COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders

NCT ID: NCT05000216

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 258 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-13
• Study Completion Date: 2024-03-28

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)

Detailed Description

Adult Population:

Stage 1 of this trial will enroll up to a maximum of 900 adult study participants (up to 60 participants per arm).

Participants will be assigned to one of 3 cohorts based on their IS regimens:

• Cohort A: Receipt of MMF or MPA
• Cohort B: Receipt of MTX
• Cohort C: Receipt of any BCDT within the past 18 months.

Treatment Arms: Participants in Cohorts A, B, and C will be assigned to receive an additional dose of the same COVID-19 vaccine as their original vaccine series. The trial initially enrolled participants who were vaccinated with the Pfizer-BioNTech COVID-19 Vaccine, the Moderna COVID-19 Vaccine, and the Janssen COVID-19 Vaccine. Update: Arms to receive an additional homologous vaccine dose after an initial Janssen COVID 19 Vaccine were closed to enrollment after the CDC updated its recommendations to express a clinical preference for individuals to receive an mRNA COVID-19 vaccine over the Janssen COVID-19 vaccine. All Adult Stage 1 treatment arms were closed to enrollment on 15 August 2022.

Participants in Cohorts A and B will be randomized into 2 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 the additional homologous vaccine dose per protocol instructions.

A participant will be enrolled in the study for a maximum of approximately 13 months.

Stage 2 of this trial will include up to a maximum of 960 adult study participants (up to 80per arm) with a Roche Elecsys® Anti-SARS-CoV-2 S result ≤2500 U/mL after previous COVID-19 vaccine administration (at least 3 doses of mRNA vaccine(s) or 2 doses of the Janssen COVID-19 Vaccine). Participants will be eligible to receive a dose of an alternative COVID-19 vaccine.

Participants may have received their previous COVID-19 vaccine prior to enrollment in the study ("newly recruited participant"), or they may have received their previous COVID-19 vaccine as a study participant and then (re-) enter into Stage 2 ("rollover participant"). Participants can also roll over into Stage 2 via two pathways:

• Stage 1 participant rolls over to Stage 2
• Stage 2 participant rolls over to a different Stage 2 treatment arm

Participants will be allocated to 1 of 3 cohorts based on their IS regimens:

• Cohort D: Receipt of MMF or MPA
• Cohort E: Receipt of MTX
• Cohort F: Receipt of any BCDT within the past 18 months.

Treatment Arms: Participants in Cohorts D, E, and F will receive a dose of an alternative COVID-19 vaccine compared to their previous COVID-19 vaccine doses. Originally, participants who previously received 3 total doses of a single mRNA vaccine (Moderna COVID-19 Vaccine OR Pfizer- BioNTech COVID-19 Vaccine) received 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 received the Moderna COVID-19 Vaccine.

Update: Beginning with v4.0 of the protocol, this trial will not utilize the Janssen vector-based COVID-19 vaccine. Participants who previously received 3 total doses of a single mRNA vaccine will receive their choice of an alternative mRNA COVID-19 vaccine or the Sanofi-GSK protein based COVID-19 vaccine. Participants who previously received 4 or more doses of a single mRNA vaccine or 3 or more doses of a mixture mRNA vaccines (Moderna COVID-19 Vaccine AND Pfizer-BioNTech COVID-19 Vaccine, in any order or combination) will receive the Sanofi-GSK protein-based COVID-19 vaccine.

Participants in Cohorts D and E will withhold their cohort-defining IS medications before and after the alternative vaccine dose per protocol instructions. Participants in Cohort F who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications before and after the alternative vaccine dose per protocol instructions.

Visits to assess endpoints will occur at Baseline (Week 0), Week 4 ± 1 week, Week 12 ± 2 weeks, Week 24 ± 2 weeks, Week 36 ± 2 weeks, and Week 48 ± 2 weeks. A participant who is newly recruited to the study for entry into Stage 2 may be on study for up to a maximum of 13 months. A participant who enters Stage 2 after a serologic negative, suboptimal, or low immune response to their Stage 1 vaccine dose may be on study for up to a maximum of 26 months. Rollover participants will discontinue follow-up as part of Stage 1 upon rollover into Stage 2. A participant who rolls over to a different Stage 2 treatment arm 2 after a serologic negative, suboptimal, or low immune response to another Stage 2 vaccine dose may be on study for up to a maximum of 38 months.

Pediatric Population:

Stage 1 in the pediatric portion of this trial will enroll up to a maximum of 800 participants (2-17 years of age) with a Roche Elecsys® Anti-SARS-CoV-2 S result ≤2500 U/mL after receiving an initial COVID-19 vaccine regimen (up to 80participants per arm). Vaccines will be included in this protocol as they receive EUA or approval by FDA for a given age group. Pediatric participants will have 1 of 4 autoimmune diseases: pediatric SLE, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), or pediatriconset multiple sclerosis (POMS). Participants will be assigned to 1 of 3 cohorts based on their IS regimens:

• Cohort A: Receipt of MMF or MPA
• Cohort B: Receipt of MTX
• Cohort C: Receipt of any BCDT within the past 18 months.

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. Based on FDA EUA status, pediatric participants were initially eligible to receive the Pfizer-BioNTech COVID-19 Vaccine only.

Participants in Cohorts A and B will be randomized into 2 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 the additional homologous vaccine dose per protocol instructions.

A participant will be enrolled in the study for a maximum of approximately 13 months.

Stage 2 of the pediatric portion of this trial will include up to a maximum of 480 pediatric study participants (up to 80 per arm) with a Roche Elecsys® Anti-SARS-CoV-2 S result ≤2500 U/mL after previous COVID-19 vaccine administration (an age-appropriate EUA-authorized or FDA-approved initial COVID-19 vaccine regimen plus 1 additional dose of the same vaccine). All participants (2-17 years of age) who previously received doses of the Pfizer-BioNTech COVID-19 Vaccine are eligible to receive an age-appropriate dose of the Moderna COVID-19 Vaccine. Participants 12 through 17 years of age who previously received doses of the Moderna COVID-19 vaccine are eligible to receive an age-appropriate dose of the Pfizer-BioNTech COVID-19 Vaccine. Participants will be eligible to receive a dose of an alternative COVID-19 vaccine. Participants may have received their previous COVID-19 vaccine as a study participant and then enter into Stage 2 ("rollover participant"), or they may have received their previous COVID-19 vaccine prior to enrollment in the study ("newly recruited participant").

Participants will be allocated to 1 of 3 cohorts based on their IS regimens:

• Cohort D: Receipt of MMF or MPA (± other rheumatic disease medications, including biologics)

o Participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) will be placed in this cohort.

• Cohort E: Receipt of MTX (± other rheumatic disease medications, including biologics)

o Participants who are taking MTX (without additional B cell depleting medications or MMF/ MPA) will be placed in this cohort.

• Cohort F: Receipt of B cell depletion therapy within the past 18 months (± other rheumatic disease medications) o Participants taking B cell depletion medications, regardless of whether they are also taking MMF or MTX, will be placed in this cohort.

Treatment Arms: Participants in Cohorts D, E, and F will receive a dose of an alternative COVID-19 vaccine compared to their previous COVID-19 vaccine doses. Participants who previously received age-appropriate doses of a single mRNA vaccine (Moderna COVID-19 Vaccine OR Pfizer-BioNTech COVID-19 Vaccine, as noted above) will receive the other mRNA COVID-19 vaccine.

Beginning with v7.0 of the protocol all vaccines used are bivalent versions replacing original monovalent versions.

Participants in Cohorts D and E will withhold their cohort-defining IS medications before and after the alternative vaccine dose per protocol instructions (see Section 7.1.1 Protocol-mandated Medications).

Participants in Cohort F who are taking MMF, MPA, or MTX in addition to B cell depletion therapies (BCDTs) will withhold these medications before and after the alternative vaccine dose per protocol instruction.

A participant who enters Stage 2 after a serologic negative, suboptimal, or low immune response to their Stage 1 vaccine dose may be on study for up to a maximum of 26 months. Rollover participants will discontinue follow-up as part of Stage 1 upon rollover into Stage 2. A participant who is newly recruited to the study for entry into Stage 2 may be on study for up to a maximum of 13 months.

Adaptive Design

An adaptive design will be employed such that cohorts and arms defined by additional vaccine doses and IS treatment plans may be added or modified based on emerging data from existing and new FDA Emergency Use Authorization (EUA) or approvals of COVID-19 vaccines:

• New cohorts may be defined based on changes in the medication groups if it becomes obvious that certain medications are highly associated with suboptimal or low immune serologic response to initial COVID-19 vaccine regimen.
• Cohorts may limit or expand the autoimmune diseases that are eligible to be included in the clinical trial and may include expansion cohorts of underrepresented diseases.
• New cohorts may include participants whose antibody response falls to suboptimal or low immune levels over time.
• Based upon timing of the FDA EUA authorization for children of each of the COVID-19 vaccines used in this trial, the age range of the inclusion criteria may be expanded.
• Allocation or randomization to treatment with new COVID-19 vaccines may be incorporated into the design when the products become available.
• Identification of additional strategies to enhance vaccine responsiveness in autoimmune diseases, including a temporary switch of immunomodulatory medications.

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)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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

Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive an additional dose of the Moderna COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

Moderna mRNA-1273

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Continue IS (MMF or MPA)

Intervention Type: DRUG

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

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

Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Continue IS (MMF or MPA)

Intervention Type: DRUG

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

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

Arm closed, effective protocol version 3.0. Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive the Janssen COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

Ad26.COV2.S

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Continue IS (MMF or MPA)

Intervention Type: DRUG

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

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

Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Moderna mRNA-1273

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Withhold IS (MMF or MPA)

Intervention Type: 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.

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

Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Withhold IS (MMF or MPA)

Intervention Type: 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.

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

Arm closed, effective protocol version 3.0. Adult participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after the Janssen COVID-19 vaccine booster (1 dose), per protocol instruction.

Group Type: EXPERIMENTAL

Ad26.COV2.S

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Withhold IS (MMF or MPA)

Intervention Type: 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.

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

Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive an additional dose of the Moderna COVID-19 vaccine booster and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

Moderna mRNA-1273

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Continue IS (MTX)

Intervention Type: DRUG

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

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

Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine booster and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Continue IS (MTX)

Intervention Type: DRUG

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

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

Arm closed, effective protocol version 3.0. Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive the Janssen COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

Ad26.COV2.S

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Continue IS (MTX)

Intervention Type: DRUG

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

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

Adult Participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Moderna mRNA-1273

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Withhold IS (MTX)

Intervention Type: 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.

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

Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine booster, per protocol instruction.

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Withhold IS (MTX)

Intervention Type: 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.

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

Arm closed, effective protocol version 3.0. Adult participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after the Janssen COVID-19 vaccine booster (1 dose), per protocol instruction.

Group Type: EXPERIMENTAL

Ad26.COV2.S

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Withhold IS (MTX)

Intervention Type: 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.

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

Adult participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive an additional dose of the Moderna COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

Moderna mRNA-1273

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Continue IS (B cell depletion therapy)

Intervention Type: BIOLOGICAL

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

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

Adult participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Continue IS (B cell depletion therapy)

Intervention Type: BIOLOGICAL

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

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

Arm closed, effective protocol version 3.0. Adult participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive the Janssen COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

Ad26.COV2.S

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Continue IS (B cell depletion therapy)

Intervention Type: BIOLOGICAL

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

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

Arm closed, effective protocol version 4.0. Adult participants who previously received an mRNA vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Janssen COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Ad26.COV2.S

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Withhold IS (MMF or MPA)

Intervention Type: 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.

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

Adult participants who previously received an mRNA vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of an alternative COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.

Group Type: EXPERIMENTAL

BNT162b2

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Withhold IS (MMF or MPA)

Intervention Type: 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.

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

BNT162b2, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Adult participants who previously received the Janssen COVID-19 vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.

Group Type: EXPERIMENTAL

Withhold IS (MMF or MPA)

Intervention Type: 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.

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Arm closed, effective protocol version 4.0. Adult participants who previously received an mRNA vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Janssen COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Ad26.COV2.S

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Withhold IS (MTX)

Intervention Type: 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.

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

Adult participants who previously received an mRNA vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of an alternative COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.

Group Type: EXPERIMENTAL

Withhold IS (MTX)

Intervention Type: 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.

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

BNT162b2, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Adult participants who previously received the Janssen COVID-19 vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.

Group Type: EXPERIMENTAL

Withhold IS (MTX)

Intervention Type: 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.

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Arm closed, effective protocol version 4.0. Adult participants who previously received an mRNA vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX ) before and after receiving a dose of the Janssen COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Ad26.COV2.S

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Withhold IS (B cell depletion therapy)

Intervention Type: 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.

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

Adult participants who previously received an mRNA vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the alternative COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.

Group Type: EXPERIMENTAL

Withhold IS (B cell depletion therapy)

Intervention Type: 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.

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

BNT162b2, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Adult participants who previously received the Janssen COVID-19 vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction. Beginning with version 6.0 of the protocol, bivalent versions of the mRNA vaccines, Moderna and Pfizer-BioNTech COVID-19 vaccines, replaced original monovalent versions.

Group Type: EXPERIMENTAL

Withhold IS (B cell depletion therapy)

Intervention Type: 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.

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Adult participants who previously received an mRNA vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Sanofi-GSK COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Monovalent [B.1.351] CoV2 preS dTM-AS03

Intervention Type: BIOLOGICAL

One dose administered intramuscularly

Withhold IS (MMF or MPA)

Intervention Type: 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.

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

Adult participants who previously received an mRNA vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Sanofi-GSK COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Monovalent [B.1.351] CoV2 preS dTM-AS03

Intervention Type: BIOLOGICAL

One dose administered intramuscularly

Withhold IS (MTX)

Intervention Type: 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.

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

Adult participants who previously received an mRNA vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the Sanofi-GSK COVID-19 vaccine, per protocol instruction

Group Type: EXPERIMENTAL

Monovalent [B.1.351] CoV2 preS dTM-AS03

Intervention Type: BIOLOGICAL

One dose administered intramuscularly

Withhold IS (B cell depletion therapy)

Intervention Type: 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.

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

Pediatric participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive an additional dose of the Moderna COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

Continue IS (MMF or MPA)

Intervention Type: DRUG

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

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

Continue IS (MMF or MPA)

Intervention Type: DRUG

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

BNT162b2, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Withhold IS (MMF or MPA)

Intervention Type: 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.

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Withhold IS (MMF or MPA)

Intervention Type: 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.

BNT162b2, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive an additional dose of the Moderna COVID-19 vaccine booster and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

Continue IS (MTX)

Intervention Type: DRUG

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

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine booster and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

Continue IS (MTX)

Intervention Type: DRUG

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

BNT162b2, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Withhold IS (MTX)

Intervention Type: 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.

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine booster, per protocol instruction.

Group Type: EXPERIMENTAL

Withhold IS (MTX)

Intervention Type: 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.

BNT162b2, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive an additional dose of the Moderna COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

Continue IS (B cell depletion therapy)

Intervention Type: BIOLOGICAL

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

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive an additional dose of the Pfizer-BioNTech COVID-19 vaccine and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing.

Group Type: EXPERIMENTAL

Continue IS (B cell depletion therapy)

Intervention Type: BIOLOGICAL

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

BNT162b2, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants who previously received the Moderna COVID-19 vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Withhold IS (MMF or MPA)

Intervention Type: 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.

BNT162b2, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants who previously received the Pfizer-BioNTech COVID-19 vaccine and who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Withhold IS (MMF or MPA)

Intervention Type: 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.

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants who previously received the Moderna COVID-19 vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Withhold IS (MTX)

Intervention Type: 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.

BNT162b2, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants who previously received the Pfizer-BioNTech COVID-19 vaccine and who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease, will withhold their immunosuppressive medications (IS) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Withhold IS (MTX)

Intervention Type: 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.

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants who previously received the Moderna COVID-19 vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Withhold IS (B cell depletion therapy)

Intervention Type: 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.

BNT162b2, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

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

Pediatric participants who previously received the Pfizer-BioNTech COVID-19 vaccine and who are taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will continue to take their prescribed BCDTs without alterations in schedule and dosing. Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction.

Group Type: EXPERIMENTAL

Withhold IS (B cell depletion therapy)

Intervention Type: 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.

Moderna mRNA-1273, Bivalent

Intervention Type: BIOLOGICAL

Administration: One dose administered intramuscularly.

Interventions

Moderna mRNA-1273

Administration: One dose administered intramuscularly.

Intervention Type: BIOLOGICAL

BNT162b2

Administration: One dose administered intramuscularly.

Intervention Type: BIOLOGICAL

Ad26.COV2.S

Administration: One dose administered intramuscularly.

Intervention Type: BIOLOGICAL

Continue IS (MMF or MPA)

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

Intervention Type: DRUG

Continue IS (MTX)

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

Intervention Type: DRUG

Continue IS (B cell depletion therapy)

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

Intervention Type: BIOLOGICAL

Monovalent [B.1.351] CoV2 preS dTM-AS03

One dose administered intramuscularly

Intervention Type: BIOLOGICAL

Withhold IS (MMF or MPA)

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

Intervention Type: DRUG

Withhold IS (MTX)

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

Intervention Type: DRUG

Withhold IS (B cell depletion therapy)

Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX ) before and after the additional vaccine dose per protocol instructions. Participants will continue to take their prescribed BCDTs without alterations in schedule and dosing.

Intervention Type: DRUG

Moderna mRNA-1273, Bivalent

Administration: One dose administered intramuscularly.

Intervention Type: BIOLOGICAL

BNT162b2, Bivalent

Administration: One dose administered intramuscularly.

Intervention Type: BIOLOGICAL

Other Intervention Names

mRNA-1273 vaccine (Moderna); Moderna COVID-19 Vaccine; SARS-CoV-2 RNA vaccine; COVID-19 vaccine; mRNA-1273 vaccine (Pfizer/BioNTech); SARS-CoV-2 RNA vaccine; Pfizer-BioNTech COVID-19 vaccine; Janssen COVID-19 Vaccine; JNJ-78436735; immunosuppressive medication; mycophenolate mofetil; MMF; CellCept®; mycophenolic acid; MPA; methotrexate; MTX; mAbs targeting CD19 or CD20; anti-BAFF mAb; Sanofi-GSK COVID-19 Vaccine; immunosuppressive medication; mycophenolate mofetil; MMF; CellCept®; mycophenolic acid; MPA; methotrexate; MTX; mAbs targeting CD19 or CD20; anti-BAFF mAb; mRNA-1273 vaccine (Moderna), Bivalent; Moderna COVID-19 Vaccine, Bivalent; SARS-CoV-2 RNA vaccine, Bivalent; COVID-19 vaccine, Bivalent; mRNA-1273 vaccine (Pfizer/BioNTech), Bivalent; SARS-CoV-2 RNA vaccine, Bivalent; Pfizer-BioNTech COVID-19 vaccine, Bivalent

Eligibility Criteria

Inclusion Criteria

1. Willing and able to sign informed consent 2. Documented full COVID-19 vaccination (CDC card or documentation in medical records) that was completed at least 4 weeks prior and no more than 52 weeks prior to the Stage 1 Screening visit, or if participating in Stage 2, no more than 48 weeks prior to the Stage 2 Screening visit.

1. Individuals 18 years of age or older that meet classification criteria for systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), multiple sclerosis (MS), or pemphigus

2. Participants must meet the 2019 ACR/EULAR or 2012 SLICC classification criteria for SLE, the 2010 ACR/EULAR classification criteria for RA, the 2013 EULAR/ACR classification criteria for SSc, the 2017 McDonald criteria for MS, and the international consensus criteria for pemphigus.

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1. If a participant has been diagnosed with more than one autoimmune disease, the participant will be assessed based on the disease that is selected for study entry 6. Must be currently taking one of the following IS medications with or without additional disease-related medications: MMF (minimum of 1000 mg per day)/MPA (minimum of 720 mg per day), MTX (minimum of 7.5mg per week), or B cell depleting agents within the past 18 months (such as rituximab, ocrelizumab, ofatumumab).

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1. If taking MMF/MPA or MTX, the participant must have initiated therapy at least 8 weeks prior to randomization and be taking the same medications (regardless of dose) as at the time of the initial COVID-19 vaccine regimen. Note: Participants who withheld their IS medications around their initial vaccinations are eligible to participate.

2. If enrolling in the BCDT cohort, the participant must have received an anti-CD20 or an anti-CD19 BCDT in the past 18 months.

7. No changes in background IS medications, including MMF/MPA or MTX, in the 4 weeks prior to Screening, excluding the following:

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1. HCQ,

2. Intraarticular steroids,

3. The addition of prednisone at ≤10mg per day or prednisone at any dose when given for ≤3 days, and

4. Corticosteroid bursts for non-autoimmune disease-related conditions, such as asthma or COPD, are permitted.

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

14. Adult female participants who are planning a pregnancy during the course of the trial.

Adult Stage 1-Specific Inclusion Criterion 5. Negative or suboptimal serologic response to initial COVID-19 vaccine regimen, defined as an Elecsys® Anti-SARS-CoV-2 S result ≤200 U/mL, at Screening visit.

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1. Initial COVID-19 vaccine regimen is defined as either:

i.2 doses of the Pfizer-BioNTech COVID-19 Vaccine ii. 2 doses of the Moderna COVID-19 Vaccine

Adult Stage 1-Specific Exclusion Criterion 7. Receipt of a COVID-19 vaccine booster prior to Screening with the Moderna COVID-19 Vaccine, Pfizer-BioNTech COVID-19 Vaccine, or Janssen COVID-19 Vaccine.

5. Negative or suboptimal serologic response to a previous COVID 19 vaccine administration in one of the qualifying regimens, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) negative result or positive result of ≤200 U/mL, or a low immune response, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) result of ≤2500 U/mL, within 4 weeks of the Stage 2 Baseline/Week 0 visit. The regimens of COVID-19 vaccination that qualify are as follows:

1. 3 doses of the Pfizer-BioNTech COVID-19 Vaccine

2. 3 doses of the Moderna COVID-19 Vaccine

3. 2 doses of the Janssen COVID-19 Vaccine

4. 4 or more doses of a single mRNA vaccine (Pfizer-BioNTech COVID-19 Vaccine OR Moderna COVID-19 Vaccine)

5. 3 or more doses of a mixture of mRNA vaccines (Pfizer-BioNTech COVID-19 Vaccine OR Moderna COVID-19 Vaccine)

1. Individuals 2-17 years of age that meet classification criteria for SLE, JIA, POMS, or JDM. Note: Juvenile idiopathic arthritis includes the following conditions: polyarticular JIA (both RF + and -), oligoarticular persistent and oligoarticular extended JIA, psoriatic arthritis, and enthesitis related JIA.

1. Participants must meet the 2017 EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups, the International League of Associations for Rheumatology (ILAR) classification for JIA, the 2017 McDonald criteria for MS, or the Bohan and Peter criteria or the 2017 EULAR/ACR classification criteria for JDM.

2. If a participant has been diagnosed with more than one autoimmune disease, the participant will be assessed based on the disease that is selected for study entry.

2. Parents/guardians of all pediatric participants and participants ages 14 - 17 must be willing and able to sign informed consent. Participants ages 7-13 must be willing and able to sign assent.

5. 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).

1. If taking MMF/MPA or MTX, the participant must have initiated therapy at least 8 weeks prior to randomization and be taking the same medications (regardless of dose) as at the time of the initial COVID-19 vaccine regimen. Note: Participants who withheld their IS medications around their initial vaccinations are eligible to participate.

2. If enrolling in the BCDT cohort, participant must have received an anti-CD20 or an anti-CD19 BCDT in the past 18 months.

6. No changes in background IS medications, including MMF/MPA or MTX, in the 8 weeks prior to Screening, excluding the following:

a. HCQ, b. Intraarticular steroids, c. The addition of prednisone at <0.15mg/kg/dose per day or prednisone at any dose when given for ≤3 days, and d. Corticosteroid bursts for non-autoimmune disease-related conditions, such as asthma or COPD, are permitted

4. Negative or suboptimal serologic response to initial EUA-authorized or FDA-approved COVID-19 vaccine doses, defined as an Elecsys® Anti-SARS-CoV-2 S result ≤200 U/mL, or a low immune response, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) result of ≤2500 U/mL, within 4 weeks of the Stage 1 Baseline/Week 0 visit

Initial COVID-19 vaccine regimen is defined as:

i. Pfizer-BioNTech COVID-19 Vaccine (2 through 4 years of age): 3 age-appropriate doses ii. Pfizer-BioNTech COVID-19 Vaccine (5 through 17 years of age): 2 age-appropriate doses iii. Moderna COVID-19 Vaccine (2 through 17 years of age): 2 age-appropriate doses.

c. Moderna COVID-19 Vaccine (12 through 17 years of age): 3 full, age-appropriate doses of the Moderna COVID-19 Vaccine

5. Negative or suboptimal serologic response to a previous COVID-19 vaccine administration in one of the qualifying regimens, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) negative result or positive result of ≤200 U/mL, or a low immune response, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) result of ≤2500 U/mL, within 4 weeks of the Stage 2 Baseline/Week 0 visit. The regimens of COVID-19 vaccination that qualify are as follows:

1. Pfizer-BioNTech COVID-19 Vaccine (2 through 5 years of age): 4 full, age-appropriate doses of the Pfizer-BioNTech COVID-19 Vaccine

2. Pfizer-BioNTech COVID-19 Vaccine (5 through 17 years old): 3 full, age-appropriate doses of the Pfizer-BioNTech COVID-19 Vaccine Note: Participants who are 5 years old and previously received the Pfizer-BioNTech COVID-19 Vaccine may have received either age-appropriate regimen.

3. Moderna COVID-19 Vaccine (12 through 17 years of age): 3 full, age-appropriate doses of the Moderna COVID-19 Vaccine

Exclusion Criteria

3. New diagnosis of malignancy that will require chemotherapy or immunotherapy, or ongoing treatment for a malignancy with chemotherapy or immunotherapy.

4. Active disease (per the Investigator's decision) resulting in inability to hold the IS therapy in the MMF/MPA or MTX arms of the study.

a. The potential impact of temporarily holding medication for participants with a recent mild disease flare within 4 weeks should be carefully considered.

5. Active disease during the Screening period resulting in:

1. An increase/addition of any IS medications, or

2. A suggestion of MS relapse per the investigator. 6. Recent or current SARS-CoV-2 infection defined as:

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1. Documented SARS-CoV-2 infection in the past 30 days (from the day the participant is diagnosed by positive test to Screening).

2. Positive result on a molecular COVID-19 test at Screening. 8. Inflammatory myocarditis/pericarditis within 6 weeks of any COVID-19 vaccine doses.

9. Participants with active, ongoing chronic infections. Note: Participants are permitted to be on chronic prophylactic antimicrobial therapy. Adults with evidence of HIV, Hepatitis B indicated by surface antigen, and Hepatitis C indicated by anti-hepatitis C antibody positivity will be excluded. If an adult is negative for Hepatitis C viral load at Screening, he/she will be eligible to participate.

10. Participants with common variable immunodeficiency disease, as well as any participants currently receiving immune globulin replacement therapy. Note: Pediatric participants on IVIG therapeutically may enter the study provided they have sufficiently quiet disease that they can withhold their IVIG from 8 weeks prior to the Screening visit through 4 weeks after vaccination.

11. Participants who received licensed or investigational monoclonal antibodies or plasma products directed against SARS-CoV-2 within 30 days of Screening.

12. Participants who have received any live vaccines within 2 months of the anticipated study vaccine dose or who will have need of a live vaccine at any time during the study.

13. Currently pregnant or breastfeeding (For pediatric participants postmenarchal females must have a negative urine pregnancy test at Screening).

15. Hemoglobin (Hgb) <8.0 g/dL (80 g/L) 16. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

17. Other investigational chemical agent within 30 days or other investigational biologic agent within 8 weeks or 5 half-lives (whichever is longer) of Screening.

18. Concurrent treatment with cyclophosphamide. Adult participants taking cladribine, alemtuzumab, or mitoxantrone will also be excluded.

19. Participants currently on any type of dialysis, or who have received a solid organ transplant.

20. Prisoners or participants who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness.

21. Taking both MMF/MPA and MTX. 22. Receiving other investigational BCDT as part of a clinical trial within 18 months of Screening, unless drug assignment is known and the participant received an anti-CD20 or CD19 drug.

23. Participants with active systemic infections who have received systemic antimicrobials within the 14 days prior to Screening.

Adult General Criteria

7. Receipt of a mixture of Janssen COVID-19 vaccines and mRNA COVID-19 vaccines (in any order or combination) prior to Stage 2 Screening.

Individuals who meet all of the following criteria are eligible to (re )enter Adult Stage 2:

2. History of severe allergic reaction to the COVID-19 vaccine, or to any component of the COVID-19 vaccine, that is to be administered in Stage 2, including polysorbate for participants receiving the Sanofi-GSK COVID-19 Vaccine, or to PEG.

5. Negative or suboptimal serologic response to a previous COVID 19 vaccine administration in one of the qualifying regimens, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) negative result or positive result of ≤200 U/mL, or a low immune response, defined as an Elecsys® Anti-SARS-CoV-2 S (RBD) result of ≤2500 U/mL, within 4 weeks of the Stage 2 Baseline/Week 0 visit. The regimens of COVID-19 vaccination that qualify are as follows:

a. 3 doses of the Pfizer-BioNTech COVID-19 Vaccine b. 3 doses of the Moderna COVID-19 Vaccine c. 2 doses of the Janssen COVID-19 Vaccine d. 4 doses of a combination of mRNA vaccines (i.e., Pfizer-BioNTech COVID-19 Vaccine, Moderna COVID-19 Vaccine)

Individuals who meet any of these criteria are not eligible for randomization/allocation as participants in the pediatric portion of the study:

7. Receipt of a COVID-19 vaccine booster prior to Screening.

7. Receipt of an additional heterologous COVID-19 vaccine dose prior to Stage 2 Screening, i.e., a participant cannot have received a mixture of mRNA vaccines.

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Autoimmunity Centers of Excellence

OTHER

Sponsor Role: collaborator

Rho Federal Systems Division, Inc.

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith A. James, MD, PhD

Role: STUDY_CHAIR

Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation

Meggan C. Mackay, MD, MS

Role: STUDY_CHAIR

Center of Autoimmune Musculoskeletal and Hematopoietic Diseases, Feinstein Institute for Medical Research

Dinesh Khanna, MBBS, MSc

Role: STUDY_CHAIR

University of Michigan Health, Michigan Medicine

Amit Bar-Or, MD, FRCP

Role: STUDY_CHAIR

Center for Neuroinflammation and Neurotherapeutics, Perelman School of Medicine, University of Pennsylvania

Virginia Pascual, MD

Role: STUDY_CHAIR

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

Stacy Ardoin, MD

Role: STUDY_CHAIR

Nationwide Children's Hospital Rheumatology Department

Natasha Mckerran Ruth, MD

Role: STUDY_CHAIR

Medical University of South Carolina, Pediatric Rheumatology

Tracey Wright, MD

Role: STUDY_CHAIR

UT Southwestern Medical Center, Pediatric Rheumatology

Locations

UCLA Medical Center: Division of Rheumatology

Los Angeles, California, United States

Yale University School of Medicine: Rheumatology, Allergy & Immunology

New Haven, Connecticut, United States

The Emory Clinic: Division of Rheumatology

Atlanta, Georgia, United States

Indiana University Medical Center, Riley Hospital for Children

Indianapolis, Indiana, United States

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

Boston, Massachusetts, United States

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

Boston, Massachusetts, United States

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

Boston, Massachusetts, United States

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

Ann Arbor, Michigan, United States

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

St Louis, Missouri, United States

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

Manhasset, New York, United States

Feinstein Institute for Medical Research

Manhasset, New York, United States

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

New York, New York, United States

Hospital for Special Surgery

New York, New York, United States

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

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Stony Brook University Hospital

Stony Brook, New York, United States

University of North Carolina Children's Hospital

Chapel Hill, North Carolina, United States

Duke University Medical Center: Division of Rheumatology and Immunology

Durham, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Nationwide Children's Hopspital

Columbus, Ohio, United States

Oklahoma Children's Hospital-Pediatrics Specialties Clinic

Oklahoma City, Oklahoma, United States

Oklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program

Oklahoma City, Oklahoma, United States

Temple Health: Rheumatology

Philadelphia, Pennsylvania, United States

University of Pennsylvania Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Medical University of South Carolina, Nexus Research Center

Charleston, South Carolina, United States

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

Charleston, South Carolina, United States

UT Southwestern (Peds)

Dallas, Texas, United States

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

Houston, Texas, United States

Benaroya Research Institute at Virginia Mason: Internal Medicine

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

https://www.autoimmunitycenters.org/

Autoimmunity Centers of Excellence (ACE)

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT)

Other Identifiers

NIAID CRMS ID#: 38873

Identifier Type: OTHER

Identifier Source: secondary_id

DAIT ACV01

Identifier Type: -

Identifier Source: org_study_id