Immune Response to Systemic and Mucosal Antigenic Challenge in the Presence of Vedolizumab
Condition: Inflammatory Bowel Disease
MeSH terms: Inflammatory Bowel Diseases
Intervention: Vedolizumab; Placebo; Hepatitis B vaccine; Oral cholera vaccine
Intervention description: Vedolizumab for intravenous infusion; Placebo intravenous infusion
Intervention MeSH terms: Vedolizumab; Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 127.0
Sex: All
Minimum age: 18 Years
Maximum age: 39 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug therapy

Summary:

      The primary purpose of this study is to determine the rates of seroconversion to a hepatitis
      B vaccine series after a single 750 mg intravenous (IV) dose of vedolizumab or placebo.
      Secondary objectives are to determine the rates of seroconversion to an oral cholera vaccine
      series, assess change in anti-hepatitis B surface antibodies and assess the safety and
      tolerability of a single 750-mg IV dose of vedolizumab.
    

Eligibility criteria:

        Inclusion criteria

          1. Male or female participants 18 to 39 years of age.

          2. Body mass index (BMI) between 18 and 32 kg/m^2, inclusive.

          3. Females who: are postmenopausal for at least 1 year before the Screening visit, OR;
             are surgically sterile, OR; if they are of childbearing potential, agree to practice 2
             effective methods of contraception, at the same time, from the time of signing the
             informed consent through 6 months after the last dose of study drug, or agree to
             completely abstain from heterosexual intercourse.

          4. Males, even if surgically sterilized (ie, status postvasectomy), who: agree to
             practice effective barrier contraception during the entire study treatment period and
             through 6 months after the last dose of study drug, or; agree to completely abstain
             from heterosexual intercourse.

          5. Is willing and able to provide written informed consent and to comply with all study
             requirements.

          6. Has suitable venous access for the study-required infusions and blood samples.

        Exclusion criteria

          1. Known exposure to hepatitis B virus.

          2. Known prior hepatitis B vaccination, irrespective of number of doses received, or any
             previous employment in a healthcare setting.

          3. Seropositivity for prior hepatitis B infection or hepatitis B vaccination during the
             Screening period.

          4. Known exposure to cholera or prior Dukoral exposure, irrespective of number of doses
             received.

          5. History of major cardiovascular, pulmonary, hepatic, renal, gastrointestinal (GI),
             genitourinary, hematological, immunological, psychiatric, or other major medical
             disorder.

          6. History of any major neurological disorder, including stroke, multiple sclerosis,
             brain tumor, or neurodegenerative disease, or any neurological disorders that would
             confound neurological examination, or results of the subjective or objective
             progressive multifocal leukoencephalopathy (PML) checklist during the study.

          7. Any history of coagulation disorders, or history or current use of anticoagulation
             therapy (eg, warfarin, heparin).

          8. Any disorder that requires chronic or regular use of any form of corticosteroid
             (including but not limited to topical, intranasal, rectal, etc), immunomodulator (eg,
             azathioprine) therapy, or other immunosuppressant (eg, mycophenolate, tacrolimus,
             tumor necrosis factor-alpha (TNF-α) antagonist).

          9. Regular use of herbal, homeopathic or natural supplements including but not limited to
             putative immune stimulants. Participants must not have used any of these agents within
             30 days of enrollment.

         10. Female participants who are lactating or have a positive serum pregnancy test during
             the Screening period or a positive urine pregnancy test on Day 1 predose; women
             considering becoming pregnant while on study are to be excluded.

         11. Acute illness within the preceding 30 days that, in the opinion of the investigator,
             could pose a threat or harm to the participant or obscure laboratory test results or
             interpretation of data on exposure to vedolizumab (eg, mononucleosis).

         12. Any history of malignancy, except for the following: (a) adequately-treated
             nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has been
             adequately treated and that has not recurred for at least 1 year prior to enrollment;
             and (c) history of cervical carcinoma in situ that has been adequately treated and
             that has not recurred for at least 3 years before enrollment.

         13. Had a surgical procedure requiring general anesthesia within 30 days before the
             initial Screening visit or is planning to undergo a surgery that requires general
             anesthesia during the study period. Minor surgeries that are medically necessary and
             that do not require general anesthesia may be allowable during the study period.

         14. One or more positive responses on the PML subjective symptom checklist at screening or
             before dosing on Day 1.

         15. Blood donation within 60 days before screening.

         16. Unable to attend all study days or comply with protocol requirements.

         17. Any other reason that, in the opinion of the investigator, would confound the conduct
             of this study or the interpretation of the results.