Proof-of-concept study of BI 655130 add-on treatment in patients with mild-to-moderately active ulcerative colitis during TNF inhibitor therapy

see section 1.1

Current biologic treatment of UC is associated with approximately one third of
patients each
failing with primary or secondary non-response. In addition, treatment may be
limited due to
safety and tolerability issues. Therefore, despite of therapeutic progress,
there remains a
significant unmet medical need for new treatment options with an improved
safety and
efficacy profile compared to the current therapeutic standard.

BI 655130 is a humanized antagonistic monoclonal IgG1 antibody blocking IL-36*,
IL-36*
and IL-36* binding to IL-36R. The IL-36 pathway has been associated with the
pathogenesis
of several inflammatory diseases including inflammatory bowel diseases,
pustular psoriasis
and psoriasis vulgaris. Emerging preclinical data suggest that IL-36R is a
potential target for
the treatment of inflammatory bowel diseases, such as ulcerative colitis.

see section 21 & 2.2

This trial aims to prove the concept of induction of mucosal healing by BI
655130 add-on
therapy in patients with mild or moderate ulcerative colitis and persisting
endoscopic activity
despite pre-existing TNFi treatment.
This trial will explore safety and efficacy of a dose of BI 655130 that was
modelled to
achieve the similar exposures as the highest exposures tested and found safe
and tolerable in
preceding single and multiple dose studies in healthy subjects, as add-on to
pre-existing TNFi
treatment. Secondary and further objectives include assessment of the
pharmacokinetic (PK)
profile of BI 655130 and early exploration of specific biomarkers with
potential usefulness to
predict clinical efficacy or safety outcome or help understand BI 655130`s mode
of action.

see section 3.1 & 3.2

This is a multi-centre, multi-national, randomised, parallel-group,
multiple-doses, placebocontrolled,
double-blind Phase IIa study. Approximately 30 eligible patients with mild to
moderate UC and persisting endoscopic activity will be randomised at 2:1 ratio,
stratified
based on concurrent infliximab use, into treatment arm (approximately 20
patients) versus
placebo (approximately 10 patients).

Overall treatment duration is 12 weeks with additional 24 weeks follow-up.
However, the
timing of start of treatment (V2) during mid cycle of the TNFi dosing cycle,
and primary
endpoint assessment at Week 8 are driven by the notation of spontaneous disease
activity
fluctuations in patients in TNFi. This will reduce the confounding effect of
such fluctuations.
A secondary endpoint assessment after 12 weeks will help to understand the
response kinetics
over a longer induction period.

See section 4.1- 4.4

treatment with BI655130 or placebo.

See section 2.3