Summary

Eligibility
for people ages 5 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion
Principal Investigator
by Maureen McMahon (ucla)

Description

Summary

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 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 ≤ 200 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 focus on 5 autoimmune diseases in adults: - Systemic Lupus Erythematosus (SLE) - Rheumatoid Arthritis (RA) - Multiple Sclerosis (MS) - Systemic Sclerosis (SSc), and - Pemphigus. This study will focus on 4 autoimmune diseases in pediatric participants: - Systemic Lupus Erythematosus (SLE) - Juvenile Idiopathic Arthritis (JIA) - Pediatric-Onset Multiple Sclerosis (POMS) - Juvenile Dermatomyositis (JDM)

Official Title

Booster Effects With Autoimmune Treatments in Patients With Poor Response to Initial COVID-19 Vaccine (ACV01)

Details

In Stage 1 of this study, adult 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 an additional dose of the same vaccine as their original vaccine series. 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 additional homologous vaccine dose, per protocol. In Stage 2 of this study, adult participants will be assigned to one of 3 cohorts based on their immunosuppressive regimens: - Cohort D: 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 E: 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 F: 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 D, E, and F will be assigned to receive an alternative COVID-19 vaccine compared to their previous COVID-19 vaccine doses. Participants who previously received 3 total doses of an mRNA vaccine (Moderna COVID-19 Vaccine OR Pfizer-BioNTech COVID-19 Vaccine) will receive their choice of either the Janssen vector-based COVID 19 vaccine or the other mRNA COVID-19 vaccine, and participants who previously received 2 doses of the Janssen vector-based COVID-19 vaccine will receive the Moderna COVID-19 Vaccine. Participants in Cohorts D, E, and F will withhold their cohort-defining IS treatment before and after the alternative vaccine dose per protocol instructions. In the pediatric portion of 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 orMTX, will be placed in this cohort. Treatment Arms: Participants in Cohorts A, B, and C will be assigned to receive an additional dose of the same vaccine as their original vaccine series. 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 homologous vaccine dose, per protocol.

Keywords

Rheumatoid Arthritis, Systemic Lupus Erythematosus (SLE), Pemphigus Vulgaris, Multiple Sclerosis, Systemic Sclerosis (SSc), Pediatric SLE, Juvenile Idiopathic Arthritis, Juvenile Dermatomyositis, Pediatric-Onset Multiple Sclerosis (POMS), 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, Arthritis, Arthritis, Juvenile, Dermatomyositis, Lupus Erythematosus, Systemic, Scleroderma, Systemic, Pemphigus, Autoimmune Diseases, Sclerosis, Mycophenolic Acid, Methotrexate, Vaccines, Moderna mRNA-1273, BNT162b2, Ad26.COV2.S, IS (MMF or MPA), IS (MTX), IS (B cell depletion therapy)

Eligibility

You can join if…

Open to people ages 5 years and up

Adults:

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

  1. Individuals that meet classification criteria for:
  2. systemic lupus erythematosus (SLE)
  3. systemic sclerosis (SSc)
  4. rheumatoid arthritis (RA)
  5. multiple sclerosis (MS), or
  6. pemphigus
  7. Participants must meet:
  8. 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
  9. the 2010 ACR/EULAR classification criteria for RA
  10. the 2013 EULAR/ACR classification criteria for SSc
  11. the 2017 McDonald criteria for MS, and
  12. 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

  1. Willing and able to sign informed consent
  2. 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 52 weeks prior to the Screening visit
  3. 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 ≤ 200 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
  • Must be currently taking one of the following IS 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 18 months (such as rituximab, ocrelizumab, or ofatumumab)
  • If taking mycophenolate mofetil (MMF)/mycophenolic acid (MPA) or methotrexate (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
  • 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 IS 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

You CAN'T join if...

Adults:

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

  1. Active disease during the Screening period resulting in:
  2. an increase/addition of immunosuppressive medications, or
  3. a suggestion of multiple sclerosis (MS) relapse per the investigator
  4. Recent or current Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection defined as:
  5. Documented SARS-CoV-2 infection in the past 30 days (from the day the participant is diagnosed by positive test to Screening), or
  6. 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:
  9. a history of autoimmune disease-related myocarditis within 3 years
  10. autoimmune disease-related pericarditis within the past year, or
  11. inflammatory myocarditis/pericarditis following initial COVID-19 vaccine regimen
  12. Participants with active bacterial or viral infections who have received antibiotics within the 14 days prior to Screening, including participants with evidence of:
  13. Human Immunodeficiency Virus (HIV)
  14. Hepatitis B as indicated by surface antigen or hepatitis B core antibody positivity
  15. Hepatitis C as indicated by anti-hepatitis C antibody positivity
  16. 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
  17. . Participants with common variable immunodeficiency disease, as well as any participants currently receiving immune globulin replacement therapy
  18. . Participants who received licensed or investigational monoclonal antibodies or plasma products directed against SARS-CoV-2 within 30 days of Screening
  19. . 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
  20. . Currently pregnant or breastfeeding
  21. . Participants who are planning a pregnancy during the course of the trial
  22. . Hemoglobin (Hgb) < 8.0 g/dL (80 g/L)
  23. . 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:
  24. may pose additional risks from participation in the study
  25. may interfere with the participant's ability to comply with study requirements, or
  26. that may impact the quality or interpretation of the data obtained from the study
  27. . Other investigational chemical agent within 30 days or other investigational biologic agent within 8 weeks or 5 half-lives (whichever is longer) of enrollment
  28. . Concurrent treatment with cyclophosphamide, cladribine, alemtuzumab, or mitoxantrone
  29. . Participants currently on any type of dialysis, or who have received a solid organ transplant
  30. . 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
  31. . Taking both MMF/MPA and MTX.
  32. . Receiving other investigational B cell depleting therapy as part of a clinical trial within one year18 months of Screening, unless drug assignment is known and the participant received an anti-CD20 or CD19 drug.
  33. . Participants with active systemic infections who have received systemic antimicrobials within the 14 days prior to Screening.

Inclusion Criteria Pediatric:

  1. Individuals 5-17 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.

  • Participants must meet the 2017 EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups [8], the International League of Associations for Rheumatology (ILAR) classification for JIA [4], the 2017 McDonald [6] criteria for MS, or the Bohan and Peter criteria or the 2017 EULAR/ACR classification criteria for JDM.
  • If a participant has been diagnosed with more than one autoimmune disease, the participant will beassessed based on the disease that is selected for study entry.
  • Parents/guardians of pediatric participants must be willing and able to sign informed consent. Participants, ages 7-17, must be willing and able to sign assent.
  • 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 Screening visit.
  • 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.
  • Initial COVID-19 vaccine regimen is defined as:
    • 2 doses (as appropriate to age) of the Pfizer-BioNTech COVID-19 Vaccine

The following vaccines have yet to receive EUA in pediatric populations. If EUA occurs for younger ages, the participants receiving age-appropriate regimens of the following

COVID-19 vaccines may be enrolled into the study:

    • Moderna COVID-19 Vaccine
    • Janssen COVID-19 Vaccine
  • Must be currently taking one of the following IS medications with or without additional disease-related medications: MMF (minimum of 250 mg per day)/MPA (minimum of 360 mg per day), MTX (minimum of 5 mg per week), or B cell depleting agents within the past 18 months (such as rituximab, ocrelizumab, or ofatumumab).
  • 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.
  • If enrolling in the B cell depleting therapy cohort, participant must have received an anti-CD20 or an anti-CD19 B cell depleting therapy in the past 18 months.
  • No changes in background IS medications, including MMF/MPA or MTX, in the 8 weeks prior to Screening, excluding the following:
  • HCQ,
  • Intraarticular steroids,
  • The addition of prednisone at ≤10mg 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 COPD, are permitted.

Exclusion Criteria Pediatric:

  1. Inability or unwillingness of a participant to give assent or of a parent/guardian to give written informed consent, or of either to 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 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.
  5. The potential impact of temporarily holding medication for participants with a recent mild disease flare within 4 weeks should be carefully considered.
  6. Active disease during the Screening period resulting in:
  7. an increase/addition of any IS medications, or
  8. a suggestion of MS relapse per the investigator
  9. Recent or current SARS-CoV-2 infection defined as:
  10. Documented SARS-CoV-2 infection in the past 30 days (from the day the participant is diagnosed by positive test to Screening).
  11. Positive result on a molecular COVID-19 test at Screening.
  12. Receipt of a COVID-19 vaccine booster prior to Screening.
  13. Inflammatory myocarditis/pericarditis following initial COVID-19 vaccine regimen.
  14. Participants with active, ongoing chronic infections, including participants with evidence of:
  15. HIV.
  16. Hepatitis B as indicated by surface antigen.
  17. Hepatitis C as indicated by anti-hepatitis C antibody positivity; 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. Note: Participants are permitted to be on chronic prophylactic antimicrobial therapy.
  18. . Participants with common variable immunodeficiency disease, as well as any participants currently receiving immune globulin replacement therapy.
  19. . Participants who received licensed or investigational monoclonal antibodies or plasma products directed against SARS-CoV-2 within 30 days of Screening.
  20. . 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.
  21. . Currently pregnant or breastfeeding (postmenarchal females must have a negative urine pregnancy test at Screening)
  22. . Hemoglobin (Hgb) <8.0 g/dL (80 g/L)
  23. . 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.
  24. . Other investigational chemical agent within 30 days or other investigational biologic agent within 8 weeks or 5 half-lives (whichever is longer) of Screening.
  25. . Concurrent treatment with cyclophosphamide.
  26. . Participants currently on any type of dialysis, or who have received a solid organ transplant.
  27. . 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 allowed to participant in this study.
  28. . Taking both MMF/MPA and MTX.
  29. . Other investigational B cell depleting therapy 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.
  30. . Participants with active systemic infections who have received systemic antimicrobials within the 14 days prior to Screening.

Locations

  • UCLA Medical Center: Division of Rheumatology accepting new patients
    Los Angeles California 90095 United States
  • Benaroya Research Institute at Virginia Mason: Internal Medicine accepting new patients
    Seattle Washington 98101 United States

Lead Scientist at University of California Health

  • Maureen McMahon (ucla)
    Professor, Medicine. Authored (or co-authored) 36 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Links
Autoimmunity Centers of Excellence (ACE) National Institute of Allergy and Infectious Diseases (NIAID) Division of Allergy, Immunology, and Transplantation (DAIT)
ID
NCT05000216
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 2340 study participants
Last Updated