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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

Phase 3
Terminated
Conditions
Pruritus
Atopic Dermatitis
Interventions
Drug: TCS Cream
Drug: Placebo
Drug: Vehicle Cream
Registration Number
NCT05387707
Lead Sponsor
Cara Therapeutics, Inc.
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).

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
287
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Difelikefalin 0.5 mg tablets plus TCS creamdifelikefalin 0.5 mgOral difelikefalin tablets administered twice daily. TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed.
Difelikefalin 0.25 mg tablets plus TCS creamdifelikefalin 0.25 mgOral difelikefalin tablets administered twice daily. TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed.
Difelikefalin 0.25 mg tablets plus TCS creamTCS CreamOral difelikefalin tablets administered twice daily. TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed.
Difelikefalin 0.5 mg tablets plus TCS creamTCS CreamOral difelikefalin tablets administered twice daily. TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed.
Placebo tablets plus TCS creamTCS CreamOral placebo tablets administered twice daily. TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed
Placebo tablets plus TCS creamPlaceboOral placebo tablets administered twice daily. TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed
Placebo tablets plus Vehicle cream (Part A only)PlaceboOral placebo tablets administered twice daily. Vehicle cream applied by study subjects to skin lesions once a day until control is achieved, then as needed
Placebo tablets plus Vehicle cream (Part A only)Vehicle CreamOral placebo tablets administered twice daily. Vehicle cream applied by study subjects to skin lesions once a day until control is achieved, then as needed
Primary Outcome Measures
NameTimeMethod
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 12Week 12
Secondary Outcome Measures
NameTimeMethod
Proportion of subjects achieving ≥ 4 point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 2Week 2
Proportion of subjects achieving ≥ 4 point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 1Week 1
Mean change and mean percent change from baseline in EASI score at Week 12.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 4Week 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 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

Trial Locations

Locations (2)

Cara Therapeutics Study Site

🇺🇸

Morgantown, West Virginia, United States

Cara Therapeutics Study Site 2

🇺🇸

Santa Monica, California, United States

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