Clinical trial NCT05387707: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Pruritus
Atopic Dermatitis
Keywords: Atopic Dermatitis
Pruritus
CR845
Chronic Itch
difelikefalin
Itch
Itching
Generalized pruritus
Eczema
Lead sponsor: Cara Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-05-24
Enrollment: 287
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part A includes 4 arms and Part B includes 2 arms.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Week 12
Secondary outcomes:
measure: Proportion of subjects achieving ≥ 4 point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 4
timeFrame: Week 4
measure: 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)
timeFrame: Week 12
measure: Proportion of subjects achieving ≥ 4 point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 2
timeFrame: Week 2
measure: Proportion of subjects achieving ≥ 4 point improvement from baseline in the weekly mean of the daily 24-hour I-NRS score at Week 1
timeFrame: Week 1
measure: Mean change and mean percent change from baseline in EASI score at Week 12.
timeFrame: Week 12
measure: 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)
timeFrame: Week 12
measure: 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)
timeFrame: Week 12
measure: 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)
timeFrame: Week 12
measure: 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)
timeFrame: Week 12
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Cara Therapeutics Study Site
state: Arizona
city: Fort Smith
country: United States
facility: Cara Therapeutics Study Site
state: Arkansas
city: Rogers
country: United States
facility: Cara Therapeutics Study Site
state: Arkansas
city: Fountain Valley
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Lomita
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Los Angeles
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Redwood City
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Sacramento
country: United States
facility: Cara Therapeutics Study Site
state: California
city: San Diego
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Santa Monica
country: United States
facility: Cara Therapeutics Study Site 2
state: California
city: Santa Monica
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Valencia
country: United States
facility: Cara Therapeutics Study Site
state: California
city: Denver
country: United States
facility: Cara Therapeutics Study Site
state: Colorado
city: Brandon
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Coral Gables
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Delray Beach
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Hollywood
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: North Miami Beach
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Orlando
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Saint Augustine
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Saint Petersburg
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Sweetwater
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Tampa
country: United States
facility: Cara Therapeutics Study Site
state: Florida
city: Marietta
country: United States
facility: Cara Therapeutics Study Site
state: Georgia
city: Indianapolis
country: United States
facility: Cara Therapeutics Study Site
state: Indiana
city: Plainfield
country: United States
facility: Cara Therapeutics Study Site
state: Indiana
city: South Bend
country: United States
facility: Cara Therapeutics Study Site
state: Indiana
city: Overland Park
country: United States
facility: Cara Therapeutics Study Site
state: Kansas
city: Louisville
country: United States
facility: Cara Therapeutics Study Site
state: Kentucky
city: Baton Rouge
country: United States
facility: Cara Therapeutics Study Site
state: Louisiana
city: Houma
country: United States
facility: Cara Therapeutics Study Site
state: Louisiana
city: Metairie
country: United States
facility: Cara Therapeutics Study Site
state: Louisiana
city: New Orleans
country: United States
facility: Cara Therapeutics Study Site
state: Louisiana
city: Rockville
country: United States
facility: Cara Therapeutics Study Site
state: Maryland
city: Brighton
country: United States
facility: Cara Therapeutics Study Site
state: Massachusetts
city: Auburn Hills
country: United States
facility: Cara Therapeutics Study Site
state: Michigan
city: Clinton Township
country: United States
facility: Cara Therapeutics Study Site
state: Michigan
city: Detroit
country: United States
facility: Cara Therapeutics Study Site
state: Michigan
city: Waterford
country: United States
facility: Cara Therapeutics Study Site
state: Michigan
city: Hackensack
country: United States
facility: Cara Therapeutics Study Site
state: New Jersey
city: Huntersville
country: United States
facility: Cara Therapeutics Study Site
state: North Carolina
city: Raleigh
country: United States
facility: Cara Therapeutics Study Site
state: North Carolina
city: Athens
country: United States
facility: Cara Therapeutics Study Site
state: Ohio
city: Bexley
country: United States
facility: Cara Therapeutics Study Site
state: Ohio
city: Boardman
country: United States
facility: Cara Therapeutics Study Site
state: Ohio
city: Oklahoma City
country: United States
facility: Cara Therapeutics Study Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: Cara Therapeutics Study Site
state: Oklahoma
city: Philadelphia
country: United States
facility: Cara Therapeutics Study Site
state: Pennsylvania
city: Plymouth Meeting
country: United States
facility: Cara Therapeutics Study Site
state: Pennsylvania
city: Sugarloaf
country: United States
facility: Cara Therapeutics Study Site
state: Pennsylvania
city: Charleston
country: United States
facility: Cara Therapeutics Study Site
state: South Carolina
city: Knoxville
country: United States
facility: Cara Therapeutics Study Site
state: Tennessee
city: Thompson's Station
country: United States
facility: Cara Therapeutics Study Site
state: Tennessee
city: Arlington
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Austin
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Bellaire
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Houston
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: San Antonio
country: United States
facility: Cara Therapeutics Study Site
state: Texas
city: Springville
country: United States
facility: Cara Therapeutics Study Site
state: Utah
city: Spokane
country: United States
facility: Cara Therapeutics Study Site
state: Washington
city: Morgantown
country: United States
facility: Cara Therapeutics Study Site
state: West Virginia
Study officials:
affiliation: Cara Therapeutics
name: Cara Therapeutics
role: STUDY_DIRECTOR
References: