COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders
- Study HIC#:2000031152
- Last Updated:01/01/0001
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.
- Age18 years and older
- GenderBoth
Contact Us
For more information about this study, including how to volunteer, contact:
Julie Heffernan
- Phone Number: 1-203-785-6631
Help Us Discover!
You can help our team find trials you might be eligible for by creating a volunteer profile in MyChart. To get started, create a volunteer profile, or contact helpusdiscover@yale.edu, or call +18779788343 for more information.
Trial Purpose and Description
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.
Eligibility Criteria
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
- pemphigus
- 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:
- 2 doses of the Pfizer-BioNTech COVID-19 vaccine
- 2 doses of the Moderna COVID-19 vaccine, or
- A single dose of the Janssen COVID-19 vaccine
- 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
- 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
- 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
- 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
- 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
- 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
- Participants with common variable immunodeficiency disease, as well as any participants currently receiving immune globulin replacement therapy
- Participants who received licensed or investigational monoclonal antibodies or plasma products directed against SARS-CoV-2 within 90 days of Screening
- 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
- 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)
- Participants with a history of heparin-induced thrombocytopenia (HIT) or thrombotic thrombocytopenic purpura (TTP)
- Currently pregnant or breastfeeding
- Participants who are planning a pregnancy during the course of the trial
- Hemoglobin (Hgb) < 8.0 g/dL (80 g/L)
- 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
- Other investigational chemical agent within 30 days or other investigational biologic agent within 8 weeks or 5 half-lives (whichever is longer) of enrollment
- Concurrent treatment with cyclophosphamide, cladribine, alemtuzumab, or mitoxantrone
- Any increase in disease activity at Screening that would necessitate a change in medications
- Participants currently on any type of dialysis, or who have received a solid organ transplant
- 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