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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03591770
Recruitment Status : Suspended (Currently suspended due to Covid-19 policies.)
First Posted : July 19, 2018
Last Update Posted : April 24, 2020
Sponsor:
Information provided by (Responsible Party):
Boston Medical Center

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.


Condition or disease Intervention/treatment Phase
Inflammatory Bowel Diseases Biological: SHINGRIX Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Immunogenicity and Safety of Shingrix Vaccine in Patients With Moderate to Severe Ulcerative Colitis on Tofacitinib
Actual Study Start Date : July 31, 2019
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Tofacitinib

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.
Biological: SHINGRIX

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.

Other Name: Recombinant zoster 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.
Biological: SHINGRIX

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.

Other Name: Recombinant zoster 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.
Biological: SHINGRIX

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.

Other Name: Recombinant zoster 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.
Biological: SHINGRIX

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.

Other Name: Recombinant zoster vaccine




Primary Outcome Measures :
  1. Change in the immunogenicity of the herpes zoster subunit vaccine in UC patients [ Time Frame: Baseline and approximately 90 days ]
    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.


Secondary Outcome Measures :
  1. Sustained T cell response [ Time Frame: Baseline to 6 months post-immunization ]
    Sustained change in CMI at 6 months will be assessed after receiving a second dose of booster vaccine post-immunization.

  2. Change in antibody response [ Time Frame: Baseline to 1 month post-immunization ]
    Antibody response will be measured by the change in VZV antibody concentration from pre-immunization to 1 month post-immunization. Varicella antibody concentrations in serum samples will be measured using a commercially available ELISA kit (Abnova, Walnut, CA) according to the manufacturer's instructions. This quantitative VZV antibody concentration will be in addition to the one that may be needed to determine previous varicella infection for study eligibility.

  3. Sustained antibody response [ Time Frame: Baseline to 6 months post-immunization ]
    Sustained change in VZV antibody concentration at 6 months after receiving a second dose of booster vaccine post-immunization will be assessed.

  4. Vaccine adverse effects at 1 month [ Time Frame: 1 month ]
    Vaccine adverse effects will be documented following immunization by evaluating participants at each clinic visit and from a phone call by study personnel.

  5. Vaccine adverse effects at 2 months [ Time Frame: 2 months ]
    Vaccine adverse effects will be documented following immunization by evaluating participants at each clinic visit and from a phone call by study personnel.

  6. Vaccine adverse effects at 3 months (1 month post-immunization) [ Time Frame: 3 months (1 months post-immunization) ]
    Vaccine adverse effects will be documented following immunization by evaluating participants at each clinic visit and from a phone call by study personnel.

  7. Vaccine adverse effects at 8 months (6 months post-immunization) [ Time Frame: 8 months (6 months post-immunization) ]
    Vaccine adverse effects will be documented following immunization by evaluating participants at each clinic visit and from a phone call by study personnel.

  8. Change in disease activity [ Time Frame: Baseline and 8 months (6 months post-immunization) ]
    The Simple Clinical Colitis Activity Index (SCCAI) will be used to measure disease activity. It is a questionnaire with six subscore topics with scores defined by UC signs and symptoms from 0 to 4 for a range of scores from 0 to 17. Total scores are interpreted as: Remission = score of 0 to 4 points, Mild Activity = score of 5 to 7 points, Moderate Activity = Score of 8 to 16 points, and Severe Activity = Score of > 16 points.



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03591770


Locations
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United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Boston Medical Center
Investigators
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Principal Investigator: Sharmeel K Wasan, MD Boston Medical Center
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Responsible Party: Boston Medical Center
ClinicalTrials.gov Identifier: NCT03591770    
Other Study ID Numbers: H-37673
First Posted: July 19, 2018    Key Record Dates
Last Update Posted: April 24, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Boston Medical Center:
Shingrix vaccine
tofacitinib monotherapy
anti-TNF monotherapy
anti-TNF agent
thiopurine
aminosalicylates
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs