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
Trial status: Open for Enrollment
Why is this study being done?
Title: 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 Study Phase: 2 Indication: Ulcerative colitis (UC) Primary Endpoint: Remission at week 8 defined by a total Mayo Score , 2 points, with no individual subscore > 1 point Key Secondary Endpoints: • Response at week 8 as defined by a decrease from baseline in the total Mayo Score of >3 points and >30%, with an accompanying decrease in the subscore for rectal bleeding of >1 point or an absolute subscore for rectal bleeding of 0 or 1 • Mucosal healing at week 8 as defined by an absolute subscore for rectosigmoidoscopy of 0 or 1 Safety Endpoints: • Adverse events • Serious adverse events • Significant changes in laboratory values and vital signs • Sample Size: 360 Summary of Subject Eligibility Criteria: Subjects must have a diagnosis of UC > 3 months, with moderate to severe disease activity at time of enrolment based on a total Mayo Score of 6 to 12 and a minimum rectosigmoidoscopy subscore of >2. Subjects must have demonstrated an inadequate response to, loss of response to, or intolerance to immunomodulators or anti-TNF agents, or to corticosteroids (non-US sites only).. Subjects may continue on stable doses of protocol specified medications to treat UC. A maximum of approximately 50% of subjects with any prior anti-TNF agent use will be allowed in the study. Subjects must have a neurological exam free of clinically significant, unexplained signs and symptoms at screening and no clinically significant change prior to randomization. In addition, subjects must be free of concurrent medical conditions at study entry as described in the protocol. If applicable, female subjects must be willing to use two highly effective methods of birth control or one highly effective and one effective method of birth control during the study. Amgen Investigational Product Dosage and Administration: Investigational Product will be administered subcutaneously. During the 24 week double blind placebo controlled period, subjects will be randomized to receive either placebo or a selected dose of AMG 181 per protocol using repeated injections until week 24. During the open label period, all subjects will receive AMG 181 per protocol using repeated injections. Control Group: The double blind period (the first 24 weeks) will be controlled. During this period, the control group will receive placebo..
Who is eligible to participate?
Inclusion Criteria: Diagnosis of 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, Demonstrated an inadequate response to, loss of response to, or intolerance to at least one of the following treatments : Immunomodulators , or Anti-TNF agents , or to 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, No known history of active tuberculosis and negative test for tuberculosis during screening, Other inclusion criteria as per protocol.
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 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 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) Other investigational procedures are excluded, Pregnant or breast feeding, Other exclusion criteria as per protocol.