A Randomized, Double Blind, Multiple Dose Placebo Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 181 in Subjects With Moderate to Severe Ulcerative Colitis

Fecha de inicio: 16 de noviembre de 2012

Inclusion Criteria: Diagnosis of ulcerative colitis (UC) established ≥ 3 months before baseline by clinical and endoscopic evidence and corroborated by a histopathology report. Moderate to severe active UC as defined by a total Mayo score of 6 to 12 with a centrally read rectosigmoidoscopy score ≥2 prior to baseline Inadequate response to, loss of response to, or intolerance to at least one of the following treatments: Immunomodulators Anti-TNF agents Corticosteroids (non-US sites only). Neurological exam free of clinically significant, unexplained signs or symptoms during screening and no clinically significant change prior to randomization Exclusion Criteria: Disease limited to the rectum (ie, within 10 cm of the anal verge) Toxic megacolon Crohn's Disease History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for UC Planned bowel surgery within 24 weeks from baseline Stool positive for C. Difficile toxin at screening History of gastrointestinal surgery within 8 weeks of baseline Primary Sclerosing Cholangitis Any uncontrolled or clinically significant systemic disease Condition or disease that, in the opinion of the investigator would pose a risk to subject safety or interfere with study evaluation, procedures or completion. Known to have tested positive for hepatitis B virus surface antigen, hepatitis C virus antibody or human immunodeficiency virus (HIV) Underlying condition that predisposes subject to infections (eg, uncontrolled diabetes; history of splenectomy) Known history of drug or alcohol abuse within 1 year of screening Malignancy (other than resected cutaneous basal or cutaneous squamous cell carcinoma, or treated in situ cervical cancer considered cured) within 5 years of screening visit (if a malignancy occurred > 5 years ago, subject is eligible with documentation of disease free state since treatment) Immunosuppressive therapy with either cyclosporine A, tacrolimus, or mycophenolate mofetil, within 1 month prior to baseline Prior exposure to anti tumor necrosis factor (TNF) agents, within 2 months, or 5 times the respective elimination half life (whichever is longer) prior to baseline Any prior exposure to vedolizumab, rituximab, efalizumab, natalizumab Use of topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids within 2 weeks prior to baseline Use of intravenous or intramuscular corticosteroids within 2 weeks prior to screening and during screening Previously treated with AMG 181 Received any type of live attenuated vaccine < 1 month prior to baseline or is planning to receive any such live attenuated vaccine over the course of the study Treatment of infection with intravenous (within 30 days of baseline) or oral (within 14 days prior to baseline) antibiotics, antivirals, or antifungals Abnormal laboratory results at screening Any other laboratory abnormality, which, in the opinion of the investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)