COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders
Study Purpose
This is a randomized, multi-site, adaptive, open-label clinical trial comparing the immune response to different additional doses of COVID-19 vaccine in participants with autoimmune disease requiring IS medications. All study participants will have negative serologic or suboptimal responses (defined as a Roche Elecsys® Anti-SARS-CoV-2 S result ≤200 U/mL) or a low immune response (defined as a Roche Elecsys® Anti-SARS-CoV-2 S result >200 U/ml and ≤2500 U/mL) to their previous doses of COVID-19 vaccine. The study will focus on 5 autoimmune diseases in adults:
- - Systemic Lupus Erythematosus (SLE) - Rheumatoid Arthritis (RA) - Multiple Sclerosis (MS) - Systemic Sclerosis (SSc), and.
- - Pemphigus.
Recruitment Criteria
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
Eligible Ages | 2 Years and Over |
Gender | All |
General Adult
Inclusion Criteria:
1. Willing and able to sign informed consent 2. Documented full COVID-19 vaccination (CDC card or documentation in medical records) that was completed at least 4 weeks prior and no more than 52 weeks prior to the Stage 1 Screening visit, or if participating in Stage 2, no more than 48 weeks prior to the Stage 2 Screening visit. General Exclusion Criteria 2. History of severe allergic reaction to the initial COVID-19 vaccine regimen, to any component of any of the COVID-19 vaccines, or to polyethylene glycol (PEG). 3. New diagnosis of malignancy that will require chemotherapy or immunotherapy, or ongoing treatment for a malignancy with chemotherapy or immunotherapy. 4. Active disease (per the Investigator's decision) resulting in inability to hold the IS therapy in the MMF/MPA or MTX arms of the study. a. 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: 1. An increase/addition of any IS medications, or. 2. A suggestion of MS relapse per the investigator. 6. Recent or current SARS-CoV-2 infection defined as: 1. Documented SARS-CoV-2 infection in the past 30 days (from the day the participant is diagnosed by positive test to Screening). 2. Positive result on a molecular COVID-19 test at Screening. 8. Inflammatory myocarditis/pericarditis within 6 weeks of any COVID-19 vaccine doses. 9. Participants with active, ongoing chronic infections. Note: Participants are permitted to be on chronic prophylactic antimicrobial therapy. Adults with evidence of HIV, Hepatitis B indicated by surface antigen, and Hepatitis C indicated by anti-hepatitis C antibody positivity will be excluded. If an adult is negative for Hepatitis C viral load at Screening, he/she will be eligible to participate. 10. Participants with common variable immunodeficiency disease, as well as any participants currently receiving immune globulin replacement therapy. Note: Pediatric participants on IVIG therapeutically may enter the study provided they have sufficiently quiet disease that they can withhold their IVIG from 8 weeks prior to the Screening visit through 4 weeks after vaccination. 11. Participants who received licensed or investigational monoclonal antibodies or plasma products directed against SARS-CoV-2 within 30 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. Currently pregnant or breastfeeding (For pediatric participants postmenarchal females must have a negative urine pregnancy test at Screening). 15. Hemoglobin (Hgb) <8.0 g/dL (80 g/L) 16. 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. 17. Other investigational chemical agent within 30 days or other investigational biologic agent within 8 weeks or 5 half-lives (whichever is longer) of Screening. 18. Concurrent treatment with cyclophosphamide. Adult participants taking cladribine, alemtuzumab, or mitoxantrone will also be excluded. 19. Participants currently on any type of dialysis, or who have received a solid organ transplant. 20. Prisoners or participants who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness. 21. Taking both MMF/MPA and MTX. 22. Receiving other investigational BCDT as part of a clinical trial within 18 months of Screening, unless drug assignment is known and the participant received an anti-CD20 or CD19 drug. 23. Participants with active systemic infections who have received systemic antimicrobials within the 14 days prior to Screening. Adult General Criteria.Inclusion Criteria:
1. Individuals 18 years of age or older 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 ACR/EULAR or 2012 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. 1. 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 6. Must be currently taking one of the following IS medications with or without additional disease-related medications: MMF (minimum of 1000 mg per day)/MPA (minimum of 720 mg per day), MTX (minimum of 7.5mg per week), or B cell depleting agents within the past 18 months (such as rituximab, ocrelizumab, ofatumumab). 1. If taking MMF/MPA or MTX, the participant must 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. Note: Participants who withheld their IS medications around their initial vaccinations are eligible to participate. 2. If enrolling in the BCDT cohort, the participant must have received an anti-CD20 or an anti-CD19 BCDT in the past 18 months. 7. No changes in background IS medications, including MMF/MPA or MTX, in the 4 weeks prior to Screening, excluding the following: 1. HCQ, 2. Intraarticular steroids, 3. The addition of prednisone at ≤10mg per day or prednisone at any dose when given for ≤3 days, and. 4. Corticosteroid bursts for non-autoimmune disease-related conditions, such as asthma or COPD, are permitted. Adult General Exclusion Criterion 1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol. 14. Adult female participants who are planning a pregnancy during the course of the trial. Adult Stage 1-Specific Inclusion Criterion 5. Negative or suboptimal serologic response to initial COVID-19 vaccine regimen, defined as an Elecsys® Anti-SARS-CoV-2 S result ≤200 U/mL, at Screening visit. 1. Initial COVID-19 vaccine regimen is defined as either: i.2 doses of the Pfizer-BioNTech COVID-19 Vaccine ii. 2 doses of the Moderna COVID-19 Vaccine. Adult Stage 1-Specific Exclusion Criterion 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. Adult Stage 2 (Newly Recruited)-Specific Inclusion Criteria 2. History of severe allergic reaction to the COVID-19 vaccine, or to any component of the COVID-19 vaccine, that is to be administered in Stage 2, including polysorbate for participants receiving the Sanofi-GSK COVID-19 Vaccine, or to PEG. 5. Negative or suboptimal serologic response to a previous COVID 19 vaccine administration in one of the qualifying regimens, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) negative result or positive result of ≤200 U/mL, or a low immune response, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) result of ≤2500 U/mL, within 4 weeks of the Stage 2 Baseline/Week 0 visit. The regimens of COVID-19 vaccination that qualify are as follows: 1. 3 doses of the Pfizer-BioNTech COVID-19 Vaccine. 2. 3 doses of the Moderna COVID-19 Vaccine. 3. 2 doses of the Janssen COVID-19 Vaccine. 4. 4 or more doses of a single mRNA vaccine (Pfizer-BioNTech COVID-19 Vaccine OR Moderna COVID-19 Vaccine) 5. 3 or more doses of a mixture of mRNA vaccines (Pfizer-BioNTech COVID-19 Vaccine OR Moderna COVID-19 Vaccine) Adult Stage 2 (Newly Recruited)-SpecificExclusion Criteria:
7. Receipt of a mixture of Janssen COVID-19 vaccines and mRNA COVID-19 vaccines (in any order or combination) prior to Stage 2 Screening. Adult Stage 2 (Rollover)-SpecificInclusion Criteria:
Individuals who were previously enrolled in Adult Stage 1 or Adult Stage 2 will have met some inclusion and exclusion criteria at that time. Only a subset of the criteria for (re-)entering Adult Stage 2 will be assessed in rollover participants at the time of screening for Stage 2. Individuals who meet all of the following criteria are eligible to (re )enter Adult Stage 2: 2. History of severe allergic reaction to the COVID-19 vaccine, or to any component of the COVID-19 vaccine, that is to be administered in Stage 2, including polysorbate for participants receiving the Sanofi-GSK COVID-19 Vaccine, or to PEG. 5. Negative or suboptimal serologic response to a previous COVID 19 vaccine administration in one of the qualifying regimens, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) negative result or positive result of ≤200 U/mL, or a low immune response, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) result of ≤2500 U/mL, within 4 weeks of the Stage 2 Baseline/Week 0 visit. The regimens of COVID-19 vaccination that qualify are as follows: a. 3 doses of the Pfizer-BioNTech COVID-19 Vaccine b. 3 doses of the Moderna COVID-19 Vaccine c. 2 doses of the Janssen COVID-19 Vaccine d. 4 doses of a combination of mRNA vaccines (i.e., Pfizer-BioNTech COVID-19 Vaccine, Moderna COVID-19 Vaccine) General Pediatric Inclusion Criteria. 1. Individuals 2-17 years of age that meet classification criteria for SLE, JIA, POMS, or JDM. Note: Juvenile idiopathic arthritis includes the following conditions: polyarticular JIA (both RF + and -), oligoarticular persistent and oligoarticular extended JIA, psoriatic arthritis, and enthesitis related JIA. 1. Participants must meet the 2017 EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups, the International League of Associations for Rheumatology (ILAR) classification for JIA, the 2017 McDonald criteria for MS, or the Bohan and Peter criteria or the 2017 EULAR/ACR classification criteria for JDM. 2. 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. 2. Parents/guardians of all pediatric participants and participants ages 14- - 17 must be willing and able to sign informed consent.
Inclusion Criteria:
4. Negative or suboptimal serologic response to initial EUA-authorized or FDA-approved COVID-19 vaccine doses, defined as an Elecsys® Anti-SARS-CoV-2 S result ≤200 U/mL, or a low immune response, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) result of ≤2500 U/mL, within 4 weeks of the Stage 1 Baseline/Week 0 visit. Initial COVID-19 vaccine regimen is defined as: i. Pfizer-BioNTech COVID-19 Vaccine (2 through 4 years of age): 3 age-appropriate doses ii. Pfizer-BioNTech COVID-19 Vaccine (5 through 17 years of age): 2 age-appropriate doses iii. Moderna COVID-19 Vaccine (2 through 17 years of age): 2 age-appropriate doses. Pediatric Stage 1-SpecificExclusion Criteria:
Individuals who meet any of these criteria are not eligible for randomization/allocation as participants in the pediatric portion of the study: 7. Receipt of a COVID-19 vaccine booster prior to Screening. Pediatric Stage 2 (Newly Recruited)-Specific Inclusion Criteria 5. Negative or suboptimal serologic response to homologous doses of COVID-19 vaccine in one of the qualifying regimens, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) negative result or positive result of ≤200 U/mL, or a low immune response, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) result of ≤2500 U/mL, within 4 weeks of the Stage 2 Baseline/Week 0 visit. The regimens of COVID-19 vaccination that qualify are as follows: a. Pfizer-BioNTech COVID-19 Vaccine (2 through 5 years of age): 4 full, age-appropriate doses of the Pfizer-BioNTech COVID-19 Vaccine b. Pfizer-BioNTech COVID-19 Vaccine (5 through 17 years old): 3 full, age-appropriate doses of the Pfizer-BioNTech COVID-19 Vaccine Note: Participants who are 5 years old and previously received the Pfizer-BioNTech COVID-19 Vaccine may have received either age-appropriate regimen. c. Moderna COVID-19 Vaccine (12 through 17 years of age): 3 full, age-appropriate doses of the Moderna COVID-19 Vaccine. Pediatric Stage 2 (Newly Recruited)-SpecificExclusion Criteria:
7. Receipt of an additional heterologous COVID-19 vaccine dose prior to Stage 2 Screening, i.e., a participant cannot have received a mixture of mRNA vaccines. Pediatric Stage 2 (Rollover)-SpecificInclusion Criteria:
5. Negative or suboptimal serologic response to a previous COVID-19 vaccine administration in one of the qualifying regimens, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) negative result or positive result of ≤200 U/mL, or a low immune response, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) result of ≤2500 U/mL, within 4 weeks of the Stage 2 Baseline/Week 0 visit. The regimens of COVID-19 vaccination that qualify are as follows: 1. Pfizer-BioNTech COVID-19 Vaccine (2 through 5 years of age): 4 full, age-appropriate doses of the Pfizer-BioNTech COVID-19 Vaccine. 2. Pfizer-BioNTech COVID-19 Vaccine (5 through 17 years old): 3 full, age-appropriate doses of the Pfizer-BioNTech COVID-19 Vaccine Note: Participants who are 5 years old and previously received the Pfizer-BioNTech COVID-19 Vaccine may have received either age-appropriate regimen. 3. Moderna COVID-19 Vaccine (12 through 17 years of age): 3 full, age-appropriate doses of the Moderna COVID-19 VaccineTrial Details
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT05000216 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 2 |
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
National Institute of Allergy and Infectious Diseases (NIAID) |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Judith A. James, MD, PhDMeggan C. Mackay, MD, MSDinesh Khanna, MBBS, MScAmit Bar-Or, MD, FRCPVirginia Pascual, MDStacy Ardoin, MDNatasha Mckerran Ruth, MDTracey Wright, MD |
Principal Investigator Affiliation | Arthritis and Clinical Immunology Program, Oklahoma Medical Research FoundationCenter of Autoimmune Musculoskeletal and Hematopoietic Diseases, Feinstein Institute for Medical ResearchUniversity of Michigan Health, Michigan MedicineCenter for Neuroinflammation and Neurotherapeutics, Perelman School of Medicine, University of PennsylvaniaDrukier Institute for Children's Health, Weill Cornell Medical CollegeNationwide Children's Hospital Rheumatology DepartmentMedical University of South Carolina, Pediatric RheumatologyUT Southwestern Medical Center, Pediatric Rheumatology |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
NIH, Other, Industry |
Overall Status | Active, not recruiting |
Countries | United States |
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Pemphigus Vulgaris, Multiple Sclerosis (MS), Systemic Sclerosis (SSc), Pediatric SLE, Juvenile Idiopathic Arthritis (JIA), Juvenile Dermatomyositis (JDM), Pediatric-Onset Multiple Sclerosis (POMS) |
Study Website: | View Trial Website |
Adult Population: Stage 1 of this trial will enroll up to a maximum of 900 adult study participants (up to 60 participants per arm). Participants will be assigned to one of 3 cohorts based on their IS regimens:
- - Cohort A: Receipt of MMF or MPA.
- - Cohort B: Receipt of MTX.
- - Cohort C: Receipt of any BCDT within the past 18 months.
- - Participants continue to take their cohort-defining IS medications without alterations in schedule and dosing.
- - Participants withhold their cohort-defining IS medications before and after the additional homologous vaccine dose per protocol instructions.
- - Stage 1 participant rolls over to Stage 2.
- - Stage 2 participant rolls over to a different Stage 2 treatment arm.
- - Cohort D: Receipt of MMF or MPA.
- - Cohort E: Receipt of MTX.
- - Cohort F: Receipt of any BCDT within the past 18 months.
- - Cohort A: Receipt of MMF or MPA.
- - Cohort B: Receipt of MTX.
- - Cohort C: Receipt of any BCDT within the past 18 months.
- - Participants continue to take their cohort-defining IS medications without alterations in schedule and dosing.
- - Participants withhold their cohort-defining IS medications before and after the additional homologous vaccine dose per protocol instructions.
- - Cohort D: Receipt of MMF or MPA (± other rheumatic disease medications, including biologics) o Participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) will be placed in this cohort.
- - Cohort E: Receipt of MTX (± other rheumatic disease medications, including biologics) o Participants who are taking MTX (without additional B cell depleting medications or MMF/ MPA) will be placed in this cohort.
- - Cohort F: Receipt of B cell depletion therapy within the past 18 months (± other rheumatic disease medications) o Participants taking B cell depletion medications, regardless of whether they are also taking MMF or MTX, will be placed in this cohort.
- - New cohorts may be defined based on changes in the medication groups if it becomes obvious that certain medications are highly associated with suboptimal or low immune serologic response to initial COVID-19 vaccine regimen.
- - Cohorts may limit or expand the autoimmune diseases that are eligible to be included in the clinical trial and may include expansion cohorts of underrepresented diseases.
- - New cohorts may include participants whose antibody response falls to suboptimal or low immune levels over time.
- - Based upon timing of the FDA EUA authorization for children of each of the COVID-19 vaccines used in this trial, the age range of the inclusion criteria may be expanded.
- - Allocation or randomization to treatment with new COVID-19 vaccines may be incorporated into the design when the products become available.
- - Identification of additional strategies to enhance vaccine responsiveness in autoimmune diseases, including a temporary switch of immunomodulatory medications.
Arms
Experimental: Cohort A, Arm A1: Moderna mRNA-1273 + Continue IS (MMF or MPA)
Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive an additional dose of the Moderna COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort A, Arm A2: BNT162b2 + Continue IS (MMF or MPA)
Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort A, Arm A3: Ad26.COV2.S + Continue IS (MMF or MPA)
Arm closed, effective protocol version 3.0. Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive the Janssen COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort A, Arm A4: Moderna mRNA-1273 + Withhold IS (MMF or MPA)
Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction.
Experimental: Cohort A, Arm A5: BNT162b2 + Withhold IS (MMF or MPA)
Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.
Experimental: Cohort A, Arm A6: Ad26.COV2.S + Withhold IS (MMF or MPA)
Arm closed, effective protocol version 3.0. Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after the Janssen COVID-19 vaccine booster (1 dose), per protocol instruction.
Experimental: Cohort B, Arm B1: Moderna mRNA-1273 + Continue IS (MTX)
Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive an additional dose of the Moderna COVID-19 vaccine booster and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort B, Arm B2: BNT162b2 + Continue IS (MTX)
Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine booster and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort B, Arm B3: Ad26.COV2.S + Continue IS (MTX)
Arm closed, effective protocol version 3.0. Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive the Janssen COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort B, Arm B4: Moderna mRNA-1273 + Withhold IS (MTX)
Adult Participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction.
Experimental: Cohort B, Arm B5: BNT162b2 + Withhold IS (MTX)
Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine booster, per protocol instruction.
Experimental: Cohort B, Arm B6: Ad26.COV2.S + Withhold IS (MTX)
Arm closed, effective protocol version 3.0. Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after the Janssen COVID-19 vaccine booster (1 dose), per protocol instruction.
Experimental: Cohort C, Arm C1: Moderna mRNA-1273 + Continue IS (B cell depletion therapy)
Adult participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive an additional dose of the Moderna COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort C, Arm C2: BNT162b2 + Continue IS (B cell depletion therapy)
Adult participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort C, Arm C3: Ad26.COV2.S + Continue IS (B cell depletion therapy)
Arm closed, effective protocol version 3.0. Adult participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive the Janssen COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort D, Arm D1: Ad26.COV2.S + Withhold IS (MMF or MPA)
Arm closed, effective protocol version 4.0. Adult participants who previously received an mRNA vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Janssen COVID-19 vaccine, per protocol instruction.
Experimental: Cohort D, Arm D2: Alternative mRNA Vaccine + Withhold IS (MMF or MPA)
Adult participants who previously received an mRNA vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of an alternative COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.
Experimental: Cohort D, Arm D3: Moderna mRNA-1273 + Withhold IS (MMF or MPA)
Adult participants who previously received the Janssen COVID-19 vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.
Experimental: Cohort E, Arm E1: Ad26.COV2.S + Withhold IS (MTX)
Arm closed, effective protocol version 4.0. Adult participants who previously received an mRNA vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Janssen COVID-19 vaccine, per protocol instruction.
Experimental: Cohort E, Arm E2: Alternative mRNA Vaccine + Withhold IS (MTX)
Adult participants who previously received an mRNA vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of an alternative COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.
Experimental: Cohort E, Arm E3: Moderna mRNA-1273 + Withhold IS (MTX)
Adult participants who previously received the Janssen COVID-19 vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.
Experimental: Cohort F, Arm F1: Ad26.COV2.S + Withhold IS (B cell depletion therapy)
Arm closed, effective protocol version 4.0. Adult participants who previously received an mRNA vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX ) before and after receiving a dose of the Janssen COVID-19 vaccine, per protocol instruction.
Experimental: Cohort F, Arm F2: Alternative mRNA Vaccine + Withhold IS (B cell depletion therapy)
Adult participants who previously received an mRNA vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the alternative COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.
Experimental: Cohort F, Arm F3: Moderna mRNA-1273 + Withhold IS (B cell depletion therapy)
Adult participants who previously received the Janssen COVID-19 vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.
Experimental: Cohort D, Arm D4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (MMF or MPA)
Adult participants who previously received an mRNA vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Sanofi-GSK COVID-19 vaccine, per protocol instruction.
Experimental: Cohort E, Arm E4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (MTX)
Adult participants who previously received an mRNA vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Sanofi-GSK COVID-19 vaccine, per protocol instruction.
Experimental: Cohort F, Arm F4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (B cell depletion therapy)
Adult participants who previously received an mRNA vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the Sanofi-GSK COVID-19 vaccine, per protocol instruction
Experimental: Cohort A, Arm A1P: Moderna mRNA-1273, Bivalent + Continue IS (MMF or MPA)
Pediatric participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive an additional dose of the Moderna COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort A, Arm A2P: BNT162b2, Bivalent + Continue IS (MMF or MPA)
Pediatric participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort A, Arm A4P: Moderna mRNA-1273, Bivalent + Withhold IS (MMF or MPA)
Pediatric participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction.
Experimental: Cohort A, Arm A5P: BNT162b2, Bivalent + Withhold IS (MMF or MPA)
Pediatric participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.
Experimental: Cohort B, Arm B1P: Moderna mRNA-1273, Bivalent + Continue IS (MTX)
Pediatric participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive an additional dose of the Moderna COVID-19 vaccine booster and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort B, Arm B2P: BNT162b2, Bivalent + Continue IS (MTX)
Pediatric participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine booster and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort B, Arm B4P: Moderna mRNA-1273, Bivalent + Withhold IS (MTX)
Pediatric participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction.
Experimental: Cohort B, Arm B5P: BNT162b2, Bivalent + Withhold IS (MTX)
Pediatric participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine booster, per protocol instruction.
Experimental: Cohort C, Arm C1P: Moderna mRNA-1273, Bivalent + Continue IS (B cell depletion therapy)
Pediatric participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive an additional dose of the Moderna COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort C, Arm C2P: BNT162b2, Bivalent + Continue IS (B cell depletion therapy)
Pediatric participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Experimental: Cohort D, Arm D1P: BNT162b2, Bivalent + Withhold IS (MMF or MPA)
Pediatric participants who previously received the Moderna COVID-19 vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.
Experimental: Cohort D, Arm D2P: Moderna mRNA-1273, Bivalent + Withhold IS (MMF or MPA)
Pediatric participants who previously received the Pfizer-BioNTech COVID-19 vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction.
Experimental: Cohort E, Arm E1P: BNT162b2, Bivalent + Withhold IS (MTX)
Pediatric participants who previously received the Moderna COVID-19 vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.
Experimental: Cohort E, Arm E2P: Moderna mRNA-1273, Bivalent + Withhold IS (MTX)
Pediatric participants who previously received the Pfizer-BioNTech COVID-19 vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction.
Experimental: Cohort F, Arm F1P: BNT162b2, Bivalent + Withhold IS (B cell depletion therapy)
Pediatric participants who previously received the Moderna COVID-19 vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.
Experimental: Cohort F, Arm F2P: Moderna mRNA-1273, Bivalent + Withhold IS (B cell depletion therapy)
Pediatric participants who previously received the Pfizer-BioNTech COVID-19 vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction.
Interventions
Biological: - Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Biological: - BNT162b2
Administration: One dose administered intramuscularly.
Biological: - Ad26.COV2.S
Administration: One dose administered intramuscularly.
Drug: - Continue IS (MMF or MPA)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Drug: - Continue IS (MTX)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Biological: - Continue IS (B cell depletion therapy)
Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing.
Biological: - Monovalent [B.1.351] CoV2 preS dTM-AS03
One dose administered intramuscularly
Drug: - Withhold IS (MMF or MPA)
Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions.
Drug: - Withhold IS (MTX)
Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions.
Drug: - Withhold IS (B cell depletion therapy)
Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX ) before and after the additional vaccine dose per protocol instructions. Participants will continue to take their prescribed BCDTs without alterations in schedule and dosing.
Biological: - Moderna mRNA-1273, Bivalent
Administration: One dose administered intramuscularly.
Biological: - BNT162b2, Bivalent
Administration: One dose administered intramuscularly.
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Address
UCLA Medical Center: Division of Rheumatology
Los Angeles, California, 90095
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Address
Yale University School of Medicine: Rheumatology, Allergy & Immunology
New Haven, Connecticut, 06519
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The Emory Clinic: Division of Rheumatology
Atlanta, Georgia, 30322
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Indiana University Medical Center, Riley Hospital for Children
Indianapolis, Indiana, 46202
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Address
Massachusetts General Hospital: Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases
Boston, Massachusetts, 02114
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Boston Children's Hospital: Department of Pediatrics, Rheumatology Program
Boston, Massachusetts, 02115
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Brigham & Women's Hospital: Department of Medicine, Rheumatology, Immunology
Boston, Massachusetts, 02115
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University of Michigan Health System: Department of Internal Medicine, Division of Rheumatology
Ann Arbor, Michigan, 48109
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Washington University School of Medicine in St. Louis: Division of Rheumatology
Saint Louis, Missouri, 63110
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Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases
Manhasset, New York, 11030
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Feinstein Institute for Medical Research
Manhasset, New York, 11030
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New York University Langone Medical Center: Department of Medicine, Division of Rheumatology
New York, New York, 10016
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Hospital for Special Surgery
New York, New York, 10021
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Columbia University Irving Medical Center: Department of Neurology, Multiple Sclerosis Center
New York, New York, 10032
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University of Rochester Medical Center
Rochester, New York, 14642
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Stony Brook University Hospital
Stony Brook, New York, 11794-8111
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University of North Carolina Children's Hospital
Chapel Hill, North Carolina, 27599
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Duke University Medical Center: Division of Rheumatology and Immunology
Durham, North Carolina, 27710
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Cleveland Clinic
Cleveland, Ohio, 44195
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Address
Nationwide Children's Hopspital
Columbus, Ohio, 43205
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Address
Oklahoma Children's Hospital-Pediatrics Specialties Clinic
Oklahoma City, Oklahoma, 73104
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Address
Oklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program
Oklahoma City, Oklahoma, 73104
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Address
Temple Health: Rheumatology
Philadelphia, Pennsylvania, 19104
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University of Pennsylvania Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, 19104
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Medical University of South Carolina, Nexus Research Center
Charleston, South Carolina, 29425
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Address
Medical University of South Carolina, Shawn Jenkins Children's Hospital
Charleston, South Carolina, 29425
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Address
UT Southwestern (Peds)
Dallas, Texas, 75325
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Address
University of Texas Houston Medical School: Division of Rheumatology and Clinical Immunogenetics
Houston, Texas, 77030
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Address
Benaroya Research Institute at Virginia Mason: Internal Medicine
Seattle, Washington, 98101