COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders

  • End date
    Dec 8, 2022
  • participants needed
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 17 October 2021
treatment regimen
pulmonary disease
autoimmune disease
progressive systemic sclerosis
disease or disorder


This is a randomized, multi-site, adaptive, open-label clinical trial comparing the immune response to different COVID-19 vaccine booster doses in participants with autoimmune disease requiring immunosuppressive medications. All study participants will have negative serologic or sub-optimal responses (defined as a Roche Elecsys Anti-SARS-CoV-2 S (RBD) result 50 U/mL) to initial COVID-19 vaccine regimen with Moderna COVID-19 vaccine, Pfizer-BioNTech COVID-19 vaccine, or Janssen COVID-19 vaccine.

The study will initially focus on 5 autoimmune diseases:

  • Systemic Lupus Erythematosus (SLE)
  • Rheumatoid Arthritis (RA)
  • Multiple Sclerosis (MS)
  • Systemic Sclerosis (SSc), and
  • Pemphigus.


In this study, participants will be assigned to one of 3 cohorts based on their immunosuppressive regimens:

  • Cohort A: Receipt of MMF or MPA ( other rheumatic disease medications, including biologics)

--Participants who are taking mycophenolate mofetil (MMF) or mycophenolic acid (MPA), without additional B cell depleting medications or methotrexate (MTX), will be placed in this cohort.

  • Cohort B: Receipt of MTX ( other rheumatic disease medications, including biologics)

--Participants who are taking MTX (without additional B cell depleting medications or MMF/ MPA) will be placed in this cohort.

  • Cohort C: Receipt of B cell depletion therapy within the past 12 months ( other rheumatic disease medications) --Participants taking B cell depletion medications, regardless of whether they are also taking MMF or MTX, will be placed in this cohort.

Treatment Arms: Participants in Cohorts A, B, and C will be assigned to receive a booster of the same vaccine as their original vaccine series (Moderna COVID-19 vaccine, Pfizer-BioNTech COVID-19 vaccine, or Janssen COVID-19 vaccine).

Participants in Cohorts A and B will be randomized into two immunosuppressive medication (IS) treatment plans as follows:

  • Participants continue to take their immunosuppressive medications without alterations in schedule and dosing.
  • Participants withhold their immunosuppressive medications before and after the booster, per protocol.

Condition Multiple Sclerosis, Autoimmune disease, CONNECTIVE TISSUE DISEASE, Rheumatoid Arthritis, Systemic sclerosis, Pemphigus, Dermatosis, SYSTEMIC LUPUS ERYTHEMATOSUS, multiple sclerosis (ms), progressive systemic sclerosis
Treatment BNT162b2, Ad26.COV2.S, Moderna mRNA-1273, IS (MMF or MPA), IS (MTX), IS (B cell depletion therapy)
Clinical Study IdentifierNCT05000216
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on17 October 2021


Yes No Not Sure

Inclusion Criteria

Individuals who meet all the following criteria are eligible for enrollment as
study participants-
Individuals that meet classification criteria for
systemic lupus erythematosus (SLE)
systemic sclerosis (SSc)
rheumatoid arthritis (RA)
multiple sclerosis (MS), or
Participants must meet
the 2019 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) or the 2012 Systemic Lupus International Collaborating Clinics Classification Criteria (SLICC) classification criteria for SLE
the 2010 ACR/EULAR classification criteria for RA
the 2013 EULAR/ACR classification criteria for SSc
the 2017 McDonald criteria for MS, and
the international consensus criteria for pemphigus
Note: If a participant has been diagnosed with more than one autoimmune
disease, the participant will be assessed based on the disease that is
selected for study entry
\. Willing and able to sign informed consent
\. Documented full COVID-19 vaccination (e.g., Centers for Disease Control
and Prevention [CDC] vaccination card or documentation in medical records)
that was completed 4 weeks prior and no more than 36 weeks prior to the
Screening visit
\. Negative serologic or suboptimal response to initial COVID-19 vaccine
regimen- defined as an Elecsys Anti-Severe Acute Respiratory Syndrome
Coronavirus-2 (anti-SARS-CoV-2-spike (S) protein receptor binding domain
(RBD)) result 50 U/mL at Screening visit
Initial COVID-19 vaccine regimen is defined as either
doses of the Pfizer-BioNTech COVID-19 vaccine
doses of the Moderna COVID-19 vaccine, or
A single dose of the Janssen COVID-19 vaccine 6. Must be currently taking one of the following immunosuppressive medications with or without additional disease related medications
mycophenolate mofetil (minimum of 1,000 mg per day)/mycophenolic acid (minimum of 720 mg per day)
methotrexate (minimum of 7.5mg per week), or
B cell depleting agents within the past 12 months (such as rituximab, ocrelizumab, ofatumumab)
If taking mycophenolate mofetil (MMF)/mycophenolic acid (MPA) or methotrexate (MTX), the participant should have initiated therapy at least 8 weeks prior to randomization and be taking the same medications (regardless of dose) as at the time of the initial COVID-19 vaccine regimen
Participants on B cell depleting therapy may enter the study if they are also taking MMF/MPA or MTX. In this case, the MMF/MPA or MTX would not be withheld for the vaccine booster dose(s)
Participants taking both MMF/MPA and MTX will be excluded from the study 7. No changes in background immunosuppressive medications in the 8 weeks prior to Screening, excluding the following
hydroxychloroquine (HCQ)
Intraarticular steroids
The addition of prednisone at 10 mg per day or prednisone at any dose when given for 3 days, and
Corticosteroid bursts for non-autoimmune disease-related conditions, such as asthma or chronic obstructive pulmonary disease (COPD), are permitted

Exclusion Criteria

Individuals who meet any of these criteria are not eligible for enrollment as
study participants-
Inability or unwillingness of a participant to give written informed consent or comply with study protocol
History of severe allergic reaction to the initial COVID-19 vaccine regimen, or any component of any of the COVID-19 vaccines, or to polyethylene glycol (PEG)
Ongoing treatment for a malignancy with chemotherapy or immunotherapy
Active disease (per the Investigator's decision) resulting in inability to hold the immunosuppressive therapy in the Mycophenolate Mofetil (MMF)/Mycophenolic Acid (MPA) or Methotrexate (MTX) arms of the study
The potential impact of temporarily holding medication for participants with a
recent mild disease flare within 4 weeks should be carefully considered
\. Active disease during the Screening period resulting in
an increase/addition of immunosuppressive medications, or
a suggestion of multiple sclerosis (MS) relapse per the investigator 6. Recent or current Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection defined as
Documented SARS-CoV-2 infection in the past 30 days (from the day the participant is diagnosed by positive test to Screening), or
A positive result on a molecular COVID-19 test at Screening 7. Receipt of a COVID-19 vaccine booster prior to Screening with the Moderna COVID-19 vaccine, Pfizer-BioNTech COVID-19 vaccine, or Janssen COVID-19 vaccine 8. Participants with
a history of autoimmune disease-related myocarditis within 3 years
autoimmune disease-related pericarditis within the past year, or
inflammatory myocarditis/pericarditis following initial COVID-19 vaccine regimen 9. Participants with active bacterial or viral infections who have received antibiotics within the 14 days prior to Screening, including participants with evidence of
Human Immunodeficiency Virus (HIV)
Hepatitis B as indicated by surface antigen or hepatitis B core antibody positivity
Hepatitis C as indicated by anti-hepatitis C antibody positivity
Note: If a participant is Hepatitis C antibody positive, they will be eligible to participate in the study if he/she is negative for viral load at Screening 10. Participants with common variable immunodeficiency disease, as well as any participants currently receiving immune globulin replacement therapy 11. Participants who received licensed or investigational monoclonal antibodies or plasma products directed against SARS-CoV-2 within 90 days of Screening 12. Participants who have received any live vaccines within 2 months of the anticipated study vaccine dose or who will have need of a live vaccine at any time during the study 13. Participants with history of arterial or venous thrombosis, and/or history of recurrent miscarriages associated with clotting antibodies (anticardiolipin antibodies, anti-beta-2 glycoprotein I antibodies, and positive lupus anticoagulant) 14. Participants with a history of heparin-induced thrombocytopenia (HIT) or thrombotic thrombocytopenic purpura (TTP) 15. Currently pregnant or breastfeeding 16. Participants who are planning a pregnancy during the course of the trial 17. Hemoglobin (Hgb) < 8.0 g/dL (80 g/L) 18. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator
may pose additional risks from participation in the study
may interfere with the participant's ability to comply with study requirements, or
that may impact the quality or interpretation of the data obtained from the study 19. Other investigational chemical agent within 30 days or other investigational biologic agent within 8 weeks or 5 half-lives (whichever is longer) of enrollment 20. Concurrent treatment with cyclophosphamide, cladribine, alemtuzumab, or mitoxantrone 21. Any increase in disease activity at Screening that would necessitate a change in medications 22. Participants currently on any type of dialysis, or who have received a solid organ transplant 23. Prisoners or participants who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
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