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

NCT ID: NCT03422653

Last Updated: 2022-04-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

378 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-20

Study Completion Date

2020-03-26

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Double-blind Phase The Double-blind Phase of the study will consist of a Screening Visit, a 7-day Run-in Period, a 12 week Double-blind Treatment Period, and a 2-week Discontinuation Period. Informed consent will be obtained prior to performing any study-specific procedures. The Screening Visit will occur within 7 to 28 days prior to randomization to assess eligibility.

Open-label Extension Phase Patients who received at least 30 doses of study drug (either active or placebo) during the 12-week Double-blind Treatment Period and continue to meet other eligibility criteria will have the option to receive open label CR845 for an additional 52 weeks. The Open-label Extension Phase will be comprised of the Open-label Treatment Period and the Follow-up Period.

The last dose of open-label study drug will be administered at the last dialysis visit on Week 52, or Early Termination. A final safety Follow up Visit will be conducted 7-10 days after the End of Treatment/Early Termination Visit.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Uremic Pruritus

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

CR845 0.5mcg/kg

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

Group Type ACTIVE_COMPARATOR

CR845 0.5 mcg/kg

Intervention Type DRUG

IV medication delivered three times/week

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

IV medication delivered three times/week

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

CR845 0.5 mcg/kg

IV medication delivered three times/week

Intervention Type DRUG

Placebo

IV medication delivered three times/week

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

CR845 Difelikefalin

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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;

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Cara Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Frédérique Menzaghi, PhD

Role: STUDY_DIRECTOR

Cara Therapeutics

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Cara Therapeutics Study Site

Homewood, Alabama, United States

Site Status

Cara Therapeutics Study Site

Huntsville, Alabama, United States

Site Status

Cara Therapeutics Study Site

Bakersfield, California, United States

Site Status

Cara Therapeutics Study Site 2

Beverly Hills, California, United States

Site Status

Cara Therapeutics Study Site

Beverly Hills, California, United States

Site Status

Cara Therapeutics Study Site

Chula Vista, California, United States

Site Status

Cara Therapeutics Study Site

Corona, California, United States

Site Status

Cara Therapeutics Study Site

Escondido, California, United States

Site Status

Cara Therapeutics Study Site

Fountain Valley, California, United States

Site Status

Cara Therapeutics

La Mesa, California, United States

Site Status

Cara Therapeutics Study Site

Long Beach, California, United States

Site Status

Cara Therapeutics Study Site

Ontario, California, United States

Site Status

Cara Therapeutics Study Site

Riverside, California, United States

Site Status

Cara Therapeutics Study Site

Roseville, California, United States

Site Status

Cara Therapeutics Study Site

San Diego, California, United States

Site Status

Cara Therapeutics Study Site

San Dimas, California, United States

Site Status

Cara Therapeutics Study Site

Tarzana, California, United States

Site Status

Cara Therapeutics Study Site

Denver, Colorado, United States

Site Status

Cara Therapeutics Study Site

Bridgeport, Connecticut, United States

Site Status

Cara Therapeutics Study Site

Hartford, Connecticut, United States

Site Status

Cara Therapeutics Study Site

Middlebury, Connecticut, United States

Site Status

Cara Therapeutics Study Site 1

Coral Springs, Florida, United States

Site Status

Cara Therapeutics Study Site

Hialeah, Florida, United States

Site Status

Cara Therapeutics Study Site

Miami, Florida, United States

Site Status

Cara Therapeutics Study Site

Miami Gardens, Florida, United States

Site Status

Cara Therapeutics Study Site

Tampa, Florida, United States

Site Status

Cara Therapeutics Study Site

Kalamazoo, Michigan, United States

Site Status

Cara Therapeutics Study Site

Roseville, Michigan, United States

Site Status

Cara Therapeutics Study Site

Minneapolis, Minnesota, United States

Site Status

Cara Therapeutics Study Site

Brookhaven, Mississippi, United States

Site Status

Cara Therapeutics Study Site

McComb, Mississippi, United States

Site Status

Cara Therapeutics Study Site

Tupelo, Mississippi, United States

Site Status

Cara Therapeutics Study Site

Kansas City, Missouri, United States

Site Status

Cara Therapeutics Study Site

Las Vegas, Nevada, United States

Site Status

Cara Therapeutics Study Site

Las Vegas, Nevada, United States

Site Status

Cara Therapeutics Study Site

Eatontown, New Jersey, United States

Site Status

Cara Therapeutics Study Site

Albuquerque, New Mexico, United States

Site Status

Cara Therapeutics Study Site

Gallup, New Mexico, United States

Site Status

Cara Therapeutics Study Site

Fresh Meadows, New York, United States

Site Status

Cara Therapeutics Study Site

Great Neck, New York, United States

Site Status

Cara Therapeutics Study Site

The Bronx, New York, United States

Site Status

Cara Therapeutics Study Site

Durham, North Carolina, United States

Site Status

Cara Therapeutics Study Site

Canton, Ohio, United States

Site Status

Cara Therapeutics Study Site

Roseburg, Oregon, United States

Site Status

Cara Therapeutics Study Site

Chattanooga, Tennessee, United States

Site Status

Cara Therapeutics Study Site

Dallas, Texas, United States

Site Status

Cara Therapeutics Study Site

Duncanville, Texas, United States

Site Status

Cara Therapeutics Study Site

Greenville, Texas, United States

Site Status

Cara Therapeutics Study Site

Houston, Texas, United States

Site Status

Cara Therapeutics Study Site

Lewisville, Texas, United States

Site Status

Cara Therapeutics Study Site

McAllen, Texas, United States

Site Status

Cara Therapeutics Study Site

Mesquite, Texas, United States

Site Status

Cara Therapeutics Study Site

San Antonio, Texas, United States

Site Status

Cara Therapeutics Study Site

Waxahachie, Texas, United States

Site Status

Cara Therapeutics Study Site

Chesapeake, Virginia, United States

Site Status

Cara Therapeutics Study Site

Hampton, Virginia, United States

Site Status

Cara Therapeutics Study Site

Wauwatosa, Wisconsin, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 39037824 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37968132 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36039153 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36016762 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33283264 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31702883 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CR845-CLIN3102

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.