Study Evaluating Efficacy and Safety of Crisaborole in Adults With Stasis Dermatitis

Study Overview
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Brief Summary
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This is a Phase 2a, randomized, double blind, vehicle controlled, parallel group, proof of concept study that will include participants with stasis dermatitis without active skin ulceration, who will receive crisaborole ointment 2% or vehicle twice daily for 6 weeks.

Detailed Description
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Study C3291038 is a Phase 2a, randomized, double-blind, vehicle-controlled, parallel-group, proof of concept study to evaluate the efficacy, safety, and local tolerability of 6 weeks of treatment with crisaborole in adult participants with SD without active skin ulceration. Approximately 70 eligible participants will be randomized into the double blind treatment period in a 1:1 ratio to receive crisaborole ointment, 2% or vehicle twice daily for 6 weeks. The study will recruit male and female participants aged ≥ 45 years with a clinical diagnosis of SD. The total duration of participation in the study will be up to 14 weeks, including up to 4 weeks for screening, a 6 week double blind treatment period, and a follow-up period of 4 weeks after treatment completion. Study enrollment and management will be de centralized, where participants do not visit an investigator or a clinic for clinical assessment. The participants will participate in the study at home. The sponsor (or designee) will provide home visits by qualified home visit practitioners (HVP), remote contact by telemedicine (or telephone), and clinical database electronic case report forms (eCRFs), eDiary, and other electronic data entries from 3rd party vendors for study data collection.

Official Title
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A Phase 2, Randomized, Double-Blind, Vehicle-Controlled, Proof-of-Concept Study to Evaluate the Efficacy, Safety, and Local Tolerability of Crisaborole Ointment, 2%, in Adult Participants With Stasis Dermatitis Without Active Skin Ulceration

Conditions
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Stasis Dermatitis

Intervention / Treatment
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* Drug: crisaborole ointment
* Other: vehicle ointment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who are ≥45 years of age and in generally stable health Participants who are in generally stable health and have a known diagnosis of Stasis Dermatitis or newly diagnosed Stasis Dermatitis Participants whose mental and physical status allows them to be able to mostly perform their activities of daily living with minimal assistance Exclusion Criteria: Participants with clinically significant active or potentially recurrent dermatitis conditions and known genetic dermatological conditions that are not Stasis Dermatitis or overlap with Stasis Dermatitis Participants with active venous stasis ulceration on either lower extremity. Participants with current infection or suspected infection of any Stasis Dermatitis lesions Women of child bearing potential (WOCBP) are not eligible for this study

Ages Eligible for Study
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Minimum Age: 45 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: crisaborole ointment<br>crisaborole ointment | Drug: crisaborole ointment<br>* crisaborole ointment<br>* Other names: Eucrisa;|
| Sham Comparator: vehicle ointment<br>vehicle ointment | Other: vehicle ointment<br>* vehicle ointment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Total Sign Score (TSS) at Week 6: In-person Assessment | TSS assesses severity of stasis dermatitis lesions. There were following 4 clinical signs of all treatable stasis dermatitis lesions: erythema, papulation/elevation, superficial erosion/denudation, and scaling. Each of 4 signs were rated on a scale of 0 to 3 (0= none, 1= mild, 2= moderate, 3= severe). TSS = sum of scores from all clinical signs; ranging from 0 (none) to 12 (most severe), where higher score indicated greater severity. The assessment was completed in person by the home visit practitioner. | Baseline, Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Treatment Success Based on Investigator's Static Global Assessment (ISGA) at Week 6: In-person Assessment | ISGA is a global assessment of stasis dermatitis lesions severity based on erythema, papulation/elevation, superficial erosion/denudation, and scaling. ISGA excludes scalp from scoring and assessment. ISGA score ranged from 0 to 4; where 0 = clear (minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicated greater severity. The assessment was completed in person by the home visit practitioner. Treatment success was defined as ISGA score of clear/almost clear with at least a 2-grade improvement from baseline. | Week 6 | 
| Percentage of Participants Who Achieved Treatment Success Based on Investigator's Static Global Assessment (ISGA) at Week 1, 2, 3, 4, 5 and 6: Central Readers Digital Images Assessment | ISGA: global assessment of stasis dermatitis lesions severity based on erythema, papulation/elevation, superficial erosion/denudation, and scaling, excluding scalp. ISGA score ranged from 0 to 4; 0 = clear (minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores = greater severity. Treatment success: ISGA score of clear/almost clear with at least a 2-grade improvement from baseline. Participants acquired static digital images of the lesions using sponsor-provisioned digital imaging equipment. Images were reviewed by central readers. | Week 1, 2, 3, 4, 5 and 6 | 
| Percentage of Participants With an Investigator's Static Global Assessment (ISGA) Score of Clear (0) or Almost Clear (1) at Week 6: In-person Assessment | ISGA is a global assessment of stasis dermatitis lesions severity based on erythema, papulation/elevation, superficial erosion/denudation, and scaling. ISGA excludes scalp from scoring and assessment. ISGA score ranged from 0 to 4; where 0 = clear (minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicated greater severity. The assessment was completed in person by the home visit practitioner. | Week 6 | 
| Percentage of Participants With an Investigator's Static Global Assessment (ISGA) Score of Clear (0) or Almost Clear (1) at Week 1, 2, 3, 4, 5 and 6: Central Readers Digital Images Assessment | ISGA is a global assessment of stasis dermatitis lesions severity based on erythema, papulation/elevation, superficial erosion/denudation, and scaling. ISGA excludes scalp from scoring and assessment. ISGA score ranged from 0 to 4; where 0 = clear (minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicated greater severity. Participants acquired static digital images of the lesions using sponsor-provisioned digital imaging equipment. Images were reviewed by central readers. | Week 1, 2, 3, 4, 5 and 6 | 
| Percent Change From Baseline in Total Sign Score (TSS) at Week 1, 2, 3, 4, 5 and 6: Central Readers Digital Images Assessment | TSS assesses severity of stasis dermatitis lesions. There were following 4 clinical signs of all treatable stasis dermatitis lesions: erythema, papulation/elevation, superficial erosion/denudation, and scaling. Each of 4 signs were rated on a scale of 0 to 3 (0= none, 1= mild, 2= moderate, 3= severe). TSS = sum of scores from all clinical signs; ranging from 0 (none) to 12 (most severe), where higher score indicated greater severity. Participants acquired static digital images of the lesions using sponsor-provisioned digital imaging equipment. Images were reviewed by central readers. | Baseline, Week 1, 2, 3, 4, 5 and 6 | 
| Percent Change From Baseline in Stasis Dermatitis Lesional Percent Body Surface Area (BSA) at Week 6: In-person Assessment | Stasis dermatitis lesional BSA was calculated using handprint method. Number of handprints (size of participant's full palmer hand) fitting in affected area was counted. One handprint represented approximately 1% of lesional BSA. Percent BSA for a body region = total number of handprints in a body region * % surface area equivalent to 1 handprint. Higher % BSA indicated greater severity. The assessment was completed in person by the home visit practitioner. | Baseline, Week 6 | 
| Percent Change From Baseline in Percent Body Surface Area (BSA) at Week 1, 2, 3, 4, 5 and 6: Central Readers Digital Images Assessment | Stasis dermatitis lesional BSA was calculated using handprint method. Number of handprints (size of participant's full palmer hand) fitting in affected area was counted. One handprint represented approximately 1% of lesional BSA. Percent BSA for a body region = total number of handprints in a body region * % surface area equivalent to 1 handprint. Higher % BSA indicated greater severity. Participants acquired static digital images of the lesions using sponsor-provisioned digital imaging equipment. Images were reviewed by central readers. | Baseline, Week 1, 2, 3, 4, 5 and 6 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An adverse event (AE) was any untoward medical occurrence attributed to a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to 4 weeks after last dose that were absent before treatment or that worsened relative to pre-treatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs included both SAEs and all non-SAEs. | Day 1 up to maximum of 4 weeks after the last dose (maximum for 10 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stasis Dermatitis, venous hypertension, venous insufficiency