Efficacy and Safety Study of Apremilast in Subjects With Moderate to Severe Atopic Dermatitis

Study Overview
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Brief Summary
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A study to evaluate the efficacy and safety of apremilast (CC-10004) in subjects with moderate to severe atopic dermatitis

Official Title
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A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate to Severe Atopic Dermatitis

Conditions
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Dermatitis, Atopic Dermatitis

Intervention / Treatment
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* Drug: Apremilast
* Drug: Apremilast
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, aged ≥ 18 years (≥ 20 for Japanese subjects) at the time of consent. Have a diagnosis of atopic dermatitis for ≥ 12 months. Have moderate to severe atopic dermatitis which is considered inappropriate for topical therapy or which cannot be adequately controlled by topical therapy. Meet the laboratory criteria as defined per protocol Females of Childbearing Potential (FCBP) must have a negative pregnancy test at Screening and Baseline. Sexually active FCBP must use one of the approved contraceptive options required per protocol while on and for at least 28 days after the last dose of study medication Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception while on and for at least 28 days after the last dose of study medication. Exclusion Criteria: Active tuberculosis (TB) or a history of inadequately treated tuberculosis. Positive for hepatitis B surface antigen or hepatitis C antibody Pregnant or breast feeding History of allergy to any component of the study medication. Active skin infection requiring systemic antimicrobials at Baseline.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apremilast 40 mg<br>Apremilast 40 mg administered orally twice daily (BID) for 12 weeks (following dose titration) during the placebo controlled phase followed by 40 mg Apremilast tablets orally administered BID for an additional 12 weeks in the active treatment phase | Drug: Apremilast<br>* Orally twice a day (BID)<br>* Other names: Otezla;|
| Experimental: Apremilast 30 mg<br>Apremilast 30 mg administered orally BID for 12 weeks (following dose titration) during the placebo controlled phase followed by 30 mg Apremilast tablets orally administered BID for an additional 12 weeks in the active treatment phase | Drug: Apremilast<br>* Orally twice a day (BID)<br>* Other names: Otezla;|
| Experimental: Placebo + Apremilast 40 mg<br>Placebo administered orally BID for 12 weeks, during the placebo controlled phase followed by 40 mg Apremilast tablets orally BID for an additional 12 weeks in the active treatment phase | Drug: Apremilast<br>* Orally twice a day (BID)<br>* Other names: Otezla;Drug: Placebo<br>* Orally twice a day (BID)<br>|
| Experimental: Placebo + Apremilast 30 mg<br>Placebo administered orally BID for 12 weeks, during the placebo controlled phase followed by 30 mg Apremilast tablets orally BID for an additional 12 weeks in the active treatment phase | Drug: Apremilast<br>* Orally twice a day (BID)<br>* Other names: Otezla;Drug: Placebo<br>* Orally twice a day (BID)<br>|
| Placebo Comparator: Placebo<br>Oral Placebo tablets administered twice daily (BID) for 12 weeks during the placebo-controlled phase. | Drug: Placebo<br>* Orally twice a day (BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in the Eczema Area and Severity Index (EASI) Score at Week 12. | EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). A representative lesion is selected for each of the four body regions for assessing the intensity of each of the four signs (erythema, induration /papulation, excoriation, and lichenification). Symptoms (eg, pruritus) and secondary signs (eg, xerosis, scaling) are excluded from the assessment. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Score of 0 (Cleared) or 1 (Almost Cleared) and at Least a 2-point Reduction From Baseline in a Static Physician's Global Assessment of Acute Signs (sPGA-A) at Week 12. | The sPGA-A is intended to assess the global severities (ie, a visual average integrating all areas of AD) of key acute clinical signs of AD, including erythema, induration/papulation, oozing/crusting (lichenification excluded) based on a 5-point scale of cleared (0), almost cleared (1), mild (2), moderate (3) and severe (4). | Baseline to Week 12 | 
| Percentage of Participants Who Achieved at Least a 50% Reduction From Baseline in the EASI Score (EASI 50) at Week 12 | The EASI 50 reduction (defined as ≥ 50% reduction from baseline in EASI score) was selected to serve as the key responder endpoint. A ≥ 50% improvement is clinically meaningful for this population. | Baseline to Week 12 | 
| The Percentage Change From Baseline in the Average Weekly Pruritus Numerical Rating Scale (NRS) Score at Week 4 | The participant completed a daily diary recording the average intensity of pruritus they experienced during the preceding 24 hrs. The intensity of pruritus was assessed using a validated 11-point NRS, ranging from 0 (no pruritus) to 10 (the worst pruritus imaginable). It should be noted that this NRS is distinct from the pruritus, Visual Analogue Scale (VAS) in the Modified SCORAD Index with respect to recall period (three days for the VAS). The weekly NRS score was calculated as the average of the NRS scores over 7 days within the specified week. A higher score indicated worse disease status, and a negative change from baseline indicated improvement. | Baseline to Week 4 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo Controlled Period | A TEAE is an adverse event with a start date on or after the date of the first dose of IP and no later than 28 days after the last dose of IP for participants who discontinued early. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre existing condition) should be considered an AE. A serious AE is any which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event. | Baseline to Week 12 | 
| Number of Participants With TEAEs During the Apremilast Exposure Period | A TEAE is an adverse event with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre existing condition) should be considered an AE. A serious AE is any which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event. | Baseline to Week 24; median duration of apremilast 30 mg was 23.3 weeks and 22.4 weeks for apremilast 40 mg | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic Dermatitis, Atopic Eczema