Ulcerative Colitis

Primary Objective(s)  To determine the effect of vedolizumab IV compared to adalimumab SC on clinical remission at Week 52. Secondary Objectives  To evaluate the effect of vedolizumab IV compared to adalimumab SC on mucosal healing at Week 52.  To evaluate the effect of vedolizumab IV compared to adalimumab SC on corticosteroid-free remission at Week 52.

ENTYVIO; KYNTELES

Vedolizumab

vial

300

Primary Endpoints
 Proportion of subjects achieving clinical remission (defined as a complete Mayo score of
≤2 points and no individual subscore >1 point) at Week 52.

Secondary Endpoints
 Proportion of subjects achieving mucosal healing (defined as Mayo endoscopic subscore
≤1 point) at Week 52.
 Proportion of subjects using oral corticosteroids at Baseline who have discontinued
corticosteroids and are in clinical remission at Week 52.

Inclusion Criteria
Subject eligibility is determined according to the following criteria prior to entry into the study:
1. In the opinion of the investigator, the subject is capable of understanding and complying with
protocol requirements.
2. The subject or, when applicable, the subject’s legally acceptable representative signs and
dates a written, informed consent form and any required privacy authorization prior to the
initiation of any study procedures.
3. The subject has a diagnosis of UC established at least 6 months prior to screening by clinical
and endoscopic evidence and corroborated by a histopathology report.
4. The subject is male or female and aged 18 to 80 years, inclusive.
5. The subject has moderately to severely active UC as determined by a Mayo score of 6 to 12
with an endoscopic subscore ≥2 within 14 days prior to the randomization.
6. The subject has evidence of UC proximal to the rectum (≥15 cm of involved colon).
7. The subject with extensive colitis (up to the hepatic flexure) or pancolitis of >8 years
duration or left-sided colitis of >12 years duration must have documented evidence that a
surveillance colonoscopy was performed within 12 months of the initial screening visit (may
be performed during the Screening Period).
8. The subject with a family history of colorectal cancer, personal history of increased
colorectal cancer risk, age >50 years, or other known risk factor must be up-to-date on
colorectal cancer surveillance (may be performed during screening).
9. The subject has had previous treatment with TNF-α antagonists without documented clinical
response to treatment or the subject is naïve to TNF-α antagonist therapy but is failing
current treatment.
10. A male subject who is nonsterilized* and sexually active with a female partner of
childbearing potential* agrees to use adequate contraception* from signing of informed
consent throughout the duration of the study and for 5 months after last dose.
11. A female subject of childbearing potential* who is sexually active with a nonsterilized* male
partner agrees to use routinely adequate contraception* from signing of informed consent
throughout the duration of the study and for 5 months after last dose.

Exclusion Criteria
The exclusion criteria are divided into 3 categories: gastrointestinal exclusion criteria, infectious
disease exclusion criteria, and general exclusion criteria. Any subject who meets any of the
following criteria will not qualify for entry into the study:
Gastrointestinal Exclusion Criteria
1. The subject has clinical evidence of abdominal abscess or toxic megacolon at the Screening
Visit.
2. The subject has had an extensive colonic resection, subtotal or total colectomy.
3. The subject has had ileostomy, colostomy, or known fixed symptomatic stenosis of the
intestine.
4. The subject has a diagnosis of Crohn’s colitis or indeterminate colitis, ischemic colitis,
radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
5. The subject has received any of the following for the treatment of underlying disease within
30 days of screening:
a) Non-biologic therapies (eg. cyclosporine, tacrolimus, thalidomide) other than those
specifically listed in Section Permitted Medications For Treatment of UC.
b) An approved non-biologic therapy in an investigational protocol.
6. The subject has received any investigational or approved biologic or biosimilar agent within
60 days or 5 half lives prior to the screening (whichever is longer).
7. The subject has previously received natalizumab, efalizumab, adalimumab, or rituximab.
8. The subject has previously received vedolizumab.
9. The subject currently requires or is anticipated to require surgical intervention for UC during
the study.
10. The subject has history or evidence of adenomatous colonic polyps that have not been
removed, or colonic mucosal dysplasia.
Infectious Disease Exclusion Criteria
11. The subject has evidence of an active infection during the Screening Period.
12. The subject has evidence of, or treatment for, C. difficile infection or other intestinal
pathogen within 28 days prior to the first dose of study drug.
13. The subject has chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
14. The subject has active or latent TB, regardless of treatment history, as evidenced by any of
the following:
a) History of TB,
b) A diagnostic TB test performed within 30 days of screening or during the Screening
Period that is positive, defined as:
– Positive QuantiFERON®
test or 2 successive indeterminate QuantiFERON tests, OR
– A TB skin test reaction ≥10 mm (≥5 mm in subjects receiving the equivalent of
>15 mg/day prednisone).
c) Chest X-ray within 3 months of screening in which active or latent pulmonary TB cannot
be excluded.
15. The subject has any identified congenital or acquired immunodeficiency (eg, common
variable immunodeficiency, human immunodeficiency virus (HIV) infection, organ
transplantation).
16. The subject has any live vaccination within 30 days prior to Screening or is planning to
receive live vaccination during participation in the study.
17. The subject has a clinically significant infection (eg, pneumonia, pyelonephritis) within
30 days prior to screening, or ongoing chronic infection.
18. The subject has used a topical (rectal) treatment with (5-ASA) or corticosteroid
enemas/suppositories within 2 weeks of the administration of the first dose of study drug.
General Exclusion Criteria
19. The subject has a history of hypersensitivity or allergies to vedolizumab or adalimumab.
20. The subject has any unstable or uncontrolled cardiovascular disorder, heart failure moderate
to severe (New York Class Association III or IV), any pulmonary, hepatic, renal, GI,
genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other
medical disorder that, in the opinion of the investigator, would confound the study results or
compromise subject safety.
21. The subject has history of lupus or lupus-related conditions.
22. The subject has had a surgical procedure requiring general anesthesia within 30 days prior to
screening or is planning to undergo major surgery during the study period.
23. The subject has a history of malignancy, except for the following: adequately-treated
nonmetastatic basal cell skin cancer; squamous cell skin cancer that has been adequately
treated and that has not recurred for at least 1 year prior to Screening; and history of cervical
carcinoma in situ that has been adequately treated and that has not recurred for at least
3 years prior to screening. Subject with remote history of malignancy (eg, >10 years since
completion of curative therapy without recurrence) will be considered based on the nature of
the malignancy and the therapy received and must be discussed with the sponsor on a caseby-case basis prior to Screening.
24. The subject has a history of any major neurological disorders, including stroke, multiple
sclerosis, brain tumor, demyelinating, or neurodegenerative disease.
25. The subject has a positive PML subjective symptom checklist prior to the administration of
the first dose of study drug.
26. The subject has any of the following laboratory abnormalities during the Screening Period:
 Hemoglobin <8 g/dL.
 White blood cells (WBC) <3 × 109
/L.
 Lymphocyte <0.5 × 109
/L.
 Platelet count <100 × 109
/ L or >1200 ×109
/L.
 Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of
normal (ULN).
 Alkaline phosphatase >3 × ULN.
 Serum creatinine >2 × ULN.
27. The subject has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
abuse within 1 year prior to the Screening Visit.
28. The subject has an active psychiatric problem that, in the investigator’s opinion, may
interfere with compliance with study procedures.
29. The subject is unable to attend all the study visits or comply with study procedures.
30. The subject is required to take excluded medications listed in Section 7.3.
31. If female, the subject is pregnant or lactating or intending to become pregnant before, during,
or within 5 months after participating in this study; or intending to donate ova during such
time period.
32. If male, the subject intends to donate sperm during the course of this study or for 5 months
thereafter.
33. The subject is an immediate family member, study site employee, or is in a dependant
relationship with a study site employee who is involved in conduct of this study (eg, spouse,
parent, child, sibling) or may consent under duress.