Shingrix Vaccine in Patients With Moderate to Severe Ulcerative Colitis on Tofacitinib

NCT03591770 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: H-37673
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), have been shown to be at increased risk of developing certain infections, such as shingles from the Herpes Zoster (HZ) virus, as a result of their underlying disease. Patients with UC are also often treated with immunosuppressants, and research has shown that IBD patients on immunosuppressants have an impaired immune response to vaccination in comparison to immunocompetent controls. Because UC patients are often treated with immunosuppressants, the live HZ vaccine was not recommended in these patients. Shingrix, however, is a new inactivated vaccine recently approved by the FDA for prevention of HZ in adults age 50 and older, and Shingrix should be safe to administer in IBD patients because it does not contain live HZ virus. Data on efficacy of the Shingrix vaccine also appears promising in immunocompromised patients. Tofacitinib citrate (Xeljanz), an immunosuppressant that works by inhibiting the Janus kinase pathway, is currently approved for treatment of certain inflammatory diseases such as rheumatoid arthritis and psoriasis. The drug is currently awaiting FDA-approval for use in moderate-to-severe UC but has been used off-label in various settings. Notably, tofacitinib was associated with an increased risk of HZ in patients with rheumatoid arthritis and psoriasis. The research hypothesis is that UC patients on tofacitinib will mount an adequate response and that the response will be slightly diminished compared to non-immunosuppressed IBD patients, comparable to those on anti-tumor necrosis alpha (anti-TNF) monotherapy, and superior to those on anti-TNF therapy in combination with a thiopurine. Strong cell mediated immunity is shown to prevent reactivation of HZ, and demonstrating a robust immune response to Shingrix may serve as a surrogate for a reduced risk of developing shingles and might alleviate prescribers' concerns regarding the use of tofacitinib. The results will also serve as pilot data to inform larger future studies evaluating the actual risk of developing shingles in patients on tofacitinib who receive Shingrix.

Conditions

Inflammatory Bowel Diseases

Keywords

Shingrix vaccine; tofacitinib monotherapy; anti-TNF monotherapy; anti-TNF agent; thiopurine; aminosalicylates

Outcome Measures

Primary Outcomes (1)

• Change in the Immunogenicity of the Herpes Zoster Subunit Vaccine in UC Patients

  Immunogenicity will be assessed by the change in cell mediated immunity (CMI) as measured by ELISPOT from pre-immunization to 1 month after receiving second dose of booster vaccine post-immunization. ELISPOT is an enzyme-linked assay for detecting and enumerating cytokine-producing lymphocytes. A colored spot indicates a cell producing IFNγ. Each well will be inspected and cytokine-producing cells will be counted using AID® imaging system. Any well with more than 300 spots will be considered too numerous to count and reported as \>300 cells/well. It will be measured from pre-immunization to 1 month after receiving second dose of booster vaccine post-immunization.

  Baseline and approximately 90 days

Secondary Outcomes (3)

• The Number of Participants With Vaccine Adverse Effects at 1 Month

  1 month

• Number of Participants With Vaccine Adverse Effects at 8 Months (6 Months Post-immunization)

  8 months (6 months post-immunization)

• Number of Participants Classified by Disease Activity

  Baseline, 2 months, and 8 months (6 months post-immunization)

Study Arms (4)

UC patients on tofacitinib monotherapy

EXPERIMENTAL

Ulcerative Colitis patients on Tofacitinib monotherapy, all patients will be treated with the standard Tofacitinib and will receive Shingrix vaccine.

Biological: SHINGRIX

UC patients on anti-TNF monotherapy

ACTIVE COMPARATOR

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.

Biological: SHINGRIX

UC patients on anti-TNF and a thiopurine

ACTIVE COMPARATOR

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.

Biological: SHINGRIX

UC pts. on aminosalicylates or off immunomodulatory therapy

ACTIVE COMPARATOR

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.

Biological: SHINGRIX

Interventions

SHINGRIX BIOLOGICAL

SHINGRIX is a vaccine indicated for prevention of herpes zoster (shingles) in adults aged 50 years and older. SHINGRIX is a suspension for injection supplied as a single-dose vial of lyophilized gE antigen component to be reconstituted with the accompanying vial of AS01B adjuvant suspension component. A single dose after reconstitution is 0.5 mL. Dose and Schedule: Two doses (0.5 mL each) administered intramuscularly according to the following schedule: A first dose at Month 0 followed by a second dose administered anytime between 2 and 6 months later.

Also known as: Recombinant zoster vaccine

UC patients on anti-TNF and a thiopurine; UC patients on anti-TNF monotherapy; UC patients on tofacitinib monotherapy; UC pts. on aminosalicylates or off immunomodulatory therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patient has a history of ulcerative colitis (UC) diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria
• 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.

You may not qualify if:

• Previous receipt of any HZ vaccine
• Allergy to zoster vaccine or a component of the vaccine
• Other underlying chronic medical conditions that could affect immunogenicity to vaccines (rheumatoid arthritis, psoriasis etc.)
• History of herpes zoster infection or post herpetic neuralgia
• Patient cannot or will not provide written informed consent
• Patient is on a non-licensed or experimental immunomodulator
• Patient is on methotrexate
• Patient has received immunoglobulin therapy or blood products with the past month
• Currently pregnant

Sponsors & Collaborators

• Boston Medical Center: lead

Study Sites (1)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Limitations and Caveats

The study was halted since the investigators were unable to recruit adequate numbers of participants to answer the research question. There were no patients enrolled in the anti-TNF and a thiopurine group.

Results Point of Contact

• Title: Sharmeel K. Wasan, MD
• Organization: Boston Medical Center

sharmeel.wasan@bmc.org

(617) 638-6116

Study Officials

• Sharmeel K Wasan, MD

  Boston Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2018
• First Posted: July 19, 2018
• Study Start: July 31, 2019
• Primary Completion: July 4, 2024
• Study Completion: July 4, 2024
• Last Updated: February 21, 2025
• Results First Posted: February 21, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)