COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Autoimmunity Centers of Excellence; Rho Federal Systems Division, Inc.
• Treatments: Methotrexate; Mycophenolic Acid; Vaccines

Criteria

Inclusion Criteria:

Individuals who meet all the following criteria are eligible for enrollment as study participants-

1. Individuals that meet classification criteria for:

• systemic lupus erythematosus (SLE)

• systemic sclerosis (SSc)

• rheumatoid arthritis (RA)

• multiple sclerosis (MS), or

• pemphigus

2. 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

3. Willing and able to sign informed consent

4. 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

5. 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

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-

1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol

2. 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)

3. Ongoing treatment for a malignancy with chemotherapy or immunotherapy

4. 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

5. 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