Abrilumab (AMG 181) in Adults With Moderate to Severe Ulcerative Colitis
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: Abrilumab; Placebo
Intervention description: Administered by subcutaneous injection.; Placebo matching to abrilumab administered by subcutaneous injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 359.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Ulcerative Colitis, IBD

Summary:

      The primary objective of this study is to evaluate the effect of abrilumab on induction of
      remission in adults with moderate to severe ulcerative colitis after 8 weeks of treatment as
      assessed by a total Mayo Score ≤ 2 points, with no individual subscore > 1 point.
    

Eligibility criteria:

        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)