Chronic colon inflammation Ulcerative colitis
Conditions
Interventions
Subjects will receive one of two dose regimens of apremilast in the
Double-blind Placebocontrolled Phase (30 mg BID or 40 mg BID), or placebo BID.
Apremilast will be provided in blister cards as 10-
Apremilast
Ulcerative Colitis
Sponsors
Celgene Corporation
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Male or female aged 18 and over at the time of signing the informed consent. 2. Must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted. 3. Must be able to adhere to the study visit schedule and other protocol requirements. 4. Diagnosis of UC with duration of at least 3 months prior to the Screening Visit 5. TMS * 6 to * 11 (range: 0-12) prior to randomization in the study. 6. Endoscopic subscore * 2 (range: 0-3) on the Mayo score prior to randomization in the study. 7. Subjects are required to have a colonoscopy if not performed within 12 months of the Screening Visit 8. Subjects must have had a therapeutic failure, been intolerant to, or have a contraindication to, at least one of the following: oral aminosalicylates (ie, 5-aminosalicylic acid [5-ASA] compounds or sulfasalazine [SSZ]), budesonide, systemic corticosteroids, or immunosuppressants (eg, 6-mercaptopurine [6-MP], azathioprine [AZA], or methotrexate [MTX]). 9. Subjects receiving oral corticosteroids may continue their use during the study, provided that the dose (prednisone * 20 mg/day or equivalent, budesonide * 9 mg/day) has been stable for 3 weeks prior to the Screening Visit. If oral corticosteroids were recently discontinued, discontinuation must have been completed at least 3 weeks prior to the Screening Visit. Corticosteroid doses should remain stable until the subject is eligible to start corticosteroids tapering, beginning at the Week 12 Visit. 10. Oral aminosalicylates are permitted during the study, provided that treatment started at least 6 weeks prior to randomization with a stable dose of at least 14 days prior to the Screening Visit. The dose of oral aminosalicylates must remain stable through Week 52 or until Week 104 for subjects who participate in the Extension Phase. 11. Must meet the following laboratory criteria: - White blood cell count * 3000/mm3 (* 3.0 X 10E9/L) and 2 times the ULN, one repeat test is allowed during the screening period - Total bilirubin * 2 mg/dL (* 34 *mol/L) or albumin > lower limit of normal (LLN). If initial test result is > 2 g/dL, one repeat test is allowed during the screening period - Hemoglobin * 9 g/dL (* 5.6 mmol/L) 12. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and the Baseline Visit. While on IP and for at least 28 days after taking the last dose of IP, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options2 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 nonlatex 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 sp
Exclusion criteria
Exclusion criteria: 1. Diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis. 2. Ulcerative colitis restricted to the distal 15 cm or less (eg, ulcerative proctitis). 3. Subjects who have had surgery as a treatment for UC or who, in the opinion of the Investigator, are likely to require surgery for UC during the study. 4. Clinical signs suggestive of fulminant colitis or toxic megacolon. 5. Evidence of pathogenic enteric infection. 6. History of colorectal cancer or colorectal dysplasia (with the exception of adenomatous colonic polyps that have been completely resected). 7. Prior use of any TNF inhibitor (or any biologic agent). 8. Prior use of mycophenolic acid, tacrolimus, sirolimus, cyclosporine or thalidomide. 9. Use of IV corticosteroids within 2 weeks of the Screening Visit 10. Use of immunosuppressants (AZA, 6-MP or MTX) within 8 weeks of the Screening Visit. 11. Use of topical treatment with 5-ASA or corticosteroid enemas or suppositories within 2 weeks of the Screening Visit 12. History of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease, or any other medical condition that, in the investigator's opinion, would preclude participation in the study. 13. Prior history of suicide attempt at any time in the subject's lifetime prior to randomization in the study or major psychiatric illness requiring hospitalization within 3 years of study randomization. 14. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she was to participate in the study or confounds the ability to interpret data from the study. 15. Pregnant or breast feeding. 16. History of any of the following cardiac conditions within 6 months of screening: myocardial infarction, acute coronary syndrome, unstable angina, new onset atrial fibrillation, new onset atrial flutter, second- or third-degree atrioventricular block, ventricular fibrillation, ventricular tachycardia, heart failure, cardiac surgery, interventional cardiac catheterization (with or without a stent placement), interventional electrophysiology procedure, or presence of implanted defibrillator. 17. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease and herpes zoster), human immunodeficiency virus (HIV), or any major episode of infection requiring hospitalization or treatment with intravenous (IV) or oral antibiotics within 4 weeks of screening. 18. Subjects with active hepatitis B infection as described in Appendix E are ineligible for the study. Subjects without current hepatitis B infection, as described in Appendix F, may participate in the study. 19. Subjects who are confirmed positive for hepatitis C antibody not eligible for the study. 20. History of congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease). 21. History of malignancy, except for: a. Treated (ie, cured) basal cell or squamous cell in situ skin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Details of the statistical analysis are outlined in Section 10 of the Protocol. Key elements of the analysis are described below. The ITT population will be the primary population for efficacy analyses. A supportive analysis using the PP population will also be performed for the primary efficacy endpoint. The comparisons for the primary efficacy endpoint will be based on two-sided statistical tests at a significance level of 0.1. A hierarchical approach will be used to adjust for multiplicity. For the primary endpoint, the first test in the hierarchy will be the apremilast 40 mg BID treatment group compared to placebo, followed by the apremilast 30 mg BID treatment group compared to placebo. If any of the active treatment groups (apremilast 30 mg or 40 mg BID) is discontinued prior to the end of the study, the treatment comparison will be conducted for the retained treatment group vs. placebo based on a two-sided statistical test at the 0.1 level. Additional endpoints subsequent to the primary endpoint comparisons may be added to the hierarchy and specified in the SAP. Summary of all efficacy endpoints over time will be provided using frequency and percent for categorical endpoints and descriptive statistics for continuous endpoints. The primary efficacy endpoint is clinical remission, as defined as a TMS of * 2 with no individual subscore > 1 at Week 12. The proportion of subjects who achieve a clinical remission at Week 12 between any apremilast (30 mg BID or 40 mg BID) group and the placebo group will be compared using the Cochran-Mantel-Haenszel (CMH) test controlling for the randomization stratification factors specified. Subjects who prematurely discontinue the study before Week 12 will be considered. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary efficacy endpoints defined in Section 3.2.1 will be analyzed using the CMH test controlling for the randomization stratification factors as will be done for the primary efficacy endpoint. | — |
Countries
The Netherlands
Outcome results
None listed