COVID-19 VaccinE Response in Rheumatology Patients

NCT05080218 | Completed Phase 4 FDA Drug

• 1 other identifier: COVER-Main
• Study Type: interventional
• Target: 841
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Rheumatoid Arthritis; Psoriatic Arthritis; Spondylarthritis

Keywords

rheumatoid arthritis; COVID vaccine booster; spondyloarthritis; psoriatic arthritis

Outcome Measures

Primary Outcomes (1)

• Quantitative ratio post booster vs. pre-booster of IgG against SARS-CoV-2 using electrochemiluminescent (ECL) technology against the receptor binding domain (RBD) of spike protein, stratified by treatment arm

  Lab-based measure for immunogenicity (humoral immunity)

  6 weeks following COVID-19 vaccine booster

Secondary Outcomes (2)

• Number of patients with score change beyond the minimal clinically important difference in the Rheumatoid Arthritis Flare Questionnaire (for patients with RA/PsA) and the BASDAI (Axial Spondyloarthritis), stratified by treatment arm

  6 weeks following COVID-19 vaccine booster

• Number of patients with individual symptoms consistent with vaccine reactogenicity, as measured by the CDC Vsafe program, stratified by treatment arm

  6 weeks following COVID-19 vaccine booster

Other Outcomes (2)

• Number of patients with clinical COVID-19 infection, as initially self-reported by the patient, and confirmed by medical records, by treatment arm

  6 months following COVID-19 vaccine booster

• Number of patients with clinical manifestations of new onset autoimmune disease and other pre-specified adverse events, as classified by CTCAE 4.0, by treatment arm

  6 months following COVID-19 vaccine booster

Study Arms (9)

Treatment Interruption - UPA

EXPERIMENTAL

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

Drug: Upadacitinib

Treatment Continuation

NO INTERVENTION

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

Treatment Interruption - ABA

EXPERIMENTAL

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

Drug: Abatacept

Treatment Interruption - TOF

EXPERIMENTAL

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

Drug: Tofacitinib

Treatment Interruption - SEC

EXPERIMENTAL

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

Drug: Secukinumab

Treatment Interruption - TNFi SQ

EXPERIMENTAL

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

Drug: TNF Inhibitor

Treatment Interruption - CAN

EXPERIMENTAL

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

Drug: Canakinumab Injection

Treatment Interruption - BAR

EXPERIMENTAL

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

Drug: Baricitinib

Treatment Interruption - IXE

EXPERIMENTAL

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

Drug: Ixekizumab

Interventions

Upadacitinib DRUG

Hold UPA x 2 weeks at time of COVID booster

Also known as: Rinvoq

Treatment Interruption - UPA

Abatacept DRUG

Hold SQ ABA x 2 weeks at time of COVID booster

Also known as: Orencia SQ

Treatment Interruption - ABA

Secukinumab DRUG

Hold SEC x 2 weeks at time of COVID booster

Also known as: Cosentyx

Treatment Interruption - SEC

Tofacitinib DRUG

Hold TOF x 2 weeks at time of COVID booster

Also known as: Xeljanz

Treatment Interruption - TOF

TNF Inhibitor DRUG

Hold SQ TNFi x 2 weeks at time of COVID booster

Also known as: Etanercept, Certolizumab, Golimumab SQ, Adalimumab

Treatment Interruption - TNFi SQ

Canakinumab Injection DRUG

Hold CAN TNFi x 2 weeks at time of COVID booster

Also known as: Ilaris

Treatment Interruption - CAN

Baricitinib DRUG

Hold BAR x 2 weeks at time of COVID booster

Also known as: Olumiant

Treatment Interruption - BAR

Ixekizumab DRUG

Hold IXE x 2 weeks at time of COVID booster

Also known as: Taltz

Treatment Interruption - IXE

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Jeffrey Curtis: lead
• University of Alabama at Birmingham: collaborator
• University of Nebraska: collaborator
• University of Pennsylvania: collaborator
• AbbVie: collaborator
• Bristol-Myers Squibb: collaborator
• Novartis: collaborator
• Eli Lilly and Company: collaborator
• Pfizer: collaborator
• Illumination Health: collaborator

Study Sites (8)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Illumination Health/Bendcare

Hoover, Alabama, 35244, United States

Location

Rheumatology Care Center

Hoover, Alabama, 35244, United States

Location

Arizona Arthritis & Rheumatology Research, PLLC

Phoenix, Arizona, 85032, United States

Location

Attune Health

Beverly Hills, California, 90211, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Metroplex Clinical Research Center

Dallas, Texas, 75231, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis, Psoriatic; Spondylarthritis

Interventions

upadacitinib; Abatacept; secukinumab; tofacitinib; Tumor Necrosis Factor Inhibitors; Etanercept; Certolizumab Pegol; Adalimumab; canakinumab; baricitinib; ixekizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Spondylarthropathies; Spondylitis; Spinal Diseases; Bone Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Anti-Inflammatory Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Immunoglobulin Constant Regions; Immunoproteins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal

Study Officials

• Jeffrey R Curtis, MD MS MPH

  Foundation for Advancing Science Technology Education and Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician Scientist

Study Record Dates

• First Submitted: October 6, 2021
• First Posted: October 15, 2021
• Study Start: November 15, 2021
• Primary Completion: April 4, 2024
• Study Completion: May 28, 2024
• Last Updated: May 2, 2025

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: At the conclusion of the study.
• Access Criteria: The investigators will share it with a secure FTP as requested by applicable parties.

Locations

US (8)