Clinical trial that will compare the efficacy and safety of apremilast versus placebo, in patients with active ulcerative colitis, a chronic inflammatory of the colon of unknown origi

Phase 1

• Conditions: Subjects with active ulcerative colitis; MedDRA version: 20.0Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2014-002981-64-DE
• Lead Sponsor: Celgene Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-08
• Last Update Posted: 5 June 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 165

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 form 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 reatment 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 < 14,000/mm3 (< 14 X 10E9/L)
- Platelet count = 100,000/mm3 (= 100 X 10E9/L)
- Serum creatinine = 1.5 mg/dL (= 132.6 µmol/L)
- AST (SGOT) and ALT (SGPT) =2 X upper limit of normal (ULN). If initial test shows ALT or AST > 2 times the ULN, one repeat test is allowed during the screening period
- Total bilirubin = 2 mg/dL (= 34 µmol/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 spermicide
13. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or nonlatex condom NOT made o

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 are 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 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
22. Any condition that could affect oral drug absorption, including

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): The primary endpoint of this study is the proportion of subjects achieving a clinical remission in the TMS at Week 12, defined as a TMS of = 2, with no individual subscore > 1.;Timepoint(s) of evaluation of this end point: Week 12;Main Objective: The primary objective of the study is to evaluate the clinical efficacy of apremilast (30 mg BID and 40 mg BID), compared with placebo, in subjects with active ulcerative colitis (UC).;Secondary Objective: The secondary objectives of the study are:<br>- To evaluate the safety and tolerability of apremilast (30 mg BID and 40 mg BID), compared with placebo, in subjects with active UC.<br>- To evaluate the long-term safety in subjects with active UC, receiving apremilast (30 mg BID or 40 mg BID)