abrilumab (amg 181) in adults with moderate to severe ulcerative colitis

Conditions: Ulcerative Colitis

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.

the study consisted of a 24-week double-blind, placebo-controlled treatment period followed by an open-label period of approximately 108 weeks. participants were eligible to enter the open-label period of the study early if they did not achieve a response at week 8 and had an inadequate response at week 12 or later or if they experienced disease worsening after achieving response and/or remission at week 8. failure to achieve response at week 8 was defined as failure to achieve a decrease from baseline in total mayo score ≥ 3 points and ≥ 30% decrease from baseline. inadequate response at week 12 or later was defined as failure to achieve a 2-point decrease and 25% improvement in partial mayo score compared with screening and minimum partial mayo score ≥ 5 points. disease worsening was defined as an increase in partial mayo score ≥ 3 points from the week 8 value and minimum partial mayo score ≥ 5 points with recto-sigmoidoscopy sub-score ≥ 2. participants were planned to be randomized in a 2:1:2:2:2 ratio to placebo or abrilumab at 7 mg, 21 mg, 70 mg (on day 1, week 2, week 4, and every 4 weeks thereafter until week 24), or 210 mg (on day 1 followed by placebo in weeks 2 and 4 and every 4 weeks thereafter until week 24), respectively. due to a consistent discrepancy between the investigational product (ip) instruction manual (ipim) description of vial positions and the actual vial positions in the ip package participants were initially randomized to 3 arms (placebo, 70 mg, and 210 mg) with a randomization ratio of 4:3:2. the study was temporarily paused while this issue was investigated. once the discrepancy was corrected, protocol amendment 3 implemented, and affected participants completed their double-blind treatment period, the study resumed enrollment and randomization per protocol. neither the randomization nor study blind was compromised and therefore the intent-to-treat principle was maintained.

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)

Keywords: ulcerative colitis, ibd