1. In the opinion of the investigator, the participant is capable of understanding and
complying with protocol requirements.
2. The participant or, when applicable, the participant's legally acceptable
representative has signed and dated a written, informed consent form and any required
privacy authorization prior to the initiation of any study procedures.
3. Is male or non-pregnant, non-breast-feeding female and aged 18 to 80 years, inclusive
at time of Screening.
4. Has an initial diagnosis of Crohn's disease (CD) established within 24 months prior to
enrollment with involvement of the ileum and/or colon that can be assessed by
5. Has moderate to severely active CD during Screening defined by:
1. Crohn's disease activity index (CDAI) score â‰¥ 220 within 10 days prior to
2. Centrally assessed simple endoscopic score for Crohn's disease (SES-CD) score â‰¥7
(or â‰¥4 if isolated ileal disease) during Screening, AND
3. Elevated biomarker of inflammation [C-reactive protein (CRP) >5 mg/L OR fecal
calprotectin level >250 Î¼g/g stool) during Screening.
6. By investigator judgement, the participant is assessed as having CD at moderate-high
risk for complications. Investigator judgement may include clinical assessment, the
Crohn's Disease Personalized Risk and Outcome Prediction Tool (PROSPECT), or criteria
defined by the 2014 American Gastroenterology Association (AGA) CD Clinical Care
7. May be receiving a stable therapeutic dose of conventional therapies for CD.
8. If on corticosteroids, must be on a stable dose of oral corticosteroids up to 20 mg of
prednisone daily or 9 mg of budesonide daily for at least 7 days prior to enrollment.
9. If on corticosteroids, must be willing to follow a mandatory taper of prednisone or
budesonide within 60 days after enrollment.
10. Must be willing to stop treatment with 5-aminosalicylate (5-ASA), antibiotics, and
probiotics for luminal CD at enrollment.
11. Male participant 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 18 weeks after last dose.
12. Female participant 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 18 weeks after last
13. Family history of colorectal cancer, personal history of increased colorectal cancer
risk, age >50 years, or other known risk factors must be up-to-date on colorectal
cancer surveillance (may be performed during Screening as standard of care).
1. Has a diagnosis of ulcerative colitis (UC) or indeterminate colitis.
2. Has clinical evidence of a current abdominal abscess or a history of prior abdominal
3. Has a known perianal fistula with abscess. (The participant may have a perianal
fistula without abscess.)
4. Has a known fistula (other than perianal fistula).
5. Had non-CD related abdominal surgery within 6 months prior to enrollment.
6. Has any prior CD-related surgery OR CD complication requiring surgery at any time
(other than seton placement for perianal fistula without abscess).
7. Has a history of 2 or more non CD related small bowel resections or diagnosis of short
8. Has extensive non CD related colonic resection, ie, subtotal or total colectomy with
<15 cm colon remaining.
9. Has an ileostomy, colostomy.
10. Has a history or evidence of adenomatous colonic polyps that have not been removed.
11. Has a history or evidence of colonic mucosal dysplasia.
12. Has intolerance or contraindication to undergo ileocolonoscopy.
13. Has known fixed stricture or stenosis of the intestine.
14. Has any identified congenital or acquired immunodeficiency [eg, common variable
immunodeficiency, human immunodeficiency virus (HIV) infection].
15. Has undergone organ transplantation.
16. Has evidence of an active infection during Screening.
17. Infections requiring treatment with oral (PO) or intravenous (IV) antibiotics,
antivirals, or antifungals within 28 days of enrollment.
18. Has active or latent tuberculosis (TB), regardless of treatment history, as evidenced
by any of the following:
1. History of TB.
2. A diagnostic TB test performed during Screening that is positive, as defined by:
â€¢ A positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests OR
3. A tuberculin skin test reaction â‰¥10 mm (â‰¥5 mm in participants receiving the
equivalent of >15 mg/day prednisone)
19. Has a history of listeria, histoplasmosis, coccidioidomycosis, blastomycosis,
candidiasis, aspergillosis, legionella, or pneumocystosis.
20. Has a history of any bacterial, viral, and other infection due to opportunistic
21. Has chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
22. Has evidence of active Clostridium difficile infection or is having treatment for C.
difficile infection or other intestinal pathogens during Screening.
23. Has received any live vaccinations within 28 days prior to enrollment.
24. Has other inflammatory or rheumatic diseases (eg, psoriasis, rheumatoid arthritis,
25. Had a surgical procedure requiring general anesthesia within 60 days prior to
enrollment or is planning to undergo major surgery during the study period.
26. Is taking, has taken, or is required to take any excluded medications.
27. Has received either approved or investigational biologic or nonbiologic agents for the
treatment of inflammatory bowel disease (IBD) in an investigational protocol.
28. Has had prior exposure to any tumor necrosis factor (TNF) antagonist including
infliximab, certolizumab pegol, golimumab, adalimumab, or biosimilar TNF antagonist
29. Has had prior exposure to vedolizumab, natalizumab, efalizumab, or rituximab.
30. Has received either approved or investigational biologic agents for the treatment of
non-inflammatory bowel disease (IBD) conditions, other than localized injections (eg,
intraocular injections for wet macular degeneration).
31. Has a history of hypersensitivity or allergies to methotrexate, vedolizumab,
adalimumab, or their components.
32. Has a medical history that contraindicates the use of vedolizumab, adalimumab, or
methotrexate as per each drug's package insert.
33. Has conditions which, in the opinion of the investigator, may interfere with the
participant's ability to comply with the study procedures.
34. Has a history of any lymphoma or lymphoproliferative disease.
35. Has a history of congestive heart failure (New York Heart Association class III/IV) or
36. Has renal insufficiency, ascites, pleural effusion, or underlying liver disease.
37. Has any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, GI,
genitourinary, hematological, coagulation, immunological, endocrine/metabolic,
neurologic, or other medical disorder that, in the opinion of the investigator, would
confound the study results or compromise participant safety.
38. Has had gastric bypass surgery.
39. Has symptoms of shortness of breath and cough and/or a diagnosis of clinically
significant lung disease.
40. 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. Participants with a 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; this must be discussed with the sponsor on a case-by-case basis prior to
41. Has a history of any major neurological disorders, including stroke, central nervous
system demyelinating disease, brain tumor, or neurodegenerative disease.
42. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom
checklist prior to the administration of study drug.
43. Has a history of pre-existing blood dyscrasias, such as bone marrow hypoplasia,
leukopenia (WBC count <3 Ã— 10^9/L), thrombocytopenia (platelet count <100 Ã— 10/L), or
significant anemia (hemoglobin level <8 g/dL).
44. Has rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or
45. Has any of the following laboratory abnormalities during the Screening period:
1. Hemoglobin level <8 g/dL.
2. WBC count <3 x 10^9/L.
3. Lymphocyte count <0.5 x 10^9/L.
4. Platelet count <100 x 10^9/L or >1200 x 10^9/L.
5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 the upper
limit of normal (ULN).
6. Alkaline phosphatase >1.5 x ULN.
7. Renal dysfunction (serum creatinine concentration greater than 1.5 mg per
deciliter [133 Âµmol per liter]) or estimated glomerular filtration rate (eGFR)
<50 mL/min/1.73 m^2 at Screening Note: Retesting laboratory values during the
screening interval may be considered with consultation from the Medical Monitor.
46. Has a history of high alcohol consumption (more than 7 drinks per week), a history of
prior alcohol abuse within 5 years prior to enrollment, has alcoholic liver disease,
has withdrawal symptoms, or a history of illicit drug use.
47. Has an active psychiatric problem that, in the investigator's opinion, may interfere
with compliance with study procedures.
48. Is unable to attend all the study visits or comply with study procedures.
49. Is an immediate family member, study site employee, or is in a dependent relationship
with a study site employee who is involved in conduct of this study (e.g, spouse,
parent, child, sibling) or may consent under duress.
50. Body mass index is >35.
51. If female, the participant is pregnant or lactating or intending to become pregnant
before, during, or within 6 months after participating in this study; or intending to
donate ova during such time period.
52. If male, the participant intends to father a child or donate sperm during the course
of this study or for 6 months thereafter.