Vedolizumab Post Op Study

Study aims: To determine the efficacy of vedolizumab in preventing mucosal recurrence of
Crohn's disease in patients undergoing resective surgery.

Methods: This is a randomized, placebo-controlled pilot study that will determine the
endoscopic recurrence of Crohn's disease 12 months after curative, resective ileal or
ileocolonic surgery in patients receiving post-operative vedolizumab or placebo. Patients
will receive the first infusion of vedolizumab (300 mg) or placebo (1:1 randomization) 2-4
weeks after surgery. Subsequent infusions of vedolizumab or placebo will occur at 2, 6, 14,
22, 30, 38, 46, and 54 weeks after the first infusion. The primary assessment for
determination of drug efficacy will be presence or absence of mucosal inflammation
(representing active Crohn's disease) at the ileocolonic anastomosis and neo-terminal ileum.
This assessment will be made by colonoscopic inspection one year after surgery. Patients with
an elevated fecal calprotectin at week 22 will undergo a 6-month post-operative clinical
colonoscopy to assess for endoscopic recurrence.

Subject population: Patients scheduled for resectional surgery for ileal or ileocolonic
Crohn's disease will be eligible for the study. Subjects will be male or female who are 18
years of age or older.

Inclusion Criteria:

1. Are men or women > 18 years of age at screening.

2. Curative resection and ileocolonic anastomosis for Crohn's disease. Patients with
isolated fibrostenotic (non-inflammatory) or minimal (not clinically significant)
disease elsewhere in gastrointestinal that is not resected will also be included.

3. Participants who have received pre-operative vedolizumab therapy may be included.

4. Concomitant medications: All concomitant medications at the time of the surgery will
be discontinued post-operatively.

5. Men and women of childbearing potential must use adequate birth control measures
(e.g., abstinence, oral contraceptives, intrauterine device, barrier method with
spermicide, implantable or injectable contraceptives or surgical sterilization) for
the duration of the study and should continue such precautions for 6 months after
receiving the last infusion).

6. Antibiotics for the treatment of Crohn's disease (eg. ciprofloxacin and metronidazole)
are allowable but must be discontinued within 12 weeks after surgery. Antibiotics for
the treatment of a concomitant infection are allowable throughout the duration of the
study as long as the primary purpose of antibiotic therapy is not for the primary
treatment of Crohn's disease.

7. Screening laboratory tests must meet the screening criteria (Hemoglobin ≥ 8.5 g/dL,
White blood cell (WBC) count ≥ 3.0 x 109/L, Neutrophils ≥ 1.0 x 109/L, Platelets ≥ 100
x 109/L, Lymphocyte count ≥ 0.5 x 109/L and SGOT (AST-aspartate aminotransferase) -< 3
times upper normal limit).

8. Are capable of providing written informed consent, and the consent must be obtained
prior to conducting any protocol-specified procedures.

9. Are willing to adhere to the study visit schedule and other protocol requirements.

10. Participants who require a temporary diverting ileostomy and then takedown will be
included. These would be participants who undergo resective surgery and primary
ileocolonic anastomosis but require a temporary diverting ostomy proximal to the
anastomotic site. Participants will be eligible for the study upon takedown of the
diverting ileostomy

Exclusion Criteria:

1. Participants with greater than 10 years of Crohn's disease requiring their FIRST
resection of a short (<10cm) fibrostenotic stricture. The rationale for excluding
these participants is that historically this group of participants is at a very low
risk of recurrence and therefore, would not be a group targeted for postoperative
medical therapy.

2. Macroscopically active disease at the anastomosis at the time of surgery.

3. Presence of a stoma.

4. Prior severe infusion reaction to vedolizumab, i.e. anaphylaxis, bronchospasm, or
hypotension.

5. History of anaphylaxis to other chimeric proteins.

6. Any of the following medications taken within 12 weeks of surgery: cyclosporine,
tacrolimus, sirolimus, mycophenolate mofetil, or other investigational drugs. Patients
who have taken these medications more than 12 weeks prior to surgery will be allowed
in the study

7. At the time of screening participants with a positive stool culture for enteric
pathogens, pathogenic ova or parasites, or Clostridium difficile toxin and have
clinically significant signs of an enteric infection, i.e. diarrhea, fever, abdominal
pain. participants will be eligible for enrollment if stool cultures are positive but
do not have clinically significant signs or symptoms or infection and receive
appropriate antibiotic treatment. A repeat stool culture will be obtained at the
completion of antibiotic treatment.

8. Women who are pregnant, nursing, or planning pregnancy during the trial or within 6
months after the last infusion (this includes father's who plan on fathering a child
within 6 months after their last infusion).

9. Have or have had an opportunistic infection (eg, herpes zoster [shingles],
cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria
other than TB) within 6 months of screening.

10. Have a chest radiograph within 3 months prior to screening that shows evidence of
malignancy, infection, or any abnormalities.

11. Documentation of seropositive for human immunodeficiency virus (HIV).

12. Documentation of a positive test for hepatitis B surface antigen or a history of
documented hepatitis C.

13. Have current signs or symptoms of systemic lupus erythematosus, or severe,
progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine,
pulmonary, cardiac, neurologic, or cerebral diseases.

14. Presence of a transplanted solid organ (with the exception of a corneal transplant > 3
months prior to randomization).

15. Have any current known malignancy other than the condition being treated or have a
history of malignancy within 5 years prior to screening (except for squamous or basal
cell carcinoma of the skin that has been fully excised with no evidence of
recurrence).

16. Have a history of lymphoproliferative disease including lymphoma, or signs or symptoms
suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual
size or location (eg, nodes in the posterior triangle of the neck, intraclavicular,
epitrochlear, or periaortic area), or splenomegaly.

17. Have had a known substance abuse (drug or alcohol) or dependency within the previous 3
years, history of noncompliance to medical regimens, or other condition/circumstance
that could interfere with the subject's adherence to protocol requirements (eg,
psychiatric disease, lack of motivation, travel, etc).

18. Are unable to or unwilling to undergo multiple venipunctures because of poor
tolerability or lack of easy access

19. Have had a chronic or recurrent infectious disease including, but not limited to,
chronic renal infection, chronic chest infection (eg, bronchiectasis), sinusitis,
recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting
cystitis), open, draining, or infected skin wound, or ulcer.

20. Have had a serious infection (eg, hepatitis, pneumonia, or pyelonephritis), have been
hospitalized for an infection, or have been treated with intravenous (IV) antibiotics
for an infection within 2 months prior to randomization. The exception being
participants whose infection is a direct consequence of their Crohn's disease and will
be completely resolved with surgery, e.g. participants with an abscess related to
penetrating Crohn's disease of the terminal ileum who have no sign of infection after
surgery. Less serious infections (eg, acute upper respiratory tract infection, enteric
infections without signs or symptoms or simple urinary tract infection) need not be
considered exclusions at the discretion of the investigator.

21. Have a serious concomitant illness that could interfere with the subject's
participation in the trial.

22. Current use of prescription doses or chronic and frequent use of over-the-counter
doses of nonsteroidal anti-inflammatory drugs (NSAIDs), except low-dose aspirin for
prevention of heart attacks, unstable angina, or transient ischemic attacks.

23. Have ulcerative colitis.

24. Are participating in another investigative trial during participation in this trial.

25. Use of any investigational drug within 30 days prior to randomization or within 5
half-lives of the investigational agent, whichever is longer.