A Multicenter, Randomized, Double-Blind, Placebo Controlled 52-Week Maintenance and an Open-Label Extension Study of the Efficacy and Safety of Risankizumab in Subjects with Crohn's Disease

The aim of medical treatment in CD has been focused on controlling inflammation
and reducing symptoms. In addition to improving symptoms, an emerging goal of
therapy is to heal the gut mucosa. Resolution of intestinal ulcers, also known
as mucosal healing has been associated with positive clinical benefits,
including higher rates of clinical remission, fewer hospitalizations, and fewer
abdominal surgeries. However, improvement of the appearance of the intestinal
mucosa may be more difficult to achieve than symptomatic improvement alone.

Conventional pharmaceutical therapies (e.g., corticosteroids, aminosalicylates,
thiopurines, methotrexate) are limited, do not always completely abate the
inflammatory process, and have significant adverse effects. The advent of
anti-TNFα agents (e.g., adalimumab) and integrin inhibitors (e.g., vedolizumab)
have been shown to achieve clinical remission in patients refractory to
conventional therapies.

Despite the benefits of available biologic therapies, many patients do not
respond to initial treatment (primary loss of response) or lose treatment over
time (secondary loss of response). Regarding anti-TNF agents, approximately 40%
of patients will experience primary non-response and secondary non-response
occurs in 38% of patients at 6 months and 50% of patients at 1 year.. Therefore
new therapeutic options are required in order to continue to improve the
outcome of patients with CD.

This study has been transitioned to CTIS with ID 2023-506399-28-00 check the CTIS register for the current data.

Sub-study 1: The objective of sub-study 1 is to evaluate the efficacy and
safety of risankizumab versus placebo as maintenance therapy in subjects with
moderately to severely active Crohn's disease (CD) who responded to
risankizumab induction treatment in Study M16-006 or Study M15-991 and had a
Baseline (of induction) eligibility SES-CD of >= 6 (>= 4 for isolated ileal
disease).

Sub-study 2: The objective of sub-study 2 is to evaluate the efficacy and
safety of two different dosing regimens for risankizumab as maintenance therapy
in subjects with moderately to severely active CD who responded to induction
treatment in Study M16-006 or Study M15-991.

Sub-study 3: The objective of sub-study 3 is to evaluate long-term safety of
risankizumab in subjects who completed Sub-study 1 or 2 or M15-989, or subjects
who responded to induction treatment in Study M16-006 or Study M15-991 with no
final endoscopy due to the coronavirus SARS-CoV-2 pandemic. OL CTE to ensure
uninterrupted care in accordance with local regulations until risankizumab is
commercially available for participants who completed Sub-study 3.

This is a phase 3, multicenter, randomized, double-blind, placebo controlled
52-week maintenance and open-label extension study to assess the efficacy and
safety of risankizumab in subjects with moderately to severely active Crohn's
Disease who responded to induction treatment in M16-006 or M15-991 or
completion of M15-989.

Subjects receive once every eight weeks SC risankizumab or SC placebo. They
receive this medication until the end of the study or till premature
discontinuation. In Sub-study 2, the first dose may be IV or SC Risankizumab
or placebo followed by once every 8 weeks of SC Risankizumab.

There will be higher burden for subjects participating in this trial compared
to their standard of care. Subject will be visiting the hospital more
frequently. During these visits study procedures will be performed including
blood sampling and filling in questionnaires. Subjects will also be tested for
TB. Subjects will also complete a daily diary. Women of Childbearing Potential
should practice a method of birth control, during the study through at least
140 days after the last dose of study drug and are tested for pregnancy.

Subjects will either receive risankizumab and/or placebo during the study. The
most common side effects reported during previous studies of risankizumab were
nausea, abdominal pain, joint pain and headache.

The hypothesis that risankizumab should be effective in targeting inflammation
in patients with Crohn's Disease who are unable to tolerate or who have had
insufficient response to treatment with some current available medication,
indicates that there is an acceptable rationale to conduct this study. The
risks and burden associated with participating in this study are acceptable in
regards to the potential benefit study subjects could possibly have.