A Study to Evaluate the Safety and Efficacy of CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Oral CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of 3 dose levels of oral CR845 compared to placebo in reducing the intensity of itch in chronic kidney disease (CKD) patients with moderate-to-severe pruritus. This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week Treatment Period, and a Follow-up Visit (approximately 7 days after the last dose of study drug).

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases; Pruritus
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: CR845 0.25 mg Oral Tablet; Drug: CR845 0.5 mg Oral Tablet; Drug: CR845 1 mg Oral Tablet

Detailed Description

This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week Treatment Period, and a Follow-up Visit (approximately 7 to 10 days after the last dose of study drug). Informed consent will be obtained prior to performing any study-specific procedures. Screening will occur within 7 to 28 days prior to randomization to assess eligibility.

If patients continue to meet all inclusion and no exclusion criteria at the end of the 7-day Run-in Period, they will be randomized in a 1:1:1:1 ratio to receive orally once daily either placebo or CR845 tablets at doses of 0.25, 0.5 or 1 mg. Randomization will be stratified according to the patient's renal disease status: moderate CKD; severe CKD non-dialysis; severe CKD on dialysis (ie, 3 categories). A final safety Follow-up Visit will be conducted 7 to 10 days after the last dose of study drug.

• Study Type: Interventional
• Enrollment (Actual): 269
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Cara Therapeutics Study Site
    • Florence, Alabama, United States, 35630
      • Cara Therapeutics Study Site
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Cara Therapeutics Study Site
    • Prescott, Arizona, United States, 86401
      • Cara Therapeutics Study Site
    • Sun City, Arizona, United States, 85351
      • Cara Therapeutics Study Site
  • Arkansas
    • Harrisburg, Arkansas, United States, 72432
      • Cara Therapeutics Study Site
  • California
    • Bakersfield, California, United States, 93309
      • Cara Therapeutics Study Site
    • Bakersfield, California, United States, 99309
      • Cara Therapeutics Study Site 2
    • Canyon Country, California, United States, 91351
      • Cara Therapeutics Study Site
    • Escondido, California, United States, 92025
      • Cara Therapeutics Study Site
    • Lomita, California, United States, 90717
      • Cara Therapeutics Study Site
    • Northridge, California, United States, 91324
      • Cara Therapeutics Study Site
    • Riverside, California, United States, 92505
      • Cara Therapeutics Study Site
    • Sacramento, California, United States, 95831
      • Cara Therapeutics Study Site
    • Whittier, California, United States, 90602
      • Cara Therapeutics Study Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Cara Therapeutics Study Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Cara Therapeutics Study Site
  • Florida
    • Edgewater, Florida, United States, 32132
      • Cara Therapeutics Study Site
    • Hialeah, Florida, United States, 33016
      • Cara Therapeutics Study Site
    • Hollywood, Florida, United States, 33024
      • Cara Therapeutics Study Site
    • Lake Worth, Florida, United States, 33467
      • Cara Therapeutics Study Site
    • Miami, Florida, United States, 33125
      • Cara Therapeutics Study Site 1
    • Miami, Florida, United States, 33155
      • Cara Therapeutics Study Site 2
    • Ocala, Florida, United States, 34471
      • Cara Therapeutics Study Site
    • Orlando, Florida, United States, 32810
      • Cara Therapeutics Study Site
    • Tampa, Florida, United States, 33614
      • Cara Therapeutics Study Site
    • Temple Terrace, Florida, United States, 33637
      • Cara Therapeutics Study Site
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Cara Therapeutics Study Site
    • Sandy Springs, Georgia, United States, 30328
      • Cara Therapeutics Study Site
  • Illinois
    • Crystal Lake, Illinois, United States, 60012
      • Cara Therapeutics Study Site
    • Evanston, Illinois, United States, 60201
      • Cara Therapeutics Study Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Cara Therapeutics Study Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Cara Therapeutics Study Site
    • New Orleans, Louisiana, United States, 70115
      • Cara Therapeutics Study Site
    • Zachary, Louisiana, United States, 70791
      • Cara Therapeutics Study Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Cara Therapeutics Study Site
    • Takoma Park, Maryland, United States, 20912
      • Cara Therapeutics Study Site
  • Michigan
    • Flint, Michigan, United States, 48503
      • Cara Therapeutics Study Site
    • Flint, Michigan, United States, 48532
      • Cara Therapeutics Study Site 2
    • Roseville, Michigan, United States, 48066
      • Cara Therapeutics Study Site
    • Saint Clair, Michigan, United States, 48081
      • Cara Therapeutics Study Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Cara Therapeutics Study Site
  • New York
    • Brooklyn, New York, United States, 11229
      • Cara Therapeutics Study Site
    • Mineola, New York, United States, 11501
      • Cara Therapeutics Study Site
  • North Carolina
    • Rocky Mount, North Carolina, United States, 27804
      • Cara Therapeutics Study Site
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Cara Therapeutics Study Site
  • Oklahoma
    • Norman, Oklahoma, United States, 73071
      • Cara Therapeutics Study Site
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Cara Therapeutics Study Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Cara Therapeutics Study Site
    • Warwick, Rhode Island, United States, 02886
      • Cara Therapeutics Study Site
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Cara Therapeutics Study Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Cara Therapeutics Study Site
  • Texas
    • Corsicana, Texas, United States, 75110
      • Cara Therapeutics Study Site
    • Gonzales, Texas, United States, 78629
      • Cara Therapeutics Study Site
    • Houston, Texas, United States, 77074
      • Cara Therapeutics Study Site
    • Houston, Texas, United States, 77081
      • Cara Therapeutics Study Site
    • Plano, Texas, United States, 75093
      • Cara Therapeutics Study Site
    • San Antonio, Texas, United States, 78207
      • Cara Therapeutics Study Site
    • San Antonio, Texas, United States, 78224
      • Cara Therapeutics Study Site
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Cara Therapeutics Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

To be eligible for inclusion into the study, a patient must meet the following criteria:

• CKD patients with stage III, IV, or V (ie, moderate renal impairment with estimated glomerular filtration rate (GFR) ≥30 and <60 mL/min/1.73 m2 or severe renal impairment with estimated GFR <30 mL/min/1.73 m2).
• For severe CKD patients on hemodialysis, they must be receiving hemodialysis 3 times per week for at least 3 months prior to the start of screening;

• Prior to randomization:

  1. Has completed at least 4 Worst Itching Intensity NRS worksheets from the start of the 7-day Run-in Period;
  2. Has a mean baseline Worst Itching Intensity NRS score ≥5, defined as the average of all non-missing scores reported from the start of the 7-day Run-in Period.

Exclusion Criteria:

A patient will be excluded from the study if any of the following criteria are met:

• Patients not currently on dialysis who are likely to initiate routine dialysis during study participation;
• Scheduled to receive a kidney transplant during the study;
• New or change of treatment received for itch including antihistamines and corticosteroids (oral, intravenous [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;
• Received ultraviolet B treatment within 30 days prior to the start of screening 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CR845 0.25 mg Oral Tablet; Oral CR845 0.25 mg to be taken orally once daily for 12 weeks	Drug: CR845 0.25 mg Oral Tablet; CR845 0.25 mg medication taken orally 1 time/day; Other Names: Difelikefalin
Experimental: CR845 0.5 mg Oral Tablet; Oral CR845 0.5 mg to be taken orally once daily for 12 weeks	Drug: CR845 0.5 mg Oral Tablet; CR845 0.5 mg medication taken orally 1 time/day; Other Names: Difelikefalin
Experimental: CR845 1 mg Oral Tablet; Oral CR845 1 mg to be taken orally once daily for 12 weeks	Drug: CR845 1 mg Oral Tablet; CR845 1 mg medication taken orally 1 time/day; Other Names: Difelikefalin
Placebo Comparator: Placebo Oral Tablet; Oral Placebo to be taken orally once daily	Drug: Placebo Oral Tablet; Placebo tablet taken orally 1 time/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score During 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". Higher scores meant worse itch intensity.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Skindex-10 Scale Score at the End of Week 12	The Skindex-10 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. The Skindex-10 has 10 questions; the total Skindex-10 score ranges from 0 to 60. A lower total score represents better quality of life.	Baseline, Week 12
Change From Baseline in 5-D Itch Scale Score at the End of Week 12	The 5-D Itch Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past 2 weeks. The questions cover five dimensions of itch including the degree, duration of itch/day, direction (improvement/worsening), disability (impact on activities such as work), and body distribution of itch. The 5-D Itch Scale has 5 questions; the total 5-D Itch Scale score ranges from 5 to 25, with higher scores indicating worse responses.	Baseline, Week 12
Reduction of Itch Intensity as Assessed by the Proportion of Patients Achieving an Improvement From Baseline ≥3 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score at Week 12		Week 12

Collaborators and Investigators

• Sponsor: Cara Therapeutics, Inc.
• Investigators: Study Director: Frédérique Menzaghi, PhD, Cara Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2018
• Primary Completion (Actual): October 24, 2019
• Study Completion (Actual): November 14, 2019

Study Registration Dates

• First Submitted: July 11, 2018
• First Submitted That Met QC Criteria: August 3, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: January 1, 2024

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; uremic pruritus; Chronic Itch; difelikefalin; Generalized pruritus; CKD-associated pruritus; CKD-aP
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Skin Manifestations; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Pruritus
• Other Study ID Numbers: CR845 210301

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
• product manufactured in and exported from the U.S.: No