CR845-CLIN3103: A Global Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
KALM-2
A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus, With a 52-Week Open Label Extension
1 other identifier
interventional
473
11 countries
92
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jul 2018
92 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 17, 2018
CompletedFirst Submitted
Initial submission to the registry
August 3, 2018
CompletedFirst Posted
Study publicly available on registry
August 17, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 30, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 30, 2020
CompletedResults Posted
Study results publicly available
April 26, 2022
CompletedApril 26, 2022
March 1, 2022
1.7 years
August 3, 2018
September 21, 2021
March 29, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (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
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.
Week 12
Secondary Outcomes (3)
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
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
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
Baseline, Week 12
Study Arms (2)
CR845 0.5mcg/kg
ACTIVE COMPARATORIV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)
Placebo
PLACEBO COMPARATORIV Placebo administered after each dialysis session (3 times/week)
Interventions
IV CR845 0.5 mcg/kg administered three times/week
Eligibility Criteria
You may qualify if:
- 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.
- Has received at least 30 doses of the planned 36 doses of study drug during the Double-blind Phase of this study;
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (92)
Cara Therapeutics Study Site
Chula Vista, California, 91910, United States
Cara Therapeutics Study Site
Fountain Valley, California, 92708, United States
Cara Therapeutics Study Site
Northridge, California, 91324, United States
Cara Therapeutics Study Site
Riverside, California, 92503, United States
Cara Therapeutics Study Site 2
San Dimas, California, 91773, United States
Cara Therapeutics Study Site
San Dimas, California, 91773, United States
Cara Therapeutics Study Site
Westminster, Colorado, 80031, United States
Cara Therapeutics Study Site
Hialeah, Florida, 33012, United States
Cara Therapeutics Study Site
Miami Gardens, Florida, 33169, United States
Cara Therapeutics Study Site
Orlando, Florida, 32810, United States
Cara Therapeutics Study Site
Athens, Georgia, 30606, United States
Cara Therapeutics Study Site
Macon, Georgia, 31201, United States
Cara Therapeutics Study Site
Baton Rouge, Louisiana, 70808, United States
Cara Therapeutics Study Site
Brockton, Massachusetts, 02301, United States
Cara Therapeutics Study Site
Kalamazoo, Michigan, 49007, United States
Cara Therapeutics Study Site
Roseville, Michigan, 48066, United States
Cara Therapeutics Study Site
Saint Clair, Michigan, 48081, United States
Cara Therapeutics Study Site
Tupelo, Mississippi, 38801, United States
Cara Therapeutics Study Site
St Louis, Missouri, 63136, United States
Cara Therapeutics Study Site
Clifton, New Jersey, 07011, United States
Cara Therapeutics Study Site
Somerville, New Jersey, 08876, United States
Cara Therapeutics Study Site
Albuquerque, New Mexico, 87109, United States
Cara Therapeutics Study Site
Long Island City, New York, 11106, United States
Cara Therapeutics Study Site
Austin, Texas, 78758, United States
Cara Therapeutics Study Site
Dallas, Texas, 75228, United States
Cara Therapeutics Study Site
McAllen, Texas, 78503, United States
Cara Therapeutics Study Site
San Antonio, Texas, 78207, United States
Cara Therapeutics Study Site
St. George, Utah, 84790, United States
Cara Therapeutics Study Site
Roanoke, Virginia, 24014, United States
Cara Therapeutics Study Site
Camperdown, New South Wales, Australia
Cara Therapeutics Study Site
Concord, New South Wales, Australia
Cara Therapeutics Study Site
Wahroonga, New South Wales, 2076, Australia
Cara Therapeutics Study Site
Westmead, New South Wales, Australia
Cara Therapeutics Study Site
Launceston, Tasmania, Australia
Cara Therapeutics Study Site
Clayton, Victoria, Australia
Cara Therapeutics Study Site
Heidelberg, Victoria, Australia
Cara Therapeutics Study Site
St Albans, Victoria, Australia
Cara Therapeutics Study Site
Adelaide, Australia
Cara Therapeutics Study Site
Halifax, Nova Scotia, Canada
Cara Therapeutics Study Site
Oshawa, Ontario, Canada
Cara Therapeutics Study Site
Scarborough Village, Ontario, Canada
Cara Therapeutics Study Site
Toronto, Ontario, Canada
Cara Therapeutics Study Site
Montreal, Quebec, Canada
Cara Therapeutics Study Site
Frýdek-Místek, Czechia
Cara Therapeutics Study Site
Prague, Czechia
Cara Therapeutics Study Site
Düsseldorf, Germany
Cara Therapeutics Study Site
Heilbronn, Germany
Cara Therapeutics Study Site
Baja, 6500, Hungary
Cara Therapeutics Study Site
Debrecen, Hungary
Cara Therapeutics Study Site 2
Pécs, Hungary
Cara Therapeutics Study Site
Pécs, Hungary
Cara Therapeutics Study Site
Szeged, 6720, Hungary
Cara Therapeutics Study Site
Székesfehérvár, Hungary
Cara Therapeutics Study Site
Szigetvár, Hungary
Cara Therapeutics Study Site
Auckland, New Zealand
Cara Therapeutics Study Site
Hamilton, New Zealand
Cara Therapeutics Study Site
New Plymouth, New Zealand
Cara Therapeutics Study Site
Brodnica, Poland
Cara Therapeutics Study Site
Brzeg, Poland
Cara Therapeutics Study Site
Bydgoszcz, Poland
Cara Therapeutics Study Site
Grójec, Poland
Cara Therapeutics Study Site
Krakow, Poland
Cara Therapeutics Study Site
Kwidzyn, Poland
Cara Therapeutics Study Site 2
Lodz, Poland
Cara Therapeutics Study Site
Lodz, Poland
Cara Therapeutics Study Site
Nakło nad Notecią, Poland
Cara Therapeutics Study Site
Olkusz, Poland
Cara Therapeutics Study Site
Olsztyn, Poland
Cara Therapeutics Study Site
Poznan, Poland
Cara Therapeutics Study Site
Warsaw, Poland
Cara Therapeutics Study Site
Wroclaw, Poland
Cara Therapeutics Study Site
Zamość, Poland
Cara Therapeutics Study Site
Żyrardów, Poland
Cara Therapeutics Study Site
Daegu, 41931, South Korea
Cara Therapeutics Study Site 2
Daegu, South Korea
Cara Therapeutics Study Site
Daejeon, South Korea
Cara Therapeutics Study Site
Goyang-si, South Korea
Cara Therapeutics Study Site
Guri-si, South Korea
Cara Therapeutics Study Site
Seogu, 49201, South Korea
Cara Therapeutics Study Site 2
Seoul, South Korea
Cara Therapeutics Study Site 3
Seoul, South Korea
Cara Therapeutics Study Site
Seoul, South Korea
Cara Therapeutics Study Site
Kaohsiung City, Taiwan
Cara Therapeutics Study Site
New Taipei City, Taiwan
Cara Therapeutics Study Site 2
Taipei, Taiwan
Cara Therapeutics Study Site
Taipei, Taiwan
Cara Therapeutics Study Site
Belfast, United Kingdom
Cara Therapeutics Study Site
Ipswich, United Kingdom
Cara Therapeutics Study Site
London, United Kingdom
Cara Therapeutics Study Site
Londonderry, United Kingdom
Cara Therapeutics Study Site
Nottingham, United Kingdom
Cara Therapeutics Study Site
Westcliff-on-Sea, United Kingdom
Related Publications (5)
Fishbane 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: 39037824DERIVEDWeiner DE, Schaufler T, McCafferty K, Kalantar-Zadeh K, Germain M, Ruessmann D, Morin I, Menzaghi F, Wen W, Stander S. Difelikefalin improves itch-related sleep disruption in patients undergoing haemodialysis. Nephrol Dial Transplant. 2024 Jun 28;39(7):1125-1137. doi: 10.1093/ndt/gfad245.
PMID: 37968132DERIVEDFishbane S, Wen W, Munera C, Lin R, Bagal S, McCafferty K, Menzaghi F, Goncalves J. 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. Kidney Med. 2022 Jun 28;4(8):100513. doi: 10.1016/j.xkme.2022.100513. eCollection 2022 Aug.
PMID: 36039153DERIVEDTopf J, Wooldridge T, McCafferty K, Schomig M, Csiky B, Zwiech R, Wen W, Bhaduri S, Munera C, Lin R, Jebara A, Cirulli J, Menzaghi F. 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. Kidney Med. 2022 Jun 28;4(8):100512. doi: 10.1016/j.xkme.2022.100512. eCollection 2022 Aug.
PMID: 36016762DERIVEDHercz 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: 33283264DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Frédérique Menzaghi, PhD
- Organization
- Cara Therapeutics
Study Officials
- STUDY DIRECTOR
Frédérique Menzaghi, PhD
Cara Therapeutics
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 3, 2018
First Posted
August 17, 2018
Study Start
July 17, 2018
Primary Completion
March 30, 2020
Study Completion
March 30, 2020
Last Updated
April 26, 2022
Results First Posted
April 26, 2022
Record last verified: 2022-03
Data Sharing
- IPD Sharing
- Will not share