COvid-19 Vaccine Booster in Immunocompromised Rheumatic Diseases

NCT ID: NCT05236491

Last Updated: 2023-01-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 287 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-09
• Study Completion Date: 2023-12-31

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.

Conditions

Rheumatoid Arthritis; Autoimmune Rheumatologic Disease; Systemic Lupus Erythematosus; Systemic Vasculitis; Systemic Sclerosis; Scleroderma; Undifferentiated Connective Tissue Diseases; Overlap Connective Tissue Disease; Immunosuppression

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Trajectory A

Participants who have received 3 doses of an mRNA vaccine, will be offered a choice between a fourth dose of an mRNA vaccine and a dose of a protein subunit vaccine (PSV) (Novavax NUVAXOVID)

For the Moderna SPIKEVAX Bivalent Original/Omicron BA.4/5: participants will receive one (1) intramuscular injection of 0.5 mL (50 mcg).

For the Novavax Nuvaxovid vaccine: participants will receive one (1) intramuscular injection of 0.5 mL (5 mcg) of Novavax Nuvaxovid.

Group Type: ACTIVE_COMPARATOR

COVID-19 vaccine

Intervention Type: BIOLOGICAL

Participants are to receive a booster dose of a COVID-19 vaccine.

Trajectory B

Participants who have already received a 4 doses or more of COVID-19 vaccine in the community at inclusion and do not wish to receive a 5th dose of vaccine in the study.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Trajectory B5

Participants who have received 4 doses of an mRNA vaccine at inclusion and wish to receive a dose of a protein subunit vaccine (PSV) (Novavax NUVAXOVID) as a fifth dose.

For the Novavax Nuvaxovid vaccine: participants will receive one (1) intramuscular injection of 0.5 mL (5 mcg) of Novavax Nuvaxovid.

Group Type: ACTIVE_COMPARATOR

COVID-19 vaccine

Intervention Type: BIOLOGICAL

Participants are to receive a booster dose of a COVID-19 vaccine.

Interventions

COVID-19 vaccine

Participants are to receive a booster dose of a COVID-19 vaccine.

Intervention Type: BIOLOGICAL

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.

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

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Paul R Fortin

OTHER

Sponsor Role: lead

Responsible Party

Paul R Fortin

Rheumatologist, Clinical Researcher, Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Paul R Fortin, MD,MPH,FRCPC

Role: PRINCIPAL_INVESTIGATOR

Centre de recherche du CHU de Québec - Université Laval

Locations

Research Institute - McGill University Health Centre

Montreal, Quebec, Canada

Site Status: RECRUITING

Centre de recherche du CHU de Québec - Université Laval

Québec, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Paul R Fortin, MD,MPH,FRCPC

Role: CONTACT

paul.fortin@crchudequebec.ulaval.ca

4185254444 ext. 48456

Alexandra Godbout, BA

Role: CONTACT

alexandra.godbout@crchudequebec.ulaval.ca

4185254444 ext. 48456

Facility Contacts

Sonia Leger-Theriault

Role: primary

Sonia.Leger@MUHC.MCGILL.CA

Alexandra Godbout

Role: primary

alexandra.godbout@crchudequebec.ulaval.ca

Other Identifiers

COVB-2022-1

Identifier Type: -

Identifier Source: org_study_id