COvid-19 Vaccine Booster in Immunocompromised Rheumatic Diseases (COVBIRD)

  • STATUS
    Recruiting
  • End date
    Jan 8, 2023
  • participants needed
    287
  • sponsor
    Paul R Fortin
Updated on 4 October 2022
rituximab
monoclonal antibodies
myositis
immunosuppression
vasculitis
arthritis
rheumatic diseases
lupus
progressive systemic sclerosis

Summary

People living with Systemic autoimmune rheumatic diseases (SARDs) face a new and urgent dilemma: immunosuppression increases risk for worse COVID-19 infection, yet an immune stimulation, such as vaccination, could re-activate their disease. Fear of vaccine-related disease reactivation is not of concern in other immunosuppressed groups (e.g. patients receiving chemotherapy or hemodialysis) but in SARDs, disease flare could lead to organ failure or even death. Specific research in this population is therefore critical. Moreover, among SARD patients, those on anti-CD-20 monoclonal antibody (mAb) (i.e. rituximab (anti-CD-20 mAb)), a medication used to treat inflammatory types of arthritis, have extremely low immunity post-COVID-19 mRNA vaccine. This study will test the hypothesis that a booster dose of a COVID-19 vaccine is safe and enhances post-vaccine humoral and cellular responses in SARDs patients on anti-CD-20 mAb treatment. The magnitude of this response depends on the type of COVID-19 vaccine administered and is optimal when the booster dose is a vaccine from a different group than the one used for primary immunization (mix-and-match approach).

Description

Systemic autoimmune rheumatic diseases (SARDs) include rheumatoid arthritis (RA), systemic lupus (SLE), systemic vasculitis, and related diseases where immune system activity causes widespread inflammation in organs, leading to sickness, organ damage, disability, high health costs, and even death. With no cure, SARDs require life-long immunosuppression. People living with SARDs now face a new and urgent dilemma: immunosuppression increases risk for worse COVID-19 infection, yet an immune stimulation, such as vaccination, could re-activate their disease. Fear of vaccine-related disease reactivation is not of concern in other immunosuppressed groups (e.g. patients receiving chemotherapy or hemodialysis) but in SARDs, disease flare could lead to organ failure or even death. Specific research in this population is therefore critical. Moreover, among SARD patients, those on anti-CD-20 monoclonal antibody (mAb) (i.e. rituximab (anti-CD-20 mAb)) have extremely low humoral immunity post-COVID-19 mRNA vaccine. As of mid-July 2021, 1489 SARDs patients were actively treated with anti-CD-20 mAb in the province of Quebec (personal communication).

This study will test the hypothesis that a booster dose of a COVID-19 vaccine is safe and enhances post-vaccine humoral and cellular responses in SARDs patients on anti-CD-20 mAb treatment. The magnitude of this response depends on the type of COVID-19 vaccine administered and is optimal when the booster dose is a vaccine from a different group than the one used for primary immunization (mix-and-match approach).

Our goal is to recruit 287 adults with SARDs on anti-CD-20 mAb treatment post-three doses of an approved mRNA-COVID-19 vaccine in a non-randomized, open label, comparative clinical trial with pragmatic features. This includes persons with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), inflammatory immune myopathies (IIM), overlap and undifferentiated connective tissue diseases (OCTD and UCTD) and ANCA-associated vasculitis (AAV). We will test at entry all participants for their anti-SARS-CoV-2-spike receptor binding domain (anti-RBD) antibody response to their previous doses of mRNA-COVID-19 vaccines. For participants who have received 3 doses of an mRNA vaccine, we will offer them a choice between a fourth dose of an mRNA (Moderna SPIKEVAX) vaccine and a dose of a protein subunit vaccine (PSV) (Novavax NUVAXOVID). For participants who have already received 4 doses of an mRNA vaccine in the community, they will be offered a dose of a protein subunit vaccine (PSV) (Novavax NUVAXOVID) as a fifth dose.

The primary study outcome will be the assessment of the safety and reactogenicity of a booster dose of COVID-19 vaccine using a mix-and-match strategy in immunocompromised rheumatic disease patients on an anti-CD-20 mAb. The secondary study outcome will be the humoral responses as measured by the anti-RBD Ab 28 days post vaccination. Exploratory outcomes include the cellular response at 28 days; the delayed humoral responses at 6 months; a comparison of the immunogenicity between types of vaccine (mRNA vs PSV); the evaluation of the effects of concomitant treatments on immunogenicity post-COVID-19 vaccine; the description of the rates of disease flares post fourth dose of COVID-19 vaccine; and a description of the decision process for vaccine selection.

Details
Condition Rheumatoid Arthritis, Autoimmune Rheumatologic Disease, Systemic Lupus Erythematosus, Systemic Vasculitis, Systemic Sclerosis, Scleroderma, Undifferentiated Connective Tissue Diseases, Overlap Connective Tissue Disease, Immunosuppression
Treatment covid-19 vaccine
Clinical Study IdentifierNCT05236491
SponsorPaul R Fortin
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Diagnosis of a SARD (Rheumatoid arthritis, systemic lupus erythematosus (SLE), juvenile inflammatory arthritis, systemic sclerosis (SSc), idiopathic inflammatory myositis (IIM), overlap connective tissue diseases, mixed connective tissue disease, undifferentiated connective tissue diseases, giant-cell arteritis, and the ANCA-Associated Vasculitis: granulomatosis with polyangiitis (GPA; formerly known as Wegener's granulomatosis), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA; previously known as Churg-Strauss syndrome)
Has received 3 or 4 doses of an mRNA vaccine
Age 18 years and older
Male or non-pregnant female
Rituximab treatment within last 12 months
Able to comprehend the study protocol and provide informed consent

Exclusion Criteria

Any medical disease or condition that, in the opinion of the site Principal Investigator or sub-investigator, precludes study participation
Significant behavioral disturbances
Previous diagnosis of hepatitis B, hepatitis C or HIV
Acute illness, with or without fever within 72 hours prior to vaccination
History of hypersensitivity or severe allergic reaction such as anaphylaxis to a component of the vaccine or to a previous vaccine
Any vaccine received in the 30 days prior to the fourth or fifth dose of COVID-19 vaccine
Any vaccine scheduled to be received in the 30 days following the administration of the fourth or fifth dose of COVID-19 vaccine and that cannot be postponed
People who experienced inflammation of the heart or lining of the heart (myocarditis or pericarditis) after a previous dose of an mRNA vaccine or protein subunit vaccine
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