CR845-CLIN3105: A Study to Evaluate the Safety and Effectiveness of CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus

NCT ID: NCT03998163

Last Updated: 2021-10-15

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

222 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-06

Study Completion Date

2020-03-06

Brief Summary

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This is a multicenter, open-label study to evaluate the safety and effectiveness of intravenous (IV) CR845 at a dose of 0.5 mcg/kg administered after each dialysis session. The study includes an up to 12-week Treatment Period.

Detailed Description

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Screening Period: The Screening Period includes a Screening Visit and a Run-In Period. Informed consent will be obtained prior to performing any study-specific procedures. The Screening Visit will occur within 21 days prior to the start of the Run-in Period. Patients will start the Run-in Period during the week prior to Treatment Period to complete eligibility verification.

Treatment Period: All scheduled study visits during the Treatment Period will be conducted on dialysis days. Patients will be administered CR845 as an IV bolus after the end of their dialysis during a Treatment Period of up to 12 weeks so that each patient will receive CR845 3 times weekly for a total of up to 36 doses. End of treatment (EOT) is defined as the first day of dialysis following the last dose of drug. The EOT procedures will be conducted on the dialysis visit following the last dose of study drug.

Follow-up Visit: A final safety Follow up Visit will be conducted 7-10 days after the EOT/Early Termination Visit.

Conditions

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Uremic Pruritus

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CR845 0.5mcg/kg

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

Group Type EXPERIMENTAL

CR845 0.5 mcg/kg

Intervention Type DRUG

IV CR845 0.5 mcg/kg administered three times/week

Interventions

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CR845 0.5 mcg/kg

IV CR845 0.5 mcg/kg administered three times/week

Intervention Type DRUG

Other Intervention Names

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CR845 Difelikefalin

Eligibility Criteria

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Inclusion Criteria

To be eligible for inclusion into 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 Treatment:

* Has completed at least 3 Worst Itching Intensity NRS questionnaires from the start of the Run-in Period up to and including the pre-dose assessment on Day 1;

Exclusion Criteria

A patient will be excluded from 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;
* New or change of prescription for opioids, gabapentin, or pregabalin within 14 days prior to screening;
* Received another investigational drug within 30 days or five half-lives (whichever is longer) prior to the start of dosing or is planning to participate in another interventional clinical study while enrolled in this study;
* Has pruritus only during the dialysis session (by patient report);
* Is receiving ongoing ultraviolet B treatment and/or anticipates receiving such treatment during the study;
* Participated in a previous clinical study with CR845.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cara Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Frédérique Menzaghi, PhD

Role: STUDY_DIRECTOR

Cara Therapeutics

Locations

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Cara Therapeutics Study Site

Escondido, California, United States

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Cara Therapeutics Study Site

Riverside, California, United States

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Cara Therapeutics Study Site

San Diego, California, United States

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Cara Therapeutics Study Site

Victorville, California, United States

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Cara Therapeutics Study Site

Denver, Colorado, United States

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Cara Therapeutics Study Site

Middlebury, Connecticut, United States

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Cara Therapeutics Study Site

Norwich, Connecticut, United States

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Cara Therapeutics Study Site

Coral Gables, Florida, United States

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Cara Therapeutics Study Site

Fort Lauderdale, Florida, United States

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Cara Therapeutics Study Site

Hollywood, Florida, United States

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Cara Therapeutics Study Site

Miami, Florida, United States

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Cara Therapeutics Study Site 2

Tampa, Florida, United States

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Cara Therapeutics Study Site

Tampa, Florida, United States

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Cara Therapeutics Study Site

Albany, Georgia, United States

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Cara Therapeutics Study Site

Boston, Massachusetts, United States

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Cara Therapeutics Study Site

Roseville, Michigan, United States

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Cara Therapeutics Study Site

Minneapolis, Minnesota, United States

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Cara Therapeutics Study Site

Kansas City, Missouri, United States

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Cara Therapeutics Study Site

Las Vegas, Nevada, United States

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Cara Therapeutics Study Site 2

Las Vegas, Nevada, United States

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Cara Therapeutics Study Site

Great Neck, New York, United States

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Cara Therapeutics Study Site

Philadelphia, Pennsylvania, United States

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Cara Therapeutics Study Site

Spartanburg, South Carolina, United States

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Cara Therapeutics Study Site

Knoxville, Tennessee, United States

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Cara Therapeutics Study Site

Austin, Texas, United States

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Cara Therapeutics Study Site

Duncanville, Texas, United States

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Cara Therapeutics Study Site

Greenville, Texas, United States

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Cara Therapeutics Study Site

Mansfield, Texas, United States

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Cara Therapeutics Study Site

Mesquite, Texas, United States

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Cara Therapeutics Study Site 2

San Antonio, Texas, United States

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Cara Therapeutics Study Site

San Antonio, Texas, United States

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Cara Therapeutics Study Site 3

San Antonio, Texas, United States

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Cara Therapeutics Study Site

Temple, Texas, United States

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Cara Therapeutics Study Site

Havlíčkův Brod, , Czechia

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Cara Therapeutics Study Site

Nové Město na Moravě, , Czechia

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Cara Therapeutics Study Site

Prague, , Czechia

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Cara Therapeutics Study Site

Sokolov, , Czechia

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Cara Therapeutics Study Site 2

Budapest, , Hungary

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Cara Therapeutics Study Site

Budapest, , Hungary

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Cara Therapeutics Study Site

Dunaújváros, , Hungary

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Cara Therapeutics Study Site

Kaposvár, , Hungary

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Cara Therapeutics Study Site

Kistarcsa, , Hungary

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Cara Therapeutics Study Site

Nyíregyháza, , Hungary

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Cara Therapeutics Study Site

Szombathely, , Hungary

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Cara Therapeutics Study Site

Ostrołęka, , Poland

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Cara Therapeutics Study Site

Radom, , Poland

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Cara Therapeutics Study Site

Sochaczew, , Poland

Site Status

Countries

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United States Czechia Hungary Poland

References

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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)

Fotheringham J, Guest J, Latus J, Lerma E, Morin I, Schaufler T, Soro M, Stander S, Zeig S. Impact of Difelikefalin on the Health-Related Quality of Life of Haemodialysis Patients with Moderate-To-Severe Chronic Kidney Disease-Associated Pruritus: A Single-Arm Intervention Trial. Patient. 2024 Mar;17(2):203-213. doi: 10.1007/s40271-023-00668-1. Epub 2024 Jan 9.

Reference Type DERIVED
PMID: 38196014 (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)

Weiner DE, Vervloet MG, Walpen S, Schaufler T, Munera C, Menzaghi F, Wen W, Bhaduri S, Germain MJ; trial investigators. Safety and Effectiveness of Difelikefalin in Patients With Moderate-to-Severe Pruritus Undergoing Hemodialysis: An Open-Label, Multicenter Study. Kidney Med. 2022 Aug 24;4(10):100542. doi: 10.1016/j.xkme.2022.100542. eCollection 2022 Oct.

Reference Type DERIVED
PMID: 36185706 (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)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CR845-CLIN3105

Identifier Type: -

Identifier Source: org_study_id