Shingrix Vaccine in Patients With Moderate to Severe Ulcerative Colitis on Tofacitinib
Keywords
Abstract
Description
The purpose of this study is to determine the immune response from the new Shingrix vaccine in UC patients on tofacitinib monotherapy in comparison to other UC therapies. the investigators plan to determine this by vaccinating IBD patients on (a) tofacitinib monotherapy, (b) anti-TNF monotherapy, (c) anti-TNF combination therapy with a thiopurine, or (d) aminosalicylates or other non-immunosuppressive therapy with the new Shingrix vaccine and measuring markers of cell-mediated immunity before vaccination and at one and six months after the last vaccine dose. Cell-mediated immunity will be measured with an interferon gamma (IFNγ) enzyme linked immunospot (ELISPOT) test to assess T-cell response. Humoral immunity will also be measured with an enzyme-linked immunosorbent assay (ELISA) kit to quantify antibody concentrations of Varicella Zoster Virus (VZV), the pathogen that when reactivated results in shingles.
The study population will include adult patients aged 50 or older with UC (diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria) receiving care at Boston Medical Center, Hospital of the University of Pennsylvania, or University of Wisconsin Hospital and Clinics. There is no randomization or use of placebo in this study. Four study groups (each containing 25 subjects) will be established -- 1. Group A - UC patients on tofacitinib monotherapy. 2. Group B - UC patients receiving anti-TNF monotherapy (adalimumab, golimumab, infliximab). 3. Group C - UC patients on an anti-TNF agent and a thiopurine (6-mercaptopurine, azathioprine). Group D - UC patients on non-immunosuppressive therapy or 5-aminosalicylates. For each subject, 3 total samples will be collected.
Methods: Eligible patients with UC will be recruited from the Center for Digestive Diseases at Boston Medical Center, the Hospital of the University of Pennsylvania, or the University of Wisconsin Hospital and Clinics. Patients will be screened for participation in the study and recruited by their primary gastroenterologist. In clinic, a handout of the risks and benefits of the clinically indicated vaccine (Shingrix) will be given to each patient from their primary gastroenterologist for their review. Patients will have the opportunity to opt in or out of the study early in the consent process upon review of the handout. If a patient elects to participate in the study, patients will sign the consent, be entered into the study with assignment of a Subject ID number, and complete the initial study assessments:
Subject contacts:
- 1 - Baseline/Enrollment Visit 1 (Day 0): Subjects will have a comprehensive medical history and physical exam performed, including vaccination history and all medications over past 30 days. They will also complete a Simple Clinical Colitis Activity Index (SCCAI) questionnaire. A baseline blood sample of approximately 20mL (4 tablespoons) will then be obtained. If proof of past varicella infection is met by appropriate history, subjects will receive the Shingrix vaccine indicated based on their vaccination history as recommended by their gastroenterologist; otherwise subjects will follow-up in 1 week to review confirmatory serology results and receive vaccine if indicated. The Shingrix vaccine will be given in a two-dose series (0.5 mL each) administered intramuscularly -first dose at Month 0 followed by a second dose anytime between 2 and 6 months later. Subjects will be instructed to call the study team for any concerns or any development of fever, chills, rash or other concerning symptom.
- 2- Follow up Visit 2 (approximately day 7): This visit is only needed for patients who require serologic confirmation of past varicella infection, therefore patients who meet proof for past varicella infection by appropriate history do not require serologic confirmation and will NOT be scheduled for this visit. Subjects will review results of the VZV antibody level test with their provider. If VZV antibody levels are positive, subjects will receive the Shingrix vaccine indicated based on their vaccination history as recommended by their gastroenterologist. Subjects will be instructed to call the study team for any concerns or any development of fever, chills, rash or other concerning symptom.
- 3 - Follow up Phone Call 1 (approximately day 14): Subjects will receive a follow-up phone call to identify any adverse effects including fevers or chills, rash, and visits to the emergency room or to their primary care physicians. They will also be reminded about their follow up visit.
- 4 - Follow up Visit 3 (approximately day 60): Subjects will complete a SCCAI questionnaire, and information will be collected to identify any adverse effects including fevers or chills, rash, and visits to the emergency room or to their primary care physician. The 2nd dose of the Shingrix vaccine will be administered.
- 5 - Follow up Phone Call 2 (approximately day 72): Subjects will receive a follow-up phone call to identify any adverse effects including fevers or chills, rash, and visits to the emergency room or to their primary care physicians. They will also be reminded about their follow up visit.
- 6 - Follow up Visit 4 (approximately day 90): Subjects will complete a SCCAI questionnaire, and information will be collected to identify any adverse effects including fevers or chills, rash, and visits to the emergency room or to their primary care physician. A blood sample of approximately 20mL (4 tablespoons) will then be obtained.
- 7 - Follow up Visit 5 (approximately day 240): Subjects will complete a SCCAI questionnaire, and information will be collected to identify any adverse effects including fevers or chills, rash, and visits to the emergency room or to their primary care physician. A blood sample of approximately 20mL (4 tablespoons) will then be obtained.
The entire procedure will be identically performed at the additional sites outside of Boston Medical Center. Subjects' duration of participation will range from 8 to 12 months, depending on when the 2nd vaccine dose is administered.
Dates
| Last Verified: | 03/31/2020 |
| First Submitted: | 07/08/2018 |
| Estimated Enrollment Submitted: | 07/08/2018 |
| First Posted: | 07/18/2018 |
| Last Update Submitted: | 04/21/2020 |
| Last Update Posted: | 04/23/2020 |
| Actual Study Start Date: | 07/30/2019 |
| Estimated Primary Completion Date: | 09/30/2020 |
| Estimated Study Completion Date: | 09/30/2020 |
Condition or disease
Intervention/treatment
Biological: SHINGRIX
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: UC patients on tofacitinib monotherapy Ulcerative Colitis patients on Tofacitinib monotherapy, all patients will be treated with the standard Tofacitinib and will receive Shingrix vaccine. | |
| Active Comparator: UC patients on anti-TNF monotherapy Ulcerative Colitis patients on anti-TNF monotherapy, all patients will be treated with the standard anti-TNF monotherapy (adalimumab, golimumab, certolizumab, infliximab)and will receive Shingrix vaccine. | |
| Active Comparator: UC patients on anti-TNF and a thiopurine Ulcerative Colitis patients on anti-TNF and a thiopurine, all patients will be treated with the standard anti-TNF monotherapy (adalimumab, golimumab, certolizumab, infliximab) and thiopurine (6-mercaptopurine, azathioprine) and will receive Shingrix vaccine. | |
| Active Comparator: UC pts. on aminosalicylates or off immunomodulatory therapy Ulcerative Colitis patients on non-immunosuppressive therapy or 5-aminosalicylates, all patients will be treated with the standard non-immunosuppressive therapy or 5-aminosalicylates and will receive Shingrix vaccine. |
Eligibility Criteria
| Ages Eligible for Study | 50 Years To 50 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: 1. Proof of primary varicella infection (chicken pox) either by appropriate history (as defined by ACIP) or otherwise confirmed with a positive VZV IgG antibody level 2. Patient has a history of ulcerative colitis (UC) diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria 3. Patient is receiving one of the following treatments for their UC: Group A: Tofacitinib monotherapy, Group B: Anti-TNF monotherapy (adalimumab, golimumab, certolizumab pegol, infliximab), Group C: Anti-TNF combination therapy with a thiopurine (6 mercaptopurine, azathioprine), Group D: 5-aminosalicylates or other non-immunomodulatory therapy. Exclusion Criteria: 1. Previous receipt of any HZ vaccine 2. Allergy to zoster vaccine or a component of the vaccine 3. Other underlying chronic medical conditions that could affect immunogenicity to vaccines (rheumatoid arthritis, psoriasis etc.) 4. History of herpes zoster infection or post herpetic neuralgia 5. Patient cannot or will not provide written informed consent 6. Patient is on a non-licensed or experimental immunomodulator 7. Patient is on methotrexate 8. Patient has received immunoglobulin therapy or blood products with the past month 9. Currently pregnant |
Outcome
Primary Outcome Measures
1. Change in the immunogenicity of the herpes zoster subunit vaccine in UC patients [Baseline and approximately 90 days]
Secondary Outcome Measures
1. Sustained T cell response [Baseline to 6 months post-immunization]
2. Change in antibody response [Baseline to 1 month post-immunization]
3. Sustained antibody response [Baseline to 6 months post-immunization]
4. Vaccine adverse effects at 1 month [1 month]
5. Vaccine adverse effects at 2 months [2 months]
6. Vaccine adverse effects at 3 months (1 month post-immunization) [3 months (1 months post-immunization)]
7. Vaccine adverse effects at 8 months (6 months post-immunization) [8 months (6 months post-immunization)]
8. Change in disease activity [Baseline and 8 months (6 months post-immunization)]
