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 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.

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).