Study of Response to Zoster Vaccine in Adults with Inflammatory Bowel Disease Treated with Medications

Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Adults with Inflammatory Bowel Disease on Biologic Immunosuppressive Therapies

This multi-center study will evaluate the safety and immune response to recombinant zoster vaccine (RZV) series in 264 patients with inflammatory bowel disease (IBD) on immunosuppressive therapy recruited from 6 study sites who can expect to be on study for up to 14 months.

Study Overview

• Status: Withdrawn
• Conditions: Inflammatory Bowel Diseases; IBD
• Intervention / Treatment: Biological: Adjuvanted Recombinant Zoster Vaccine (RZV)

Detailed Description

Study Visits:

• Visit 1 (V1) - day 1 - blood draw, RZV dose 1

  • Follow up (FU) 1 - between days 7-15
  • FU 2 - between days 22-29

• Visit 2 (V2) - between days 30-90 - RZV dose 2

  • FU 3 - V2 + 7-14 days
• Visit 3 (V3) - V2 + 21-50 days - blood draw
• Visit 4 (V4) - V2 + approximately 360 days - blood draw

Primary Objective:

• To demonstrate a 10% higher humoral immunogenicity following two doses of RZV in patients on non-TNF biologic therapy compared to those on anti-TNF biologic therapy.

Secondary Objectives:

• To evaluate the vaccine response rate (VRR) for anti-glycoprotein E (gE) humoral immune responses in patients on non-TNF biologic therapy compared to those on anti-TNF biologic therapy.
• To characterize the anti-gE humoral immunogenicity at visit 1 (V1), visit 3 (V3), and visit 4 (V4) in patients on non-TNF biologic therapy compared to those on anti-TNF biologic therapy.
• To evaluate the safety and reactogenicity following administration of RZV, up to 30 days post-last vaccination and during the entire post-vaccination follow-up period.
• To evaluate IBD activity following administration of RZV, up to 30 days post-last vaccination and during the entire post-vaccination follow-up period.

Tertiary/Exploratory Objectives:

• To characterize gE-specific CD4+ T-cell mediated immune responses in patients on non-TNF biologic therapy compared to those on anti-TNF biologic therapy.
• To characterize gE-specific CD4+ T-cell mediated immune responses in patients on JAKs.
• To evaluate the VRR for anti-gE humoral immune responses in patients on Janus Kinase inhibitors (JAKs).
• To characterize the anti-gE humoral immunogenicity at V1, V3, and V4 in patients on JAKs.
• To determine the relationship between gut microbiota and response to RZV series.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
  • New York
    • New York, New York, United States, 10012
      • New York University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt University
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • UW Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient is between the ages of 19 and 85 years with a diagnosis of IBD based on standard clinical and histological criteria.
• Can provide appropriate written informed consent.
• Patient has a history of ulcerative colitis or Crohn's disease diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria.

• Patient is receiving one of the following treatments for their IBD:

  • Anti-TNF therapy (infliximab, adalimumab, certolizumab, or golimumab)

    • On anti-TNF monotherapy
    • Or anti-TNF therapy in combination with either 10mg of methotrexate or azathioprine at least 1.0mg/kg or 6-Mercaptopurine (6MP) 0.5mg/kg

  • Non-TNF therapy

    • On ustekinumab monotherapy or in combination with either 10mg of methotrexate or azathioprine at least 1.0mg/kg or 6MP 0.5mg/kg
    • On vedolizumab monotherapy or in combination with either 10mg of methotrexate or azathioprine at least 1.0mg/kg or 6MP 0.5mg/kg
    • On Risankizumab monotherapy or in combination with either 10mg of methotrexate or azathioprine at least 1.0mg/kg or 6MP 0.5mg/kg
    • On mirikizumab monotherapy or in combination with either 10mg of methotrexate or azathioprine at least 1.0mg/kg or 6MP 0.5mg/kg

  • Janus Kinase Inhibitor

    • On tofacitinib at least 5mg PO twice per day (BID)
    • On upadactinib at least 15mg PO BID
• Patient has been on stable biologic or JAK treatment for IBD for at least two months.

• Patient is in stable clinical remission

  o No recent corticosteroid prescription within the past two months.

• Female participant of non-childbearing potential (pre-menarche, current tubal ligation, hysterectomy, oophorectomy or post-menopause) and childbearing potential (if they had: practiced adequate contraception (include IUD or equivalent, hormonal contraceptive (e.g. pill, patch, ring, implant or an injection used consistently and that has reached full effect prior to the first dose of vaccine), hysterectomy and/or a bilateral tubal ligation or bilateral oophorectomy) for 1 month prior to vaccination and agrees to continue adequate contraception during the primary treatment period, and for 2 months after completion of the vaccination series). Non-pregnant females with a negative pregnancy test who are willing to practice adequate contraception during the primary treatment period, and for 2 months after completion of the vaccination series).

Exclusion Criteria:

• Patient cannot or will not provide written informed consent.
• Patient has been taking any dose of oral or intravenous steroids for more than 3 days within 2 months prior to immunization.
• Any confirmed or suspected HIV, primary immunodeficiency disease, disseminated or untreated malignancy, or systemic infection.
• Previous vaccination against HZ or varicella within the 12M preceding the first dose of RZV.
• Occurrence of varicella or HZ per clinical history, within the 12M preceding the first dose of RZV.
• Evidence or high suspicion, in the opinion of the investigator, of noncompliance or nonadherence to the use of induction and/or maintenance immunosuppressive therapies.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine or study material and equipment.
• Any condition which, in the judgment of the investigator, would make intramuscular injection unsafe.
• Any condition which, in the judgment of the investigator, would make intramuscular injection unsafe.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) before Month 3 (i.e. 2 months after last dose of study V2).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adults with IBD	Biological: Adjuvanted Recombinant Zoster Vaccine (RZV); The RZV vaccine is indicated for prevention of herpes zoster (HZ) in adults aged 18 years and older who are or will be at increased risk of HZ. Patients with IBD on immunosuppressive therapy are at increased risk for HZ.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Concentrations of Anti-gE Antibodies	Anti-gE antibody concentrations expressed as geometric mean concentrations (GMCs) at V3, following 2 doses of RZV, in patients on non-TNF biologic therapy compared to those on anti-TNF biologic therapy.	Visit 3 (between 50 and 140 days on study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccine response rate (VRR)	Vaccine response rate (VRR) with exact 95% confidence intervals at V3 in those on non-TNF biologic therapy compared to those on anti-TNF biologic therapy.	Visit 3 (between 50 and 140 days on study)
Seropositivity rate	Seropositivity rate with exact 95% confidence interval (CI) at V1, V3, and V4 in patients on non-TNF biologic therapy compared to those on anti-TNF biologic therapy.	Visit 1 (day 1), Visit 3 (between 50 and 140 days on study), Visit 4 (approximately 360 days)
Geometric Mean Concentrations of Anti-gE Antibodies	Anti-gE antibody concentrations expressed as GMC with 95% CI at V1, V3, and V4 in patients on non-TNF biologic therapy compared to those on anti-TNF biologic therapy.	Visit 1 (day 1), Visit 3 (between 50 and 140 days on study), Visit 4 (approximately 360 days)
Number of Participants with Solicited Adverse Events (AEs)	Number and percentage of patients reporting each solicited local AE and each solicited systemic AE within 7 days (Days 1-7) after each dose and overall for all study groups. Solicited local AEs are: injection site pain, redness, swelling. Solicited systemic AEs are: fatigue, myalgia, arthralgia, headache, shivering/chills, fever and gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain).	Up to 7 days after Visit 1, up to 7 days after Visit 2
Number of Participants with Unsolicited Adverse Events	Number and percentage of patients reporting unsolicited AEs within 30 days (Days 1-30) after each dose and overall, for all study groups.	up to 30 days after Visit 1, up to 30 days after Visit 2
Number of Participants Reporting Potential Immune-Mediated Diseases (pIMDs)	Number and percentage of patients reporting pIMDs from first vaccination up to study end for all study groups.	up to 14 months
Number of Participants with Serious Adverse Events (SAEs)	Number and percentage of patients reporting SAEs and fatal SAEs from first vaccination up to study end for all study groups.	up to 14 months
Number of Herpes Zoster Events	Number of cases of suspected HZ from study entry to last follow up date.	up to 14 months
Number of Participants Reporting Complications from HZ	Number and percentage of patients reporting any complications of HZ reported as AEs from study entry to last follow up date.	up to 14 months
Number of Participants reporting disease flares of IBD	Number and percentage of patients reporting disease flares of IBD in both study groups which will be assessed by monitoring disease activity using the Short Crohn's Activity Index (SCAI) for patients with Crohn's disease or the Simple Clinical Colitis Activity Index (SCCAI) questionnaire for patients with Ulcerative colitis at the baseline visit V1, Follow up 2 (FU2), V2, V3, and V4 visit.	baseline, Visit 1 (day 1), Follow-Up 2 (up to 29 days), Visit 2 (up to 90 days), Visit 3 (up to 140 days on study), Visit 4 (up to 360 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of gE-specific CD4 cells expressing at least 2 activation markers	The number of gE-specific CD4 cells expressing at least 2 activation markers at V3 and at V4 compared to V1.	Visit 1 (day 1), Visit 3 (up to 140 days on study), Visit 4 (up to 360 days)
Vaccine response rate (VRR) in patients on JAKs	VRR with exact 95% CIs at V3.	Visit 3 (up to 140 days on study)
Seropositivity rate in patients on JAKs	Seropositivity rate with exact 95% CI at V1, V3, and V4	Visit 1 (day 1), Visit 3 (up to 140 days on study), Visit 4 (up to 360 days)
Geometric Mean Concentrations of Anti-gE Antibodies in Patients on JAKs	Anti-gE antibody concentrations expressed as GMC with 95% CI at V1, V3, and V4 in patients on JAK's.	Visit 1 (day 1), Visit 3 (up to 140 days on study), Visit 4 (up to 360 days)
Geometric Mean Concentrations of Anti-gE Antibodies by Alpha Diversity of Microbiome	Anti-gE antibody concentrations expressed as GMC with 95% CI at V3 by alpha diversity of microbiome	Visit 3 (up to 140 days on study)

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Freddy Caldera, DO, MS, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: January 16, 2024
• First Submitted That Met QC Criteria: January 24, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: immunosuppressed; Recombinant Zoster Vaccine
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: 2023-1727; A534250 (Other Identifier: UW Madison); Protocol Version 6/14/2024 (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.: Yes