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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Pruritus, Atopic Dermatitis

Intervention / Treatment
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* Drug: difelikefalin 0.25 mg
* Drug: difelikefalin 0.5 mg
* Drug: difelikefalin 1.0 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Difelikefalin 0.25 mg<br>Oral difelikefalin 0.25 mg tablet administered twice daily | Drug: difelikefalin 0.25 mg<br>* Oral difelikefalin 0.25 mg administered twice daily<br>* Other names: CR845;|
| Active Comparator: Difelikefalin 0.5 mg<br>Oral difelikefalin 0.5 mg tablet administered twice daily | Drug: difelikefalin 0.5 mg<br>* Oral difelikefalin 0.5 mg administered twice daily<br>* Other names: CR845;|
| Active Comparator: Difelikefalin 1.0 mg<br>Oral difelikefalin 1.0 mg tablet administered twice daily | Drug: difelikefalin 1.0 mg<br>* Oral difelikefalin 1.0 mg administered twice daily<br>* Other names: CR845;|
| Placebo Comparator: Placebo<br>Oral placebo tablet administered twice daily | Drug: Placebo<br>* Oral Placebo administered twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic Dermatitis, Pruritus, CR845, Chronic Itch, difelikefalin, Itch, Itching, Generalized pruritus, Eczema