Back to resultsAdditional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations
Primary Purpose
Immunosuppression, COVID-19
Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
NVX-CoV2372
Sponsored by
About this trial
This is an interventional prevention trial for Immunosuppression focused on measuring Immunogenicity, IBD, solid organ transplant
Eligibility Criteria
Inclusion Criteria: • Patient has a history of ulcerative colitis (UC) or Crohn's disease diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria. or patient is a solid organ transplant recipient (e.g. lung, kidney, liver) Have received at least three doses of a 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 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 every 8 weeks Upadactinib Therapy Group: on upadactinib at least 15mg orally Ozanimod: 0.92mg once daily Corticosteroid Therapy Group: on any one of the therapies above and stable doses of corticosteroids 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. Recent IBD flare requiring initiation of systemic corticosteroids within the past month.
Sites / Locations
- UW School of Medicine and Public Health
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Participants who have had Solid Organ Transplants
Participants with IBD
Arm Description
Male and females aged 18 to 85 who are solid organ transplant recipients and receive the study intervention.
Male and females aged 18 to 85 who have IBD and receive the study intervention.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Seropositivity Rates
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
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
An interferon gamma response will be considered any measurable response
Interferon gamma responses at 6 months compared to 1 month
An interferon gamma response will be considered any measurable response
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 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
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)
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)
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
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
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.
Full Information
NCT ID
NCT06027229
First Posted
August 31, 2023
Last Updated
October 23, 2023
Sponsor
University of Wisconsin, Madison
Collaborators
Novavax
1. Study Identification
Unique Protocol Identification Number
NCT06027229
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
Novavax
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immunosuppression, COVID-19
Keywords
Immunogenicity, IBD, solid organ transplant
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Participants who have had Solid Organ Transplants
Arm Type
Experimental
Arm Description
Male and females aged 18 to 85 who are solid organ transplant recipients and receive the study intervention.
Arm Title
Participants with IBD
Arm Type
Experimental
Arm Description
Male and females aged 18 to 85 who have IBD and receive the study intervention.
Intervention Type
Biological
Intervention Name(s)
NVX-CoV2372
Other Intervention Name(s)
Novavax COVID-19 Vaccine
Intervention Description
Novavax COVID-19 Vaccine Booster for Omicron XBB.1.5
Primary Outcome Measure Information:
Title
Change in Antibody Concentration from Baseline (visit 1) at 1 month (visit 2)
Description
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).
Time Frame
baseline and 1 month
Secondary Outcome Measure Information:
Title
Seropositivity Rates
Description
Seropositive will be defined by positive anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2 performed by Labcorp.
Time Frame
1 month, 6 months
Title
Percent of Participants Seronegative at Baseline and Subsequently Seropositive
Description
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.
Time Frame
baseline, 1 month, 6 months
Title
Interferon gamma responses at 1 month compared to baseline
Description
An interferon gamma response will be considered any measurable response
Time Frame
baseline and 1 month
Title
Interferon gamma responses at 6 months compared to 1 month
Description
An interferon gamma response will be considered any measurable response
Time Frame
1 month, 6 months
Title
Solicited Adverse Events (AEs)
Description
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).
Time Frame
up to 7 days on study
Title
Unsolicited Adverse Events
Description
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.
Time Frame
up to 30 days on study
Title
Potential Immune-Mediated Diseases (pIMDs)
Description
The number of participants reporting pIMDs from the booster dose to the study end will be summarized for both study groups.
Time Frame
up to 6 months
Title
Serious Adverse Events (SAEs)
Description
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.
Time Frame
up to 6 months
Title
Number of participants reporting disease flares of IBD
Description
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.
Time Frame
up to 6 months
Title
Number of participants reporting acute rejection of their transplant
Description
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.
Time Frame
up to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
• Patient has a history of ulcerative colitis (UC) or Crohn's disease diagnosed by standard clinical, radiographic, endoscopic, and histopathologic criteria.
or patient is a solid organ transplant recipient (e.g. lung, kidney, liver)
Have received at least three doses of a 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 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 every 8 weeks
Upadactinib Therapy Group: on upadactinib at least 15mg orally
Ozanimod: 0.92mg once daily
Corticosteroid Therapy Group: on any one of the therapies above and stable doses of corticosteroids
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.
Recent IBD flare requiring initiation of systemic corticosteroids within the past month.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials Institute
Phone
608.265.3132
Email
info@clinicaltrials.wisc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Freddy Caldera, DO, MS
Organizational Affiliation
UW School of Medicine and Public Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
UW School of Medicine and Public Health
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations
We'll reach out to this number within 24 hrs