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

• Hemodialysis and Home Hemodialysis: Research Abstracts
  October 23, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Dialysis

• 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

• Wooldridge, Thomas D., Nephrology and Hypertension Associates, Ltd., Tupelo, Mississippi, United States

Thomas D. Wooldridge, MD



Thomas D. Wooldridge, M.D. graduated medical school from The University of Mississippi Medical Center in 1972. Following graduation he completed an internship in internal medicine at University Hospital of Jacksonville followed by residency at University of Mississippi Medical Center. Dr. Wooldridge completed a fellowship in Clinical Nephrology at the University of Mississippi Medical Center in 1976 and was a Clinical Research Fellow 1976-1977. He is Board Certified in Nephrology and has been practicing in Tupelo, MS since 1977. He is an active member in several different Nephrology organizations, including, The American Society of Nephrology. Dr. Wooldridge has numerous publications that he has authored or co-authored along with several abstracts that he has presented.

• Mccafferty, Kieran, The Royal London Hospital - Barts Health NHS Trust, London, United Kingdom

Kieran Mccafferty,

• Schoemig, Michael, Dialysezentrum Heilbronn, Heilbronn, Germany

Michael Schoemig,

• Csiky, Botond Szabolcs, FMC Szatellita Dialysis Center Pecs, Pecs, Hungary

Botond Szabolcs Csiky,

• Zwiech, Rafal, Norbert Barlicki Memorial Teaching Hospital No. 1 of the Medical University of Lodz, Lodz, Poland

Rafal Zwiech,

• Wen, Warren, Cara Therapeutics, Stamford, Connecticut, United States

Warren Wen,

• Munera, Catherine, Cara Therapeutics, Stamford, Connecticut, United States

Catherine Munera,

• Menzaghi, Frederique, Cara Therapeutics, Stamford, Connecticut, United States

Frederique Menzaghi,

Background

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).

Methods

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.

Results

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.

Conclusion

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.

Funding

• Commercial Support – This study was funded by Cara Therapeutics