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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

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: TCS Cream
* Drug: Placebo
* Drug: Vehicle Cream


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 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.

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
Interventional Model Description: Part A includes 4 arms and Part B includes 2 arms.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Difelikefalin 0.25 mg tablets plus TCS cream<br>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<br>* Oral difelikefalin 0.25 mg tablets administered twice daily<br>* Other names: CR845;Drug: TCS Cream<br>* TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed<br>|
| Experimental: Difelikefalin 0.5 mg tablets plus TCS cream<br>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<br>* Oral difelikefalin 0.5 mg tablets administered twice daily<br>* Other names: CR845;Drug: TCS Cream<br>* TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed<br>|
| Active Comparator: Placebo tablets plus TCS cream<br>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<br>* TCS cream applied by study subjects to skin lesions once a day until control is achieved, then as needed<br>Drug: Placebo<br>* Oral Placebo tablets administered twice daily<br>|
| Placebo Comparator: Placebo tablets plus Vehicle cream (Part A only)<br>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<br>* Oral Placebo tablets administered twice daily<br>Drug: Vehicle Cream<br>* Vehicle Cream applied by study subjects to skin lesions once a day until control is achieved, then as needed<br>|

What is the study measuring?
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Primary Outcome Measures

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

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

 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