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

NCT ID: NCT01981616

Last Updated: 2014-07-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2012-07-31

Brief 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.

Conditions

Inflammatory Bowel Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Vedolizumab 750 mg

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.

Group Type: EXPERIMENTAL

Vedolizumab

Intervention Type: DRUG

Vedolizumab for intravenous infusion

Hepatitis B vaccine

Intervention Type: BIOLOGICAL

Oral cholera vaccine

Intervention Type: BIOLOGICAL

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo intravenous infusion

Hepatitis B vaccine

Intervention Type: BIOLOGICAL

Oral cholera vaccine

Intervention Type: BIOLOGICAL

Interventions

Vedolizumab

Vedolizumab for intravenous infusion

Intervention Type: DRUG

Placebo

Placebo intravenous infusion

Intervention Type: DRUG

Hepatitis B vaccine

Intervention Type: BIOLOGICAL

Oral cholera vaccine

Intervention Type: BIOLOGICAL

Other Intervention Names

Entyvio; MLN0002; MLN02; LDP-02; HBVAXPRO; Dukoral

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

ICON Development Solutions

Manchester, , United Kingdom

Countries

United Kingdom

References

Wyant T, Leach T, Sankoh S, Wang Y, Paolino J, Pasetti MF, Feagan BG, Parikh A. Vedolizumab affects antibody responses to immunisation selectively in the gastrointestinal tract: randomised controlled trial results. Gut. 2015 Jan;64(1):77-83. doi: 10.1136/gutjnl-2014-307127. Epub 2014 Apr 24.

Reference Type: DERIVED

PMID: 24763133 (View on PubMed)

Other Identifiers

2011-001874-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1147-3216

Identifier Type: REGISTRY

Identifier Source: secondary_id

C13013

Identifier Type: -

Identifier Source: org_study_id