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Trial · Interventional

CompletedPhase 3Results postedRegistry data

CR845-CLIN3103: A Global Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus

Short name KALM-2

NCTNCT03636269 (opens ClinicalTrials.gov in a new tab)Other idCR845-CLIN3103
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
473 participants (actual)
Sponsor
Cara Therapeutics, Inc. · Industry
Design
Randomized · Triple masking
Countries
11 countries

United States, Australia, Canada, Czechia, Germany, Hungary, New Zealand, Poland, South Korea, Taiwan, United Kingdom

Start
17 Jul 2018
Primary completion
30 Mar 2020
Completion
30 Mar 2020
First posted
17 Aug 2018
Last update posted
26 Apr 2022
Conditions
Uremic Pruritus

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2018201920202021
  1. Ph 3

    KALM-2

    NCT03636269

    17 Jul 2018 to 30 Mar 2020

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This is a multicenter, international 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 randomized, double-blind, placebo-controlled Phase and a 52-week Open-label Extension Phase.

Interventions

  • CR845 0.5 mcg/kgDrug
  • PlaceboDrug

Arms2

  • Active comparator

    CR845 0.5mcg/kg

    IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)

  • Placebo comparator

    Placebo

    IV Placebo administered after each dialysis session (3 times/week)

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. 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

    Time frame · Week 12

    Registry description

    Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable". LS means estimated percent, odds ratio and P value used a logistic regression model.

Secondary outcomes(3)

  1. 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

    Time frame · Week 12

    Registry description

    Intensity of itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable". LS means estimated percent, odds ratio and P value used a logistic regression model.

  2. 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

    Time frame · Baseline, Week 12

    Registry description

    The Skindex-10 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. The Skindex-10 has 10 questions; the total Skindex-10 score ranges from 0 to 60. A lower total score represents better quality of life.

  3. 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

    Time frame · Baseline, Week 12

    Registry description

    The 5-D Itch Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past 2 weeks. The questions cover five dimensions of itch including the degree, duration of itch/day, direction (improvement/worsening), disability (impact on activities such as work), and body distribution of itch. The 5-D Itch Scale has 5 questions; the total 5-D Itch Scale score ranges from 5 to 25, with higher scores indicating worse responses.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· Week 12

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

GroupValue (percentage of subjects)
CR845 0.5mcg/kg54.0
Placebo42.2
Secondary and other outcome results(3)
Secondary outcomeNumber· Week 12

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

GroupValue (percentage of subjects)
Double-blind CR845 0.5mcg/kg41.2
Double-blind Placebo28.4
Secondary outcomeLeast squares mean· Baseline, Week 12

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

GroupValue (score on a scale)
Double-blind CR845 0.5mcg/kg-16.6
Double-blind Placebo-14.8
Secondary outcomeLeast squares mean· Baseline, Week 12

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

GroupValue (score on a scale)
Double-blind CR845 0.5mcg/kg-4.9
Double-blind Placebo-3.8

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Double-blind CR845 0.5mcg/kgIV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week) CR845 0.5 mcg/kg: IV CR845 0.5 mcg/kg administered three times/week2 / 23558 / 23556 / 235
Double-blind PlaceboIV Placebo administered after each dialysis session (3 times/week) Placebo: IV placebo administered three times/week2 / 23651 / 23643 / 236
Open-label CR845 0.5mcg/kgIV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week) CR845 0.5 mcg/kg: IV CR845 0.5 mcg/kg administered three times/week15 / 399130 / 399204 / 399

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies3

Studies that cite this trial.

Studies with results

3 studies on this page

Indexing hint: Randomized controlled trial · 2024

1 result

Difelikefalin improves itch-related sleep disruption in patients undergoing haemodialysis.

Weiner et al. 2024Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Associationcited by 13

PMID 37968132PMC11210984DOI 10.1093/ndt/gfad245PUB-37968132

CC BY1 result
Download PDFSee results (1)

PubMed tag: none · 2022

6 results

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.

Topf et al. 2022Kidney medicinecited by 67

PMID 36016762PMC9396406DOI 10.1016/j.xkme.2022.100512PUB-36016762

Free to read · publisher termsCC BY-NC-ND6 results
Read at sourceSee results (6)

PubMed tag: none · 2022

14 results

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.

Fishbane et al. 2022Kidney medicinecited by 38

PMID 36039153PMC9418597DOI 10.1016/j.xkme.2022.100513PUB-36039153

Free to read · publisher termsCC BY-NC-ND14 results
Read at sourceSee results (14)

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedFishbane SN, Block GA, Evenepoel P, Budden J, Morin I, Menzaghi F, Wen W, Lerma EV. Pruritus Severity and Serum Phosphate in CKD: A Post Hoc Analysis of Difelikefalin Studies. Kidney360. 2024 Sep 1;5(9):1270-1280. doi: 10.34067/KID.0000000000000520. Epub 2024 Jul 22. PMID 39037824
  • DerivedHercz D, Jiang SH, Webster AC. Interventions for itch in people with advanced chronic kidney disease. Cochrane Database Syst Rev. 2020 Dec 7;12(12):CD011393. doi: 10.1002/14651858.CD011393.pub2. PMID 33283264

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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