KIND-1: 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

Sponsor

Cara Therapeutics, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05387707

Collaborator

(none)

280

Enrollment

Arms

43.1

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Pruritus Atopic Dermatitis	Drug: difelikefalin 0.25 mg Drug: difelikefalin 0.5 mg Drug: TCS Cream Drug: Placebo Drug: Vehicle Cream	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

280 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Part A includes 4 arms and Part B includes 2 arms.Part A includes 4 arms and Part B includes 2 arms.

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Feb 1, 2025

Anticipated Study Completion Date :

Feb 1, 2026

Arms and Interventions

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: difelikefalin 0.5 mg Oral difelikefalin 0.5 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
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

Outcome Measures

Primary Outcome Measures

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

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]

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 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.