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

• ClinicalTrials.gov Identifier: NCT06027229
• Recruitment Status: Suspended
• First Posted: September 7, 2023
• Last Update Posted: May 10, 2024
• Sponsor: University of Wisconsin, Madison
• Collaborator: Novavax
• Information provided by (Responsible Party): University of Wisconsin, Madison

Tracking Information

• First Submitted Date: August 31, 2023
• First Posted Date: September 7, 2023
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: November 20, 2023
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 31, 2023)

Change in Antibody Concentration from Baseline (visit 1) at 1 month (visit 2) [ Time Frame: baseline and 1 month ]

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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 31, 2023)

• Seropositivity Rates [ Time Frame: 1 month, 6 months ]
  Seropositive will be defined by positive anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2 performed by Labcorp.
• Percent of Participants Seronegative at Baseline and Subsequently Seropositive [ Time Frame: baseline, 1 month, 6 months ]
  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.
• Interferon gamma responses at 1 month compared to baseline [ Time Frame: baseline and 1 month ]
  An interferon gamma response will be considered any measurable response
• Interferon gamma responses at 6 months compared to 1 month [ Time Frame: 1 month, 6 months ]
  An interferon gamma response will be considered any measurable response
• Solicited Adverse Events (AEs) [ Time Frame: up to 7 days on study ]
  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 for both study groups.

  • 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).
• Unsolicited Adverse Events [ Time Frame: up to 30 days on study ]
  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.
• Potential Immune-Mediated Diseases (pIMDs) [ Time Frame: up to 6 months ]
  The number of participants reporting pIMDs from the booster dose to the study end will be summarized for both study groups.
• Serious Adverse Events (SAEs) [ Time Frame: up to 6 months ]
  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.
• Number of participants reporting disease flares of IBD [ Time Frame: up to 6 months ]
  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.
• Number of participants reporting acute rejection of their transplant [ Time Frame: up to 6 months ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Immunosuppression
• COVID-19

Intervention

Biological: NVX-CoV2372

Novavax COVID-19 Vaccine Booster for Omicron XBB.1.5

Other Name: Novavax COVID-19 Vaccine

Study Arms

• 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.
  Intervention: Biological: NVX-CoV2372
• Experimental: Participants with IBD
  Male and females aged 18 to 85 who have IBD and receive the study intervention.
  Intervention: Biological: NVX-CoV2372

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Suspended
• Estimated Enrollment (submitted: August 31, 2023): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: March 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06027229
• Other Study ID Numbers: 2023-1208; Protocol Version 11/6/2023 ( Other Identifier: UW Madison ); SMPH/MEDICINE/GASTROENT ( Other Identifier: UW Madison ); A534250 ( Other Identifier: UW Madison )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of Wisconsin, Madison
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Wisconsin, Madison
• Original Study Sponsor: Same as current
• Collaborators: Novavax

Investigators

• Principal Investigator: Freddy Caldera, DO, MS; UW School of Medicine and Public Health

• PRS Account: University of Wisconsin, Madison
• Verification Date: May 2024