COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders

NCT05000216 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: DAIT ACV01NIAID CRMS ID#: 38873
• Study Type: interventional
• Target: 258
• Locations: 1 country
• Sites: 29

Brief 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 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. 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)

Conditions

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)

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Percent of Stage 1 Adult Participants Who Have a Protective Antibody Response at Week 4

  Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center (NIAID-VRC) Meso Scale Discovery (MSD) 3 plex assay (Wu-1 full-length spike, receptor binding domain (RBD), and N proteins). A threshold for achieving a protective antibody response was not established for the NIAID VRC MSD assay. The intent was to use a pre-established threshold to define a protective antibody response. However, correlates from previous studies could not be extrapolated to the CoV-2 variants circulating over the entire course of this trial.

  Week 4 Status Post Receipt of COVID-19 Vaccination

• Percent of Stage 2 Adult Participants Who Have a Protective Antibody Response at Week 4

  Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center (NIAID-VRC) Meso Scale Discovery (MSD) 3 plex assay (Wu-1 full-length spike, receptor binding domain (RBD), and N proteins). A threshold for achieving a protective antibody response was not established for the NIAID VRC MSD assay. The intent was to use a pre-established threshold to define a protective antibody response. However, correlates from previous studies could not be extrapolated to the CoV-2 variants circulating over the entire course of this trial.

  Week 4 Status Post Receipt of COVID-19 Vaccination

• Percent of Stage 2 Pediatric Participants Who Have a Protective Antibody Response at Week 4

  Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center (NIAID-VRC) Meso Scale Discovery (MSD) 3 plex assay (Wu-1 full-length spike, receptor binding domain (RBD), and N proteins). A threshold for achieving a protective antibody response was not established for the NIAID VRC MSD assay. The intent was to use a pre-established threshold to define a protective antibody response. However, correlates from previous studies could not be extrapolated to the CoV-2 variants circulating over the entire course of this trial.

  Week 4 Status Post Receipt of COVID-19 Vaccination

Secondary Outcomes (55)

• Percentage of Stage 1 Adult Participants Who Seroconverted

  Week 4 Status Post Receipt of COVID-19 Vaccination

• Percentage of Stage 2 Adult Participants Who Seroconverted

  Week 4 Status Post Receipt of COVID-19 Vaccination

• Fold Increase in Stage 1 Adult Anti-COVID-19 Antibody Levels

  Week 4 Status Post Receipt of COVID-19 Vaccination

• Fold Increase in Stage 2 Adult Anti-COVID-19 Antibody Levels

  Week 4 Status Post Receipt of COVID-19 Vaccination

• Change in Stage 1 Adult Anti-COVID-19 Antibody Response

  Week 0 and Weeks 4 and 12 Status Post Receipt of COVID-19 Vaccination

Study Arms (43)

Cohort A, Arm A1: Moderna mRNA-1273 + Continue IS (MMF or MPA)

EXPERIMENTAL

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.

Biological: Moderna mRNA-1273; Drug: Continue IS (MMF or MPA)

Cohort A, Arm A2: BNT162b2 + Continue IS (MMF or MPA)

EXPERIMENTAL

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.

Biological: BNT162b2; Drug: Continue IS (MMF or MPA)

Cohort A, Arm A3: Ad26.COV2.S + Continue IS (MMF or MPA)

EXPERIMENTAL

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.

Biological: Ad26.COV2.S; Drug: Continue IS (MMF or MPA)

Cohort A, Arm A4: Moderna mRNA-1273 + Withhold IS (MMF or MPA)

EXPERIMENTAL

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.

Biological: Moderna mRNA-1273; Drug: Withhold IS (MMF or MPA)

Cohort A, Arm A5: BNT162b2 + Withhold IS (MMF or MPA)

EXPERIMENTAL

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.

Biological: BNT162b2; Drug: Withhold IS (MMF or MPA)

Cohort A, Arm A6: Ad26.COV2.S + Withhold IS (MMF or MPA)

EXPERIMENTAL

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.

Biological: Ad26.COV2.S; Drug: Withhold IS (MMF or MPA)

Cohort B, Arm B1: Moderna mRNA-1273 + Continue IS (MTX)

EXPERIMENTAL

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.

Biological: Moderna mRNA-1273; Drug: Continue IS (MTX)

Cohort B, Arm B2: BNT162b2 + Continue IS (MTX)

EXPERIMENTAL

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.

Biological: BNT162b2; Drug: Continue IS (MTX)

Cohort B, Arm B3: Ad26.COV2.S + Continue IS (MTX)

EXPERIMENTAL

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.

Biological: Ad26.COV2.S; Drug: Continue IS (MTX)

Cohort B, Arm B4: Moderna mRNA-1273 + Withhold IS (MTX)

EXPERIMENTAL

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.

Biological: Moderna mRNA-1273; Drug: Withhold IS (MTX)

Cohort B, Arm B5: BNT162b2 + Withhold IS (MTX)

EXPERIMENTAL

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.

Biological: BNT162b2; Drug: Withhold IS (MTX)

Cohort B, Arm B6: Ad26.COV2.S + Withhold IS (MTX)

EXPERIMENTAL

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.

Biological: Ad26.COV2.S; Drug: Withhold IS (MTX)

Cohort C, Arm C1: Moderna mRNA-1273 + Continue IS (B cell depletion therapy)

EXPERIMENTAL

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.

Biological: Moderna mRNA-1273; Biological: Continue IS (B cell depletion therapy)

Cohort C, Arm C2: BNT162b2 + Continue IS (B cell depletion therapy)

EXPERIMENTAL

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.

Biological: BNT162b2; Biological: Continue IS (B cell depletion therapy)

Cohort C, Arm C3: Ad26.COV2.S + Continue IS (B cell depletion therapy)

EXPERIMENTAL

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.

Biological: Ad26.COV2.S; Biological: Continue IS (B cell depletion therapy)

Cohort D, Arm D1: Ad26.COV2.S + Withhold IS (MMF or MPA)

EXPERIMENTAL

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.

Biological: Ad26.COV2.S; Drug: Withhold IS (MMF or MPA)

Cohort D, Arm D2: Alternative mRNA Vaccine + Withhold IS (MMF or MPA)

EXPERIMENTAL

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.

Biological: BNT162b2; Drug: Withhold IS (MMF or MPA); Biological: Moderna mRNA-1273, Bivalent; Biological: BNT162b2, Bivalent

Cohort D, Arm D3: Moderna mRNA-1273 + Withhold IS (MMF or MPA)

EXPERIMENTAL

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.

Drug: Withhold IS (MMF or MPA); Biological: Moderna mRNA-1273, Bivalent

Cohort E, Arm E1: Ad26.COV2.S + Withhold IS (MTX)

EXPERIMENTAL

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.

Biological: Ad26.COV2.S; Drug: Withhold IS (MTX)

Cohort E, Arm E2: Alternative mRNA Vaccine + Withhold IS (MTX)

EXPERIMENTAL

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.

Drug: Withhold IS (MTX); Biological: Moderna mRNA-1273, Bivalent; Biological: BNT162b2, Bivalent

Cohort E, Arm E3: Moderna mRNA-1273 + Withhold IS (MTX)

EXPERIMENTAL

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.

Drug: Withhold IS (MTX); Biological: Moderna mRNA-1273, Bivalent

Cohort F, Arm F1: Ad26.COV2.S + Withhold IS (B cell depletion therapy)

EXPERIMENTAL

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.

Biological: Ad26.COV2.S; Drug: Withhold IS (B cell depletion therapy)

Cohort F, Arm F2: Alternative mRNA Vaccine + Withhold IS (B cell depletion therapy)

EXPERIMENTAL

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.

Drug: Withhold IS (B cell depletion therapy); Biological: Moderna mRNA-1273, Bivalent; Biological: BNT162b2, Bivalent

Cohort F, Arm F3: Moderna mRNA-1273 + Withhold IS (B cell depletion therapy)

EXPERIMENTAL

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.

Drug: Withhold IS (B cell depletion therapy); Biological: Moderna mRNA-1273, Bivalent

Cohort D, Arm D4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (MMF or MPA)

EXPERIMENTAL

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.

Biological: Monovalent [B.1.351] CoV2 preS dTM-AS03; Drug: Withhold IS (MMF or MPA)

Cohort E, Arm E4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (MTX)

EXPERIMENTAL

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.

Biological: Monovalent [B.1.351] CoV2 preS dTM-AS03; Drug: Withhold IS (MTX)

Cohort F, Arm F4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (B cell depletion therapy)

EXPERIMENTAL

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

Biological: Monovalent [B.1.351] CoV2 preS dTM-AS03; Drug: Withhold IS (B cell depletion therapy)

Cohort A, Arm A1P: Moderna mRNA-1273, Bivalent + Continue IS (MMF or MPA)

EXPERIMENTAL

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.

Drug: Continue IS (MMF or MPA); Biological: Moderna mRNA-1273, Bivalent

Cohort A, Arm A2P: BNT162b2, Bivalent + Continue IS (MMF or MPA)

EXPERIMENTAL

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.

Drug: Continue IS (MMF or MPA); Biological: BNT162b2, Bivalent

Cohort A, Arm A4P: Moderna mRNA-1273, Bivalent + Withhold IS (MMF or MPA)

EXPERIMENTAL

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.

Drug: Withhold IS (MMF or MPA); Biological: Moderna mRNA-1273, Bivalent

Cohort A, Arm A5P: BNT162b2, Bivalent + Withhold IS (MMF or MPA)

EXPERIMENTAL

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.

Drug: Withhold IS (MMF or MPA); Biological: BNT162b2, Bivalent

Cohort B, Arm B1P: Moderna mRNA-1273, Bivalent + Continue IS (MTX)

EXPERIMENTAL

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.

Drug: Continue IS (MTX); Biological: Moderna mRNA-1273, Bivalent

Cohort B, Arm B2P: BNT162b2, Bivalent + Continue IS (MTX)

EXPERIMENTAL

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.

Drug: Continue IS (MTX); Biological: BNT162b2, Bivalent

Cohort B, Arm B4P: Moderna mRNA-1273, Bivalent + Withhold IS (MTX)

EXPERIMENTAL

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.

Drug: Withhold IS (MTX); Biological: Moderna mRNA-1273, Bivalent

Cohort B, Arm B5P: BNT162b2, Bivalent + Withhold IS (MTX)

EXPERIMENTAL

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.

Drug: Withhold IS (MTX); Biological: BNT162b2, Bivalent

Cohort C, Arm C1P: Moderna mRNA-1273, Bivalent + Continue IS (B cell depletion therapy)

EXPERIMENTAL

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.

Biological: Continue IS (B cell depletion therapy); Biological: Moderna mRNA-1273, Bivalent

Cohort C, Arm C2P: BNT162b2, Bivalent + Continue IS (B cell depletion therapy)

EXPERIMENTAL

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.

Biological: Continue IS (B cell depletion therapy); Biological: BNT162b2, Bivalent

Cohort D, Arm D1P: BNT162b2, Bivalent + Withhold IS (MMF or MPA)

EXPERIMENTAL

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.

Drug: Withhold IS (MMF or MPA); Biological: BNT162b2, Bivalent

Cohort D, Arm D2P: Moderna mRNA-1273, Bivalent + Withhold IS (MMF or MPA)

EXPERIMENTAL

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.

Drug: Withhold IS (MMF or MPA); Biological: Moderna mRNA-1273, Bivalent

Cohort E, Arm E1P: BNT162b2, Bivalent + Withhold IS (MTX)

EXPERIMENTAL

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.

Drug: Withhold IS (MTX); Biological: BNT162b2, Bivalent

Cohort E, Arm E2P: Moderna mRNA-1273, Bivalent + Withhold IS (MTX)

EXPERIMENTAL

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.

Drug: Withhold IS (MTX); Biological: Moderna mRNA-1273, Bivalent

Cohort F, Arm F1P: BNT162b2, Bivalent + Withhold IS (B cell depletion therapy)

EXPERIMENTAL

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.

Drug: Withhold IS (B cell depletion therapy); Biological: BNT162b2, Bivalent

Cohort F, Arm F2P: Moderna mRNA-1273, Bivalent + Withhold IS (B cell depletion therapy)

EXPERIMENTAL

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.

Drug: Withhold IS (B cell depletion therapy); Biological: Moderna mRNA-1273, Bivalent

Interventions

Moderna mRNA-1273 BIOLOGICAL

Administration: One dose administered intramuscularly.

Also known as: mRNA-1273 vaccine (Moderna), Moderna COVID-19 Vaccine, SARS-CoV-2 RNA vaccine, COVID-19 vaccine

Cohort A, Arm A1: Moderna mRNA-1273 + Continue IS (MMF or MPA); Cohort A, Arm A4: Moderna mRNA-1273 + Withhold IS (MMF or MPA); Cohort B, Arm B1: Moderna mRNA-1273 + Continue IS (MTX); Cohort B, Arm B4: Moderna mRNA-1273 + Withhold IS (MTX); Cohort C, Arm C1: Moderna mRNA-1273 + Continue IS (B cell depletion therapy)

BNT162b2 BIOLOGICAL

Administration: One dose administered intramuscularly.

Also known as: mRNA-1273 vaccine (Pfizer/BioNTech), SARS-CoV-2 RNA vaccine, Pfizer-BioNTech COVID-19 vaccine

Cohort A, Arm A2: BNT162b2 + Continue IS (MMF or MPA); Cohort A, Arm A5: BNT162b2 + Withhold IS (MMF or MPA); Cohort B, Arm B2: BNT162b2 + Continue IS (MTX); Cohort B, Arm B5: BNT162b2 + Withhold IS (MTX); Cohort C, Arm C2: BNT162b2 + Continue IS (B cell depletion therapy); Cohort D, Arm D2: Alternative mRNA Vaccine + Withhold IS (MMF or MPA)

Ad26.COV2.S BIOLOGICAL

Administration: One dose administered intramuscularly.

Also known as: Janssen COVID-19 Vaccine, JNJ-78436735

Cohort A, Arm A3: Ad26.COV2.S + Continue IS (MMF or MPA); Cohort A, Arm A6: Ad26.COV2.S + Withhold IS (MMF or MPA); Cohort B, Arm B3: Ad26.COV2.S + Continue IS (MTX); Cohort B, Arm B6: Ad26.COV2.S + Withhold IS (MTX); Cohort C, Arm C3: Ad26.COV2.S + Continue IS (B cell depletion therapy); Cohort D, Arm D1: Ad26.COV2.S + Withhold IS (MMF or MPA); Cohort E, Arm E1: Ad26.COV2.S + Withhold IS (MTX); Cohort F, Arm F1: Ad26.COV2.S + Withhold IS (B cell depletion therapy)

Continue IS (MMF or MPA) DRUG

Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.

Also known as: immunosuppressive medication, mycophenolate mofetil, MMF, CellCept®, mycophenolic acid, MPA

Cohort A, Arm A1: Moderna mRNA-1273 + Continue IS (MMF or MPA); Cohort A, Arm A1P: Moderna mRNA-1273, Bivalent + Continue IS (MMF or MPA); Cohort A, Arm A2: BNT162b2 + Continue IS (MMF or MPA); Cohort A, Arm A2P: BNT162b2, Bivalent + Continue IS (MMF or MPA); Cohort A, Arm A3: Ad26.COV2.S + Continue IS (MMF or MPA)

Continue IS (MTX) DRUG

Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.

Also known as: methotrexate, MTX

Cohort B, Arm B1: Moderna mRNA-1273 + Continue IS (MTX); Cohort B, Arm B1P: Moderna mRNA-1273, Bivalent + Continue IS (MTX); Cohort B, Arm B2: BNT162b2 + Continue IS (MTX); Cohort B, Arm B2P: BNT162b2, Bivalent + Continue IS (MTX); Cohort B, Arm B3: Ad26.COV2.S + Continue IS (MTX)

Continue IS (B cell depletion therapy) BIOLOGICAL

Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing.

Also known as: mAbs targeting CD19 or CD20, anti-BAFF mAb

Cohort C, Arm C1: Moderna mRNA-1273 + Continue IS (B cell depletion therapy); Cohort C, Arm C1P: Moderna mRNA-1273, Bivalent + Continue IS (B cell depletion therapy); Cohort C, Arm C2: BNT162b2 + Continue IS (B cell depletion therapy); Cohort C, Arm C2P: BNT162b2, Bivalent + Continue IS (B cell depletion therapy); Cohort C, Arm C3: Ad26.COV2.S + Continue IS (B cell depletion therapy)

Monovalent [B.1.351] CoV2 preS dTM-AS03 BIOLOGICAL

One dose administered intramuscularly

Also known as: Sanofi-GSK COVID-19 Vaccine

Cohort D, Arm D4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (MMF or MPA); Cohort E, Arm E4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (MTX); Cohort F, Arm F4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (B cell depletion therapy)

Withhold IS (MMF or MPA) DRUG

Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions.

Also known as: immunosuppressive medication, mycophenolate mofetil, MMF, CellCept®, mycophenolic acid, MPA

Cohort A, Arm A4: Moderna mRNA-1273 + Withhold IS (MMF or MPA); Cohort A, Arm A4P: Moderna mRNA-1273, Bivalent + Withhold IS (MMF or MPA); Cohort A, Arm A5: BNT162b2 + Withhold IS (MMF or MPA); Cohort A, Arm A5P: BNT162b2, Bivalent + Withhold IS (MMF or MPA); Cohort A, Arm A6: Ad26.COV2.S + Withhold IS (MMF or MPA); Cohort D, Arm D1: Ad26.COV2.S + Withhold IS (MMF or MPA); Cohort D, Arm D1P: BNT162b2, Bivalent + Withhold IS (MMF or MPA); Cohort D, Arm D2: Alternative mRNA Vaccine + Withhold IS (MMF or MPA); Cohort D, Arm D2P: Moderna mRNA-1273, Bivalent + Withhold IS (MMF or MPA); Cohort D, Arm D3: Moderna mRNA-1273 + Withhold IS (MMF or MPA); Cohort D, Arm D4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (MMF or MPA)

Withhold IS (MTX) DRUG

Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions.

Also known as: methotrexate, MTX

Cohort B, Arm B4: Moderna mRNA-1273 + Withhold IS (MTX); Cohort B, Arm B4P: Moderna mRNA-1273, Bivalent + Withhold IS (MTX); Cohort B, Arm B5: BNT162b2 + Withhold IS (MTX); Cohort B, Arm B5P: BNT162b2, Bivalent + Withhold IS (MTX); Cohort B, Arm B6: Ad26.COV2.S + Withhold IS (MTX); Cohort E, Arm E1: Ad26.COV2.S + Withhold IS (MTX); Cohort E, Arm E1P: BNT162b2, Bivalent + Withhold IS (MTX); Cohort E, Arm E2: Alternative mRNA Vaccine + Withhold IS (MTX); Cohort E, Arm E2P: Moderna mRNA-1273, Bivalent + Withhold IS (MTX); Cohort E, Arm E3: Moderna mRNA-1273 + Withhold IS (MTX); Cohort E, Arm E4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (MTX)

Withhold IS (B cell depletion therapy) DRUG

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.

Also known as: mAbs targeting CD19 or CD20, anti-BAFF mAb

Cohort F, Arm F1: Ad26.COV2.S + Withhold IS (B cell depletion therapy); Cohort F, Arm F1P: BNT162b2, Bivalent + Withhold IS (B cell depletion therapy); Cohort F, Arm F2: Alternative mRNA Vaccine + Withhold IS (B cell depletion therapy); Cohort F, Arm F2P: Moderna mRNA-1273, Bivalent + Withhold IS (B cell depletion therapy); Cohort F, Arm F3: Moderna mRNA-1273 + Withhold IS (B cell depletion therapy); Cohort F, Arm F4: Monovalent [B.1.351] CoV2 preS dTM-AS03 + Withhold IS (B cell depletion therapy)

Moderna mRNA-1273, Bivalent BIOLOGICAL

Administration: One dose administered intramuscularly.

Also known as: mRNA-1273 vaccine (Moderna), Bivalent, Moderna COVID-19 Vaccine, Bivalent, SARS-CoV-2 RNA vaccine, Bivalent, COVID-19 vaccine, Bivalent

Cohort A, Arm A1P: Moderna mRNA-1273, Bivalent + Continue IS (MMF or MPA); Cohort A, Arm A4P: Moderna mRNA-1273, Bivalent + Withhold IS (MMF or MPA); Cohort B, Arm B1P: Moderna mRNA-1273, Bivalent + Continue IS (MTX); Cohort B, Arm B4P: Moderna mRNA-1273, Bivalent + Withhold IS (MTX); Cohort C, Arm C1P: Moderna mRNA-1273, Bivalent + Continue IS (B cell depletion therapy); Cohort D, Arm D2: Alternative mRNA Vaccine + Withhold IS (MMF or MPA); Cohort D, Arm D2P: Moderna mRNA-1273, Bivalent + Withhold IS (MMF or MPA); Cohort D, Arm D3: Moderna mRNA-1273 + Withhold IS (MMF or MPA); Cohort E, Arm E2: Alternative mRNA Vaccine + Withhold IS (MTX); Cohort E, Arm E2P: Moderna mRNA-1273, Bivalent + Withhold IS (MTX); Cohort E, Arm E3: Moderna mRNA-1273 + Withhold IS (MTX); Cohort F, Arm F2: Alternative mRNA Vaccine + Withhold IS (B cell depletion therapy); Cohort F, Arm F2P: Moderna mRNA-1273, Bivalent + Withhold IS (B cell depletion therapy); Cohort F, Arm F3: Moderna mRNA-1273 + Withhold IS (B cell depletion therapy)

BNT162b2, Bivalent BIOLOGICAL

Administration: One dose administered intramuscularly.

Also known as: mRNA-1273 vaccine (Pfizer/BioNTech), Bivalent, SARS-CoV-2 RNA vaccine, Bivalent, Pfizer-BioNTech COVID-19 vaccine, Bivalent

Cohort A, Arm A2P: BNT162b2, Bivalent + Continue IS (MMF or MPA); Cohort A, Arm A5P: BNT162b2, Bivalent + Withhold IS (MMF or MPA); Cohort B, Arm B2P: BNT162b2, Bivalent + Continue IS (MTX); Cohort B, Arm B5P: BNT162b2, Bivalent + Withhold IS (MTX); Cohort C, Arm C2P: BNT162b2, Bivalent + Continue IS (B cell depletion therapy); Cohort D, Arm D1P: BNT162b2, Bivalent + Withhold IS (MMF or MPA); Cohort D, Arm D2: Alternative mRNA Vaccine + Withhold IS (MMF or MPA); Cohort E, Arm E1P: BNT162b2, Bivalent + Withhold IS (MTX); Cohort E, Arm E2: Alternative mRNA Vaccine + Withhold IS (MTX); Cohort F, Arm F1P: BNT162b2, Bivalent + Withhold IS (B cell depletion therapy); Cohort F, Arm F2: Alternative mRNA Vaccine + Withhold IS (B cell depletion therapy)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.

You may not qualify if:

• \. New diagnosis of malignancy that will require chemotherapy or immunotherapy, or ongoing treatment for a malignancy with chemotherapy or immunotherapy.
• \. 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.
• \. Active disease during the Screening period resulting in:
• An increase/addition of any IS medications, or
• A suggestion of MS relapse per the investigator. 6. Recent or current SARS-CoV-2 infection defined as:
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• Documented SARS-CoV-2 infection in the past 30 days (from the day the participant is diagnosed by positive test to Screening).
• Positive result on a molecular COVID-19 test at Screening. 8. Inflammatory myocarditis/pericarditis within 6 weeks of any COVID-19 vaccine doses.
• \. 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.
• \. 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.
• \. Participants who received licensed or investigational monoclonal antibodies or plasma products directed against SARS-CoV-2 within 30 days of Screening.
• \. Participants who have received any live vaccines within 2 months of the anticipated study vaccine dose or who will have need of a live vaccine at any time during the study.
• \. Currently pregnant or breastfeeding (For pediatric participants postmenarchal females must have a negative urine pregnancy test at Screening).
• \. 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Autoimmunity Centers of Excellence: collaborator
• Rho Federal Systems Division, Inc.: collaborator

Study Sites (29)

UCLA Medical Center: Division of Rheumatology

Los Angeles, California, 90095, United States

Location

Yale University School of Medicine: Rheumatology, Allergy & Immunology

New Haven, Connecticut, 06519, United States

Location

The Emory Clinic: Division of Rheumatology

Atlanta, Georgia, 30322, United States

Location

Indiana University Medical Center, Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital: Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital: Department of Pediatrics, Rheumatology Program

Boston, Massachusetts, 02115, United States

Location

Brigham & Women's Hospital: Department of Medicine, Rheumatology, Immunology

Boston, Massachusetts, 02115, United States

Location

University of Michigan Health System: Department of Internal Medicine, Division of Rheumatology

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine in St. Louis: Division of Rheumatology

St Louis, Missouri, 63110, United States

Location

Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases

Manhasset, New York, 11030, United States

Location

Feinstein Institute for Medical Research

Manhasset, New York, 11030, United States

Location

New York University Langone Medical Center: Department of Medicine, Division of Rheumatology

New York, New York, 10016, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Columbia University Irving Medical Center: Department of Neurology, Multiple Sclerosis Center

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794-8111, United States

Location

University of North Carolina Children's Hospital

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center: Division of Rheumatology and Immunology

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hopspital

Columbus, Ohio, 43205, United States

Location

Oklahoma Children's Hospital-Pediatrics Specialties Clinic

Oklahoma City, Oklahoma, 73104, United States

Location

Oklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program

Oklahoma City, Oklahoma, 73104, United States

Location

Temple Health: Rheumatology

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pennsylvania Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina, Nexus Research Center

Charleston, South Carolina, 29425, United States

Location

Medical University of South Carolina, Shawn Jenkins Children's Hospital

Charleston, South Carolina, 29425, United States

Location

UT Southwestern (Peds)

Dallas, Texas, 75325, United States

Location

University of Texas Houston Medical School: Division of Rheumatology and Clinical Immunogenetics

Houston, Texas, 77030, United States

Location

Benaroya Research Institute at Virginia Mason: Internal Medicine

Seattle, Washington, 98101, United States

Location

Related Publications (1)

• Mackay M, Wagner CA, Pinckney A, Cohen JA, Wallace ZS, Khosroshahi A, Sparks JA, Lord S, Saxena A, Caricchio R, Kim AH, Kamen DL, Koumpouras F, Askanase AD, Smith K, Guthridge JM, Pardo G, Mao-Draayer Y, Macwana S, McCarthy S, Sherman MA, Daneshfar Hamrah S, Veri M, Walker S, York K, Tedeschi SK, Wang J, Dziubla GE, Castro M, Carroll R, Narpala SR, Lin BC, Serebryannyy L, McDermott AB, Barry WT, Goldmuntz E, McNamara J, Payne AS, Bar-Or A, Khanna D, James JA. Prospective SARS-CoV-2 additional vaccination in immunosuppressant-treated individuals with autoimmune diseases in a randomized controlled trial. JCI Insight. 2025 Nov 25:e191266. doi: 10.1172/jci.insight.191266. Online ahead of print.

  PMID: 41289027 DERIVED

Related Links

• Autoimmunity Centers of Excellence (ACE)
• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

MeSH Terms

Conditions

Arthritis, Rheumatoid; Lupus Erythematosus, Systemic; Pemphigus; Multiple Sclerosis; Scleroderma, Systemic; Arthritis, Juvenile; Dermatomyositis; COVID-19; Autoimmune Diseases

Interventions

2019-nCoV Vaccine mRNA-1273; COVID-19 Vaccines; BNT162 Vaccine; Ad26COVS1; Mycophenolic Acid; Methotrexate; BNT162b5

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases; Skin Diseases, Vesiculobullous; Skin Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Polymyositis; Myositis; Muscular Diseases; Neuromuscular Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; Viral Vaccines; Antigens; Biological Factors; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Vaccines, Combined

Limitations and Caveats

The trial was closed prior to fully enrolling because of slow enrollment due to increasing infections in the general population with resulting elevated antibody titers, changing CDC vaccination recommendations, and vaccine hesitancy. Original enrollment goals were 60 participants per arm.

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• 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

  STUDY CHAIR

• Virginia Pascual, MD

  Drukier Institute for Children's Health, Weill Cornell Medical College

  STUDY CHAIR

• Stacy Ardoin, MD

  Nationwide Children's Hospital Rheumatology Department

  STUDY CHAIR

• Natasha Mckerran Ruth, MD

  Medical University of South Carolina, Pediatric Rheumatology

  STUDY CHAIR

• Tracey Wright, MD

  UT Southwestern Medical Center, Pediatric Rheumatology

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Adults and Pediatrics Stage 1: Participants in Cohorts A and B will be randomized into two immunosuppressive (IS) medication treatment plans as follows: * 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 additional homologous vaccine dose, per protocol instruction * Cohort C: No randomization-Participants continue to take their IS medications without alterations in schedule and dosing. * Stage 2: Participants in Cohorts D and E will withhold their cohort-defining IS medications before and after additional alternative vaccine dose, per protocol instruction. Cohort F: No randomization-Participants withhold their IS medications before and after additional alternative vaccine dose, per protocol instruction

Study Record Dates

• First Submitted: August 6, 2021
• First Posted: August 11, 2021
• Study Start: August 13, 2021
• Primary Completion: June 22, 2023
• Study Completion: March 28, 2024
• Last Updated: August 22, 2025
• Results First Posted: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access.

Locations

US (29)