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

An Open-Label, Multicenter Study to Evaluate the Safety and Effectiveness of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus

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.

Study Overview

• Status: Completed
• Conditions: Uremic Pruritus
• Intervention / Treatment: Drug: CR845 0.5 mcg/kg

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 222
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Havlíčkův Brod, Czechia
    • Cara Therapeutics Study Site
  • Nové Město Na Moravě, Czechia
    • Cara Therapeutics Study Site
  • Praha, Czechia
    • Cara Therapeutics Study Site
  • Sokolov, Czechia
    • Cara Therapeutics Study Site
• Hungary
  • Budapest, Hungary
    • Cara Therapeutics Study Site 2
  • Budapest, Hungary
    • Cara Therapeutics Study Site
  • Dunaújváros, Hungary
    • Cara Therapeutics Study Site
  • Kaposvár, Hungary
    • Cara Therapeutics Study Site
  • Kistarcsa, Hungary
    • Cara Therapeutics Study Site
  • Nyíregyháza, Hungary
    • Cara Therapeutics Study Site
  • Szombathely, Hungary
    • Cara Therapeutics Study Site
• Poland
  • Ostrołęka, Poland
    • Cara Therapeutics Study Site
  • Radom, Poland
    • Cara Therapeutics Study Site
  • Sochaczew, Poland
    • Cara Therapeutics Study Site
• United States
  • California
    • Escondido, California, United States, 92025
      • Cara Therapeutics Study Site
    • Riverside, California, United States, 92505
      • Cara Therapeutics Study Site
    • San Diego, California, United States, 92111
      • Cara Therapeutics Study Site
    • Victorville, California, United States, 92395
      • Cara Therapeutics Study Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Cara Therapeutics Study Site
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Cara Therapeutics Study Site
    • Norwich, Connecticut, United States, 06382
      • Cara Therapeutics Study Site
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Cara Therapeutics Study Site
    • Fort Lauderdale, Florida, United States, 33308
      • Cara Therapeutics Study Site
    • Hollywood, Florida, United States, 33024
      • Cara Therapeutics Study Site
    • Miami, Florida, United States, 33169
      • Cara Therapeutics Study Site
    • Tampa, Florida, United States, 33614
      • Cara Therapeutics Study Site
    • Tampa, Florida, United States, 33614
      • Cara Therapeutics Study Site 2
  • Georgia
    • Albany, Georgia, United States, 31701
      • Cara Therapeutics Study Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Cara Therapeutics Study Site
  • Michigan
    • Roseville, Michigan, United States, 48066
      • Cara Therapeutics Study Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Cara Therapeutics Study Site
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Cara Therapeutics Study Site
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cara Therapeutics Study Site
    • Las Vegas, Nevada, United States, 89128
      • Cara Therapeutics Study Site 2
  • New York
    • Great Neck, New York, United States, 11021
      • Cara Therapeutics Study Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Cara Therapeutics Study Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29302
      • Cara Therapeutics Study Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Cara Therapeutics Study Site
  • Texas
    • Austin, Texas, United States, 78751
      • Cara Therapeutics Study Site
    • Duncanville, Texas, United States, 75137
      • Cara Therapeutics Study Site
    • Greenville, Texas, United States, 75402
      • Cara Therapeutics Study Site
    • Mansfield, Texas, United States, 76063
      • Cara Therapeutics Study Site
    • Mesquite, Texas, United States, 75080
      • Cara Therapeutics Study Site
    • San Antonio, Texas, United States, 78251
      • Cara Therapeutics Study Site
    • San Antonio, Texas, United States, 78221
      • Cara Therapeutics Study Site 2
    • San Antonio, Texas, United States, 78258
      • Cara Therapeutics Study Site 3
    • Temple, Texas, United States, 76502
      • Cara Therapeutics Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key 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;

Key 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CR845 0.5mcg/kg; IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)	Drug: CR845 0.5 mcg/kg; IV CR845 0.5 mcg/kg administered three times/week; Other Names: Difelikefalin; CR845

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With AEs.	Assessed by monitoring of adverse events.	Up to Follow-Up Visit (Week 13-14)

Collaborators and Investigators

• Sponsor: Cara Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2019
• Primary Completion (Actual): February 26, 2020
• Study Completion (Actual): March 6, 2020

Study Registration Dates

• First Submitted: May 7, 2019
• First Submitted That Met QC Criteria: June 24, 2019
• First Posted (Actual): June 26, 2019

Study Record Updates

• Last Update Posted (Actual): October 15, 2021
• Last Update Submitted That Met QC Criteria: September 21, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; CKD; Itch; Dialysis; Hemodialysis; Pruritus; Itching; CR845; ESRD (end stage renal disease); Kidney failure, chronic; Kidney dysfunction; Chronic Itch; difelikefalin; Generalized pruritus; Uremic Pruritus; CKD-associated pruritus; CKD-aP; KALM
• Additional Relevant MeSH Terms: Skin Diseases; Skin Manifestations; Pruritus
• Other Study ID Numbers: CR845-CLIN3105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No