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

Inflammatory Bowel Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06224270
• Other study ID #: 2023-1727
• Secondary ID: A534250Protocol
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: May 2024
• Est. completion date: July 2027

Study information

• Verified date: March 2024
• Source: University of Wisconsin, Madison
• Contact: Ali Moellner, MPH
• Phone: (608) 265-5229
• Email: moellner[@]wisc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 264
• Est. completion date: July 2027
• Est. primary completion date: July 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 85 Years

Eligibility

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
• 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 for 1 month (M) prior to vaccination, a negative pregnancy test on the day of the first vaccination and agrees to continue adequate contraception during the primary treatment period, and for 2M 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.
• 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.

Related Conditions & MeSH terms

• IBD
• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

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.

Locations

Country	Name	City	State
United States	Mercy Medical Center	Baltimore	Maryland
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Mayo Clinic	Jacksonville	Florida
United States	UW Hospital and Clinics	Madison	Wisconsin
United States	Vanderbilt University	Nashville	Tennessee
United States	New York University	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	Vaccine response rate (VRR) in patients on JAKs	VRR with exact 95% CIs at V3.	Visit 3 (up to 140 days on study)
Other	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)
Other	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)
Other	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Herpes Zoster Events	Number of cases of suspected HZ from study entry to last follow up date.	up to 14 months
Secondary	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
Secondary	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)