Phase 3
Completed N=378
A Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-1)
Uremic Pruritus
Source: ClinicalTrials.gov NCT03422653 ↗
Enrolled (actual)
378
Serious AEs
37.3%
Results posted
Apr 2022
Primary outcomePrimary: Reduction of Itch Intensity as Assessed by the Percentage of Patients Achieving an Improvement From Baseline ≥3 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score at Week 12 — 51.0; 27.6 percentage of subjects — p=<0.001
◆ Published Evidence
Highly cited
112citations · ~28 / year
Efficacy of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis of KALM-1 and KALM-2 Phase 3 Studies.
Summary
This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of intravenous (IV) CR845 at a dose of 0.5 mcg/kg administered after each dialysis session. The study includes a 12-week Double-blind Phase and a 52-week Open-label Extension Phase.
Linked Publications (5)
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Efficacy of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis of KALM-1 and KALM-2 Phase 3 Studies.
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Interventions for itch in people with advanced chronic kidney disease.
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Safety and Tolerability of Difelikefalin for the Treatment of Moderate to Severe Pruritus in Hemodialysis Patients: Pooled Analysis From the Phase 3 Clinical Trial Program.
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Difelikefalin improves itch-related sleep disruption in patients undergoing haemodialysis.
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Pruritus Severity and Serum Phosphate in CKD: A Post Hoc Analysis of Difelikefalin Studies.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Reduction of Itch Intensity as Assessed by the Percentage of Patients Achieving an Improvement From Baseline ≥3 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score at Week 12 |
51.0; 27.6 | <0.001 sig |
| SECONDARY Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in 5-D Itch Scale Score at the End of Week 12 |
-5.0; -3.7 | <0.001 sig |
| SECONDARY Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in Total Skindex-10 Scale Score at the End of Week 12 |
-17.2; -12.0 | <0.001 sig |
| SECONDARY Reduction of Itch Intensity as Assessed by the Percentage of Patients Achieving an Improvement From Baseline ≥4 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score at Week 12 |
38.9; 18.0 | <0.001 sig |
Eligibility Criteria
Key Inclusion Criteria
To be eligible for inclusion into the Double-blind Phase of the study, a patient must meet the following criteria:
- Has end-stage renal disease (ESRD) and has been on hemodialysis 3 times per week for at least 3 months prior to the start of screening;
- Has at least 2 single-pool Kt/V measurements ≥1.2, or at least 2 urea reduction ratio measurements ≥65%, or 1 single pool Kt/V measurement ≥1.2 and 1 urea reduction ratio measurement ≥65% on different dialysis days during the 3 months period prior to screening;
- Prior to randomization:
- Has completed Worst Itching Intensity NRS worksheets up to 8 days prior to 1st dose;
- Has a mean baseline Worst Itching Intensity NRS indicative of moderate to severe uremic pruritus.
- To be eligible for inclusion into the Open-label Extension Phase of the study, each patient will have to fulfill the additional key following criteria at the time of entry into the Open-label Extension Phase:
- Has received at least 30 doses of the planned 36 doses of study drug during the Double-blind Phase of this study;
- Continues to meet inclusion criteria.
Key Exclusion Criteria
A patient will be excluded from the Double-blind Phase of the study if any of the following criteria are met:
- Known noncompliance with dialysis treatment that in the opinion of the investigator would impede completion or validity of the study;
- Scheduled to receive a kidney transplant during the study;
- New or change of treatment received for itch including antihistamines and corticosteroids (oral, IV, or topical) within 14 days prior to screening;
- Received another investigational drug within 30 days prior to the start of screening or is planning to participate in another clinical study while enrolled in this study;
- Has pruritus only during the dialysis session (by patient report);
- Is receiving ongoing ultraviolet B and anticipates receiving such treatment during the study;
- Participated in a previous clinical study with CR845.
- A patient will be excluded from the Open-label Extension Phase of the study if any of the additional key following criteria are met at the time of entry into the Open-label Extension Phase:
- Completed the Double-blind Phase of this study but exhibited adverse events during the course of the Treatment Period that may preclude continued exposure to the study drug;
- Was noncompliant with protocol procedures during the Double-blind Phase of this study which is indicative of an inability to follow protocol procedures.
Data sourced from ClinicalTrials.gov (NCT03422653) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.