Inflammatory Bowel Disease
Conditions
Keywords
Drug therapy
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.
Interventions
DRUGPlacebo
Placebo intravenous infusion
BIOLOGICALHepatitis B vaccine
BIOLOGICALOral cholera vaccine
DRUGVedolizumab
Vedolizumab for intravenous infusion
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 39 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Immune Response to Hepatitis B Vaccine at Day 74 | Day 74 | Immune response was defined as hepatitis B surface antibody (anti-HBs) ≥ 10 IU/L. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an Immune Response to Oral Cholera Vaccine | 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. |
| 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 | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants took part in the study at one investigative site in the United Kingdom from 13 September 2011 to 13 July 2012.
Pre-assignment details
Healthy participants were randomized in a 1:1 ratio to receive a single dose of placebo or vedolizumab.
Participants by arm
| Arm | Count |
|---|---|
| Vedolizumab 750 mg Vedolizumab 750 mg solution, 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. | 64 |
| Placebo Vedolizumab placebo-matching solution, 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. | 63 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Vedolizumab 750 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 27.7 years STANDARD_DEVIATION 5.64 | 27.3 years STANDARD_DEVIATION 5.33 | 27.5 years STANDARD_DEVIATION 5.47 |
| Body Mass Index (BMI) | 24.8 kg/m^2 STANDARD_DEVIATION 3.34 | 25.4 kg/m^2 STANDARD_DEVIATION 2.71 | 25.1 kg/m^2 STANDARD_DEVIATION 3.04 |
| Height | 173.4 cm STANDARD_DEVIATION 8.89 | 173.1 cm STANDARD_DEVIATION 7.94 | 173.3 cm STANDARD_DEVIATION 8.4 |
| Race/Ethnicity, Customized Asian | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Black | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 64 participants | 62 participants | 126 participants |
| Race/Ethnicity, Customized Other | 0 participants | 4 participants | 4 participants |
| Race/Ethnicity, Customized White | 62 participants | 56 participants | 118 participants |
| Region of Enrollment United Kingdom | 64 participants | 63 participants | 127 participants |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 40 Participants |
| Sex: Female, Male Male | 44 Participants | 43 Participants | 87 Participants |
| Weight | 75.0 kg STANDARD_DEVIATION 13.48 | 76.2 kg STANDARD_DEVIATION 11.53 | 75.6 kg STANDARD_DEVIATION 12.51 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 64 | 25 / 63 |
| serious Total, serious adverse events | 0 / 64 | 1 / 63 |
Outcome results
Primary
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.
Time frame: Day 74
Population: The Per Protocol Population consisted of all participants who received any amount of study drug and who met predefined evaluability criteria, including receiving the correct and complete dose of study drug, completed both Baseline and day 72 serology assessments and full schedule of hepatitis B vaccine and immunomodulator or corticosteroid use.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vedolizumab 750 mg | Percentage of Participants With an Immune Response to Hepatitis B Vaccine at Day 74 | 88.5 percentage of participants |
| Placebo | Percentage of Participants With an Immune Response to Hepatitis B Vaccine at Day 74 | 90.3 percentage of participants |
95% CI: [-12.7, 9.1]
Secondary
Anti-Hepatitis B Surface Antibody Over Time
Time frame: Baseline and Days 18, 32, 60 and 74
Population: Per Protocol Population; n indicates the number of participants with available data at each time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Vedolizumab 750 mg | Anti-Hepatitis B Surface Antibody Over Time | Day 18 (n=39, 40) | 2.5 IU/L | Geometric Coefficient of Variation 501 |
| Vedolizumab 750 mg | Anti-Hepatitis B Surface Antibody Over Time | Day 60 (n=58, 59) | 16.3 IU/L | Geometric Coefficient of Variation 501.3 |
| Vedolizumab 750 mg | Anti-Hepatitis B Surface Antibody Over Time | Day 32 (n=37, 41) | 2.3 IU/L | Geometric Coefficient of Variation 472.8 |
| Vedolizumab 750 mg | Anti-Hepatitis B Surface Antibody Over Time | Day 74 (n=59, 62) | 129.6 IU/L | Geometric Coefficient of Variation 359.3 |
| Vedolizumab 750 mg | Anti-Hepatitis B Surface Antibody Over Time | Baseline (n=24, 31) | 1.2 IU/L | Geometric Coefficient of Variation 51.9 |
| Placebo | Anti-Hepatitis B Surface Antibody Over Time | Day 74 (n=59, 62) | 114.4 IU/L | Geometric Coefficient of Variation 539.6 |
| Placebo | Anti-Hepatitis B Surface Antibody Over Time | Baseline (n=24, 31) | 1.0 IU/L | Geometric Coefficient of Variation 12.5 |
| Placebo | Anti-Hepatitis B Surface Antibody Over Time | Day 18 (n=39, 40) | 1.3 IU/L | Geometric Coefficient of Variation 73.5 |
| Placebo | Anti-Hepatitis B Surface Antibody Over Time | Day 32 (n=37, 41) | 1.6 IU/L | Geometric Coefficient of Variation 99.9 |
| Placebo | Anti-Hepatitis B Surface Antibody Over Time | Day 60 (n=58, 59) | 15.2 IU/L | Geometric Coefficient of Variation 365.8 |
Secondary
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.
Time frame: From the first dose of study medication through Day 127
Population: The Safety Population was defined as all participants who received any amount of study drug (vedolizumab or placebo) based on what they actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vedolizumab 750 mg | Number of Participants With Adverse Events (AEs) | Any adverse event | 41 participants |
| Vedolizumab 750 mg | Number of Participants With Adverse Events (AEs) | Drug-related adverse event | 22 participants |
| Vedolizumab 750 mg | Number of Participants With Adverse Events (AEs) | Adverse event resulting in study discontinuation | 0 participants |
| Vedolizumab 750 mg | Number of Participants With Adverse Events (AEs) | Serious adverse event | 0 participants |
| Vedolizumab 750 mg | Number of Participants With Adverse Events (AEs) | Serious infection adverse events | 0 participants |
| Vedolizumab 750 mg | Number of Participants With Adverse Events (AEs) | Drug-related serious adverse event | 0 participants |
| Vedolizumab 750 mg | Number of Participants With Adverse Events (AEs) | Serious adverse event resulting in discontinuation | 0 participants |
| Vedolizumab 750 mg | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Any adverse event | 50 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Serious infection adverse events | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Drug-related adverse event | 22 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Serious adverse event resulting in discontinuation | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Adverse event resulting in study discontinuation | 1 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Drug-related serious adverse event | 0 participants |
| Placebo | Number of Participants With Adverse Events (AEs) | Serious adverse event | 1 participants |
Secondary
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.
Time frame: Baseline and Day 74
Population: The Dukoral Population was defined as all participants who had evaluable samples for assessing immune response to cholera vaccine (Dukoral) vaccine at any visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vedolizumab 750 mg | Percentage of Participants With an Immune Response to Oral Cholera Vaccine | 82.5 percentage of participants |
| Placebo | Percentage of Participants With an Immune Response to Oral Cholera Vaccine | 96.8 percentage of participants |
95% CI: [-24.6, -3.9]