A Phase IIb Randomized, Placebo-Controlled Study to Evaluate the Clinical Efficacy and Safety of Induction and Maintenance Therapy with BMS-936557 in Subjects with Active Ulcerative Colitis (UC)

Induction of clinical response and remission over a 6 to 8 week period,
followed by long-term maintenance of response is a well-accepted treatment
paradigm in Inflammatory Bowel Disease (IBD). Upon successful induction
therapy, with decreased burden of acute inflammation, less intensive therapy
can usually be used in the maintenance setting. Consistent with the IBD
treatment paradigm, the current study is designed with an induction and a
maintenance period. While dose selection in the induction period is based on an
exposure response model constructed from the data of the Phase IIa study, there
is insufficient information available to determine the dose required to obtain
maintenance of response. As such, the maintenance period is an exploratory
study designed to gain information on the exposure-response relationship in the
maintenance setting. The open label period is available as an option to ensure
that subjects who enrolled into the clinical study are guaranteed to receive
the potential clinical benefit offered by the study drug and for subjects who
have experienced clinical benefit from the study drug at any point in time,
that they can continue to receive the study drug upon disease relapse or at the
end of the maintenance period.

Primary objective:
Compare the efficacy of BMS-936557 versus placebo for induction of clinical
remission (defined as Mayo score * 2 points with no individual subscore > 1
point) at Week 7 (IP-50).

Secondary objective
* Compare the efficacy of BMS-936557 versus placebo for induction of clinical
response (defined as reduction from baseline in Mayo score * 3 points and *
30%, and decrease from baseline in rectal bleeding subscore * 1 point or
absolute rectal bleeding subscore * 1 point) at Week 7 (IP-50)
* Compare the efficacy of BMS-936557 versus placebo for induction of mucosal
healing (defined as endoscopy subscore of * 1 point) at Week 7 (IP-50)
* Assess health-related quality of life outcome (IBDQ) of BMS-936557 and
placebo in the induction period
* Assess the safety of BMS-936557 in the induction period.

This study includes three periods (Screening, Induction, and Maintenance) and
an Open Label Extension period (OL). Following the brief Screening Period,
eligible subjects will enter a 7-week placebo-controlled Induction Period with
staged cohort design. The placebo controlled Induction Period (IP) will serve
as a dose-finding study and is adequately powered to demonstrate with
statistical rigor the efficacy of BMS-936557 for the induction of clinical
response, remission, and mucosal healing in subjects with moderate to severely
active UC.
Subjects from all 3 cohorts who are responders at Day IP-50 (Week 7) during the
Induction Period will enter the randomized, double-blind, and
placebo-controlled Maintenance Period (MP). The MP will serve as an exploratory
dose-finding study and is not statistically powered.
Subjects who complete the IP or MP, or who experience Disease Relapse during
the first year of MP, or who are not in remission or have unsatisfactory
clinical response after the first year of MP, have the option to enter the OL.

BMS-936557 will be administered intravenously. During the Induction Period on
Days IP-1, IP-8, IP-22 and IP-36, subjects will receive placebo or BMS-936557
at a dose of 15 mg/kg or 25 mg/kg. After randomization in the Maintenance
Period, subjects will receive placebo or BMS-936557 at a dose of 5 mg/kg, 10
mg/kg or 20 mg/kg on Days MP-1, MP-8 and every 14 days thereafter up to MP-757.
In the Open-label Period, subjects will receive 15 mg/kg BMS-936557 until
marketed in local country or study is discontinued.

There is a possibility that BMS-936557 may be an effective treatment for
colitis ulcerosa. However, it is not known if individual patients entering this
trial will benefit directly. The information gained from this study may help
future patients with colitis ulcerosa. Patients will have the inconvenience of
more frequent interventions/procedures and longer visits to the hospital than
would be usual for routine clinical care. They will also have to undergo
additional procedures. Potential side effects are known from research studies
in a small number of subjects. Additional unforeseen side effects could occur
and some side effects could be life threatening or fatal. Safety monitoring is
included throughout the protocol. At all times throughout the study, the
patient has the right to withdraw consent without their usual standard of care
being affected.