Immune Response to Systemic and Mucosal Antigenic Challenge in the Presence of Vedolizumab

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1, Randomized, Double-Blinded, Placebo-Controlled, Single Dose Study in Healthy Subjects to Determine the Immune Response to Systemic and Mucosal Antigenic Challenge in the Presence of Vedolizumab

Conditions
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Inflammatory Bowel Disease

Intervention / Treatment
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* Drug: Vedolizumab
* Drug: Placebo
* Biological: Hepatitis B vaccine
* Biological: Oral cholera vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Male or female participants 18 to 39 years of age. Body mass index (BMI) between 18 and 32 kg/m^2, inclusive. 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. 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. Is willing and able to provide written informed consent and to comply with all study requirements. Has suitable venous access for the study-required infusions and blood samples. Exclusion criteria Known exposure to hepatitis B virus. Known prior hepatitis B vaccination, irrespective of number of doses received, or any previous employment in a healthcare setting. Seropositivity for prior hepatitis B infection or hepatitis B vaccination during the Screening period. Known exposure to cholera or prior Dukoral exposure, irrespective of number of doses received. History of major cardiovascular, pulmonary, hepatic, renal, gastrointestinal (GI), genitourinary, hematological, immunological, psychiatric, or other major medical disorder. 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. Any history of coagulation disorders, or history or current use of anticoagulation therapy (eg, warfarin, heparin). 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). 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. 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. 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). 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. 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. One or more positive responses on the PML subjective symptom checklist at screening or before dosing on Day 1. Blood donation within 60 days before screening. Unable to attend all study days or comply with protocol requirements. Any other reason that, in the opinion of the investigator, would confound the conduct of this study or the interpretation of the results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vedolizumab 750 mg<br>Vedolizumab 750 mg, intravenous (IV) infusion, once on Day 1. Also 3 doses of a hepatitis B vaccine series on Days 4, 32 and 60, and 2 doses of an oral cholera vaccine on Days 4 and 18. | Drug: Vedolizumab<br>* Vedolizumab for intravenous infusion<br>* Other names: LDP-02;Biological: Hepatitis B vaccine<br> <br> * Other names: HBVAXPRO;Biological: Oral cholera vaccine<br> <br> * Other names: Dukoral;|
| Placebo Comparator: Placebo<br>Vedolizumab placebo-matching, IV infusion, once on Day 1. Also 3 doses of a hepatitis B vaccine series on Days 4, 32 and 60, and 2 doses of an oral cholera vaccine on Days 4 and 18. | Drug: Placebo<br>* Placebo intravenous infusion<br>Biological: Hepatitis B vaccine<br> <br> * Other names: HBVAXPRO;Biological: Oral cholera vaccine<br> <br> * Other names: Dukoral;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Immune Response to Hepatitis B Vaccine at Day 74 | Immune response was defined as hepatitis B surface antibody (anti-HBs) ≥ 10 IU/L. | Day 74 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Immune Response to Oral Cholera Vaccine | A positive immune response was defined as an increase of greater than 4-fold over the Baseline immunoglobulin M (IgM), IgG, or IgA anticholera antibodies. | Baseline and Day 74 | 
| Anti-Hepatitis B Surface Antibody Over Time |  | Baseline and Days 18, 32, 60 and 74 | 
| Number of Participants With Adverse Events (AEs) | An AE was defined as any untoward medical occurrence in a subject administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment. Serious adverse event (SAE) meant any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly/birth defect or was a medically important event. Relationship of each AE to study drug was determined by the Investigator. | From the first dose of study medication through Day 127 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug therapy