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

NCT01981616 | Completed Phase 1 Results

• 3 other identifiers: C130132011-001874-24U1111-1147-3216
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

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

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Percentage of Participants With an Immune Response to Oral Cholera Vaccine

  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)

  From the first dose of study medication through Day 127

Study Arms (2)

Vedolizumab 750 mg

EXPERIMENTAL

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; Biological: Hepatitis B vaccine; Biological: Oral cholera vaccine

Placebo

PLACEBO COMPARATOR

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; Biological: Hepatitis B vaccine; Biological: Oral cholera vaccine

Interventions

Vedolizumab DRUG

Vedolizumab for intravenous infusion

Also known as: Entyvio, MLN0002, MLN02, LDP-02

Vedolizumab 750 mg

Placebo DRUG

Placebo intravenous infusion

Placebo

Hepatitis B vaccine BIOLOGICAL

Also known as: HBVAXPRO

Placebo; Vedolizumab 750 mg

Oral cholera vaccine BIOLOGICAL

Also known as: Dukoral

Placebo; Vedolizumab 750 mg

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (1)

ICON Development Solutions

Manchester, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 24763133 DERIVED

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

vedolizumab; LDP-02; Hepatitis B Vaccines; Cholera Vaccines; Dukoral

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Viral Hepatitis Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Bacterial Vaccines

Results Point of Contact

• Title: Medical Director
• Organization: Millennium Pharmaceuticals Inc.

clinicaltrialregistry@tpna.com

800-778-2860

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2013
• First Posted: November 11, 2013
• Study Start: September 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: July 1, 2012
• Last Updated: July 21, 2014
• Results First Posted: July 21, 2014

Record last verified: 2014-06

Locations

GB (1)