A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Behçet Disease

• Pain of oral/genital ulcers [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: No ]
• # of ulcer free subjects & those with ≥ 50% reduction [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: No ]
• BD Current Activity Form score [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: No ]
• Safety (ECG, AE, Labs) [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: Yes ]
• New BD manifestations [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: No ]
• PRO questionnaires [ Time Frame: Day 85 and Day 169 ] [ Designated as safety issue: No ]

The purpose of this study is to assess whether Apremilast is safe and effective in the treatment of patients with Behcet Disease.

• Drug: Apremilast (CC-10004)

  Treatment Phase Days 1-7: Titration from 10 mg BID apremilast tablets arm A (or matching placebo arm B) to 30 mg BID apremilast arm A(or matching placebo arm B) Day 8-84: Maintenance of 30 mg BID apremilast arm A (or matching placebo arm B) Dose reductions to 20 mg BID apremilast arm A (or matching placebo arm B) are permitted.

  Extension Phase All subjects will be given active drug Days 85-91: All placebo subjects from Treatment phase will be dose titrated from 10 mg BID apremilast tablets arm A to 30 mg BID Apremilast.

  Day 92-169: Maintenance of 30 mg BID apremilast arm A or dose reductions to 20 mg BID apremilast arm A (if not previously down titrated)

• Drug: Placebo

  Treatment Phase Days 1-7: Titration from 10mg BID matching placebo (arm B) to 30mg BID placebo (arm B) Day 8-84: Maintenance of 30mg BID placebo (arm B). Dose reductions to 20 mg BID matching placebo (arm B) are permitted.

  Extension Phase All subjects will be given active drug Days 85-91: All placebo subjects from Treatment phase will be dose titrated from 10 mg BID apremilast tablets arm A to 30 mg BID Apremilast.

  Day 92-169: Maintenance of 30 mg BID apremilast or dose reductions to 20 mg BID apremilast (if not previously down titrated)

• Active Comparator: A. Apremilast
  Intervention: Drug: Apremilast (CC-10004)
• Placebo Comparator: B. Placebo Comparator
  Intervention: Drug: Placebo

Inclusion Criteria:

• Diagnosis of Behçet Disease. At the time of diagnosis, subjects must meet the international study group criteria for Behçet Disease
• Females of childbearing potential (FCBP) must have negative pregnancy tests and agree to use two forms of contraception throughout the study.
• Males must use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP
• Laboratory criteria: Hgb ≥ 9 g/dL, WBC count ≥ 3000 /microL and ≤14,000/microL, platelet count ≥ 100,000 /microL,, serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L), total bilirubin ≤ 2.0 mg/dL, AST and ALT ≤ 1.5 X ULN
• Two or more oral ulcers over the 28 day period before screening, with or without current treatment
• Two or more oral ulcers at the time of randomization (Visit 2, Baseline)

Exclusion Criteria:

• Pregnant or breast feeding
• Any condition which places the subject at risk
• Systemic fungal infection
• History of TB infection within 3 years
• History of recurrent bacterial infection
• Mycobacterium TB as indicated by a positive PPD skin test
• History of incompletely treated Mycobacterium tuberculosis
• Clinically significant chest x-ray abnormality at screening.
• Clinically significant ECG abnormality at screening
• History of HIV infection
• History of congenital or acquired immunodeficiency
• Hepatitis B surface antigen positive or Hepatitis B core antibody positive at screening
• Antibodies to Hepatitis C at screening
• History of malignancy (except for treated basal-cell skin carcinomas > 3 years prior to screening)
• Any active major organ involvement of Behçet Disease
• Use of concomitant immune modulating therapy or topical corticosteroids.
• Use of ocular corticosteroids
• Use of any investigational medication within 4 weeks prior to randomization or 5 PK/PD half-lives (whichever is longer)