Cara Therapeutics announced the completion of an interim statistical assessment of its pivotal KALM-2 Phase 3 global clinical trial of KORSUVA™ (CR845/difelikefalin) Injection in hemodialysis patients with moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP).
Based on the Independent Data Monitoring Committee’s (IDMC) recommendation, the size of the trial will be increased by approximately 20 percent, from an original enrollment target of 350 patients to 430 patients, to maintain the pre-specified statistical power of 90 percent or greater on the trial’s primary endpoint. The IDMC charter allowed for the trial size to be increased up to a maximum of 500 patients. The IDMC’s recommendation was based on the results of a prespecified interim conditional power assessment conducted after approximately 50 percent of the targeted patient number completed the designated 12-week treatment period.
“The IDMC recommendation to increase the target enrollment of KALM-2 aligns with our objective to maintain similar statistical power in this global trial to that of our positive KALM-1 US trial,” said Derek Chalmers, Ph.D., D.Sc., President and Chief Executive Officer of Cara Therapeutics. “As we have already randomized a significant number of patients in KALM-2, beyond the initial target enrollment of 350, we expect the trial to be fully enrolled by the end of this quarter and remain on track to file our New Drug Application (NDA) for KORSUVA Injection for the treatment of moderate-to-severe CKD-aP in hemodialysis patients in the second half of 2020.”
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The Phase 3, global, multicenter, randomized, double-blind, placebo-controlled, 12-week trial (with a 52-week open label extension phase) is designed to evaluate the safety and efficacy of 0.5 mcg/kg KORSUVA (CR845/difelikefalin) 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 in the weekly mean of the daily 24 hour Worst Itching Intensity Numeric Rating Scale (WI-NRS) score at week 12. Secondary endpoints include assessment of the proportion of patients achieving >4-point improvement from baseline in weekly mean of the daily 24-hour WI-NRS score at week 12 as well as itch-related quality of life changes measured using the validated self-assessment 5-D itch and Skindex-10 scales.
The pivotal KALM-1 Phase 3 US trial is complete and topline data were reported in May 2019. The trial met the primary endpoint, with a statistically significant improvement in the proportion of patients on KORSUVA Injection achieving a 3-point or greater improvement in the mean WI-NRS score versus placebo (p=0.000019). The trial also met all secondary endpoints and KORSUVA Injection was generally well-tolerated through 12 weeks of treatment with a safety profile consistent with prior clinical trials.