COVID-19, Immunosuppression
Conditions
Keywords
Immunogenicity, IBD, solid organ transplant
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.
Interventions
BIOLOGICALNVX-CoV2372
Novavax COVID-19 Vaccine Booster for Omicron XBB.1.5
Sponsors
Novavax
University of Wisconsin, Madison
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Antibody Concentration From Baseline (Visit 1) at 1 Month (Visit 2) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Seronegative at Baseline and Subsequently Seropositive | 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. |
| Change in Interferon Gamma Responses at 1 Month Compared to Baseline | baseline and 1 month | An interferon gamma response will be considered any measurable response, reported is change in cells per million from baseline to 1 month. |
| Change in Interferon Gamma Responses at 6 Months Compared to 1 Month | 1 month, 6 months | An interferon gamma response will be considered any measurable response, reported is change in cells per million from 1 month to 6 months. |
| Solicited Adverse Events (AEs) | 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. * 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). |
| Seropositivity Rates | baseline, 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. |
| Potential Immune-Mediated Diseases (pIMDs) | up to 6 months | The number of participants reporting pIMDs from the booster dose to the study end will be summarized. |
| Serious Adverse Events (SAEs) | 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 | 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 | 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. |
| Unsolicited Adverse Events | 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. |
Countries
United States
Participant flow
Pre-assignment details
21 participants were assessed for eligibility, 1 patient was withdrawn due to inadvertent administration of an messenger ribonucleic acid (mRNA) vaccine.
Participants by arm
| Arm | Count |
|---|---|
| Immunosuppressed Participants Male and females aged 18 to 85 who are solid organ transplant recipients or have IBD and receive the study intervention.
NVX-CoV2372: Novavax COVID-19 Vaccine Booster for Omicron XBB.1.5 | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Immunosuppressed Participants |
|---|---|
| Age, Continuous | 47.6 years STANDARD_DEVIATION 14.9 |
| Body Mass Index (BMI) | 79.59 kilograms per meter squared STANDARD_DEVIATION 10.2 |
| Current IBD Medications Azathioprine | 1 Participants |
| Current IBD Medications Entyvio | 5 Participants |
| Current IBD Medications Humira | 4 Participants |
| Current IBD Medications Metho | 2 Participants |
| Current IBD Medications Remicade | 4 Participants |
| Current IBD Medications Skyrizi | 1 Participants |
| Current IBD Medications Stelara | 2 Participants |
| Current IBD Medications Xeljanz | 1 Participants |
| Current Transplantation Medications Azathioprine | 1 Participants |
| Current Transplantation Medications Mycophenolate | 2 Participants |
| Current Transplantation Medications Prednisone | 2 Participants |
| Current Transplantation Medications Tacrolimus | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| History of COVID-19 infection Never | 9 Participants |
| History of COVID-19 infection Once | 8 Participants |
| History of COVID-19 infection Thrice | 1 Participants |
| History of COVID-19 infection Twice | 2 Participants |
| Length of IBD | 16 years STANDARD_DEVIATION 12.2 |
| Number of COVID-19 Vaccines Received | 4.7 vaccinations |
| Previous Surgical Resection | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
| Smoking Status Current | 0 Participants |
| Smoking Status Former | 6 Participants |
| Smoking Status Never | 14 Participants |
| Type of IBD Left Sided Disease | 1 Participants |
| Type of IBD Pancolitis | 2 Participants |
| Type of IBD Proctitis | 1 Participants |
| Type of IBD Proctosigmoiditis | 1 Participants |
| Type of Immunosuppression IBD | 17 Participants |
| Type of Immunosuppression Solid Organ Transplantation | 3 Participants |
| Type of Transplant Liver | 1 Participants |
| Type of Transplant Lung | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 12 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
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).
Time frame: baseline and 1 month
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Immunosuppressed Participants | Change in Antibody Concentration From Baseline (Visit 1) at 1 Month (Visit 2) | baseline | 22968.5 Endotoxin Units per milliliter (EU/mL) |
| Immunosuppressed Participants | Change in Antibody Concentration From Baseline (Visit 1) at 1 Month (Visit 2) | 1 month | 66639 Endotoxin Units per milliliter (EU/mL) |
Secondary
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.
Time frame: baseline and 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immunosuppressed Participants | Change in Interferon Gamma Responses at 1 Month Compared to Baseline | 28 cells per million | Standard Deviation 101 |
Secondary
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.
Time frame: 1 month, 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Immunosuppressed Participants | Change in Interferon Gamma Responses at 6 Months Compared to 1 Month | -0.625 cells per million | Standard Deviation 164 |
Secondary
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.
Time frame: up to 6 months
Population: 3 participants had solid organ transplants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunosuppressed Participants | Number of Participants Reporting Acute Rejection of Their Transplant | 0 Participants |
Secondary
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.
Time frame: up to 6 months
Population: 17 participants had IBD
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunosuppressed Participants | Number of Participants Reporting Disease Flares of IBD | 0 Participants |
Secondary
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.
Time frame: baseline, 1 month, 6 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Immunosuppressed Participants | Percent of Participants Seronegative at Baseline and Subsequently Seropositive | baseline | 0 Participants |
| Immunosuppressed Participants | Percent of Participants Seronegative at Baseline and Subsequently Seropositive | 1 month | 0 Participants |
| Immunosuppressed Participants | Percent of Participants Seronegative at Baseline and Subsequently Seropositive | 6 months | 0 Participants |
Secondary
Potential Immune-Mediated Diseases (pIMDs)
The number of participants reporting pIMDs from the booster dose to the study end will be summarized.
Time frame: up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunosuppressed Participants | Potential Immune-Mediated Diseases (pIMDs) | 0 Participants |
Secondary
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.
Time frame: up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunosuppressed Participants | Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Seropositivity Rates
Seropositive will be defined by positive anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2 performed by Labcorp.
Time frame: baseline, 1 month, 6 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Immunosuppressed Participants | Seropositivity Rates | baseline | 20 Participants |
| Immunosuppressed Participants | Seropositivity Rates | 1 month | 20 Participants |
| Immunosuppressed Participants | Seropositivity Rates | 6 months | 20 Participants |
Secondary
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).
Time frame: up to 7 days on study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunosuppressed Participants | Solicited Adverse Events (AEs) | 12 Participants |
Secondary
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.
Time frame: up to 30 days on study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunosuppressed Participants | Unsolicited Adverse Events | 1 Participants |