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

A Multicenter, Randomized, Double-blind, Placebo-controlled 12-Week Study to Evaluate the Safety and Efficacy of Oral Difelikefalin in Advanced Chronic Kidney Disease Subjects With Moderate-to-Severe Pruritus With an up to 52-Week Long-term Extension

This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of oral difelikefalin administered as a 1 mg tablet once daily compared to placebo in reducing the intensity of itch in advanced chronic kidney disease (CKD) patients with moderate-to-severe pruritus. This study is comprised of an Efficacy Assessment Phase and a Long-term Extension Phase. The Efficacy Assessment Phase includes a double-blind 12-week Treatment Period (Treatment Period 1), and the Long-term Extension Phase includes a double-blind Treatment Period (Treatment Period 2) of up to 52 weeks.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases; Pruritus
• Intervention / Treatment: Drug: Difelikefalin 1 mg Oral Tablet; Drug: Placebo Oral Tablet

Detailed Description

This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week double-blind Efficacy Assessment Phase (Treatment Period 1), a double-blind Long-term Extension Phase (Treatment Period 2) of up to 52 weeks, and a Follow-up Visit (7 to 10 days after the End of Treatment (EOT)/Early Termination (ET) Visit).

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 ratio to receive once daily oral difelikefalin tablets at a dose of 1 mg or placebo for 12 weeks. Subjects will be stratified according to their use or nonuse of medications to treat pruritus prior to randomization as well as the presence or absence of specific medical conditions. During the Long-term Extension Phase, patients will be re-randomized on Day 1 of Treatment Period 2 to receive either oral difelikefalin 1 mg or placebo, once daily for up to an additional 52 weeks. A final safety Follow-up Visit will be conducted 7 to 10 days after the EOT/ET.

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.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Cara Therapeutics; Phone Number: 203-406-3700; Email: clinicaltrials.gov@caratherapeutics.com

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Recruiting
      • Cara Therapeutics Study Site
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Recruiting
      • Cara Therapeutics Study Site
    • Surprise, Arizona, United States, 85374
      • Recruiting
      • Cara Therapeutics Study Site
  • California
    • Anaheim, California, United States, 92801
      • Recruiting
      • Cara Therapeutics Study Site
    • Bakersfield, California, United States, 93308
      • Recruiting
      • Cara Therapeutics Study Site
    • Beverly Hills, California, United States, 90211
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      • Cara Therapeutics Study Site
    • Chula Vista, California, United States, 91910
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      • Cara Therapeutics Study Site
    • El Centro, California, United States, 92243
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      • Cara Therapeutics Study Site
    • Garden Grove, California, United States, 92844
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      • Cara Therapeutics Study Site
    • La Mesa, California, United States, 91942
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      • Cara Therapeutics Study Site
    • Northridge, California, United States, 91324
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      • Cara Therapeutics Study Site
    • Ontario, California, United States, 91762
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      • Cara Therapeutics Study Site
    • Riverside, California, United States, 92505
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      • Cara Therapeutics Study Site
    • S. Gate, California, United States, 90280
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      • Cara Therapeutics Study Site
    • Santa Clara, California, United States, 91351
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      • Cara Therapeutics Study Site
    • Tarzana, California, United States, 91356
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      • Cara Therapeutics Study Site
    • Vacaville, California, United States, 95687
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      • Cara Therapeutics Study Site
    • Valencia, California, United States, 91355
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      • Cara Therapeutics Study Site
    • Victorville, California, United States, 92392
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      • Cara Therapeutics Study Site
  • Colorado
    • Arvada, Colorado, United States, 80002
      • Recruiting
      • Cara Therapeutics Study Site
    • Denver, Colorado, United States, 80230
      • Recruiting
      • Cara Therapeutics Study Site
  • Connecticut
    • New Haven, Connecticut, United States, 06511
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      • Cara Therapeutics Study Site
  • Florida
    • Atlantis, Florida, United States, 33462
      • Recruiting
      • Cara Therapeutics Study Site
    • Cape Coral, Florida, United States, 33914
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      • Cara Therapeutics Study Site
    • Coral Gables, Florida, United States, 33134
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      • Cara Therapeutics Study Site
    • Fort Lauderdale, Florida, United States, 33308
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      • Cara Therapeutics Study Site
    • Hialeah, Florida, United States, 33010
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      • Cara Therapeutics Study Site
    • Miami, Florida, United States, 33143
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      • Cara Therapeutics Study Site
    • Miami, Florida, United States, 33173
      • Recruiting
      • Cara Therapeutics Study Site
    • Orange City, Florida, United States, 32763
      • Recruiting
      • Cara Therapeutics Study Site
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Cara Therapeutics Study Site 2
    • Orlando, Florida, United States, 32808
      • Recruiting
      • Cara Therapeutics Study Site
    • Pembroke Pines, Florida, United States, 33024
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      • Cara Therapeutics Study Site
    • Riverview, Florida, United States, 33578
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      • Cara Therapeutics Study Site
    • Tampa, Florida, United States, 33603
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      • Cara Therapeutics Study Site
    • West Palm Beach, Florida, United States, 33401
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      • Cara Therapeutics Study Site
  • Georgia
    • Albany, Georgia, United States, 31701
      • Recruiting
      • Cara Therapeutics Study Site
    • East Point, Georgia, United States, 30344
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      • Cara Therapeutics Study Site
  • Idaho
    • Nampa, Idaho, United States, 83687
      • Recruiting
      • Cara Therapeutics Study Site
  • Illinois
    • Huntley, Illinois, United States, 60142
      • Recruiting
      • Cara Therapeutics Study Site
    • Palos Hills, Illinois, United States, 60465
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      • Cara Therapeutics Study Site
  • Kansas
    • Kansas City, Kansas, United States, 48504
      • Recruiting
      • Cara Therapeutics Study Site
  • Kentucky
    • Louisville, Kentucky, United States, 40205
      • Recruiting
      • Cara Therapeutics Study Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Recruiting
      • Cara Therapeutics Study Site
    • Metairie, Louisiana, United States, 70006
      • Recruiting
      • Cara Therapeutics Study Site
    • Shreveport, Louisiana, United States, 71101
      • Recruiting
      • Cara Therapeutics Study Site
    • Zachary, Louisiana, United States, 70791
      • Recruiting
      • Cara Therapeutics Study Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Recruiting
      • Cara Therapeutics Study Site
  • Michigan
    • Flint, Michigan, United States, 48504
      • Recruiting
      • Cara Therapeutics Study Site
    • Kalamazoo, Michigan, United States, 49007
      • Recruiting
      • Cara Therapeutics Study Site
    • Roseville, Michigan, United States, 48066
      • Recruiting
      • Cara Therapeutics Study Site
    • Saint Clair, Michigan, United States, 48081
      • Recruiting
      • Cara Therapeutics Study Site
    • Saint Joseph, Michigan, United States, 49085
      • Recruiting
      • Cara Therapeutics Study Site
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Recruiting
      • Cara Therapeutics Study Site
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Recruiting
      • Cara Therapeutics Study Site
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Recruiting
      • Cara Therapeutics Study Site
  • New York
    • Bronx, New York, United States, 10455
      • Recruiting
      • Cara Therapeutics Study Site
    • Laurelton, New York, United States, 11413
      • Recruiting
      • Cara Therapeutics Study Site
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • Recruiting
      • Cara Therapeutics Study Site
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Recruiting
      • Cara Therapeutics Study Site
    • Lima, Ohio, United States, 45805
      • Recruiting
      • Cara Therapeutics Study Site
  • Oklahoma
    • Ardmore, Oklahoma, United States, 73401
      • Recruiting
      • Cara Therapeutics Study Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18107
      • Recruiting
      • Cara Therapeutics Study Site
    • Upland, Pennsylvania, United States, 19013
      • Recruiting
      • Cara Therapeutics Study Site
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Recruiting
      • Cara Therapeutics Study Site
    • Providence, Rhode Island, United States, 02904
      • Recruiting
      • Cara Therapeutics Study Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29302
      • Recruiting
      • Cara Therapeutics Study Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Recruiting
      • Cara Therapeutics Study Site
    • Jackson, Tennessee, United States, 38305
      • Recruiting
      • Cara Therapeutics Study Site
    • Knoxville, Tennessee, United States, 37924
      • Recruiting
      • Cara Therapeutics Study Site
  • Texas
    • Austin, Texas, United States, 78751
      • Recruiting
      • Cara Therapeutics Study Site
    • Corsicana, Texas, United States, 75110
      • Recruiting
      • Cara Therapeutics Study Sites
    • El Paso, Texas, United States, 79902
      • Recruiting
      • Cara Therapeutics Study Site
    • Greenville, Texas, United States, 75402
      • Recruiting
      • Cara Therapeutics Study Site
    • Houston, Texas, United States, 77079
      • Recruiting
      • Cara Therapeutics Study Site
    • Houston, Texas, United States, 77081
      • Recruiting
      • Cara Therapeutics Study Site
    • Houston, Texas, United States, 77099
      • Recruiting
      • Cara Therapeutics Study Site 2
    • Lewisville, Texas, United States, 75057
      • Recruiting
      • Cara Therapeutics Study Site
    • McAllen, Texas, United States, 78503
      • Recruiting
      • Cara Therapeutics Study Site
    • McKinney, Texas, United States, 75069
      • Recruiting
      • Cara Therapeutics Study Site
    • Pasadena, Texas, United States, 77504
      • Recruiting
      • Cara Therapeutics Study Site
    • Sherman, Texas, United States, 75090
      • Recruiting
      • Cara Therapeutics Study Site
  • Virginia
    • Hampton, Virginia, United States, 23666
      • Recruiting
      • Cara Therapeutics Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (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:

• Advanced stage 4 and 5 CKD and end stage renal disease on hemodialysis
• Subject self-reports experiencing at least near-daily (eg, most days of a week) pruritus for at least 6 months prior to screening.
• Inadequate response to current or prior treatments (including emollients/moisturizers, topical medications, or systemic treatments) for pruritus prior to screening.

Prior to randomization on Day 1 of Treatment Period 1:

1. Has recorded at least 4 WI-NRS scores during the 7-day Run-in Period; and
2. Has a mean baseline WI-NRS score ≥ 5, defined as the average of all non-missing scores reported during the 7-day Run-in Period.

Exclusion Criteria:

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

• Scheduled to receive a renal replacement therapy (dialysis or kidney transplant) during the study.
• Has a concomitant disease, significant medical condition or physical/laboratory/ECG/vital signs abnormality that, in the opinion of the investigator, puts the subject at undue risk or interferes with interpretation of study results, impedes completion of the study procedures, or compromises the validity of the study measurements.
• New or change of treatment received for itch, including antihistamines and corticosteroids (oral, intravenous, or topical), within 14 days prior to the start of run-in.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Difelikefalin 1 mg Oral Tablet; Patients receive oral difelikefalin 1 mg once daily	Drug: Difelikefalin 1 mg Oral Tablet; Difelikefalin 1 mg medication taken orally 1 time/day; Other Names: CR845
Placebo Comparator: Placebo Oral Tablet; Patients receive oral placebo 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
Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS score at Week 12 of Treatment Period 1	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".	Week 12 of Treatment Period 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the WI-NRS at Week 8 of Treatment Period 1.	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".	Week 8 of Treatment Period 1
Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects achieving at least a 4-point improvement from baseline with respect to the weekly mean of the WI-NRS at Week 4 of Treatment Period 1.	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".	Week 4 of Treatment Period 1
Efficacy Assessment Phase (Treatment Period 1): Proportion of subjects who are "complete itch responders" defined as subjects with ≥ 70% of the non-missing 24-hour WI-NRS scores equal to 0 or 1 at Week 12 of Treatment Period 1.	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".	Week 12 of Treatment Period 1
Efficacy Assessment Phase (Treatment Period 1): Change from baseline in Sleep Quality Questionnaire score at the end of Week 12 of Treatment Period 1.	Sleep Quality will be measured using an NRS used to indicate how much itch has interfered with sleep during the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "did not interfere" and "10" represents "completely interfered".	Week 12 of Treatment Period 1

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2022
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: April 18, 2022
• First Submitted That Met QC Criteria: April 18, 2022
• First Posted (Actual): April 22, 2022

Study Record Updates

• Last Update Posted (Actual): January 3, 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: CR845-310301

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