Apremilast 30 mg BID Combined With Dupilumab

Study Overview
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Brief Summary
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Open label phase 2 investigational study of efficacy and safety of apremilast 30 mg BID in chronic atopic dermatitis when added to the FDA approved treatment dupilumab for atopic dermatitis that is not providing adequate clinical responses.

Detailed Description
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The purpose of this study is to determine if apremilast as a combined treatment for atopic dermatitis will provide increased efficacy outcomes in subjects who are currently using the FDA approved therapy of dupilumab but have responded only partially or inadequately to this therapy. Our hypothesis is that adding apremilast will allow patients to go from an inadequate response to dupilumab to an adequate response defined as an Investigator Global Assessment (IGA) of 0 (clear) or 1 (almost clear).

Official Title
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Apremilast 30 mg BID Combined With Dupilumab for the Treatment of Recalcitrant Moderate-to-Severe Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Apremilast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent indicating the subject has been informed of all aspects of the study Subject is willing and able to comply with treatment plan, study drug administration, and study protocol requirements Subject has a documented clinical diagnosis of chronic atopic dermatitis for at least 6 months prior to screening visit and is a candidate for systemic therapy Subjects must fulfill criteria outlined in the following clinical categories: Subjects must be currently using and experiencing an inadequate response to dupilumab which is FDA approved for the treatment of moderate to severe atopic dermatitis. An inadequate response is defined as an IGA of 2 or more. At the time of screening, subject must have a partial or inadequate response to their current treatment regimen. A partial or inadequate response at screening is defined as having both of the following: Not having achieved an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear). Subjects must be on dupilumab for at least 12 weeks and willing to continue on dupilumab on a stable dose (40 mg weekly or every other week) while also receiving the study drug Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. While on investigational product and for at least 28 days after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]) while on study medication and for at least 28 days after the last dose of study medication If receiving concomitant medications for any reason, must be on a stable regimen and willing to stay on a stable regimen. This includes emollients, which should stay stable throughout the study Exclusion Criteria: 1. Prior hypersensitivity reaction or exposure to apremilast 2. Untreated or unstable depression or suicidality, including prior history of suicide attempt at any time in the subject's lifetime prior to Baseline Visit or major psychiatric illness requiring hospitalization within 3 years prior to Baseline Visit. Depression and suicidality will be assessed through standard-of-care questioning 3. Other than atopic dermatitis, any clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major disease that is currently uncontrolled 4. Any condition, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study 6. Pregnant or lactating females 7. Concomitant therapy with CYP450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin), which may cause loss of efficacy of apremilast. 8. Prolonged sun exposure or use of tanning booths, which may confound the ability to interpret data from the study. 9. Active substance abuse or a history of substance abuse within 6 months prior to Screening. Subjects will be asked about any history of substance use using standard of care questioning. 10. Malignancy or history of malignancy, except for: treated [i.e., cured] basal cell or squamous cell in situ skin carcinomas; treated [i.e., cured] cervical intraepithelial neoplasia (CIN) or carcinoma in situ of cervix with no evidence of recurrence within the previous 5 years. 11. Use of dupilimab in combination with any other systemic immunosuppressant medication within 4 weeks prior to randomization or 5 pharmacokinetic/pharmacodynamic half lives, whichever is longer. 12. Use of any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half lives, if known (whichever is longer)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apremilast<br>Apremilast will be administered to patients as 30 mg oral tablets taken twice daily for 24 weeks. An initial 5-day titration will be implemented to improve tolerability. | Drug: Apremilast<br>* 30 mg BID<br>* Other names: Otezla;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who achieve an Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) from Baseline at Week 16. | Clinical improvement in a patient's eczematous lesions corresponds with a decrease in IGA, and a score of 0 (clear) or 1 (almost clear) is considered a significant clinical response. | Baseline and Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Surface Area less than 3% | Percentage of subjects achieving BSA < 3% from Baseline at Week 16. | Baseline and Week 16 | 
| Body Surface Area Involvement | percentage change from baseline in percent of BSA involvement at Week 16. | Baseline and Week 16 | 
| Dermatology Life Quality Index (DLQI) | Percent change of the Dermatology Life Quality Index (DLQI) from baseline at Week 16. | Baseline and Week 16 | 
| Numerical Rating Scale (NRS) | Percentage change from baseline in itch on NRS pruritus scale at Week 16. | Baseline and Week 16 | 
| Eczema Area and Severity Index (EASI) | Percentage change from baseline in EASI score at Week 16. | Baseline and Week 16 |