A Phase 3 Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Active Behçet's Disease
Condition: Behçet's Syndrome
MeSH terms: Behcet Syndrome
Intervention: Apremilast; Placebo
Intervention description: Tablets for oral administration; Tablets for oral administration
Intervention MeSH terms: Apremilast
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 207.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: APREMILAST (CC-10004); CC-10004; Efficacy; Safety; Phase 3; Behçet's Disease

Summary:

      The main objective of this study is to evaluate the efficacy and safety of apremilast in the
      treatment of oral ulcers in adults with active Behçet's disease (BD).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Understand and voluntarily sign an informed consent document prior to any study
             related assessments/procedures being conducted.

          2. Male and female subjects ≥ 18 years of age at the time of signing the informed consent
             document.

          3. Able to adhere to the study visit schedule and other protocol requirements.

          4. Diagnosed with Behcet's disease meeting th4 International Study Group (ISG) criteria,

          5. Oral ulcers that occurred at least 3 times in the previous 12-month period, including
             oral ulcers at the screening visit.

          6. Subjects must have at least 2 oral ulcers at Visit 1 (Screening Visit), and:

               1. At least 2 oral ulcers at Visit 2 (day of randomization), when Visit 2 occurs at
                  least 14 days after Visit 1. OR

               2. At least 3 oral ulcers at Visit 2 (day of randomization), when Visit 2 occurs at
                  any time between 1 day and 42 days after Visit 1.

          7. Have prior treatment with at least 1 non-biologic Behçet's disease therapy, such as,
             but not limited to, topical corticosteroids, or systemic treatment.

          8. Candidate for systemic therapy, for the treatment of oral ulcers.

             a. A candidate for systemic therapy is a subject judged by the study Investigator as
             someone whose mucocutaneous ulcers are considered inappropriate for topical therapy
             based on the severity of disease and extent of the affected area, or whose oral ulcers
             cannot be adequately controlled by topical therapy.

          9. Laboratory Measures: Must meet the following laboratory measures:

               -  Hemoglobin > 9 g/dL

               -  White blood cell (WBC) count ≥ 3000 /L(≥ 3.0 X 10^9/L) and ≤ 14,000/L (≤ 14 X
                  10^9/L )

               -  Platelet count ≥ 100,000 /L (≥ 100 X 10^9/L)

               -  Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)

               -  Total bilirubin ≤ 2.0 mg/dL

               -  Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and
                  alanine transaminase (ALT [serum glutamate pyruvic transaminase, SGPT]) ≥ 1.5 X
                  ULN. Subjects who fail screening due to ≥ 1.5 X ULN AST/SGOT and/or ALT/SGPT will
                  be allowed to repeat AST/SGOT and/or ALT/SGPT tests within the screening phase.
                  Repeat test results should be ≤ ULN (within reference range) to be eligible.

        Laboratory tests will be allowed to be repeated 1 time if, in the Investigator's clinical
        judgment, there is a reasonable possibility of the repeat tests not meeting the exclusion
        values, and with concurrence from the Medical Monitor.

        Contraception Requirements:

        All Females of Child Bearing Potential (FCBP) must use one of the approved contraceptive
        options as described below while taking apremilast and for at least 28 days after
        administration of the last dose of the apremilast.

        At the time of study entry, and at any time during the study when a FCBP's contraceptive
        measures or ability to become pregnant changes, the Investigator will educate the subject
        regarding contraception options and the correct and consistent use of effective
        contraceptive methods in order to successfully prevent pregnancy.

        All FCBP must have a negative pregnancy test at Visits 1 and 2. All FCBP subjects who
        engage in activity in which conception is possible must use one of the approved
        contraceptive options described below:

        Option 1: Any one of the following highly effective methods: hormonal contraception (oral,
        injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal
        ligation; or partner's vasectomy; OR Option 2: Male or female condom (latex condom or
        non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]);
        PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with
        spermicide; or (c) contraceptive sponge with spermicide.

        Male subjects (including those who have had a vasectomy) who engage in activity in which
        conception is possible must use barrier contraception (latex or non-latex condoms NOT made
        out of natural [animal] membrane [for example, polyurethane]) while on IP and for at least
        28 days after the last dose of IP.

        Exclusion Criteria: The presence of any of the following will exclude a subject from the
        study enrollment.

        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).