ≥3 points with respect to the weekly mean of the daily 24-hour Worst Itch NRS score at Week 12.
Primary Endpoint: Patients treated with the 1 mg tablet strength of Oral KORSUVA™ achieved the primary endpoint of statistically significant reduction in weekly mean of the daily WI-NRS scores vs. placebo after the 12-week treatment period (-4.4 KORSUVA vs. -3.3 placebo, p=0.018). The treatment effect was statistically significant after two weeks of treatment and sustained through the 12-week treatment period.
Secondary Endpoints: The proportion of patients on 1 mg tablet strength achieving a 3 point or greater improvement from baseline in the weekly mean of the daily WI-NRS score at week 12 was 72% vs. 58% for placebo but did not achieve statistical significance.
Patients on 1 mg tablet strength showed positive improvements vs. placebo in itch- related quality of life endpoints as measured using self-assessment Skindex-10 and 5-D Itch scales but did not achieve statistical significance.
Oral KORSUVA was generally well-tolerated with a safety profile consistent with that seen in earlier KORSUVA clinical trials. Overall, the incidence of treatment emergent adverse events (AEs) were similar across KORSUVA and placebo groups. The most common treatment emergent AEs reported in >5% of patients in the 1 mg KORSUVA group vs. placebo were dizziness (7.5% KORSUVA vs. 0% placebo), fall (6% KORSUVA vs. 0% placebo), diarrhea (6% KORSUVA vs. 1.5% placebo) and constipation (KORSUVA 6% vs. 3% placebo).
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