Study to Evaluate the Efficacy and Safety of Oral Difelikefalin as Adjunct Therapy to a Topical Corticosteroid for Moderate to Severe Pruritus in Subjects With Atopic Dermatitis (KIND-1)

A Two-part, Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Oral Difelikefalin as Adjunct Therapy to a Topical Corticosteroid for Moderate-to-Severe Pruritus in Adult Subjects With Atopic Dermatitis

This is a two-part, multicenter, randomized, double-blind study to evaluate the efficacy and safety of oral difelikefalin as adjunct therapy to a topical corticosteroid (TCS) for moderate-to-severe pruritus in adult subjects with atopic dermatitis (AD).

Study Overview

• Status: Terminated
• Conditions: Pruritus; Atopic Dermatitis
• Intervention / Treatment: Drug: difelikefalin 0.25 mg; Drug: TCS Cream; Drug: difelikefalin 0.5 mg; Drug: Placebo; Drug: Vehicle Cream

Detailed Description

Part A of this study includes a 12-week Double-blind Treatment Period and a 52-week Open-label Extension Period. Subjects will be randomized to receive oral difelikefalin 0.25 mg tablets BID plus TCS cream, difelikefalin 0.5 mg tablets BID plus TCS cream, placebo tablets BID plus TCS cream or placebo tablets BID plus vehicle cream.

Part B of this study includes a 12-week Double-blind Treatment Period and 52-week Open-label Extension Period. Subjects will be randomized to receive oral difelikefalin 0.25 mg or 0.5 mg tablets BID plus TCS cream or oral placebo tablets BID plus TCS cream. Part A results at week 12 will inform Part B.

Subjects who participated in Part A of the study may not participate in Part B.

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

• Study Type: Interventional
• Enrollment (Actual): 287
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • Cara Therapeutics Study Site
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • Cara Therapeutics Study Site
    • Rogers, Arkansas, United States, 72758
      • Cara Therapeutics Study Site
  • California
    • Fountain Valley, California, United States, 92708
      • Cara Therapeutics Study Site
    • Lomita, California, United States, 90717
      • Cara Therapeutics Study Site
    • Los Angeles, California, United States, 90033
      • Cara Therapeutics Study Site
    • Redwood City, California, United States, 94063
      • Cara Therapeutics Study Site
    • Sacramento, California, United States, 95815
      • Cara Therapeutics Study Site
    • San Diego, California, United States, 92123
      • Cara Therapeutics Study Site
    • Santa Monica, California, United States, 90404
      • Cara Therapeutics Study Site
    • Santa Monica, California, United States, 90404
      • Cara Therapeutics Study Site 2
    • Valencia, California, United States, 91355
      • Cara Therapeutics Study Site
  • Colorado
    • Denver, Colorado, United States, 80210
      • Cara Therapeutics Study Site
  • Florida
    • Brandon, Florida, United States, 33511
      • Cara Therapeutics Study Site
    • Coral Gables, Florida, United States, 33134
      • Cara Therapeutics Study Site
    • Delray Beach, Florida, United States, 33484
      • Cara Therapeutics Study Site
    • Hollywood, Florida, United States, 33021
      • Cara Therapeutics Study Site
    • North Miami Beach, Florida, United States, 33162
      • Cara Therapeutics Study Site
    • Orlando, Florida, United States, 32819
      • Cara Therapeutics Study Site
    • Saint Augustine, Florida, United States, 32080
      • Cara Therapeutics Study Site
    • Saint Petersburg, Florida, United States, 33709
      • Cara Therapeutics Study Site
    • Sweetwater, Florida, United States, 33172
      • Cara Therapeutics Study Site
    • Tampa, Florida, United States, 33607
      • Cara Therapeutics Study Site
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Cara Therapeutics Study Site
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Cara Therapeutics Study Site
    • Plainfield, Indiana, United States, 46168
      • Cara Therapeutics Study Site
    • South Bend, Indiana, United States, 46617
      • Cara Therapeutics Study Site
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Cara Therapeutics Study Site
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Cara Therapeutics Study Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Cara Therapeutics Study Site
    • Houma, Louisiana, United States, 70364
      • Cara Therapeutics Study Site
    • Metairie, Louisiana, United States, 70006
      • Cara Therapeutics Study Site
    • New Orleans, Louisiana, United States, 70115
      • Cara Therapeutics Study Site
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Cara Therapeutics Study Site
  • Massachusetts
    • Brighton, Massachusetts, United States, 02135
      • Cara Therapeutics Study Site
  • Michigan
    • Auburn Hills, Michigan, United States, 48326
      • Cara Therapeutics Study Site
    • Clinton Township, Michigan, United States, 48038
      • Cara Therapeutics Study Site
    • Detroit, Michigan, United States, 48202
      • Cara Therapeutics Study Site
    • Waterford, Michigan, United States, 48328
      • Cara Therapeutics Study Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Cara Therapeutics Study Site
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Cara Therapeutics Study Site
    • Raleigh, North Carolina, United States, 27617
      • Cara Therapeutics Study Site
  • Ohio
    • Athens, Ohio, United States, 45701
      • Cara Therapeutics Study Site
    • Bexley, Ohio, United States, 43209
      • Cara Therapeutics Study Site
    • Boardman, Ohio, United States, 44512
      • Cara Therapeutics Study Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73118
      • Cara Therapeutics Study Site
    • Oklahoma City, Oklahoma, United States, 73170
      • Cara Therapeutics Study Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Cara Therapeutics Study Site
    • Plymouth Meeting, Pennsylvania, United States, 19462
      • Cara Therapeutics Study Site
    • Sugarloaf, Pennsylvania, United States, 18249
      • Cara Therapeutics Study Site
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Cara Therapeutics Study Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Cara Therapeutics Study Site
    • Thompson's Station, Tennessee, United States, 37179
      • Cara Therapeutics Study Site
  • Texas
    • Arlington, Texas, United States, 76011
      • Cara Therapeutics Study Site
    • Austin, Texas, United States, 78759
      • Cara Therapeutics Study Site
    • Bellaire, Texas, United States, 77401
      • Cara Therapeutics Study Site
    • Houston, Texas, United States, 77004
      • Cara Therapeutics Study Site
    • San Antonio, Texas, United States, 78209
      • Cara Therapeutics Study Site
  • Utah
    • Springville, Utah, United States, 84663
      • Cara Therapeutics Study Site
  • Washington
    • Spokane, Washington, United States, 99202
      • Cara Therapeutics Study Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Cara Therapeutics Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

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 chronic pruritus 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
Experimental: Difelikefalin 0.25 mg tablets plus TCS cream; Oral difelikefalin tablets administered twice daily. TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed.	Drug: difelikefalin 0.25 mg; Oral difelikefalin 0.25 mg tablets administered twice daily; Other Names: CR845; Drug: TCS Cream; TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed
Experimental: Difelikefalin 0.5 mg tablets plus TCS cream; Oral difelikefalin tablets administered twice daily. TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed.	Drug: TCS Cream; TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed; Drug: difelikefalin 0.5 mg; Oral difelikefalin 0.5 mg tablets administered twice daily; Other Names: CR845
Active Comparator: Placebo tablets plus TCS cream; Oral placebo tablets administered twice daily. TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed	Drug: TCS Cream; TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed; Drug: Placebo; Oral Placebo tablets administered twice daily
Placebo Comparator: Placebo tablets plus Vehicle cream (Part A only); Oral placebo tablets administered twice daily. Vehicle cream applied by study subjects to skin lesions once a day until control is achieved, then as needed	Drug: Placebo; Oral Placebo tablets administered twice daily; Drug: Vehicle Cream; Vehicle Cream applied by study subjects to skin lesions once a day until control is achieved, then as needed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects achieving ≥ 4 point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 4	Week 4
Proportion of subjects with ≥ 3 point improvement from baseline in the weekly mean of the daily 24-hour Sleep Disturbance NRS score at the end of Week 12 (among subjects with a Sleep Disturbance NRS score of > 3 at baseline)	Week 12
Proportion of subjects achieving ≥ 4 point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 2	Week 2
Proportion of subjects achieving ≥ 4 point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 1	Week 1
Mean change and mean percent change from baseline in EASI score at Week 12.	Week 12
Proportion of subjects achieving a vIGA-ADTM score of clear (0) or almost clear (1) with a 2-point improvement from baseline at Week 12 (among subjects with a vIGA-ADTM score ≥ 3 at Day 1)	Week 12
Proportion of subjects achieving a vIGA-ADTM score of clear (0) or almost clear (1) with a 2-point improvement from baseline at Week 12 (among subjects with a vIGA-ADTM score ≥ 2 at Day 1)	Week 12
Proportion of subjects achieving at least ≥ 3-point improvement in the Skin Pain NRS score at Week 12 (among subjects with a Skin Pain NRS score > 3 at Day 1)	Week 12
Proportion of subjects with ≥ 4 point improvement from baseline in Dermatology Life Quality Index (DLQI) score at Week 12 (among subjects with DLQI score > 4 at baseline)	Week 12

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2022
• Primary Completion (Actual): February 2, 2024
• Study Completion (Actual): February 2, 2024

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: May 19, 2022
• First Posted (Actual): May 24, 2022

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

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: CR845-310501

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