A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 181 in Subjects With Moderate to Severe Crohn s Disease
Trial status: Open for Enrollment
Why is this study being done?
Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 181 in Subjects with Moderate to Severe Crohn's Disease Study Phase: 2 Indication: Crohn's Disease (CD) Primary Endpoint: Remission at week 8, as defined by a CDAI score of < 150 Key Secondary Endpoints: Response at week 8 or week 12, as defined by either remission or a CDAI reduction from baseline of > 100 • Remission at week 12, as defined by a CDAI score of < 150 Other Secondary Endpoints: • Sustained remission, defined as achieving the criteria for remission at week 8 or 12 and week 24 • Change from baseline in CDAI score at week 8 or week 12 Safety Endpoints: • Adverse events • Serious adverse events • Significant changes in laboratory values and vital signs • Anti-AMG 181 antibodies Sample Size: 252 Summary of Subject Eligibility Criteria: Subjects must have a diagnosis of ileal, ileo-colonic, or colonic Crohn's disease for a minimum of 6 months prior to baseline, with moderate to severe disease activity at baseline defined as a CDAI score ≥ 220 and ≤ 450. Subjects must have demonstrated an inadequate response to, loss of response to, or intolerance to immunomodulators and/or anti-TNF agents or to corticosteroids (non-US sites only). Subjects may continue on stable doses of protocol specified medications to treat CD. 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 significant concurrent medical conditions at study entry. If applicable, female subjects must be willing to use two highly effective methods of birth control or one highly effective method and one effective method of birth control during the study. Amgen Investigational Product Dosage and Administration: Investigational Product will be administered subcutaneously (SC). During the 24-week double-blind placebo-controlled period, subjects will be randomized to receive either placebo or a selected dose of AMG181 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 (first 24 weeks) will be controlled. During this period, the control group will receive placebo
Who is eligible to participate?
Diagnosed with ileal, ileo-colonic, or colonic Crohn's disease for a minimum of 6 months prior to initiating Study Product Moderately to severely active Crohn's disease, as defined by a CDAI score > 220 and <450 at baseline Evidence of active inflammation within 12 weeks prior to baseline Demonstrated an inadequate response to, loss of response to, or intolerance to at least one of the following agents: Immunomodulators and/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 Subject has no known history of active tuberculosis and has a negative test for tuberculosis during screening
Short bowel syndrome Stricture with obstructive symptoms within 3 months Bowel surgery within 12 weeks prior baseline, or has planned bowel surgery within 24 weeks from baseline Ileostomy and/or colostomy Any gastric or intestinal pouch Evidence of an infected abscess Bowel perforation or evidence of noninflammatory obstruction during the 6 months Stool positive for C. difficile toxin at screening Any uncontrolled or clinically significant systemic disease Known to have tested positive for hepatitis B virus surface antigen, hepatitis C virus antibody, or HIV Any underlying condition that predisposes subject to infections Subject has malignancy (other than resected cutaneous basal or cutaneous squamous cell carcinoma, or treated in situ cervical cancer considered cured) within 5 years of baseline Received an anti-TNF agent, cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, tacrolimus, topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids, intravenous or intramuscular corticosteroids within protocol-specified time periods.
Any prior exposure to antagonists of integrins or integrin ligands (eg, natalizumab, efalizumab, or vedolizumab), rituximab, or TNF kinoid immunotherapies, AMG 181, or any form of cell-based transplantation Received treatment of infection with intravenous (within 30 days of baseline) or oral (within 14 days prior to baseline) antibiotics, antivirals, or antifungals Significant Laboratory abnormalities Pregnant or breast feeding