A Phase 3 Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects with Moderate to Severe Ulcerative Colitis (FIGARO UC 301)

Subjects must meet all of the following inclusion criteria to be eligible for
enrollment into the study.
1. Subjects and/or their parent or legally authorized representative must have
an understanding, ability, and willingness to fully comply with study
procedures and restrictions.
2. Subjects must be able to voluntarily provide written, signed, and dated
(personally or via a legally authorized representative) informed consent and/or
assent, as applicable, to participate in the study.
3. Subjects must be between *16 and *80 years of age at the time of the signing
of the informed consent/assent form.
NOTE: Subjects <18 years of age must weigh *40 kg and must have body mass index
(BMI) *16.5 kg/m2.
4. Subjects must have a documented diagnosis (radiologic or endoscopic with
histology) of UC for *3 months before screening. The following must be
available in each subject*s source documentation:
* A biopsy report to confirm the histological diagnosis.
* A report documenting disease duration based upon prior colonoscopy.
NOTE: If this documentation is not available at the time of screening, a
colonoscopy with biopsy to confirm the diagnosis is required during the
screening period.
5. Subjects must be willing to undergo a flexible sigmoidoscopy or colonoscopy
(if preferred), including biopsy sample collection, during screening after all
other inclusion criteria have been met.
6. Subjects must have moderate to severe active UC, defined as a total Mayo
score of *6, including a centrally read endoscopic subscore *2, rectal bleeding
subscore *1, and stool frequency subscore *1 at baseline (Visit 2).
7. Subjects must have evidence of UC extending proximal to the rectum (ie, not
limited to proctitis).
8. Subjects must have had an inadequate response to, or lost response to, or
had an intolerance to at least 1 conventional treatment such as mesalamine (5
aminosalicylic acid [5-ASA]), glucocorticoids, immunosuppressants (azathioprine
[AZA], 6 mercaptopurine [6 MP], or methotrexate [MTX]), or anti-TNF.
9. Subjects receiving any treatment(s) for UC described in Section 5.2.1 of the
protocol are eligible provided they have been, and are anticipated to be, on a
stable dose for the designated period of time.
10. Subjects are males or nonpregnant, nonlactating females who, if sexually
active, agree to comply with the contraceptive requirements of the protocol, or
females of nonchildbearing potential. Males and females of reproductive
potential who are sexually active must agree to use appropriate contraception
(ie, highly effective methods for female and medically appropriate methods for
male study subjects) (as described in Section 4.4 of the protocol) for the
duration of the study.

Subjects are excluded from the study if any of the following exclusion criteria
are met:
1. Subjects with indeterminate colitis, microscopic colitis, non-steroidal
anti-inflammatory drug-induced colitis, ischemic ischemic colitis, infectious
colitis, or clinical/histologic findings suggestive of Crohn*s disease.
2. Subjects with colonic dysplasia or neoplasia. (Subjects with prior history
of adenomatous polyps will be eligible if the polyps have been completely
removed.)
3. Subjects with past medical history or presence of toxic megacolon.
4. Subjects with colonic stricture, past medical history of colonic resection,
a history of bowel surgery within 6 months before screening, or who are likely
to require surgery for UC during the treatment period.
5. Subjects at risk for colorectal cancer must have a colonoscopy performed
during the screening period with results available within 10 days before the
baseline visit (Visit 2), unless the subject has had a surveillance colonoscopy
performed within 1 year prior to screening, and any adenomatous polyps found at
that examination have been excised. Colonoscopy report and pathology report (if
biopsies are obtained) from the colonoscopy performed during screening or in
the prior year confirming no evidance of dysplasia and colon colon must be
available in the source documents.
Subjects at risk for colorectal cancer include, but are not limited to:
* Subjects with extensive colitis for *8 years or disease limited to left side
of colon (ie, distal to splenic flexure) for *10 years before screening,
regardless of age.
* Subjects *50 years of age at the time of signing of the informed consent form.
6. Subjects have had prior treatment with ontamalimab (formerly PF-00547659;
SHP647).
7. Subjects with known or suspected intolerance or hypersensitivity to the
investigational product(s), closely related compounds, or any of the stated
ingredients.
8. Subjects have received anti-TNF treatment within 60 days before baseline
(Visit 2).
9. Subjects have received any biologic with immunomodulatory properties (other
than anti TNFs) within 90 days before baseline (Visit 2).
10. Subjects have received any nonbiologic treatment with immunomodulatory
properties (other than their current background UC treatment) within 30 days
before baseline (Visit 2).
11. Subjects have ever received anti-integrin/adhesion molecule treatment (eg,
natalizumab, vedolizumab, efalizumab, etrolizumab, or any other investigational
anti-integrin/adhesion molecule).
12. Subjects have received parenteral or rectal glucocorticoids, or rectal
5-ASA, within 14 days before screening endoscopic procedure.
13. Subjects have received leukocyte apheresis or selective lymphocyte,
monocyte, or granulocyte apheresis or plasma exchange within 30 days before
baseline (Visit 2).
14. Subjects have participated in other investigational studies within either
30 days or 5 half lives of investigational product used in the study (whichever
is longer) before baseline (Visit 2).
15. Subjects have received a live (attenuated) vaccine within 30 days before
the baseline visit (Visit 2).
16. Subjects with active enteric infections (positive stool culture and
sensitivity), Clostridium difficile infection or pseudomembranous colitis
[subjects with C. difficile infection at screening may be allowed re-test after
treatment], evidence of active cytomegalovirus infection or Listeria
monocytogenes, known active invasive fungal infections such as histoplasmosis
or parasitic infections, clinically significant underlying disease that could
predispose the subjects to infections, or a history of serious infection
(requiring parenteral antibiotic and/or hospitalization) within 4 weeks before
the baseline visit (Visit 2).
17. Subjects with abnormal chest x-ray findings at screening (Visit 1), such as
presence of active tuberculosis (TB), general infections, heart failure, or
malignancy. (A chest x ray performed up to 12 weeks before study entry
[screening, Visit 1] may be used if available; documentation of the official
reading must be located and available in the source documentation.)
18. Subjects with evidence of active or latent infection with Mycobacterium
tuberculosis (TB) or subjects with this history who have not completed a
generally accepted full course of treatment before randomization are excluded.
All other subjects must have either the Mantoux (purified protein derivative
[PPD]) tuberculin skin test or interferon gamma release assay (IGRA) performed.
Subjects who have no history of previously diagnosed active or latent
tuberculosis are excluded if they have a positive Mantoux (PPD) tuberculin skin
test (ie *5 mm induration) or a positive IGRA (the latter to be tested at the
site*s local laboratory) during screening or within 12 weeks before
randomization. If IGRA test cannot be performed locally, a central laboratory
may be used, with prior agreement from the sponsor.
* An IGRA is strongly recommended for subjects with a prior Bacillus
Calmette-Guérin (BCG) vaccination, but may be used for any subject.
Documentation of IGRA product used and the test result must be in the subject's
source documentation if performed locally. Acceptable IGRA products include
QuantiFERON TB Gold Plus In-Tube Test.
* If the results of the IGRA are indeterminate, the test may be repeated, and
if a negative result is obtained, enrollment may proceed. In subjects with no
history of treated active or latent tuberculosis, a positive test on repeat
will exclude the subject. Subjects with a history of active or latent
tuberculosis infection must follow instructions for *Subjects with a prior
diagnosis of active or latent tuberculosis are excluded unless both of the
following criteria are met* in this criterion.
* Subjects with repeat indeterminate IGRA results, with no prior TB history,
may be enrolled after consultation with a pulmonary or infectious disease
specialist who determines low risk of infection (ie, subject would be
acceptable for immunosuppressant [eg, anti-TNF] treatment without additional
action). This consultation must be included in source documentation.
Results from a chest x-ray, taken within the 3 months before or during
screening (Visit 1) must show no abnormalities suggestive of active TB
infection as determined by a qualified medical specialist.
Subjects with a prior diagnosis of active or latent tuberculosis are excluded
unless both of the following criteria are met:
* The subject has previously received an adequate course of treatment for
either latent (eg, 9 months of isoniazid or an acceptable alternative regimen,
in a locale where rates of primary multidrug TB resistance are <5%. Subjects
from regions with higher rates of primary multidrug TB resistance are excluded)
or active (acceptable multidrug regimen) TB infection. Evidence of diagnosis
and treatment must be included in source documentation. Consultation with a
pulmonary or infectious disease specialist to confirm adequate treatment (ie,
subject would be acceptable for immunosuppressant [eg, anti-TNF] treatment
without additional action) must be performed during the screening period. The
consultation report must be included in source documentation prior to
enrollment.
* A chest x-ray performed within 3 months prior to screening (Visit 1) or
during screening (Visit 1) indicates no evidence of active or recurrent
disease, and documentation of interpretation by a qualified medical specialist
must be included in source documentation.
19. Subjects with a pre existing demyelinating disorder such as multiple
sclerosis or new onset seizures, unexplained sensory motor, or cognitive
behavioral, neurological deficits, or significant abnormalities noted during
screening.
20. Subjects with any unexplained symptoms suggestive of progressive multifocal
leukoencephalopathy (PML) based on the targeted neurological assessment during
the screening period.