AMG 181 Phase 2 Study in Subjects With Moderate to Severe Ulcerative Colitis

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..

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.