Clinical trial NCT05236491: COvid-19 Vaccine Booster in Immunocompromised Rheumatic Diseases
Official title: COvid-19 Vaccine Booster in Immunocompromised Rheumatic Diseases
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Rheumatoid Arthritis
Autoimmune Rheumatologic Disease
Systemic Lupus Erythematosus
Systemic Vasculitis
Systemic Sclerosis
Scleroderma
Undifferentiated Connective Tissue Diseases
Overlap Connective Tissue Disease
Immunosuppression
Lead sponsor: CHU de Quebec-Universite Laval
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2022-02-11
Enrollment: 287
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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).

Detailed 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 (vaccine and a dose of a protein subunit vaccine (PSV). 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) 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 booster dose of COVID-19 vaccine; and a description of the decision process for vaccine selection.

Eligibility criteria: Inclusion Criteria

1. 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);
2. Has received 3 or more doses of an mRNA vaccine;
3. Age 18 years and older;
4. Male or non-pregnant female;
5. Rituximab treatment within last 12 months;
6. Able to comprehend the study protocol and provide informed consent.

Exclusion Criteria

1. Any medical disease or condition that, in the opinion of the site Principal Investigator or sub-investigator, precludes study participation;
2. Significant behavioral disturbances;
3. Previous diagnosis of hepatitis B, hepatitis C or HIV;
4. History of hypersensitivity or severe allergic reaction such as anaphylaxis to a component of the vaccine or to a previous vaccine;
5. 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.

Primary outcomes:
measure: Safety of a booster dose of COVID-19 vaccine in patients on anti-CD-20 mAb.
timeFrame: 28 days
measure: Reactogenicity of a booster dose of COVID-19 vaccine in patients on anti-CD-20 mAb.
timeFrame: 28 days
Secondary outcomes:
measure: Humoral response
timeFrame: 28 days post vaccination
Other outcomes:
measure: Humoral response
timeFrame: 180 days post vaccination
measure: Humoral response
timeFrame: 335 days post vaccination
Locations:
city: Montréal
country: Canada
facility: Research Institute - McGill University Health Centre
state: Quebec
city: Québec
country: Canada
facility: Centre de recherche du CHU de Québec - Université Laval
state: Quebec
Study officials:
affiliation: Centre de recherche du CHU de Québec - Université Laval
name: Paul R Fortin, MD,MPH,FRCPC
role: PRINCIPAL_INVESTIGATOR
References: