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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis; Herpes Zoster
• Intervention / Treatment: Biological: Shingrix

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Digestive Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient is between the ages of 18-70 years, inclusive.
2. 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
3. Patient has a history of ulcerative colitis (UC) or Crohn's disease diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria.
4. Patient is receiving one of the following treatments for their IBD Group A: Anti-TNF monotherapy (adalimumab, certolizumab, golimumab, infliximab) Group B: Vedolizumab monotherapy
5. Patient has been on stable treatment for IBD for at least three months.

Exclusion Criteria:

1. Previous receipt of any HZ vaccine
2. Allergy to zoster vaccine or a component of it
3. Other underlying chronic medical condition that could affect immunogenicity to vaccines (rheumatoid arthritis, etc.)
4. History of herpes zoster or post herpetic neuralgia within the past year.
5. Patient cannot or will not provide written informed consent.
6. Patient is being administered immunomodulators currently or within the past three months
7. Patient has been taking any dose of oral or intravenous steroids within 30 days prior to immunization.
8. Patient has received polyclonal immunoglobulin therapy or blood products within the last year.
9. Patient is pregnant per self-reporting or older than age 70 years
10. Unable to provide appropriate informed consent due to being illiterate or impairment in decision-making capacity.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Anti-TNF monotherapy; 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; 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.; Other Names: Recombinant zoster vaccine
Active Comparator: Vedolizumab; 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; 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.; Other Names: Recombinant zoster vaccine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Boston Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2019
• Primary Completion (Actual): October 12, 2023
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: January 2, 2019
• First Submitted That Met QC Criteria: January 8, 2019
• First Posted (Actual): January 10, 2019

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Virus Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; DNA Virus Infections; Skin Diseases, Infectious; Skin Diseases, Viral; Herpesviridae Infections; Varicella Zoster Virus Infection; Inflammatory Bowel Diseases; Crohn Disease; Intestinal Diseases; Herpes Zoster; Herpes Simplex; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 2018-1037; SMPH/MEDICINE/GASTROENT (Other Identifier: UW Madison); A534250 (Other Identifier: UW Madison); Protocol Version 9/22/2021 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No