Clinical trial NCT06027229: Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations
Official title: Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Immunosuppression
COVID-19
Keywords: Immunogenicity
IBD
solid organ transplant
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Novavax
First posted: 2023-09-07
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: To determine whether providing a recombinant booster COVID-19 vaccine improves sustained humoral and cell-mediated immunogenicity against SARS-CoV-2 in immunosuppressed patients with Inflammatory Bowel Disease (IBD) and/or solid organ transplant recipients. 120 participants will be enrolled and can expect to be on study for 6 months.

Detailed description: This will be a single-center, prospective, unblinded, non-randomized study of 120 immunosuppressed patients who are planning to receive a recombinant COVID-19 vaccine booster dose as standard of care and are willing to participate in the study. At least 35 patients will have inflammatory bowel disease and at least 35 patients will be a solid organ transplant recipient. After obtaining informed consent, individuals who meet the inclusion criteria and none of the exclusion criteria will be invited to participate in the study. Blood samples will be collected from each participant at the baseline visit (V1), at 1 month post-booster (V2 visit), and 6 months post-booster (V3).

Aim 1: To determine whether providing a recombinant booster COVID-19 vaccine improves sustained humoral and cell-mediated immunogenicity against SARS-CoV-2 in immunosuppressed patients with IBD and/or solid organ transplant recipients.

The investigators hypothesize that solid organ transplant recipients receiving a combination of immunosuppressive regimens will have lower antibody concentrations than patients with IBD because previous work has shown that patients with IBD have higher rates of seroconversion than solid organ transplant recipients.

Per Protocol Amendment Approved 10/23/24: The 2024-2025 season activities will not proceed as originally planned due to the withdrawal of financial support. Study will be completed with 21 participants per updated analyses.

Eligibility criteria: Inclusion Criteria:

• Patient has a history of ulcerative colitis (UC), Crohn's disease, pouchitis, or indeterminate colitis diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria.

And / or patient is a solid organ transplant recipient (e.g. lung, kidney, liver)

* Have received at least three doses of a COVID-19 vaccine.

  * Three mRNA vaccines, or
  * One or two viral vector vaccine and one or two mRNA vaccines.
* 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 for 1 month prior to vaccination and agreement to use such for an additional 8 weeks after administration of the Novavax COVID-19 vaccine). Non-pregnant females with a negative pregnancy test who are willing to practice adequate contraception 8 weeks after administration of the Novavax COVID-19 vaccine.
* On one of the following treatment regimens

  * IBD

    * Thiopurine Therapy Group: on azathioprine at least 2.0mg/kg or 6MP 1.0mg/kg
    * Anti-TNF Therapy Group: on maintenance therapy infliximab (at least 8 every 8 weeks), golimumab (at least monthly), adalimumab (at least every 2 weeks), or certolizumab (at least monthly)
    * 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.
    * Vedolizumab Therapy Group: either vedolizumab monotherapy at least every 8 week dosing or combination therapy Group: on vedolizumab therapy at with azathioprine or methotrexate
    * Ustekinumab Therapy Group: either ustekinumab monotherapy or combination therapy with methotrexate or azathioprine.
    * Tofacitinib Therapy Group: on tofacitinib at least 5mg orally, twice per day
    * Risankizumab Therapy: 360mg at least every 8 weeks
    * Upadactinib Therapy Group: on upadactinib at least 15mg orally
    * Ozanimod: 0.92mg once daily
  * Solid organ transplant recipient (on any dose of the following regimens: patients can be on more than one of the regimens below)

    * Mycophenolate
    * Tacrolimus or cyclosporine
    * Sirolimus or everolimus
    * Azathioprine
    * Corticosteroids
    * Belatacept

Exclusion Criteria:

* Allergy to recombinant COVID-19 vaccine or any component of it
* Patient cannot or will not provide written informed consent.
* Unable to provide appropriate informed consent because of illiteracy or impairment in decision-making capacity.
* Active antibody-mediated or cellular rejection within the past six months
* Recent IBD flare requiring initiation of systemic corticosteroids within the past month.
* Previous history of myocarditis or pericarditis ever.
* Patients who are pregnant
* Patients who are lactating
* Patients with an active COVID-19 infection
* Patients with a COVID-19 infection within the past two months

Primary outcomes:
measure: Change in Antibody Concentration from Baseline (visit 1) at 1 month (visit 2)
timeFrame: baseline and 1 month
Secondary outcomes:
measure: Seropositivity Rates
timeFrame: 1 month, 6 months
measure: Percent of Participants Seronegative at Baseline and Subsequently Seropositive
timeFrame: baseline, 1 month, 6 months
measure: Interferon gamma responses at 1 month compared to baseline
timeFrame: baseline and 1 month
measure: Interferon gamma responses at 6 months compared to 1 month
timeFrame: 1 month, 6 months
measure: Solicited Adverse Events (AEs)
timeFrame: up to 7 days on study
measure: Unsolicited Adverse Events
timeFrame: up to 30 days on study
measure: Potential Immune-Mediated Diseases (pIMDs)
timeFrame: up to 6 months
measure: Serious Adverse Events (SAEs)
timeFrame: up to 6 months
measure: Number of participants reporting disease flares of IBD
timeFrame: up to 6 months
measure: Number of participants reporting acute rejection of their transplant
timeFrame: up to 6 months
Other outcomes:
Locations:
city: Madison
country: United States
facility: UW School of Medicine and Public Health
state: Wisconsin
Study officials:
affiliation: UW School of Medicine and Public Health
name: Freddy Caldera, DO, MS
role: PRINCIPAL_INVESTIGATOR
References: