A Study to Evaluate the Safety and Efficacy of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus (KALM-1)

NCT03422653 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: CR845-CLIN3102
• Study Type: interventional
• Target: 378
• Locations: 1 country
• Sites: 57

Brief 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.

Conditions

Uremic Pruritus

Keywords

CR845; Pruritus; Chronic Itch; Itch; Itching; difelikefalin; Hemodialysis; Uremic Pruritus; Dialysis; CKD; CKD-associated pruritus; CKD-aP; ESRD (end stage renal disease); KALM; Chronic Kidney Disease; Kidney failure, chronic; Kidney dysfunction; Generalized pruritus

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)

• 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

• 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

• 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

Study Arms (2)

CR845 0.5mcg/kg

ACTIVE COMPARATOR

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

Drug: CR845 0.5 mcg/kg

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

CR845 0.5 mcg/kg DRUG

IV medication delivered three times/week

Also known as: CR845, Difelikefalin

CR845 0.5mcg/kg

Placebo DRUG

IV medication delivered three times/week

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Sponsors & Collaborators

• Cara Therapeutics, Inc.: lead

Study Sites (57)

Cara Therapeutics Study Site

Homewood, Alabama, 35209, United States

Location

Cara Therapeutics Study Site

Huntsville, Alabama, 35805, United States

Location

Cara Therapeutics Study Site

Bakersfield, California, 93309-5030, United States

Location

Cara Therapeutics Study Site 2

Beverly Hills, California, 90211, United States

Location

Cara Therapeutics Study Site

Beverly Hills, California, 90211, United States

Location

Cara Therapeutics Study Site

Chula Vista, California, 91910, United States

Location

Cara Therapeutics Study Site

Corona, California, 92881, United States

Location

Cara Therapeutics Study Site

Escondido, California, 92025, United States

Location

Cara Therapeutics Study Site

Fountain Valley, California, 92708, United States

Location

Cara Therapeutics

La Mesa, California, 91942, United States

Location

Cara Therapeutics Study Site

Long Beach, California, 90807, United States

Location

Cara Therapeutics Study Site

Ontario, California, 91762, United States

Location

Cara Therapeutics Study Site

Riverside, California, 92505, United States

Location

Cara Therapeutics Study Site

Roseville, California, 95661, United States

Location

Cara Therapeutics Study Site

San Diego, California, 92111, United States

Location

Cara Therapeutics Study Site

San Dimas, California, 91773, United States

Location

Cara Therapeutics Study Site

Tarzana, California, 91356, United States

Location

Cara Therapeutics Study Site

Denver, Colorado, 80218, United States

Location

Cara Therapeutics Study Site

Bridgeport, Connecticut, 06606, United States

Location

Cara Therapeutics Study Site

Hartford, Connecticut, 06112, United States

Location

Cara Therapeutics Study Site

Middlebury, Connecticut, 06762, United States

Location

Cara Therapeutics Study Site 1

Coral Springs, Florida, 33071, United States

Location

Cara Therapeutics Study Site

Hialeah, Florida, 33016, United States

Location

Cara Therapeutics Study Site

Miami, Florida, 33125, United States

Location

Cara Therapeutics Study Site

Miami Gardens, Florida, 33169, United States

Location

Cara Therapeutics Study Site

Tampa, Florida, 33614, United States

Location

Cara Therapeutics Study Site

Kalamazoo, Michigan, 49007, United States

Location

Cara Therapeutics Study Site

Roseville, Michigan, 48066, United States

Location

Cara Therapeutics Study Site

Minneapolis, Minnesota, 55404, United States

Location

Cara Therapeutics Study Site

Brookhaven, Mississippi, 39601, United States

Location

Cara Therapeutics Study Site

McComb, Mississippi, 39648, United States

Location

Cara Therapeutics Study Site

Tupelo, Mississippi, 38801, United States

Location

Cara Therapeutics Study Site

Kansas City, Missouri, 64111, United States

Location

Cara Therapeutics Study Site

Las Vegas, Nevada, 89102, United States

Location

Cara Therapeutics Study Site

Las Vegas, Nevada, 89106, United States

Location

Cara Therapeutics Study Site

Eatontown, New Jersey, 07724, United States

Location

Cara Therapeutics Study Site

Albuquerque, New Mexico, 87109, United States

Location

Cara Therapeutics Study Site

Gallup, New Mexico, 87301, United States

Location

Cara Therapeutics Study Site

Fresh Meadows, New York, 11365, United States

Location

Cara Therapeutics Study Site

Great Neck, New York, 11021, United States

Location

Cara Therapeutics Study Site

The Bronx, New York, 10461, United States

Location

Cara Therapeutics Study Site

Durham, North Carolina, 27704, United States

Location

Cara Therapeutics Study Site

Canton, Ohio, 44718, United States

Location

Cara Therapeutics Study Site

Roseburg, Oregon, 97471, United States

Location

Cara Therapeutics Study Site

Chattanooga, Tennessee, 37408, United States

Location

Cara Therapeutics Study Site

Dallas, Texas, 75231, United States

Location

Cara Therapeutics Study Site

Duncanville, Texas, 75137, United States

Location

Cara Therapeutics Study Site

Greenville, Texas, 75402, United States

Location

Cara Therapeutics Study Site

Houston, Texas, 77054, United States

Location

Cara Therapeutics Study Site

Lewisville, Texas, 75057, United States

Location

Cara Therapeutics Study Site

McAllen, Texas, 78503, United States

Location

Cara Therapeutics Study Site

Mesquite, Texas, 75150, United States

Location

Cara Therapeutics Study Site

San Antonio, Texas, 78207, United States

Location

Cara Therapeutics Study Site

Waxahachie, Texas, 75165, United States

Location

Cara Therapeutics Study Site

Chesapeake, Virginia, 23320, United States

Location

Cara Therapeutics Study Site

Hampton, Virginia, 23666, United States

Location

Cara Therapeutics Study Site

Wauwatosa, Wisconsin, 53226, United States

Location

Related Publications (6)

• 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: 39037824 DERIVED

• Weiner 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: 37968132 DERIVED

• Fishbane 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: 36039153 DERIVED

• Topf 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: 36016762 DERIVED

• Hercz 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 DERIVED

• Fishbane S, Jamal A, Munera C, Wen W, Menzaghi F; KALM-1 Trial Investigators. A Phase 3 Trial of Difelikefalin in Hemodialysis Patients with Pruritus. N Engl J Med. 2020 Jan 16;382(3):222-232. doi: 10.1056/NEJMoa1912770. Epub 2019 Nov 8.

  PMID: 31702883 DERIVED

MeSH Terms

Conditions

Pruritus; Renal Insufficiency, Chronic; Kidney Failure, Chronic

Interventions

difelikefalin

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes

Results Point of Contact

• Title: Frédérique Menzaghi, PhD
• Organization: Cara Therapeutics

clinicaltrials.gov@caratherapeutics.com

203-406-3700

Study Officials

• Frédérique Menzaghi, PhD

  Cara Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2018
• First Posted: February 6, 2018
• Study Start: February 20, 2018
• Primary Completion: April 6, 2019
• Study Completion: March 26, 2020
• Last Updated: April 26, 2022
• Results First Posted: April 26, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (57)