Immunogenicity of Herpes Zoster Subunit Vaccine in Inflammatory Bowel Disease Patients Treated With Vedolizumab

Study Overview
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Brief Summary
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Inflammatory bowel disease (IBD) is a chronic inflammatory state of the gastrointestinal tract(1) affecting 1.6-3.1 million people in the United States. Patients with IBD are treated with immunosuppressants that increase their risk of herpes zoster (HZ), also known as shingles. Those with IBD have a two-fold increased risk for HZ compared to age matched controls. Because most IBD patients are treated with systemic immunosuppressants, which are an independent risk factor for HZ, the live attenuated HZ vaccine was not recommended. However, the release of the new inactivated HZ vaccine, Shingrix (GlaxoSmithKline), presents new opportunities for preventive care.

Detailed Description
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The purpose of this study is to determine the immunogenicity of the herpes zoster subunit vaccine in inflammatory bowel disease patients on vedolizumab compared to those on anti-tumor necrosis factor (TNF) monotherapy. The study will evaluate humoral and cell mediated immunity in patients with IBD on vedolizumab who receive the two-dose herpes zoster vaccine. The investigators will evaluate short term, one month after second vaccination dose and sustained immunogenicity at 6 and 12 months post vaccination. The central hypothesis of this proposal is that IBD patients on vedolizumab should be able to mount a normal vaccine response comparable to those on anti-TNF monotherapy who might benefit from a third dose of the subunit vaccine as has been evaluated in HIV and transplant populations. The hypothesis is that IBD patients on vedolizumab will be able to mount a superior response to those on anti-TNF therapy. A recent study showed that hepatitis B vaccine immunogenicity was not affected by vedolizumab. The study population will include adult patients aged 50 or older with IBD(diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria) receiving care at University of Wisconsin Hospital and Clinics or Boston Medical Center. There is no randomization or use of placebo in this study. Two study groups (each containing 15 subjects) will be established Group A: Patients with IBD on anti-TNF monotherapy and Group B patients with IBD on vedolizumab monotherapy. Methods: Eligible patients with IBD will be recruited from the University of Wisconsin Hospital and Clinics or from Center for Digestive Diseases at Boston Medical Center.

Official Title
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A Pilot Study Evaluating Immunogenicity of Herpes Zoster Subunit Vaccine in Inflammatory Bowel Disease Patients Treated With Vedolizumab

Conditions
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Herpes Zoster, Inflammatory Bowel Diseases, Crohn Disease, Ulcerative Colitis

Intervention / Treatment
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* Biological: Shingrix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is between the ages of 18-70 years, inclusive. History of primary varicella infection (chicken pox) Confirmed by a previous history of positive varicella zoster virus (VZV) Immunoglobulin G antibody or history of chicken pox Patient has a history of ulcerative colitis (UC) or Crohn's disease diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria. Patient is receiving one of the following treatments for their IBD Group A: Anti-TNF monotherapy (adalimumab, certolizumab, golimumab, infliximab) Group B: Vedolizumab monotherapy Patient has been on stable treatment for IBD for at least three months. Exclusion Criteria: Previous receipt of any HZ vaccine Allergy to zoster vaccine or a component of it Other underlying chronic medical condition that could affect immunogenicity to vaccines (rheumatoid arthritis, etc.) History of herpes zoster or post herpetic neuralgia within the past year. Patient cannot or will not provide written informed consent. Patient is being administered immunomodulators currently or within the past three months Patient has been taking any dose of oral or intravenous steroids within 30 days prior to immunization. Patient has received polyclonal immunoglobulin therapy or blood products within the last year. Patient is pregnant per self-reporting or older than age 70 years Unable to provide appropriate informed consent due to being illiterate or impairment in decision-making capacity.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Anti-TNF monotherapy<br>Patients with IBD on Anti-TNF monotherapy will be given the shingrix vaccine. Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later. | Biological: Shingrix<br>* Biological: SHINGRIX SHINGRIX is a vaccine indicated for prevention of herpes zoster (shingles) in adults aged 18 years and older. SHINGRIX is a suspension for injection supplied as a single-dose vial of lyophilized glycoprotein e (ge) antigen component to be reconstituted with the accompanying vial of AS01B adjuvant suspension component. A single dose after reconstitution is 0.5 mL. Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later.<br>* Other names: Recombinant zoster vaccine;|
| Active Comparator: Vedolizumab<br>Patients with IBD on vedolizumab monotherapy will be given the shingrix vaccine. Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later. | Biological: Shingrix<br>* Biological: SHINGRIX SHINGRIX is a vaccine indicated for prevention of herpes zoster (shingles) in adults aged 18 years and older. SHINGRIX is a suspension for injection supplied as a single-dose vial of lyophilized glycoprotein e (ge) antigen component to be reconstituted with the accompanying vial of AS01B adjuvant suspension component. A single dose after reconstitution is 0.5 mL. Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later.<br>* Other names: Recombinant zoster vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cell mediated immunity | The primary objective will be the change in cell mediated immunity (CMI) as measured by ELISPOT from pre-immunization to one month after receiving second dose of vaccine. | It will be measured from pre-immunization to 1 month after receiving second dose of booster vaccine post-immunization. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of participants with sustained cell mediated immunity measured via ELISPOT after immunization. | Sustained change in CMI at 6 months will be assessed after receiving a second dose of booster vaccine post-immunization. CMI will be measured via ELISPOT | Baseline to 6 months post-immunization 2nd dose of vaccine. | 
| Percent of participants with a change in antibody concentration post immunization | A secondary outcome will be the change in varicella zoster virus (VZV) antibody concentration comparing pre-immunization to post immunization antibody concentration. | pre-immunization to one month 2nd dose post-immunization | 
| Percent of participants with a change in antibody concentration that is sustained at 6 months | Sustained change in VZV antibody concentration at 6 months after receiving a second dose of booster vaccine post-immunization will be assessed. | Baseline to 6 months post-immunization | 
| Incidence of Vaccine related adverse effects | To evaluate for adverse effects following immunization patients will receive phone calls from study personnel to ascertain vaccine-related adverse effects. | This will be done at months 1, 2 and 3. | 
| Incidence of change in disease activity post immunization | The Simple Clinical Colitis Activity Index (SCCAI) will be used to measure disease activity. It is a questionnaire with six subscore topics with scores defined by UC signs and symptoms from 0 to 4 for a range of scores from 0 to 17. Total scores are interpreted as: Remission = score of 0 to 4 points, Mild Activity = score of 5 to 7 points, Moderate Activity = Score of 8 to 16 points, and Severe Activity = Score of > 16 points. | at the baseline visit and one month after receipt of each vaccine |