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

• ClinicalTrials.gov Identifier: NCT01981616
• Recruitment Status: Completed
• First Posted: November 11, 2013
• Results First Posted: July 21, 2014
• Last Update Posted: July 21, 2014
• Sponsor: Millennium Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Millennium Pharmaceuticals, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Inflammatory Bowel Disease	Drug: Vedolizumab; Drug: Placebo; Biological: Hepatitis B vaccine; Biological: Oral cholera vaccine	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 127 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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
• Study Start Date: September 2011
• Actual Primary Completion Date: May 2012
• Actual Study Completion Date: July 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: Vedolizumab; Vedolizumab for intravenous infusion; Other Names: Entyvio; MLN0002; MLN02; LDP-02; Biological: Hepatitis B vaccine; Other Name: HBVAXPRO; Biological: Oral cholera vaccine; Other Name: Dukoral
Placebo Comparator: 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.	Drug: Placebo; Placebo intravenous infusion; Biological: Hepatitis B vaccine; Other Name: HBVAXPRO; Biological: Oral cholera vaccine; Other Name: Dukoral

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Percentage of Participants With an Immune Response to Oral Cholera Vaccine [ Time Frame: Baseline and Day 74 ]
   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.
2. Anti-Hepatitis B Surface Antibody Over Time [ Time Frame: Baseline and Days 18, 32, 60 and 74 ]
3. Number of Participants With Adverse Events (AEs) [ Time Frame: From the first dose of study medication through Day 127 ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 39 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United Kingdom

ICON Development Solutions

Manchester, United Kingdom

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Monitor; Millennium Pharmaceuticals, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Millennium Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01981616
• Other Study ID Numbers: C13013; 2011-001874-24 ( EudraCT Number ); U1111-1147-3216 ( Registry Identifier: WHO )
• First Posted: November 11, 2013
• Results First Posted: July 21, 2014
• Last Update Posted: July 21, 2014
• Last Verified: June 2014

Keywords provided by Millennium Pharmaceuticals, Inc.:

Drug therapy

Additional relevant MeSH terms:

Inflammatory Bowel Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Vedolizumab; Vaccines; Immunologic Factors; Physiological Effects of Drugs; Gastrointestinal Agents