The COVID-19 VaccinE Response and Co-Administration in Rheumatology Patients (COVER-CoAd)

NCT ID: NCT05543642

Last Updated: 2025-09-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 129 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-11
• Study Completion Date: 2026-08-31

Brief Summary

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.

Detailed Description

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.

Conditions

Rheumatic Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Arm 1 (control group, sequential administration)

Individuals with other chronic conditions and not active rheumatic disease (defined as being treated), who are eligible to receive their tdap booster and hepA vaccines, and receiving a COVID-19 booster vaccination.

This arm will receive sequential administration of both tdap booster and hepA vaccinations.

Group Type: ACTIVE_COMPARATOR

Hepatitis A vaccine

Intervention Type: BIOLOGICAL

Vaccination series administered to prevent hepA infection.

Diphtheria, pertussis, and tetanus booster vaccine

Intervention Type: BIOLOGICAL

Vaccination booster administered to prevent diphtheria, pertussis, and tetanus

Arm 2 (co-administration group)

Individuals with other chronic conditions and not active rheumatic disease (defined as being treated), who are eligible to receive their tdap booster and hepA vaccines, and receiving a COVID-19 booster vaccination.

This arm will receive co-administration of hepA vaccination.

Group Type: ACTIVE_COMPARATOR

Hepatitis A vaccine

Intervention Type: BIOLOGICAL

Vaccination series administered to prevent hepA infection.

Arm 3 (co-administration group)

Individuals with other chronic conditions and not active rheumatic disease (defined as being treated), who are eligible to receive their tdap booster and hepA vaccines, and receiving a COVID-19 booster vaccination.

This arm will receive co-administration of tdap booster vaccination.

Group Type: ACTIVE_COMPARATOR

Diphtheria, pertussis, and tetanus booster vaccine

Intervention Type: BIOLOGICAL

Vaccination booster administered to prevent diphtheria, pertussis, and tetanus

Arm 4 (Inflammatory arthritis patients using DMARDS)

Individuals with inflammatory arthritis patients using DMARDS, who are eligible to receive their tdap booster and hepA vaccines, and receiving a COVID-19 booster vaccination.

This arm will only receive the standard of care COVID-19 booster vaccination.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Hepatitis A vaccine

Vaccination series administered to prevent hepA infection.

Intervention Type: BIOLOGICAL

Diphtheria, pertussis, and tetanus booster vaccine

Vaccination booster administered to prevent diphtheria, pertussis, and tetanus

Intervention Type: BIOLOGICAL

Other Intervention Names

Havrix; Boostrix

Eligibility Criteria

Inclusion Criteria

• Must be 18 years of age or older
• Must live in the United States
• Scheduled for SARS-CoV-2 booster vaccination
• Patients in Rheumatic Disease arm (arm 4) must have inflammatory arthritis (e.g. rheumatoid arthritis, psoriatic arthritis, other) and be receiving stable doses of one of the following medication classes: TNF antagonists, B-cell depletion agents, IL-6 inhibitors, JAK inhibitors, IL-12/23 or IL-23 blockers, IL-17 inhibitors, methotrexate, sulfasalazine, leflunamide, or chronic prednisone (>15mg/day). Stable dosing is defined as no change in dose in the 30 days prior to enrolment.
• For Arms 1-3: patients seen by rheumatologists who do not have active rheumatic disease requiring immunosuppressive therapy. These will include patients with a past history of auto-immune disease that is no longer active, as well as those with other chronic conditions not associated with autoimmune condition such as osteoarthritis, osteoporosis, or other.
• Patients in the Co-administration arms (arms 2 and 3) must meet ACIP recommendations for the use of HAVRIX® (i.e. not previously vaccinated) and BOOSTRIX® (i.e. last immunization >9 years ago).
• Patients who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the REDCap/diary cards, capable of receiving text messages and/or have a personal email address, return for follow-up visits).

Exclusion Criteria

• Active infection with SARS-CoV-2 (symptom onset or first positive test in the 14 days prior to recruitment) / disease
• Any known contraindication to SARS-CoV-2 (booster) vaccination, including severe allergy to vaccine components
• Prior use of adenoviral COVID-19 vaccination
• Known or history of HIV/AIDS
• Currently receiving radiation or chemotherapy for any type of malignancy
• Receipt of any immunizations other than SARS-CoV-2 within two weeks prior planned SARS-CoV-2 vaccination, or scheduled within 10 weeks after visit 1
• Significant underlying illness that would be expected to prevent completion of the study (e.g., life-threatening disease likely to limit survival to < 1 year)
• Patients who have a previous history of pericarditis/myocarditis associated with vaccination
• Any other reason that, in the opinion of the site investigator, would interfere with required study related evaluations (e.g. uncontrolled comorbidity)
• Prior receipt of any hepatitis A containing vaccine
• Prior receipt of diphtheria, acellular pertussis, or tetanus vaccination within the last 9 years
• History of physician-diagnosed or laboratory confirmed pertussis within the past 5 years; any history of diphtheria, tetanus disease, or hepatitis A.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oregon Health and Science University

OTHER

Sponsor Role: lead

Responsible Party

Kevin Winthrop

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

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

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Cumberland Rheumatology

Crossville, Tennessee, United States

Advanced Rheumatology of Houston

Woodland, Texas, United States

Countries

United States

Other Identifiers

COVER-CoAd

Identifier Type: -

Identifier Source: org_study_id