A Long-Term Extension Study to Evaluate the Safety of Filgotinib in
Subjects with Ulcerative Colitis

Ulcerative colitis (UC) is a chronic, intermittent, relapsing disease
characterized by inflammation
of the colonic mucosa, which is limited to the colon and rectum. The disease
characteristically
commences in the rectum and may extend proximally in an uninterrupted pattern
into the colon.
It can involve the entire colon (pan-colitis), the left colon, or isolated
recto-sigmoid disease with
patients being equally distributed in those 3 phenotypes. In the United States
(US), the
prevalence of UC has been estimated to be 238 per 100,000 adults {Kappelman et
al 2007}.
Europe has the highest reported prevalence values for inflammatory bowel disease
(IBD; 505 per 100,000 persons for UC and 322 for Crohn*s Disease [CD]). The
incidence and prevalence of inflammatory bowel disease (IBD) appear to be
increasing over time globally. The hallmark symptoms of the disease are bloody
diarrhea, rectal urgency, and tenesmus. The clinical coursetends to wax and
wane with periods of remission interspersed with periods of active disease.
Ulcerative colitis may also be associated with extra-intestinal manifestations
including ocular
lesions, skin lesions, arthritis, and primary sclerosing cholangitis. The exact
pathophysiology is
not known, but a combination of genetic predisposition and environmental
factors appear to
contribute to a disordered immune response in these patients {Rutgeerts et al
2005}.
In addition to the abdominal pain and frequent passage of bloody stools that
impact activities of
daily living and quality of life for patients with UC, the disease also carries
with it an increased
risk of colorectal cancer due to the chronic inflammation associated with the
disease {Velayos et
al 2006}. With poorly controlled
disease, the rate of developing colorectal cancer increases with time. Ten
years after diagnosis,
the cumulative probability of developing colorectal cancer is 2% and increases
to 18% after
30 years. Overall, the risk of a UC patient developing colorectal cancer may be
as high as
23-fold compared to the general population {Triantafillidis et al 2009}. Thus,
UC represents a
serious, life-threatening disease for which new therapies are needed to
interrupt the inflammatory
process to prevent disease progression and risk of colorectal cancer.
Treatment of UC is dependent on the severity and the location of disease. Goals
of treatment
include improved quality of life, reduction in long-term corticosteroid use,
and minimization of
cancer risk. Mild to moderate distal colitis may be treated with oral
aminosalicylates, topical
mesalamine, or topical steroids {Kornbluth et al 2010}. For moderate disease,
oral
corticosteroids, and immunomodulators such as azathioprine and 6-mercaptopurine
(6-MP) may
be utilized {Danese et al 2011}. For more moderate to severe disease, patients
are commonly
treated with a tumor necrosis factor-alpha (TNFα) antagonist infusion or
injection such as
infliximab (Remicade®), adalimumab (Humira®), and golimumab (Simponi®).
Vedolizumab
(Entyvio®), an injectable integrin α4β7 monoclonal antibody, is also approved
for moderately to
severely active disease. Ustekinumab (Stelara®, CNTO 1275; an IL-12 and IL-23
monoclonal.
antibody), tofacitinb (CP-690,550; JAK1 and JAK3 inhibitor), etrolizumab
(PRO145223;
monoclonal antibody targeting the β7 subunit of the heterodimeric integrins
α4β7 and αEβ7), and
ozanimod (RPC1063; selective S1P1 and S1P5 receptor agonist) are currently
being tested in
Phase 3 clinical trials. Despite several classes of treatment options for
patients with UC, there remains an unmet
medical need, particularly in the treatment of moderately to severely active
disease. Agents with
novel mechanisms of action that target the inflammatory cascade, with oral
dosing and
acceptable immunomodulatory and hematologic effects, remain the most promising
option to
address these unmet needs.

The primary objective of this study is:
* To observe the long-term safety of filgotinib in subjects who have completed
or met protocol specified efficacy discontinuation criteria in a prior
Gilead-Sponsored filgotinib treatment study in UC

The secondary objective of this study is:
* To evaluate the effect of filgotinib on partial Mayo Clinic Score (MCS)

The exploratory objectives of this study are:
* To evaluate the association of clinical response (based on partial MCS) on
systemic or localized inflammatory biomarkers (eg, including but not limited to
C-reactive protein [CRP], fecal calprotectin, fecal lactoferrin, and fecal
MMP-9)
* To evaluate health-related quality of life (HRQoL)

Long-term extension study to evaluate the safety of filgotinib administered to
subjects with UC.

NVT

Please refer to the risks section in the ICF for a full overview of the risks
associated with Filgotinib.