COVID-19 VaccinE Response in Rheumatology Patients

Study Purpose

The COVID-19 VaccinE Response in Rheumatology patients (COVER) study is a multicenter randomized controlled trial designed to evaluate the efficacy and safety of a mRNA COVID-19 vaccine supplemental dose (booster) in patients with autoimmune conditions and to evaluate the impact of different immunomodulatory therapies on vaccine response. The investigators propose to recruit up to 1000- patients with autoimmune conditions who have a completed 2-dose regime of mRNA COVID-19 vaccine (>28 days prior) and who are planning to receive an additional dose of mRNA COVID-19 vaccine (i.e., booster). Participants in this study will be men and women 18 years and older with confirmed rheumatic disease, including psoriatic arthritis (PsA), axial spondyloarthritis (SpA) and rheumatoid arthritis (RA) who express a decision to receive the mRNA vaccination booster within 30 days post enrollment. A primary objective of this study is to test the hypothesis that holding certain medications for a brief period of time around the time of COVID-19 vaccination might improve the response to the vaccine while not unduly having safety concerns with respect to the effects of their disease. During the study, participants using the immunomodulatory therapies described outlined in protocol will be randomized to temporarily hold (for 2 weeks) versus continue after they receive the COVID-19 vaccine supplemental dose. Patients who temporarily stop one of their medications for their autoimmune inflammatory disease may be at increased risk of flares of their autoimmune condition. If these occur, they are expected to occur within 2

  • - 4 weeks of treatment interruption.
Detailed protocol outlines the hold schedules for the therapies to be randomized in this study.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 85 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

*Patients must meet all of the inclusion criteria at the time of screening*
  • - Must have a rheumatology provider diagnosis of one or more of the following autoimmune inflammatory conditions: - Rheumatoid arthritis or adults previously diagnosed with Juvenile idiopathic arthritis (analyzed as a single category) - Psoriatic arthritis (PsA), Ankylosing spondylitis (ASp), or other Spondyloarthritis (SpA) - Must have completed the 2-dose regimen of either of the two mRNA COVID-19 vaccines more than 28 days previous to enrollment.
  • - Must be scheduled for an additional dose of mRNA COVID-19 vaccination booster (or with plans to schedule booster) within the next 30 days.
  • - Must have a cell phone capable of receiving text messages, and/or a personal email address.
  • - Currently receiving one of the medications described in Table 1.
  • - Must be on stable immunomodulatory therapy for 8 weeks (with no dose changes, or interruptions > 2 weeks) prior to study enrollment.
This would include both the qualifying immunomodulatory drug listed in Table 2, as well as any background immunomodulatory therapies (e.g. methotrexate, leflunomide) or glucocorticoids.
  • - Must be 18 years of age or older.
  • - Must live in the United States.

Exclusion Criteria:

  • - • Already received a non-mRNA COVID-19 vaccine dose (J&J) - Any use in the past 90 days of a monoclonal antibody against COVID-19 (e.g., bamlanivimab, casirivimab, imdevimab) - Any known contraindication to COVID-19 vaccination, including allergic reaction to prior COVID-19 vaccination, and severe allergy to vaccine components (e.g., pegloticase) - Known HIV/AIDS or any other immunodeficient condition.
  • - Use of immunomodulatory therapy for any non-rheumatologic indication (e.g., organ transplantation) - Currently receiving radiation or chemotherapy for any type of malignancy.
  • - Receipt of any immunization other than COVID-19 within two weeks prior to the COVID-19 vaccine supplemental dose.
- 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) - Any other reason that, in the opinion of the site investigator, would interfere with required study related evaluations (e.g., uncontrolled disease flare, uncontrolled comorbidity)

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05080218
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 4
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Jeffrey Curtis
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Jeffrey R Curtis, MD MS MPH
Principal Investigator Affiliation Foundation for Advancing Science Technology Education and Research
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Rheumatoid Arthritis, Psoriatic Arthritis, Spondylarthritis
Additional Details

There is an urgent need to determine the immunogenicity and safety of COVID-19 vaccines in people living with rheumatic disease on immunomodulatory therapies. Given the experience with influenza, pneumococcal, shingles, and other vaccinations in rheumatic disease populations, it is clear that disease modifying therapies (DMARDs) and the immunomodulatory therapies used to treat immune-mediated inflammatory diseases have the capacity to blunt immune responses to vaccinations. A number of mostly small studies have examined the optimal management of DMARDs with regard to the timing of vaccination in order to maximize the immunogenicity of various vaccines, with immunogenicity serving as a lab-based proxy for clinical effectiveness. As various development programs near completion with regard to a vaccine for SARS-CoV-2 virus, it will be imperative to understand how best to vaccinate immunosuppressed patients, and in particular, to optimize vaccine response resulting from a supplemental (booster) dose in those patients using immunomodulatory biologic and targeted small molecule therapies. In concert with the American College of Rheumatology's (ACR) task force focused on developing COVID-19 vaccination guidance, the proposed real-world study will address major knowledge gaps that exist with the SARS-CoV-2 vaccination in rheumatic disease patients who have not been included in vaccine studies. Currently, the ACR task force for COVID-19 vaccination guidance recommends that patients temporarily (1-2 weeks) stop one of their medications for their autoimmune inflammatory disease. However, it is not known if stopping medications may increase risk of flares in their autoimmune condition. If these occur, they are expected to occur within 2-4 weeks of treatment interruption. Approximately 1000 patients will be studied to address these questions about the vaccine response following supplemental (booster) dosing associated with the use of upadacitinib, baricitinib, abatacept, canakinumab, secukinumab, ixekizumab, tofacitinib, TNFi, guselkumab (conditional on resource availability), and ustekinumab (conditional on resource availability). Participants will be randomized to hold these treatments for two weeks, or to continue their medication without interruption. Study Objectives and Hypotheses. To conduct a large, randomized controlled trial to evaluate SARS-CoV-2 vaccine supplemental dose response in a large population of patients with autoimmune conditions, designed to meet three specific objectives and aims: 1. Specific Aim 1: Evaluate the immunogenicity of SARS-CoV-2 vaccination in patients with autoimmune conditions, randomizing patients to briefly interrupt (i.e., hold for 2 weeks) versus continue various immunomodulatory therapies at the time that they receive a supplemental (i.e., booster) mRNA vaccine dose.

  • - Primary outcome: quantitative measurement of immunoglobulin G (IgG) against SARS-CoV-2 using electrochemiluminescent (ECL) technology against the receptor binding domain (RBD) of spike protein.
  • - Primary Hypothesis (H1a): The mean titer of anti-RBD IgG antibodies specific to SARS-CoV-2 measured post a third (booster) vaccine dose will be greater in patients randomized to temporarily hold (e.g., 2 weeks) versus those who continue immunomodulatory therapies.
  • - Exploratory outcomes (with the randomized patients as the primary analysis population, and all patients as an additional analysis population): - Measures of cell-mediated immunity and neutralizing assay or other assays to be specified in the future (E1a).
  • - Live-viral neutralization capacity post-vaccination (E1b).
  • - Comparison of mean titer of anti-RBD IgG antibodies specific to SARS-CoV-2 measured post supplemental dose for each immunomodulatory therapy to be studied compared to tumor necrosis factor inhibitors.
  • - Comparison of mean titer of anti-RBD IgG antibodies specific to SARS-CoV-2 measured post supplemental dose compared to general population.
  • - Comparison of mean titer of anti-RBD IgG antibodies specific to SARS-CoV-2 measured post supplemental dose in patients receiving concomitant methotrexate (MTX) compared to patients not receiving concomitant MTX.
  • - Comparison of mean titer of anti-RBD IgG antibodies specific to SARS-CoV-2 spike protein measured at baseline, by immunomodulatory medication received at the time of the initial vaccine series, and according to whether the immunomodulatory medication was held or not.
2. Specific Aim 2: Evaluate the safety and tolerability of SARS-CoV-2 vaccination in patients with different autoimmune conditions.
  • - Secondary outcomes: - Flare and disease worsening of underlying autoimmune/inflammatory disease within 4 weeks of the supplemental vaccine dose.
  • - Vaccine reactogenicity within 1 week of the supplemental vaccine dose.
  • - Other safety events (e.g., allergic reactions, anaphylaxis, potential immune mediated adverse events).
  • - Secondary Hypothesis #2 (H2b): the frequency of disease flare after the initial vaccine series and a supplemental vaccine dose will be higher in patients who hold immunomodulatory therapy compared to those who do not.
Disease flare will be collected retrospectively through clinical measurements and patient reported outcomes for the initial vaccine series, and prospectively after receipt of the supplemental vaccine dose.
  • - Exploratory outcomes: Comparison of circulating measures of inflammation (e.g., autoantibodies, cytokines, chemokines) between those holding and those continuing immunomodulatory therapy at the time of receipt of a supplemental dose of vaccine [conditional on funding availability].
3. Specific Aim 3 : Determine the clinical effectiveness of SARS-CoV-2 vaccination in patients with different autoimmune conditions and the subgroups of patients receiving different immunomodulatory therapies.
  • - Exploratory outcome: clinical efficacy (i.e., clinically-recognized COVID infection events) as ascertained by active surveillance, as well as passive linkage to administrative health plan claims and electronic health record (EHR) data.

Arms & Interventions

Arms

Experimental: Treatment Interruption - UPA

Treatment Interruption of Immunomodulatory Therapy for 2 Weeks at the time of COVID Vaccine Booster

No Intervention: Treatment Continuation

Treatment Continuation of All Immunomodulatory Therapy at the time of COVID Vaccine Booster

Experimental: Treatment Interruption - ABA

Treatment Interruption of Immunomodulatory Therapy for 2 Weeks at the time of COVID Vaccine Booster

Experimental: Treatment Interruption - TOF

Treatment Interruption of Immunomodulatory Therapy for 2 Weeks at the time of COVID Vaccine Booster

Experimental: Treatment Interruption - SEC

Treatment Interruption of Immunomodulatory Therapy for 2 Weeks at the time of COVID Vaccine Booster

Experimental: Treatment Interruption - TNFi SQ

Treatment Interruption of Immunomodulatory Therapy for 2 Weeks at the time of COVID Vaccine Booster

Experimental: Treatment Interruption - CAN

Treatment Interruption of Immunomodulatory Therapy for 2 Weeks at the time of COVID Vaccine Booster

Experimental: Treatment Interruption - BAR

Treatment Interruption of Immunomodulatory Therapy for 2 Weeks at the time of COVID Vaccine Booster

Experimental: Treatment Interruption - IXE

Treatment Interruption of Immunomodulatory Therapy for 2 Weeks at the time of COVID Vaccine Booster

Interventions

Drug: - Upadacitinib

Hold UPA x 2 weeks at time of COVID booster

Drug: - Abatacept

Hold SQ ABA x 2 weeks at time of COVID booster

Drug: - Secukinumab

Hold SEC x 2 weeks at time of COVID booster

Drug: - Tofacitinib

Hold TOF x 2 weeks at time of COVID booster

Drug: - TNF Inhibitor

Hold SQ TNFi x 2 weeks at time of COVID booster

Drug: - Canakinumab Injection

Hold CAN TNFi x 2 weeks at time of COVID booster

Drug: - Baricitinib

Hold BAR x 2 weeks at time of COVID booster

Drug: - Ixekizumab

Hold IXE x 2 weeks at time of COVID booster

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Alabama at Birmingham, Birmingham, Alabama

Status

Not yet recruiting

Address

University of Alabama at Birmingham

Birmingham, Alabama, 35294

Site Contact

Jeffrey Curtis, MD

[email protected]

205-975-2176

Bendcare, Hoover, Alabama

Status

Not yet recruiting

Address

Bendcare

Hoover, Alabama, 35244

Site Contact

Jessica L Ryan, MPH

[email protected]

205-538-3450

Rheumatology Care Center, Hoover, Alabama

Status

Recruiting

Address

Rheumatology Care Center

Hoover, Alabama, 35244

Site Contact

Katrina Kirby

[email protected]

205-538-3450

Phoenix, Arizona

Status

Recruiting

Address

Arizona Arthritis & Rheumatology Research, PLLC

Phoenix, Arizona, 85032

Site Contact

Rebecca Martinez

[email protected]

205-538-3450

Attune Health, Beverly Hills, California

Status

Recruiting

Address

Attune Health

Beverly Hills, California, 90211

Site Contact

Natalie Fortune

[email protected]

205-538-3450

University of Nebraska Medical Center, Omaha, Nebraska

Status

Not yet recruiting

Address

University of Nebraska Medical Center

Omaha, Nebraska, 68198

Site Contact

Ted Mikuls, MD MSMPH

[email protected]

205-538-3450

Philadelphia, Pennsylvania

Status

Recruiting

Address

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104

Site Contact

Michael George, MD

[email protected]

610-592-8144

Metroplex Clinical Research Center, Dallas, Texas

Status

Recruiting

Address

Metroplex Clinical Research Center

Dallas, Texas, 75231

Site Contact

Laura Rice

[email protected]

205-538-3450

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