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COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders

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ClinicalTrials.gov Identifier: NCT05000216
Recruitment Status : Recruiting
First Posted : August 11, 2021
Last Update Posted : October 15, 2021
Sponsor:
Collaborators:
Autoimmunity Centers of Excellence
Rho Federal Systems Division, Inc.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief 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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Systemic Lupus Erythematosus (SLE) Pemphigus Vulgaris Multiple Sclerosis Systemic Sclerosis (SSc) Biological: Moderna mRNA-1273 Biological: BNT162b2 Biological: Ad26.COV2.S Drug: IS (MMF or MPA) Drug: IS (MTX) Biological: IS (B cell depletion therapy) Phase 2

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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

  • Participants continue to take their immunosuppressive (IS) medications without alterations in schedule and dosing
  • Participants withhold their immunosuppressive (IS) medications before and after the vaccine booster, per protocol instruction

Cohort C: No randomization-Participants continue to take their immunosuppressive (IS) medications without alterations in schedule and dosing.

Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Booster Effects With Autoimmune Treatments in Patients With Poor Response to Initial COVID-19 Vaccine (ACV01)
Actual Study Start Date : August 13, 2021
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: Cohort A, Arm A1: Moderna mRNA-1273 +IS (MMF or MPA)
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 Moderna COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA-1273 vaccine (Moderna)
  • Moderna COVID-19 Vaccine
  • SARS-CoV-2 RNA vaccine
  • COVID-19 vaccine

Drug: IS (MMF or MPA)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
  • immunosuppressive medication
  • mycophenolate mofetil
  • MMF
  • CellCept®
  • mycophenolic acid
  • MPA

Experimental: Cohort A, Arm A2: BNT162b2 +IS (MMF or MPA)
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 Pfizer-BioNTech COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Biological: BNT162b2
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA-1273 vaccine (Pfizer/BioNTech)
  • SARS-CoV-2 RNA vaccine
  • Pfizer-BioNTech COVID-19 vaccine

Drug: IS (MMF or MPA)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
  • immunosuppressive medication
  • mycophenolate mofetil
  • MMF
  • CellCept®
  • mycophenolic acid
  • MPA

Experimental: Cohort A, Arm A3: Ad26.COV2.S + IS (MMF or MPA)
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.
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
  • Janssen COVID-19 Vaccine
  • JNJ-78436735

Drug: IS (MMF or MPA)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
  • immunosuppressive medication
  • mycophenolate mofetil
  • MMF
  • CellCept®
  • mycophenolic acid
  • MPA

Experimental: Cohort A, Arm A4: Moderna mRNA-1273
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 Moderna COVID-19 vaccine booster (1 dose), per protocol instruction.
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA-1273 vaccine (Moderna)
  • Moderna COVID-19 Vaccine
  • SARS-CoV-2 RNA vaccine
  • COVID-19 vaccine

Experimental: Cohort A, Arm A5: BNT162b2
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 Pfizer-BioNTech COVID-19 vaccine booster (1 dose), per protocol instruction.
Biological: BNT162b2
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA-1273 vaccine (Pfizer/BioNTech)
  • SARS-CoV-2 RNA vaccine
  • Pfizer-BioNTech COVID-19 vaccine

Experimental: Cohort A, Arm A6: Ad26.COV2.S
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.
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
  • Janssen COVID-19 Vaccine
  • JNJ-78436735

Experimental: Cohort B, Arm B1: Moderna mRNA-1273 + IS (MTX)
Participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive the Moderna COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA-1273 vaccine (Moderna)
  • Moderna COVID-19 Vaccine
  • SARS-CoV-2 RNA vaccine
  • COVID-19 vaccine

Drug: IS (MTX)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
  • methotrexate
  • MTX

Experimental: Cohort B, Arm B2: BNT162b2 + IS (MTX)
Participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive the Pfizer-BioNTech COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Biological: BNT162b2
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA-1273 vaccine (Pfizer/BioNTech)
  • SARS-CoV-2 RNA vaccine
  • Pfizer-BioNTech COVID-19 vaccine

Drug: IS (MTX)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
  • methotrexate
  • MTX

Experimental: Cohort B, Arm B3: Ad26.COV2.S + IS (MTX)
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.
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
  • Janssen COVID-19 Vaccine
  • JNJ-78436735

Drug: IS (MTX)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
  • methotrexate
  • MTX

Experimental: Cohort B, Arm B4: Moderna mRNA-1273
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 Moderna COVID-19 vaccine booster (1 dose), per protocol instruction.
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA-1273 vaccine (Moderna)
  • Moderna COVID-19 Vaccine
  • SARS-CoV-2 RNA vaccine
  • COVID-19 vaccine

Experimental: Cohort B, Arm B5: BNT162b2
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 Pfizer-BioNTech COVID-19 vaccine booster (1 dose), per protocol instruction.
Biological: BNT162b2
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA-1273 vaccine (Pfizer/BioNTech)
  • SARS-CoV-2 RNA vaccine
  • Pfizer-BioNTech COVID-19 vaccine

Experimental: Cohort B, Arm B6: Ad26.COV2.S
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.
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
  • Janssen COVID-19 Vaccine
  • JNJ-78436735

Experimental: Cohort C, Arm C1: Moderna mRNA-1273 +IS (B cell depletion therapy)
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 Moderna COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA-1273 vaccine (Moderna)
  • Moderna COVID-19 Vaccine
  • SARS-CoV-2 RNA vaccine
  • COVID-19 vaccine

Biological: IS (B cell depletion therapy)
Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing.
Other Names:
  • mAbs targeting CD19 or CD20
  • anti-BAFF mAb

Experimental: Cohort C, Arm C2: BNT162b2+IS (B cell depletion therapy)
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 Pfizer-BioNTech COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.
Biological: BNT162b2
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA-1273 vaccine (Pfizer/BioNTech)
  • SARS-CoV-2 RNA vaccine
  • Pfizer-BioNTech COVID-19 vaccine

Biological: IS (B cell depletion therapy)
Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing.
Other Names:
  • mAbs targeting CD19 or CD20
  • anti-BAFF mAb

Experimental: Cohort C, Arm C3: Ad26.COV2.S +IS (B cell depletion therapy)
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.
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
  • Janssen COVID-19 Vaccine
  • JNJ-78436735

Biological: IS (B cell depletion therapy)
Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing.
Other Names:
  • mAbs targeting CD19 or CD20
  • anti-BAFF mAb




Primary Outcome Measures :
  1. Proportion of participants who have a protective antibody response at Week 4 [ Time Frame: Week 4 Status Post Receipt of COVID-19 Vaccine Booster Dose ]
    Efficacy measure.


Secondary Outcome Measures :
  1. Percentage of Subset Participants Who Seroconverted [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48 ]
    Efficacy measure, evaluated in subset of participants who are anti-COVID-19 antibody negative at Baseline.

  2. Fold increase in anti-COVID-19 antibody levels at Week 4, following participant receipt of a booster dose of COVID-19 vaccine [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster), Week 4 Status Post Receipt of COVID-19 Vaccine Booster Dose ]
    Efficacy measure, evaluated in subset of participants who are anti-COVID-19 antibody positive at Week 0 (Baseline).

  3. Change in anti-COVID-19 antibody response [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48 ]
    Efficacy measure.

  4. Change in anti-SARS-CoV-2 neutralizing antibody levels [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48 ]
    Efficacy measure, employing neutralization and pseudo-neutralization assays.

  5. Change in disease activity after receipt of COVID-19 vaccine booster as measured by the Clinical Global Impression of Change (CGI-C) [ Time Frame: Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose ]

    A measure of disease activity and efficacy.

    CGI-C: Clinician's global impression of a participant's clinical condition in terms of change relative to the start of treatment. Rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). Higher score = more affected.


  6. Change in disease activity as measured by the Physician's Global Assessment [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose ]
    A measure of disease activity and efficacy.

  7. Change in disease activity in participant subset with Systemic Lupus Erythematosus (SLE) as measured by Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose ]
    A measure of SLE disease activity and efficacy.

  8. Change in disease activity in participant subset with Systemic Lupus Erythematosus (SLE) as measured by Thanou modified SELENA-SLEDAI Flare Index for Systemic Lupus Erythematosus (SLE) [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48 ]
    A measure of SLE disease activity and efficacy.

  9. Change in disease activity in participant subset with Rheumatoid Arthritis (RA) as measured by Disease Activity Score 28 C-reactive Protein (DAS28-CRP) [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose ]
    A measure of RA disease activity and efficacy.

  10. Change in disease activity in participant subset with Systemic Sclerosis (SSc) as measured by Disease Flare Activity [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose ]

    A measure of SSc disease activity and efficacy.

    SSc disease flare assessments (including participant self- reported flare assessment). A flare is indicative of increased SSc-related disease activity.


  11. Change in disease activity in participant subset with Pemphigus as measured by Disease Area Index (PDAI) for Pemphigus [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose ]

    A measure of pemphigus disease activity and efficacy.

    The PDAI is specific cutaneous and mucosal disease activity assessment performed by the physician and is based on evaluation of lesions in well-defined anatomical locations.


  12. Change in disease activity in participant subset with Multiple Sclerosis (MS) as measured by Physician assessed relapse for MS [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose ]
    A measure of MS disease activity and efficacy.

  13. Change in disease activity as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS-29) [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose ]
    A measure of disease activity and efficacy. The Patient-Reported Outcomes Measurement Information System (PROMIS-29) self-report assesses functioning and well-being in physical, mental and social domains of health. The PROMIS-29 consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance.

  14. Change in disease activity as measured by the Patient Global Assessment [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose ]
    A measure of disease activity and efficacy. The patient global assessment of disease activity is measured using a 100mm Visual Analog Scale (VAS) ranging from 0=very good to 100=very bad. Change=<week status post receipt of booster vaccine> score minus baseline score. A negative score indicates an improvement in disease activity and a positive score indicates worsening.

  15. Change in disease activity as measured by the Patient Global Impression of Change (PGI-C) [ Time Frame: Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose ]
    A measure of disease activity and efficacy. Participant's Global Impression of Change Reported on PGI-C Scale (1-7 Point Scale Ranging From 1 "Very Much Improved" to 7 "Very Much Worse").

  16. Proportion of participants who experience any solicited Grade 1 or higher adverse events related to the COVID-19 vaccine booster [ Time Frame: Through Day 7 post study vaccination ]
    Safety measure status post receipt of study vaccination.

  17. Proportion of participants who experience any unsolicited Grade 1 or higher adverse events related to the COVID-19 vaccine booster [ Time Frame: Through Day 28 post study vaccination ]
    Safety measure status post receipt of study vaccination.

  18. Proportion of participants who experience any serious adverse events (SAEs) [ Time Frame: Up to Week 48 post study vaccination ]
    Safety measure status post receipt of study vaccination.

  19. Proportion of participants who experience any medically attended adverse events (MAAEs) [ Time Frame: Up to Week 48 post study vaccination ]
    Safety measure status post receipt of study vaccination.

  20. Proportion of participants who experience any New Onset Chronic Medical Conditions (NOCMCs) [ Time Frame: Up to Week 48 post study vaccination ]
    Safety measure status post receipt of study vaccination.

  21. Proportion of participants who experience any Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection [ Time Frame: Up to Week 48 post study vaccination ]
    Efficacy measure.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05000216


Locations
Show Show 18 study locations
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Autoimmunity Centers of Excellence
Rho Federal Systems Division, Inc.
Investigators
Layout table for investigator information
Study Chair: Judith A. James, MD, PhD Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation
Study Chair: Meggan C. Mackay, MD, MS Center of Autoimmune Musculoskeletal and Hematopoietic Diseases, Feinstein Institute for Medical Research
Study Chair: Dinesh Khanna, MBBS, MSc University of Michigan Health, Michigan Medicine
Study Chair: Amit Bar-Or, MD, FRCP Center for Neuroinflammation and Neurotherapeutics, Perelman School of Medicine, University of Pennsylvania
Additional Information:
Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT05000216    
Other Study ID Numbers: DAIT ACV01
NIAID CRMS ID#: 38873 ( Other Identifier: DAIT NIAID )
First Posted: August 11, 2021    Key Record Dates
Last Update Posted: October 15, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Time Frame: On average, within 24 months after database lock for the trial.
Access Criteria: Open access.
URL: https://www.immport.org/home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
SARS-CoV-2 Infection
COVID-19
autoimmune disease
non-responders to COVID-19 vaccination
suboptimal response to COVID-19 vaccination
COVID-19 booster vaccine
booster effects with autoimmune treatments
Additional relevant MeSH terms:
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COVID-19
Multiple Sclerosis
Lupus Erythematosus, Systemic
Scleroderma, Systemic
Pemphigus
Autoimmune Diseases
Sclerosis
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Immune System Diseases
Connective Tissue Diseases
Skin Diseases
Skin Diseases, Vesiculobullous
Mycophenolic Acid
Methotrexate
Vaccines