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Kidney Week

Abstract: FR-OR24

Efficacy and Safety of Difelikefalin for Moderate-to-Severe CKD–Associated Pruritus: A Global Phase 3 Study in Hemodialysis Patients (KALM-2)

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis


  • Wooldridge, Thomas D., Nephrology and Hypertension Associates, Ltd., Tupelo, Mississippi, United States
  • Mccafferty, Kieran, The Royal London Hospital - Barts Health NHS Trust, London, United Kingdom
  • Schoemig, Michael, Dialysezentrum Heilbronn, Heilbronn, Germany
  • Csiky, Botond Szabolcs, FMC Szatellita Dialysis Center Pecs, Pecs, Hungary
  • Zwiech, Rafal, Norbert Barlicki Memorial Teaching Hospital No. 1 of the Medical University of Lodz, Lodz, Poland
  • Wen, Warren, Cara Therapeutics, Stamford, Connecticut, United States
  • Munera, Catherine, Cara Therapeutics, Stamford, Connecticut, United States
  • Menzaghi, Frederique, Cara Therapeutics, Stamford, Connecticut, United States

Chronic kidney disease (CKD)-associated pruritus (CKD-aP) is a common and distressing condition in CKD patients (pts) and has a serious negative impact on quality of life (QoL). Difelikefalin (DFK), a novel, peripherally restricted and selective kappa opioid receptor agonist, demonstrated efficacy in a US phase 3 study (KALM-1) in hemodialysis (HD) pts with CKD-aP. Here we report primary results from the global phase 3 study of DFK in HD pts with CKD-aP (KALM-2; NCT03636269).


HD pts with moderate-to-severe CKD-aP in the US, Europe, and Asia were randomized to receive intravenous DFK 0.5 mcg/kg (N=237) or placebo (PBO; N=236) after dialysis sessions. The primary endpoint was the proportion of pts who achieved ≥3-point improvement from baseline (BL) in the weekly mean of the daily Worst Itching Intensity Numerical Rating Scale (WI-NRS) score at wk 12. Secondary endpoints were the proportion of pts who achieved ≥4-point improvement in WI-NRS score and mean change in itch-related QoL scores (5-D Itch and Skindex-10) from BL to wk 12.


BL mean weekly WI-NRS scores were 7.3 and 7.1 in the DFK and PBO groups. The primary endpoint was met, with 54% of pts who received DFK achieving a ≥3-point improvement in WI-NRS score vs 42% in the PBO group (P=.020). The proportion of pts who achieved a ≥4-point improvement in WI-NRS score was also significantly greater with DFK vs PBO (41% vs 28%, P=.010). Itch reduction was evident at wk 1 and was sustained through wk 12. Improvement in itch-related QoL assessed by 5-D Itch and Skindex-10 was observed. Treatment-emergent AEs ≥5% with DFK vs PBO were diarrhea (8.1% vs 5.5%), fall (6.8% vs 5.1%), dizziness (5.5% vs 5.1%), vomiting (6.4% vs 5.9%), and nausea (6.4% vs 4.2%). The incidence of serious AEs was similar across the groups.


In this second phase 3 study, IV DFK demonstrated rapid and sustained itch reduction in HD pts with CKD-aP in multiple regions of the world. DFK was generally well tolerated; safety was consistent with findings in prior studies. With no approved therapies for CKD-aP in the US or Europe, DFK is a potential therapeutic that may address this unmet need.


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