Study to Evaluate the Efficacy and Safety of Oral Difelikefalin (CR845) for Moderate to Severe Pruritus in Subjects With Atopic Dermatitis (KARE)

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Oral Difelikefalin (CR845) for Moderate to Severe Pruritus in Adult Subjects With Atopic Dermatitis

This is a multicenter, randomized, double-blind, 4-arm, placebo-controlled study to evaluate the efficacy and safety of twice-daily (BID) oral difelikefalin (CR845) in adult subjects with atopic dermatitis (AD) and moderate to severe pruritus.

Study Overview

• Status: Completed
• Conditions: Pruritus; Atopic Dermatitis
• Intervention / Treatment: Drug: difelikefalin 0.25 mg; Drug: difelikefalin 0.5 mg; Drug: difelikefalin 1.0 mg; Drug: Placebo

Detailed Description

The study will consist of a 30-day Screening period, a 7-day Run-In period, a 12-week Placebo-Controlled Treatment period followed by a 4-week Active Extension period and a Follow Up visit approximately 7 days after the last dose of study drug.

All subjects will sign an informed consent form (ICF) and undergo screening for study eligibility.

Subjects will be randomized to receive either placebo or difelikefalin (CR845) tablets at a dose of 0.25 mg, 0.5 mg, or 1.0 mg, orally BID. Intake of the first dose of study drug will be at Day 1.

Subjects who complete the Placebo-Controlled Treatment period of the study will transition into the Active Extension upon completion of the Week 12 visit assessments. All subjects in the Active Extension will receive difelikefalin (CR845).

• Study Type: Interventional
• Enrollment (Actual): 401
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada
      • Cara Therapeutics Study Site
  • Quebec
    • Montréal, Quebec, Canada
      • Cara Therapeutics Study Site
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Cara Therapeutics Study Site
    • Birmingham, Alabama, United States, 35209
      • Cara Therapeutics Study Site
  • Arizona
    • Scottsdale, Arizona, United States, 85254
      • Cara Therapeutics Study Site
  • Arkansas
    • Bryant, Arkansas, United States, 72022
      • Cara Therapeutics Study Site
  • California
    • Fountain Valley, California, United States, 92708
      • Cara Therapeutics Study Site
    • Lomita, California, United States, 90717
      • Cara Therapeutics Study Site
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • Cara Therapeutics Study Site
    • Farmington, Connecticut, United States, 06030
      • Cara Therapeutics Study Site
  • Florida
    • Aventura, Florida, United States, 33180
      • Cara Therapeutics Study Site
    • Miami, Florida, United States, 33125
      • Cara Therapeutics Study Site 2
    • Miami, Florida, United States, 33174
      • Cara Therapeutics Study Site
    • Miami Lakes, Florida, United States, 33014
      • Cara Therapeutics Study Site
    • Ocala, Florida, United States, 34470
      • Cara Therapeutics Study Site
    • Sarasota, Florida, United States, 34239
      • Cara Therapeutics Study Site
    • Sweetwater, Florida, United States, 33172
      • Cara Therapeutics Study Site
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Cara Therapeutics Study Site
  • Idaho
    • Boise, Idaho, United States, 83704
      • Cara Therapeutics Study Site
    • Boise, Idaho, United States, 83713
      • Cara Therapeutics Study Site 2
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Cara Therapeutics Study Site
    • Metairie, Louisiana, United States, 70006
      • Cara Therapeutics Study Site
    • New Orleans, Louisiana, United States, 70115
      • Cara Therapeutics Study Site
  • Massachusetts
    • Brighton, Massachusetts, United States, 02135
      • Cara Therapeutics Study Site
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Cara Therapeutics Study Site 2
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Cara Therapeutics Study Site
  • New York
    • Horseheads, New York, United States, 14845
      • Cara Therapeutics Study Site
    • New York, New York, United States, 10016
      • Cara Therapeutics Study Site
    • New York, New York, United States, 10023
      • Cara Therapeutics Study Site
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Cara Therapeutics Study Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73118
      • Cara Therapeutics Study Site
    • Tulsa, Oklahoma, United States, 74136
      • Cara Therapeutics Study Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Cara Therapeutics Study Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Cara Therapeutics Study Site
  • Texas
    • Austin, Texas, United States, 78745
      • Cara Therapeutics Study Site 2
    • Austin, Texas, United States, 78759
      • Cara Therapeutics Study Site
    • Cypress, Texas, United States, 77433
      • Cara Therapeutics Study Site
    • Dallas, Texas, United States, 75225
      • Cara Therapeutics Study Site
  • Utah
    • Salt Lake City, Utah, United States, 84117
      • Cara Therapeutics Study Site
  • Virginia
    • Richmond, Virginia, United States, 23226
      • Cara Therapeutics Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 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:

• Subject has clinically confirmed diagnosis of active AD;
• Subject has at least a 12-month history of AD;
• Subject has chronic itch related to AD;
• Subject has moderate to severe pruritus;
• Female subject is not pregnant or nursing during any period of the study.

Key Exclusion Criteria:

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

• Subject has clinically infected AD;
• Subject has pruritus attributed to a cause other than AD;
• Subject has any clinically significant medical condition or physical/laboratory/ECG/vital signs abnormality that would, in the opinion of the investigator, put the subject at undue risk or interfere with interpretation of study results.

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
Active Comparator: Difelikefalin 0.25 mg; Oral difelikefalin 0.25 mg tablet administered twice daily	Drug: difelikefalin 0.25 mg; Oral difelikefalin 0.25 mg administered twice daily; Other Names: CR845
Active Comparator: Difelikefalin 0.5 mg; Oral difelikefalin 0.5 mg tablet administered twice daily	Drug: difelikefalin 0.5 mg; Oral difelikefalin 0.5 mg administered twice daily; Other Names: CR845
Active Comparator: Difelikefalin 1.0 mg; Oral difelikefalin 1.0 mg tablet administered twice daily	Drug: difelikefalin 1.0 mg; Oral difelikefalin 1.0 mg administered twice daily; Other Names: CR845
Placebo Comparator: Placebo; Oral placebo tablet administered twice daily	Drug: Placebo; Oral Placebo administered twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the weekly mean of the daily 24-hour Itch-Numeric Rating Scale (I-NRS) score at Week 12.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Reduction of itch intensity as assessed by the proportion of patients achieving an improvement from baseline ≥4 points with respect to the weekly mean of the daily 24-hour I-NRS score at Week 12	Week 12
Improvement in itch-related quality of life as assessed by the change from baseline to Week 12 in 5-D Itch Scale score	Baseline, Week 12
Improvement in itch-related quality of life as assessed by the change from baseline to Week 12 in total Skindex-10 Scale score	Baseline, Week 12
Improvement in itch-related quality of life as assessed by the change from baseline to Week 12 in Sleep Quality Assessment.	Baseline, Week 12
Percent of subjects with adverse events.	Baseline, Week 12

Collaborators and Investigators

• Sponsor: Cara Therapeutics, Inc.
• Investigators: Study Director: Kristine Nograles, Cara Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2019
• Primary Completion (Actual): April 1, 2021
• Study Completion (Actual): April 1, 2021

Study Registration Dates

• First Submitted: July 9, 2019
• First Submitted That Met QC Criteria: July 10, 2019
• First Posted (Actual): July 12, 2019

Study Record Updates

• Last Update Posted (Actual): April 4, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Itch; Atopic Dermatitis; Pruritus; Eczema; Itching; CR845; Chronic Itch; difelikefalin; Generalized pruritus
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Manifestations; Skin Diseases, Eczematous; Dermatitis; Eczema; Pruritus; Dermatitis, Atopic
• Other Study ID Numbers: CR845-210501

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