NCT05236491

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).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
287

participants targeted

Target at P75+ for phase_2 rheumatoid-arthritis

Timeline
Completed

Started Mar 2022

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 10, 2022

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 11, 2022

Completed
26 days until next milestone

Study Start

First participant enrolled

March 9, 2022

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2023

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2023

Completed
Last Updated

January 17, 2023

Status Verified

January 1, 2023

Enrollment Period

1.2 years

First QC Date

February 10, 2022

Last Update Submit

January 13, 2023

Conditions

Outcome Measures

Primary Outcomes (2)

  • Safety of a booster dose of COVID-19 vaccine in patients on anti-CD-20 mAb.

    Assessment of SARDs flares (self-reported and physician-confirmed) in relation to the time of the last dose of vaccine received. The frequency of 'significant flares' will be defined as worsening of RA symptoms (i.e., increase in DAS28 \>1.2 or \>0.6 if DAS28 at baseline was ≥3.2) with an increase in the number of swollen joints confirmed by a rheumatologist that is actionable (requires treatment intensification). For SLE, a flare will be defined as mild/moderate when the index SLEDAI increases by \>3 and severe when it increases by \>10. The need for treatment intensification (e.g., increase in the dose of steroids) will also be recorded as an indication of SLE flare. For AAV and other SARDs that do not have standard instruments to define flares, we will use the physician's assessment of the presence of a clinically significant flare to the general question " Has this patient experienced a clinically significant flare of their SARD? " and document relevant change in medication.

    28 days

  • Reactogenicity of a booster dose of COVID-19 vaccine in patients on anti-CD-20 mAb.

    Documentation of the reactogenicity to the booster dose of the vaccine. Reactogenicity post-booster dose will be based on the patient's diary and questionnaire collected at visit 28 days post booster dose vaccination.

    28 days

Secondary Outcomes (1)

  • Humoral response

    28 days post vaccination

Other Outcomes (2)

  • Humoral response

    180 days post vaccination

  • Humoral response

    335 days post vaccination

Study Arms (3)

Trajectory A

ACTIVE COMPARATOR

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.

Biological: COVID-19 vaccine

Trajectory B

NO INTERVENTION

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.

Trajectory B5

ACTIVE COMPARATOR

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.

Biological: COVID-19 vaccine

Interventions

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

Trajectory ATrajectory B5

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 more 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.

You may not qualify if:

  • 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;
  • History of hypersensitivity or severe allergic reaction such as anaphylaxis to a component of the vaccine or to a previous vaccine;
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Research Institute - McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Centre de recherche du CHU de Québec - Université Laval

Québec, Quebec, G1V 4G2, Canada

RECRUITING

MeSH Terms

Conditions

Arthritis, RheumatoidLupus Erythematosus, SystemicSystemic VasculitisScleroderma, SystemicScleroderma, DiffuseUndifferentiated Connective Tissue DiseasesMASS syndrome

Interventions

COVID-19 Vaccines

Condition Hierarchy (Ancestors)

ArthritisJoint DiseasesMusculoskeletal DiseasesRheumatic DiseasesConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System DiseasesVasculitisVascular DiseasesCardiovascular DiseasesSkin Diseases

Intervention Hierarchy (Ancestors)

Viral VaccinesVaccinesBiological ProductsComplex Mixtures

Study Officials

  • Paul R Fortin, MD,MPH,FRCPC

    Centre de recherche du CHU de Québec - Université Laval

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Rheumatologist, Clinical Researcher, Principal Investigator

Study Record Dates

First Submitted

February 10, 2022

First Posted

February 11, 2022

Study Start

March 9, 2022

Primary Completion

June 1, 2023

Study Completion

December 1, 2023

Last Updated

January 17, 2023

Record last verified: 2023-01

Data Sharing

IPD Sharing
Will not share

Locations