Clinical trial NCT06224270: Study of Response to Zoster Vaccine in Adults with Inflammatory Bowel Disease Treated with Medications
Official title: Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Adults with Inflammatory Bowel Disease on Biologic Immunosuppressive Therapies
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Inflammatory Bowel Diseases
IBD
Keywords: immunosuppressed
Recombinant Zoster Vaccine
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2024-01-25
Enrollment: 0
Sex: ALL
Minimum age (years): 19
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open label, multicenter trial evaluating the safety and immunogenicity of recombinant herpes zoster vaccine in adults with IBD on immunosuppressive therapy.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Geometric Mean Concentrations of Anti-gE Antibodies
timeFrame: Visit 3 (between 50 and 140 days on study)
Secondary outcomes:
measure: Vaccine response rate (VRR)
timeFrame: Visit 3 (between 50 and 140 days on study)
measure: Seropositivity rate
timeFrame: Visit 1 (day 1), Visit 3 (between 50 and 140 days on study), Visit 4 (approximately 360 days)
measure: Geometric Mean Concentrations of Anti-gE Antibodies
timeFrame: Visit 1 (day 1), Visit 3 (between 50 and 140 days on study), Visit 4 (approximately 360 days)
measure: Number of Participants with Solicited Adverse Events (AEs)
timeFrame: Up to 7 days after Visit 1, up to 7 days after Visit 2
measure: Number of Participants with Unsolicited Adverse Events
timeFrame: up to 30 days after Visit 1, up to 30 days after Visit 2
measure: Number of Participants Reporting Potential Immune-Mediated Diseases (pIMDs)
timeFrame: up to 14 months
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: up to 14 months
measure: Number of Herpes Zoster Events
timeFrame: up to 14 months
measure: Number of Participants Reporting Complications from HZ
timeFrame: up to 14 months
measure: Number of Participants reporting disease flares of IBD
timeFrame: 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 outcomes:
measure: Number of gE-specific CD4 cells expressing at least 2 activation markers
timeFrame: Visit 1 (day 1), Visit 3 (up to 140 days on study), Visit 4 (up to 360 days)
measure: Vaccine response rate (VRR) in patients on JAKs
timeFrame: Visit 3 (up to 140 days on study)
measure: Seropositivity rate in patients on JAKs
timeFrame: Visit 1 (day 1), Visit 3 (up to 140 days on study), Visit 4 (up to 360 days)
measure: Geometric Mean Concentrations of Anti-gE Antibodies in Patients on JAKs
timeFrame: Visit 1 (day 1), Visit 3 (up to 140 days on study), Visit 4 (up to 360 days)
measure: Geometric Mean Concentrations of Anti-gE Antibodies by Alpha Diversity of Microbiome
timeFrame: Visit 3 (up to 140 days on study)
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: New York
country: United States
facility: New York University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Madison
country: United States
facility: UW Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Freddy Caldera, DO, MS
role: PRINCIPAL_INVESTIGATOR
References: