Pilot Study of the Safety and Efficacy of Apremilast in Subjects With Moderate to Severe Alopecia Areata

Exclusion Criteria

• •The presence of any of the following will exclude a subject from enrollment:
• •Clinically significant (as determined by the investigator) cardiac, endocrine, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, or immunologic disease, or other major uncontrolled diseases that will affect the health of the subject during the study or interfere with the interpretation of study results.
• •Hepatitis B surface antigen positive at Screening (Visit 1). Hepatitis C antibody positive at Screening (Visit 1). History of positive human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency \[CVID\]). Subjects deemed at risk by the study investigator, may also undergo testing for human immunodeficiency virus (HIV). Subjects deemed at risk include those with a history of injection drug use, homosexual subjects, and subjects with known sexual contact with an HIV positive partner.
• •Active TB or a history of inadequately treated TB. Active substance abuse or a history of substance abuse within six months prior to Screening.
• •Pregnant or breast feeding. History of allergy to any component of the IP.
• •Major surgery within eight weeks prior to Screening (Visit 1) and/or planned surgery during the length of the study.
• •Malignancy or history of malignancy, except for:
• •treated (ie, cured) basal cell or squamous cell in situ skin carcinomas; treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within 5 years prior to Screening (Visit 1).
• •Unstable asthma (eg, acute episodes of exacerbation \[nocturnal episodes, sudden episodes triggered by unidentifiable factors\] despite a stable regimen of anti-asthmatic medications); prior episode(s) of life-threatening asthma; or asthma that requires inhaled budesonide or equivalent at \>1200 μg/day or fluticasone propionate at \> 880 μg/day along with another anti-asthmatic drug such as a long-acting beta-agonist.
• •A history of and/or concurrent condition of serious hypersensitivity (eg, anaphylaxis) to drugs, foods, or other allergens without access to emergency rescue medication such as epinephrine.
• •Persistent or recurring bacterial infection requiring systemic antibiotics, or clinically significant viral or fungal infections, within two weeks of Screening (Visit 1). Any treatment for such infections must have been completed at least two weeks prior to the Screening Visit and no new/recurrent infections should have occurred prior to the Baseline Visit.
• •Active skin infection requiring systemic antimicrobials at Baseline/Randomization (Visit 2).
• •Skin lesion(s) due to conditions other than AA that would interfere with the study specified assessments.
• •Prior treatment with apremilast, or participation in a clinical study involving apremilast.
• •Use of phototherapy (ie, UVB, UVA) or systemic immunosuppressive drugs (including, but not limited to, cyclosporine, corticosteroids, mycophenolate mofetil, azathioprine, Methotrexate, or tacrolimus), or oral preparations of herbal immunomodulatory medications within four weeks prior to Baseline/Randomization (Visit 2).
• •Use of interferon-γ within 12 weeks prior to Baseline/Randomization (Visit 2). Use of abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, or tocilizumab within 12 weeks prior to Baseline/Randomization (Visit 2).
• •Use of oral janus kinase (JAK) inhibitors (e.g. tofacitinib, ruxolitinib) within 12 weeks prior to Baseline/Randomization (Visit 2).
• •Use of omalizumab, rituximab, ustekinumab, alefacept, briakinumab, or other therapeutic antibody products within 24 weeks prior to Baseline/Randomization (Visit 2).
• •Use of any investigational drug within four weeks or five PK or PD half lives (whichever is longer) prior to Baseline/Randomization (Visit 2).
• •Use of topical corticosteroid preparations, topical calcineurin inhibitors, or other topical preparations with immunomodulatory properties within 2 weeks prior to Baseline/Randomization (Visit 2).
• •Prior history of suicide attempt at any time in the subject's lifetime prior to Baseline (Visit 2) or major psychiatric illness requiring hospitalization within 3 years prior to Baseline (Visit 2).
• •History of male or female pattern hair loss Ludwig stage III or Hamilton \> stage V.
• •Patients in whom the diagnosis of alopecia areata is in question, or subjects with scarring alopecia.