A Phase 3 Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Active Behçet's Disease

Exclusion Criteria

• •Disease Specific Exclusions:
• •1. Behçet's disease-related active major organ involvement - pulmonary (eg, pulmonary artery aneurysm), vascular (eg, thrombophlebitis), gastrointestinal (eg, ulcers along the gastrointestinal tract), and central nervous systems (eg, meningoencephalitis) manifestations, and ocular lesions (eg, uveitis) requiring immunosuppressive therapy; however:
• •1. Previous major organ involvement is allowed if it occurred at least 1 year prior to Visit 1 (Screening Visit) and is not active at time of enrollment.
• •2. Subjects with mild BD-related ocular lesions not requiring systemic immunosuppressive therapy are allowed.
• •3. Subjects with BD-related arthritis and BD-skin manifestations are also allowed.
• •2. Previous exposure to biologic therapies for the treatment of BD oral ulcers ( Previous biologic therapy exposure is allowed for other indications, including other manifestations of BD)
• •3. Prior use of apremilast.
• •4. Use of any investigational medication within 4 weeks prior to Visit 2 or 5 pharmacokinetic/pharmacodynamic half-lives (whichever is longer).
• •5. Current use of strong cytochrome P450 enzyme inducers (eg, rifampin, phenobarbital, carbamazepine, phenytoin)
• •6. Having received concomitant immune modulating therapy (except oral or topical corticosteroids) within:
• •* Seven days prior to Visit 2 (Baseline Visit; day of randomization) for colchicines
• •* Ten days prior to Visit 2 (Baseline Visit; day of randomization) for azathioprine and mycophenolate mofetil
• •* Four weeks (28 days) prior to Visit 2 (Baseline Visit; day of randomization) for cyclosporine, methotrexate, cyclophosphamide, thalidomide, and dapsone.
• •Note: Oral and topical corticosteroids must have been tapered as appropriate and discontinued prior to the day of Visit 2 (day of randomization).
• •* At least 5 terminal half-lives for all biologics, including, but not limited to, those listed below; within:
• •* Four weeks prior to Visit 2 (Baseline Visit; day of randomization) for etanercept
• •* Eight weeks prior to Visit 2 (Baseline Visit; day of randomization) for infliximab
• •* Ten weeks prior to Visit 2 (Baseline Visit; day of randomization) for adalimumab, golimumab, certolizumab, abatacept, and tocilizumab
• •* Six months prior to Visit 2 (Baseline Visit; day of randomization) for secukinumab
• •7. Having received intra-articular or parenteral corticosteroids within 6 weeks (42 days) prior to Visit 2 (Baseline Visit; day of randomization).
• •8. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• •9. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• •10. Inability to provide voluntary consent.
• •11. Pregnant women or breast feeding mothers.
• •12. Systemic or opportunistic fungal infection.
• •13. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C and herpes zoster, histoplasmosis, coccidiomycosis, but excluding onychomycosis) or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of the Screening Phase.
• •14. Clinically significant abnormality on chest radiograph.
• •15. Clinically significant abnormality on 12-lead electrocardiogram (ECG).
• •16. History of positive test for, or any clinical suspicion of, human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).
• •17. Malignancy or history of malignancy, except for:
• •1. treated (ie, cured) basal cell or squamous cell in situ skin carcinomas;
• •2. treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years of Visit 1.
• •18. Any condition that confounds the ability to interpret data from the study.
• •19. Scheduled surgery or other interventions that would interrupt the subject's participation in the study.
• •20. Prior history of suicide attempt at any time in the subject's lifetime prior to Visit 2 (Baseline Visit; day of randomization) or major psychiatric illness requiring hospitalization within 3 years prior to Visit 2 (Baseline Visit; day of randomization).