Sustained Humoral and Cell-Mediated Immunogenicity of COVID-19 Vaccines in Patients With Inflammatory Bowel Disease

• ClinicalTrials.gov Identifier: NCT05014555
• Recruitment Status: Not yet recruiting
• First Posted: August 20, 2021
• Last Update Posted: June 18, 2023
• Sponsor: GI Alliance
• Collaborators: Janssen, LP; University of Wisconsin, Madison; Mayo Clinic
• Information provided by (Responsible Party): GI Alliance

Tracking Information

• First Submitted Date: August 13, 2021
• First Posted Date: August 20, 2021
• Last Update Posted Date: June 18, 2023
• Estimated Study Start Date: July 5, 2023
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 14, 2023)

Evaluation of the immunogenicity of the COVID-19 vaccines by measuring geometric mean titers (GMT) of SARS-CoV-2 antibody concentrations, and quantitative assays to evaluate RBD-binding IgG levels [ Time Frame: 6 and 12 months after third dose of the COVID-19 vaccine, with primary outcome being sustained antibody concentrations at 12 months ]

Evaluation of the immunogenicity of the COVID-19 vaccines prior to patients receiving a COVID-19 booster during the Fall 2023 through Spring 2024 and at approximately six months after the Fall2023/Spring 2024 COVID-19 booster. Quantitative assays will be used to evaluate RBD-binding IgG levels.

Original Primary Outcome Measures (submitted: August 18, 2021)

Evaluation of the immunogenicity of the COVID-19 vaccines by measuring geometric mean titers (GMT) of SARS-CoV-2 antibody concentrations, and quantitative assays to evaluate RBD-binding IgG levels [ Time Frame: 6 and 12 months after second dose of the COVID-19 vaccine, with primary outcome being sustained antibody concentrations at 12 months ]

Evaluation of the immunogenicity of the COVID-19 vaccines by measuring geometric mean titers (GMT) of SARS-CoV-2 antibody concentrations at 6 and 12 months after the 2nd dose of the vaccine in patients with IB. Quantitative assays will be used to evaluate RBD-binding IgG levels.

Current Secondary Outcome Measures (submitted: June 14, 2023)

• Sustained cell-mediated immunity against Covid-spike proteins will be evaluated using IFN-ϒ ELISpot, which detects both CD4 and CD8 T cell effectors. [ Time Frame: during the Fall 2023 through Spring 2024 and at approximately six months after the Fall2023/Spring 2024 COVID-19 booster ]
  Evaluation of sustained cell mediated immunity against Covid-spike proteins. IFN-ϒ ELISpot, which detects both CD4 and CD8 T cell effectors, will be used to detect T-cell immunity to the Covid-spike protein or peptides.
• Evaluate the persistence of memory B cell using memory B cell analysis. [ Time Frame: during the Fall 2023 through Spring 2024 and at approximately six months after the Fall2023/Spring 2024 COVID-19 booster ]
  Evaluation of the persistence of memory B cell in approximately one-third of participants.
• Sustained antibody concentration evaluating spike protein and receptor binding [ Time Frame: during the Fall 2023 through Spring 2024 and at approximately six months after the Fall2023/Spring 2024 COVID-19 booster ]
  The NIH ELISA assay will be used to evaluate change in S and RBD (IgG and IgM) antibody titers.

Original Secondary Outcome Measures (submitted: August 18, 2021)

• Sustained cell-mediated immunity against Covid-spike proteins will be evaluated using IFN-ϒ ELISpot, which detects both CD4 and CD8 T cell effectors. [ Time Frame: 6 and 12 months after second dose of the COVID-19 vaccine ]
  Evaluation of sustained cell mediated immunity against Covid-spike proteins. IFN-ϒ ELISpot, which detects both CD4 and CD8 T cell effectors, will be used to detect T-cell immunity to the Covid-spike protein or peptides.
• Evaluate the persistence of memory B cell using memory B cell analysis. [ Time Frame: 6 and 12 months after second dose of the COVID-19 vaccine ]
  Evaluation of the persistence of memory B cell in approximately one-third of participants.
• Sustained antibody concentration evaluating spike protein and receptor binding [ Time Frame: 6 and 12 months after second dose of the COVID-19 vaccine ]
  The NIH ELISA assay will be used to evaluate change in S and RBD (IgG and IgM) antibody titers.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sustained Humoral and Cell-Mediated Immunogenicity of COVID-19 Vaccines in Patients With Inflammatory Bowel Disease
• Official Title: Sustained Humoral and Cell-Mediated Immunogenicity of COVID-19 Vaccines in Patients With Inflammatory Bowel Disease
• Brief Summary: The aim of this study is to determine the impact of systemic immunosuppression on sustained antibody COVID-19 concentrations in patients with IBD who received a COVID-19 vaccine.
• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

whole blood

• Sampling Method: Non-Probability Sample
• Study Population: Inflammatory bowel disease patients, Gastroenterology practice
• Condition: Inflammatory Bowel Diseases

Intervention

Biological: COVID-19 Vaccine

Three-dose mRNA COVID-19 vaccine per standard of care

Study Groups/Cohorts

• Group A Non-biologic Group
  Participants on treatment regimen of mesalamine monotherapy or thiopurine monotherapy, or corticosteroids.
  Intervention: Biological: COVID-19 Vaccine
• Group B Anti-TNF Group
  Participants on treatment regimen of maintenance montherapy of infliximab (at least 8 every 8 weeks), golilumamb (at least monthly), adalimumab (at least every 2 weeks), or certolizumab (at least monthly), or combination therapy of anti-TNF therapy as described above along with either 15mg of methotrexate or azathiprine at least 1.0mg/kg or 6MP 0.5mg/kg.
  Intervention: Biological: COVID-19 Vaccine
• Group C Ustekinumab Group
  Participants on treatment regimen of ustekinumab monotherapy or combination therapy with methotrexate or azathioprine.
  Intervention: Biological: COVID-19 Vaccine
• Group D Vedolizumab Group
  Participants on vedolizumab monotherapy or combination therapy with methotrexate or azathioprine.
  Intervention: Biological: COVID-19 Vaccine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: August 18, 2021): 400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2024
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

A patient will be eligible for inclusion in this study if he or she meets all the following criteria:

• Patient is between the ages of 18-85 years, inclusive
• Patient has a history of ulcerative colitis (UC), or Crohn's disease diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria

• On one of the following treatment regimens for at least three months at the time of immunization and continued same therapy at the time of recruitment. Should be on stable doses defined as: Group A should have taken a dose of medication within the past week; Group B infliximab within the previous 8 weeks, golimumab within the previous 4 weeks, adalimumab within the previous 2 weeks, or certolizumab within the previous 4 weeks; Those on combination therapy in group B will have taken azathioprine or methotrexate within the past week. Group C ustekinumab at least within the previous 4 weeks. Those on combination therapy in group C will have taken azathioprine or methotrexate within the past week; Group D vedolizumab at least within the previous 4 weeks. Those on combination therapy in group D will have taken azathioprine or methotrexate within the past week

  • Group A non-biologic group: mesalamine monotherapy or thiopurine monotherapy
  • Group B: Anti-TNF Therapy Group: on maintenance therapy infliximab (at least 5mg/kg every 8 weeks), golimumab (at least monthly), adalimumab (at least every 2 weeks), or certolizumab (at least monthly Combination Therapy Anti- TNF Combination Therapy Group: on anti-TNF therapy as described above along with either 15mg of methotrexate or azathioprine at least 1.0mg/kg or 6MP 0.5mg/kg at least 40% of the group; Approximately 40-50% of the group will be combination therapy
  • Group C: Ustekinumab on either ustekinumab monotherapy or combination therapy with methotrexate or azathioprine
  • Group D: Vedolizumab Therapy Group: Vedolizumab Therapy: on either vedolizumab monotherapy or combination therapy with methotrexate or azathioprine
• Patient received at least two doses of mRNA COVID-19 vaccine per standard of care

A patient will not be eligible for inclusion in this study if he or she meets all the following criteria:

• Patient cannot or will not provide written informed consent
• Unable to provide appropriate informed consent due to being illiterate or impairment in decision-making capacity
• Received a COVID-19 booster within the previous 28 days

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Melinda Dollar; 4699303107; melinda.dollar@gialliance.com

Contact: Jo Ann Gilbert; 9726378546; joann.gilbert@gialliance.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05014555
• Other Study ID Numbers: CNTO1275IBD4005
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: All IPD that underlie results in a publication
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Immediately following publication.
• Access Criteria: With researchers who provide a methodically sound proposal, to achieve aims in the approved proposal. Proposals should be directed to Tim.Ritter@GIAlliance.com.

• Current Responsible Party: GI Alliance
• Original Responsible Party: Same as current
• Current Study Sponsor: GI Alliance
• Original Study Sponsor: Same as current

Collaborators

• Janssen, LP
• University of Wisconsin, Madison
• Mayo Clinic

Investigators

• Principal Investigator: Tim Ritter, MD; GI Alliance

• PRS Account: GI Alliance
• Verification Date: June 2023