Based on the experience with influenza, pneumococcal, and shingles vaccinations in rheumatic disease populations, it is clear that some disease modifying anti-rheumatic drugs and the immunomodulatory therapies used to treat immune-mediated inflammatory diseases have the capacity to blunt immune responses to COVID-19 vaccines. Several studies have suggested that patients with autoimmune conditions may be at increased risk of poor COVID-19 outcomes. There is an urgent need to better clarify the immunogenicity and safety of COVID-19 vaccines in people living with rheumatic disease who use immunomodulatory therapies. Boosters at annual or other frequency are available, and there is a need to understand whether these vaccines can be given concurrently with other routine vaccines.
The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has infected a substantial portion of the world population, leading to millions of deaths since its first description in December of 2019. Recently, several SARS-CoV-2 vaccines have shown excellent efficacy and tolerability in the general population and have been either fully approved or given emergency use authorization by the US Food and Drug Administration (FDA), while several other vaccines are in late-stage clinical trials. Patients with autoimmune conditions, however, particularly those receiving immunomodulatory therapies, have largely been excluded from clinical trials. Yet, certain immunomodulatory therapies have been shown to affect responses to vaccines, with effects varying depending on the medication and type of vaccine. In line with the experience with influenza, pneumococcal and shingles vaccinations in rheumatic disease populations, it is clear that some disease modifying anti-rheumatic drugs (DMARDs) and the immunomodulatory therapies used to treat immune-mediated inflammatory diseases have the capacity to blunt immune responses to COVID-19 vaccines. In addition, a hypothetical concern is that stimulation of the immune system could lead to flares of autoimmune conditions, or new onset autoimmune manifestations. Concerns about flare or disease worsening with vaccination is also substantial among patients themselves, and can sometimes be a reason for vaccine hesitancy or refusal. Due to recent development and subsequent massive deployment of SARS-CoV-2 vaccines to combat the pandemic, their safety and immunogenicity in patients receiving immunomodulatory therapies had received limited evaluation to date. At the same time, several studies have suggested that patients with autoimmune conditions may be at increased risk of poor COVID-19 outcomes, including hospitalization and death, raising the importance of effective vaccination in this setting. In this context, there is an urgent need to better clarify the immunogenicity and safety of COVID-19 vaccines in people living with rheumatic disease who use immunomodulatory therapies. Additionally, the likelihood that patients will need to be vaccinated in the future again for COVID-19 is high. Boosters at annual or other frequency are likely for all (and have now already been recommended for immunocompromised individuals), and the need to understand whether these vaccines can be given concurrently with other routine vaccines will be important for both patients and clinicians, as well as public health officials. The "vaccine moment" clinically frequently offers the opportunity to give multiple vaccines at one time. Vaccines for other respiratory pathogens (e.g. influenza), hepatitis A, pertussis, and other disease are indicated in large segments of the population, including being of utmost importance in the elderly and those with various chronic conditions and/or immunosuppression. It is imperative to understand whether co-administrated vaccines affect the immunogenicity, efficacy, or safety of COVID-19 vaccines and those vaccines of public health significance given concurrently. With this background in mind and the momentum of the vaccine campaign in the US to date, whereby the majority of at-risk rheumatology and other populations have received their initial vaccine series, this protocol will focus on evaluating vaccine responses in those receiving a booster mRNA SARS-CoV-2 vaccination. This is important, as boosters are now recommended for all adult patients in the US who have received any prior SARS-CoV-2 vaccination. Further, given a large percentage of rheumatology patients can have sub-optimal or lower immune responses, booster vaccinations will be likely of utmost importance to these and other immunosuppressed groups.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
129
Vaccination series administered to prevent hepA infection.
Vaccination booster administered to prevent diphtheria, pertussis, and tetanus
Center for Rheumatic Diseases
Northport, Alabama, United States
Sun Valley Arthritis
Peoria, Arizona, United States
Ocean Wellness Center
Miami Gardens, Florida, United States
Southwest Florida Rheumatology
Riverview, Florida, United States
St. Luke's Rheumatology
Boise, Idaho, United States
Ravenswood Rheumatology
Chicago, Illinois, United States
University Medical Center - New Orleans/LSU
New Orleans, Louisiana, United States
St. Paul Rheumatology
Eagan, Minnesota, United States
Jayashree Sinha, MD
Clovis, New Mexico, United States
Oregon Health & Science University
Portland, Oregon, United States
...and 3 more locations
Ratio of participants' anti-RBD IgG antibodies specific to SARS-CoV-2 measured post-vaccination for those who received only the SARS-CoV-2 booster compared to those who received sequential vaccination with the SARS-CoV-2 booster.
Descriptively evaluate the immunogenicity of anti-spike IgG among patients receiving SARS-CoV-2 booster vaccines alone (Arm 4 N=100) as compared to patients receiving SARS-CoV-2 booster vaccine with sequential vaccination (Arm 1 N=100). The geometric mean concentration ratio (GMC) of Arm 4 to Arm 1 at Week 4 will be reported.
Time frame: 2 years
Ratio of participants' anti-RBD IgG antibodies specific to SARS-CoV-2 for those who received sequential vaccination with the SARS-CoV-2 booster compared to those who received a tdap booster co-administered with the SARS-CoV-2 booster.
Descriptively evaluate the immunogenicity of anti-spike IgG among patients receiving SARS-CoV-2 booster vaccines with sequential vaccination (Arm 1 N=100) as compared to patient receiving SARS-CoV-2 booster vaccine with co-administration of BOOSTRIX® (Arm 2 N=100). The geometric mean concentration ratio (GMC) of Arm 1 to Arm 2 at each 4-week interval for Arm 1 (e.g. Week 4, 8, and 36) will be reported.
Time frame: 2 years
Ratio of participants' anti-RBD IgG antibodies specific to SARS-CoV-2 for those who received sequential vaccination with the SARS-CoV-2 booster compared to those who received a hepA vaccination co-administered with the SARS-CoV-2 booster.
Descriptively evaluate the immunogenicity of anti-spike IgG among patients receiving SARS-CoV-2 booster vaccines with sequential vaccination (Arm 1 N=100) as compared to patient receiving SARS-CoV-2 booster vaccine with co-administration of HAVRIX® (Arm 3 N=100). The geometric mean concentration ratio (GMC) of Arm 1 to Arm 3 at each 4-week interval for Arm 1 (e.g. Week 4, 8, and 36) will be reported.
Time frame: 2 years
Number of participants with solicited localized and general symptoms (Arm 4 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines alone (Arm 4 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine with sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of participants with solicited local and general symptoms that occur within an 8 day period following each vaccine dose administered as assessed by CTCAE will be reported.
Time frame: 2 years
Number of participants with unsolicited events (Arm 4 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines alone (Arm 4 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine with sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of participants with unsolicited events occurring within a 31 day period following each vaccine dose administered as assessed by CTCAE will be reported.
Time frame: 2 years
Number of medically attended events (Arm 4 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of BOOSTRIX® (Arm 2 N=100; cell-mediated immunity subset N=50 of first enrolled) or co-administration of HAVRIX® (Arm 3 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). All medically attended events.
Time frame: 2 years
Number of confirmed cases of COVID-19 (Arm 4 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of BOOSTRIX® (Arm 2 N=100; cell-mediated immunity subset N=50 of first enrolled) or co-administration of HAVRIX® (Arm 3 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of confirmed cases of COVID-19 as diagnosed by PCR or antigen-based testing.
Time frame: 2 years
Number of potential immune-mediated diseases (Arm 4 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of BOOSTRIX® (Arm 2 N=100; cell-mediated immunity subset N=50 of first enrolled) or co-administration of HAVRIX® (Arm 3 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of potential immune-mediated diseases (pIMDs; new onset or exacerbation of current).
Time frame: 2 years
Number of serious adverse events (Arm 4 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of BOOSTRIX® (Arm 2 N=100; cell-mediated immunity subset N=50 of first enrolled) or co-administration of HAVRIX® (Arm 3 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of serious adverse events as assessed by CTCAE.
Time frame: 2 years
Ratio of participants' anti-RBD IgG antibodies specific to SARS-CoV-2 for those who received a tdap booster co-administered with the SARS-CoV-2 booster compared to those who received sequential vaccination with the SARS-CoV-2 booster.
Descriptively evaluate the immunogenicity of anti-spike IgG among patients receiving SARS-CoV-2 booster vaccine with co-administration of BOOSTRIX® (Arm 2 N=100) as compared to patients receiving SARS-CoV-2 booster vaccine with sequential vaccination (Arm 1 N=100). The geometric mean concentration ratio (GMC) of Arm 2 to Arm 1 at 4 weeks post-vaccination for SARS CoV-2 and BOOSTRIX®.
Time frame: 2 years
Ratio of participants' anti-RBD IgG antibodies specific to SARS-CoV-2 for those who received a hepA vaccination co-administered with the SARS-CoV-2 booster compared to those who received sequential vaccination with the SARS-CoV-2 booster.
Descriptively evaluate the immunogenicity of anti-spike IgG among patients receiving SARS-CoV-2 booster vaccine with co-administration of HAVRIX® (Arm 3 N=100) as compared to patients receiving SARS-CoV-2 booster vaccine with sequential vaccination (Arm 1 N=100). The geometric mean concentration ratio (GMC) of Arm 3 to Arm 1 at 4 weeks post-vaccination for dose 2 of HAVRIX® will be reported.
Time frame: 2 years
Number of participants with solicited localized and general symptoms (Arm 2 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of BOOSTRIX® (Arm 2 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of participants with solicited local and general symptoms that occur within an 8 day period following each vaccine dose administered as assessed by CTCAE.
Time frame: 2 years
Number of participants with unsolicited events (Arm 2 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of BOOSTRIX® (Arm 2 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of participants with unsolicited events occurring within a 31 day period following each vaccine dose administered as assessed by CTCAE.
Time frame: 2 years
Number of medically attended events (Arm 2 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of BOOSTRIX® (Arm 2 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). All medically attended events.
Time frame: 2 years
Number of confirmed cases of COVID-19 (Arm 2 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of BOOSTRIX® (Arm 2 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of confirmed cases of COVID-19 as diagnosed by PCR or antigen-based testing.
Time frame: 2 years
Number of potential immune-mediated diseases (Arm 2 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of BOOSTRIX® (Arm 2 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of potential immune-mediated diseases (pIMDs; new onset or exacerbation of current).
Time frame: 2 years
Number of serious adverse events (Arm 2 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of BOOSTRIX® (Arm 2 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of serious adverse events.
Time frame: 2 years
Number of participants with solicited localized and general symptoms (Arm 3 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of HAVRIX® (Arm 3 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of participants with solicited local and general symptoms that occur within an 8 day period following each vaccine dose administered as assessed by CTCAE.
Time frame: 2 years
Number of participants with unsolicited events (Arm 3 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of HAVRIX® (Arm 3 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of participants with unsolicited events occurring within a 31 day period following each vaccine dose administered as assessed by CTCAE
Time frame: 2 years
Number of medically attended events (Arm 3 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of HAVRIX® (Arm 3 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). All medically attended events
Time frame: 2 years
Number of confirmed cases of COVID-19 (Arm 3 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of HAVRIX® (Arm 3 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of confirmed cases of COVID-19 as diagnosed by PCR or antigen-based testing
Time frame: 2 years
Number of potential immune-mediated diseases (Arm 3 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of HAVRIX® (Arm 3 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of potential immune-mediated diseases (pIMDs; new onset or exacerbation of current).
Time frame: 2 years
Number of serious adverse events (Arm 3 to Arm 1)
Descriptively evaluate the safety and reactogenicity of patients receiving SARS-CoV-2 booster vaccines with either co-administration of HAVRIX® (Arm 3 N=100; cell-mediated immunity subset N=50 of first enrolled) as compared to patients receiving SARS-CoV-2 booster vaccine sequential vaccination (Arm 1 N=100; cell-mediated immunity subset N=50 of first enrolled). Number of serious adverse events as assessed by CTCAE.
Time frame: 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.