Abstract: FR-OR134
Efficacy and Safety of Difelikefalin in Patients Undergoing Hemodialysis with Pruritus: Results from a Phase 3 Randomized, Controlled Study (KALM-1)
Session Information
- High-Impact Clinical Trials
November 08, 2019 | Location: Ballroom C, Walter E. Washington Convention Center
Abstract Time: 02:45 PM - 03:00 PM
Category: Dialysis
- No subcategory defined
Authors
- Fishbane, Steven, Northwell Health, Commack, New York, United States
- Jamal, Aamir Z., North America Research Institute, San Dimas, California, United States
- Wen, Warren, Cara Therapeutics, Inc., Stamford, Connecticut, United States
- Munera, Catherine, Cara Therapeutics, Inc., Stamford, Connecticut, United States
- Menzaghi, Frederique, Cara Therapeutics, Inc., Stamford, Connecticut, United States
Background
There is an unmet need for effective treatments for pruritus associated with chronic kidney disease (CKD-aP or uremic pruritus), a debilitating condition prevalent in patients undergoing hemodialysis (HD). Difelikefalin (DFK; CR845) is a novel, peripherally restricted kappa opioid receptor (KOR)-specific agonist in development for treatment of pruritus. Here we report on the first Phase 3 study of DFK in HD patients with CKD-aP.
Methods
Patients with moderate-to-severe CKD-aP undergoing HD (N=377) were randomized 1:1 to receive an IV bolus of DFK 0.5 mcg/kg (N=189) or placebo (PBO) (N=188), thrice weekly post dialysis, over 12 weeks. The primary endpoint was the proportion of patients achieving ≥3-point improvement from baseline (BL) to Week 12 in the weekly mean of 24-hr daily Worst Itching Intensity Numerical Rating Scale (WI-NRS) scores. Secondary endpoints included the change in itch-related QoL measured by 5-D Itch and Skindex-10 questionnaires and the proportion of patients achieving ≥4-point WI-NRS score improvement from BL to Week 12. Safety was assessed based on vital signs, clinical laboratory results, ECG, and adverse event (AE) reporting.
Results
The primary and all secondary efficacy endpoints were met. BL mean WI-NRS scores were 7.1 and 7.3 in DFK and PBO groups. Percentages of patients with ≥3-point improvement and ≥4-point improvement in mean WI-NRS scores at Week 12 were 51% vs 28% (p<0.001; odds ratio (OR) 2.7) and 39% vs 18% (p<0.001, OR 2.9) for DFK vs PBO. Separation from PBO in WI-NRS score change from baseline was observed at Week 1. All QoL measures were significantly improved vs PBO (p<0.001). Serious AE incidence was similar for DFK vs PBO; most common treatment emergent AEs were diarrhea (9.5% vs 3.7%), dizziness (6.9% vs 1.1), and vomiting (5.3% vs 3.2%).
Conclusion
This study demonstrated that DFK significantly reduced itch intensity in HD patients. Patients treated with DFK were about 3 times (based on OR) more likely to have a clinically meaningful reduction in itch intensity vs PBO and had significant improvements in QoL. DFK was generally well tolerated with an acceptable safety profile. DFK could represent an important advance for treatment of pruritus in HD patients.
Funding
- Commercial Support – Cara Therapeutics, Inc.