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

Sponsor

Cara Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT04018027

Collaborator

(none)

401

Enrollment

Locations

Arms

21.1

Actual Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pruritus Atopic Dermatitis	Drug: difelikefalin 0.25 mg Drug: difelikefalin 0.5 mg Drug: difelikefalin 1.0 mg Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

401 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 29, 2019

Actual Primary Completion Date :

Apr 1, 2021

Actual Study Completion Date :

Apr 1, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cara Therapeutics Study Site	Anniston	Alabama	United States	36207
2	Cara Therapeutics Study Site	Birmingham	Alabama	United States	35209
3	Cara Therapeutics Study Site	Scottsdale	Arizona	United States	85254
4	Cara Therapeutics Study Site	Bryant	Arkansas	United States	72022
5	Cara Therapeutics Study Site	Fountain Valley	California	United States	92708
6	Cara Therapeutics Study Site	Lomita	California	United States	90717
7	Cara Therapeutics Study Site	Cromwell	Connecticut	United States	06416
8	Cara Therapeutics Study Site	Farmington	Connecticut	United States	06030
9	Cara Therapeutics Study Site	Aventura	Florida	United States	33180
10	Cara Therapeutics Study Site	Miami Lakes	Florida	United States	33014
11	Cara Therapeutics Study Site 2	Miami	Florida	United States	33125
12	Cara Therapeutics Study Site	Miami	Florida	United States	33174
13	Cara Therapeutics Study Site	Ocala	Florida	United States	34470
14	Cara Therapeutics Study Site	Sarasota	Florida	United States	34239
15	Cara Therapeutics Study Site	Sweetwater	Florida	United States	33172
16	Cara Therapeutics Study Site	Columbus	Georgia	United States	31904
17	Cara Therapeutics Study Site	Boise	Idaho	United States	83704
18	Cara Therapeutics Study Site 2	Boise	Idaho	United States	83713
19	Cara Therapeutics Study Site	Baton Rouge	Louisiana	United States	70809
20	Cara Therapeutics Study Site	Metairie	Louisiana	United States	70006
21	Cara Therapeutics Study Site	New Orleans	Louisiana	United States	70115
22	Cara Therapeutics Study Site	Brighton	Massachusetts	United States	02135
23	Cara Therapeutics Study Site 2	Las Vegas	Nevada	United States	89119
24	Cara Therapeutics Study Site	Berlin	New Jersey	United States	08009
25	Cara Therapeutics Study Site	Horseheads	New York	United States	14845
26	Cara Therapeutics Study Site	New York	New York	United States	10016
27	Cara Therapeutics Study Site	New York	New York	United States	10023
28	Cara Therapeutics Study Site	Cleveland	Ohio	United States	44122
29	Cara Therapeutics Study Site	Oklahoma City	Oklahoma	United States	73118
30	Cara Therapeutics Study Site	Tulsa	Oklahoma	United States	74136
31	Cara Therapeutics Study Site	Medford	Oregon	United States	97504
32	Cara Therapeutics Study Site	Rapid City	South Dakota	United States	57702
33	Cara Therapeutics Study Site 2	Austin	Texas	United States	78745
34	Cara Therapeutics Study Site	Austin	Texas	United States	78759
35	Cara Therapeutics Study Site	Cypress	Texas	United States	77433
36	Cara Therapeutics Study Site	Dallas	Texas	United States	75225
37	Cara Therapeutics Study Site	Salt Lake City	Utah	United States	84117
38	Cara Therapeutics Study Site	Richmond	Virginia	United States	23226
39	Cara Therapeutics Study Site	London	Ontario	Canada
40	Cara Therapeutics Study Site	Montréal	Quebec	Canada