Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; Immunosuppression
• Intervention / Treatment: Biological: NVX-CoV2372

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • UW School of Medicine and Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 messenger RNA (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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants who have had Solid Organ Transplants; Male and females aged 18 to 85 who are solid organ transplant recipients and receive the study intervention.	Biological: NVX-CoV2372; Novavax COVID-19 Vaccine Booster for Omicron XBB.1.5; Other Names: Novavax COVID-19 Vaccine
Experimental: Participants with IBD; Male and females aged 18 to 85 who have IBD and receive the study intervention.	Biological: NVX-CoV2372; Novavax COVID-19 Vaccine Booster for Omicron XBB.1.5; Other Names: Novavax COVID-19 Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Antibody Concentration From Baseline (Visit 1) at 1 Month (Visit 2)	Antibody concentrations 1 month after the recombinant vaccine booster (V2) in patients with IBD and solid organ transplant recipients compared to their baseline visit (V1).	baseline and 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants Seronegative at Baseline and Subsequently Seropositive	Percentages (and 2-sided 95% Confidence Intervals) of participants who were seronegative at baseline and became seropositive after immunization will be evaluated in each group. For initially seropositive subjects at V1, antibody concentration at post-vaccination (V2) ≥ 4 fold the pre-vaccination antibody concentration.	baseline, 1 month, 6 months
Unsolicited Adverse Events	The number of participants reporting unsolicited AEs within 30 days (Days 1-30) after the booster dose and overall will be summarized for both the study groups.	up to 30 days on study
Serious Adverse Events (SAEs)	The number of participants reporting SAEs and fatal SAEs from the booster dose administration to the study end will be summarized for both the study groups.	up to 6 months
Seropositivity Rates	Seropositive will be defined by positive anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2 performed by Labcorp.	baseline, 1 month, 6 months
Change in Interferon Gamma Responses at 1 Month Compared to Baseline	An interferon gamma response will be considered any measurable response, reported is change in cells per million from baseline to 1 month.	baseline and 1 month
Change in Interferon Gamma Responses at 6 Months Compared to 1 Month	An interferon gamma response will be considered any measurable response, reported is change in cells per million from 1 month to 6 months.	1 month, 6 months
Solicited Adverse Events (AEs)	The number of participants reporting each solicited local AE and each solicited systemic AE within seven days (Days 1-7) after the booster dose and overall will be summarized.; Solicited local AEs included injection site pain, redness, and swelling.; Solicited systemic AEs included fatigue, myalgia, arthralgia, headache, shivering/chills, fever, and gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain).	up to 7 days on study
Potential Immune-Mediated Diseases (pIMDs)	The number of participants reporting pIMDs from the booster dose to the study end will be summarized.	up to 6 months
Number of Participants Reporting Disease Flares of IBD	Disease activity will be assessed by monitoring disease activity using the Short Crohn's Activity Index (SCAI)18 for patients with Crohn's disease or the Simple Clinical Colitis Activity Index (SCCAI) questionnaire for patients with Ulcerative colitis at the baseline visit (V1), V2, and V3 visits. The incidence of IBD flares will be evaluated in all patients receiving recombinant boosters. This will be quantified by patients who were in clinical remission who develop a disease flare after receiving a recombinant COVID-19 booster.	up to 6 months
Number of Participants Reporting Acute Rejection of Their Transplant	Participants will be asked if they have been diagnosed with acute rejection after their baseline visit (V1). Episodes of acute rejection will be collected by searching electronic medical records and asking patients at each clinic visit (V2 and V3). Acute rejection will be defined as a notation of a new episode of acute rejection (cellular or antibody-mediated), a steroid bolus and taper in the absence of another indication, or administration of a T or B cell depleting agent or immune globulin. This will be quantified by patients who were who developing acute rejection of their transplant after receiving a recombinant COVID-19 booster.	up to 6 months

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Novavax
• Investigators: Principal Investigator: Freddy Caldera, DO, MS, UW School of Medicine and Public Health

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2023
• Primary Completion (Actual): April 24, 2024
• Study Completion (Actual): September 9, 2024

Study Registration Dates

• First Submitted: August 31, 2023
• First Submitted That Met QC Criteria: August 31, 2023
• First Posted (Actual): September 7, 2023

Study Record Updates

• Last Update Posted (Estimated): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Immunogenicity; IBD; solid organ transplant
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Immunologic Factors; Physiological Effects of Drugs; NVX-CoV2373 adjuvated lipid nanoparticle
• Other Study ID Numbers: 2023-1208; SMPH/MEDICINE/GASTROENT (Other Identifier: UW Madison); A534250 (Other Identifier: UW Madison); Protocol Version 10/5/2024 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: No