Study to test whether apremilast is better than placebo (inactive substance in the same form as the drug) for the treatment of active Behçet’s disease (oral ulcers). This study also tests how well the body tolerates apremilast. The study is conducted in several centers in different countries.
- Conditions
- SUBJECTS WITH ACTIVE BEHÇET’S DISEASEMedDRA version: 18.0Level: LLTClassification code 10004212Term: Behcet's diseaseSystem Organ Class: 100000004866Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2014-002108-25-IT
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 204
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 Behçet’s disease meeting the International Study Group (ISG) criteria.
5. Oral ulcers that occurred at least 3 times in the previous 12-month period prior randomization
6. Oral ulcers at Visit 2:
a. Have at least 3 oral ulcers at baseline (this may be considered as 1 occurrence of the required 3 occurrences in the previous 12 month period in Inclusion #5)
OR
b. Have at least 2 oral ulcers during screening and at least 2 oral ulcers at baseline. The Screening Visit should be within 2 weeks of the Baseline Visit (this may be considered as 1 occurrence of the required 3 occurrences in the previous 12 month period in Inclusion Criteria #5).
7. Have prior treatment with at least 1 non-biologic BD 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 /microL (= 3.0 X 109/L) and =14,000/microL (=14 X 109/L)
• Platelet count = 100,000 /microL (= 100 X 109/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 period. 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.
10. Contraception Requirements:
All 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
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:
• Previous major organ involvement is allowed if it occurred at least 1 year prior to screening and is not active at time of enrollment.
• Subjects with mild BD-related ocular lesions not requiring systemic immunosuppressive therapy are allowed.
• Subjects with BD-related arthritis and BD-skin manifestations are also allowed.
Previous and Current Medications:
2. Prior use of a biological therapy.
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 or topical corticosteroids
within:
? Ten days prior to Visit 2 (Baseline Visit; day of randomization) for azathioprine
and mycophenolate mofetil
? Two weeks (14 days) prior to Visit 2 (Baseline Visit; day of randomization) for
topical corticosteroids
? Four weeks (28 days) prior to Visit 2 (Baseline Visit; day of randomization) for
oral corticosteroids, colchicine, cyclosporine, methotrexate, cyclophosphamide,
thalidomide, and dapsone
7. Having received intra-articular or parenteral corticosteroids within 6 weeks (42 days)
prior to Visit 2 (Baseline Visit; day of randomization).
General Health:
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 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:
a. treated (ie, cured) basal cell or squamous cell in situ skin carcinomas;
b. 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 majo
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of apremilast in the treatment of oral ulcers in active Behçet’s disease;Secondary Objective: - To evaluate the efficacy of apremilast in subjects with Behçet’s disease<br>- To evaluate the effect of apremilast on Patient Reported Outcomes (PROs) in subjects with Behçet’s disease<br>;Primary end point(s): Area under the curve (AUC) for the number of oral ulcers from baseline through Week 12;Timepoint(s) of evaluation of this end point: 12 weeks after the start of the double-blind, placebo-controlled phase
- Secondary Outcome Measures
Name Time Method