COVID-19 Booster Vaccine in Autoimmune Disease Non-Responders
Study Details
Study Description
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 immunosuppressive medications. All study participants will have negative serologic or sub-optimal responses (defined as a Roche Elecsys® Anti-SARS-CoV-2 S (RBD) result ≤ 200 U/mL) to initial COVID-19 vaccine regimen with Moderna COVID-19 vaccine, Pfizer-BioNTech COVID-19 vaccine, or Janssen COVID-19 vaccine.
The study will focus on 5 autoimmune diseases in adults:
-
Systemic Lupus Erythematosus (SLE)
-
Rheumatoid Arthritis (RA)
-
Multiple Sclerosis (MS)
-
Systemic Sclerosis (SSc), and
-
Pemphigus.
This study will focus on 4 autoimmune diseases in pediatric participants:
-
Systemic Lupus Erythematosus (SLE)
-
Juvenile Idiopathic Arthritis (JIA)
-
Pediatric-Onset Multiple Sclerosis (POMS)
-
Juvenile Dermatomyositis (JDM)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
In Stage 1 of this study, adult participants will be assigned to one of 3 cohorts based on their immunosuppressive regimens:
-Cohort A: Receipt of MMF or MPA (± other rheumatic disease medications, including biologics)
- Participants who are taking mycophenolate mofetil (MMF) or mycophenolic acid (MPA), without additional B cell depleting medications or methotrexate (MTX), will be placed in this cohort.
-Cohort B: Receipt of MTX (± other rheumatic disease medications, including biologics)
- Participants who are taking MTX (without additional B cell depleting medications or MMF/ MPA) will be placed in this cohort.
-Cohort C: Receipt of B cell depletion therapy within the past 12 months (± other rheumatic disease medications)
- Participants taking B cell depletion medications, regardless of whether they are also taking MMF or MTX, will be placed in this cohort.
Treatment Arms: Participants in Cohorts A, B, and C will be assigned to receive an additional dose of the same vaccine as their original vaccine series.
Participants in Cohorts A and B will be randomized into two immunosuppressive medication (IS) treatment plans as follows:
-
Participants continue to take their immunosuppressive medications without alterations in schedule and dosing.
-
Participants withhold their immunosuppressive medications before and after the additional homologous vaccine dose, per protocol.
In Stage 2 of this study, adult participants will be assigned to one of 3 cohorts based on their immunosuppressive regimens:
-
Cohort D: Receipt of MMF or MPA (± other rheumatic disease medications, including biologics) --Participants who are taking mycophenolate mofetil (MMF) or mycophenolic acid (MPA), without additional B cell depleting medications or methotrexate (MTX), will be placed in this cohort.
-
Cohort E: Receipt of MTX (± other rheumatic disease medications, including biologics)
--Participants who are taking MTX (without additional B cell depleting medications or MMF/ MPA) will be placed in this cohort.
- Cohort F: Receipt of B cell depletion therapy within the past 12 months (± other rheumatic disease medications) --Participants taking B cell depletion medications, regardless of whether they are also taking MMF or MTX, will be placed in this cohort.
Treatment Arms: Participants in Cohorts D, E, and F will be assigned to receive an alternative COVID-19 vaccine compared to their previous COVID-19 vaccine doses. Participants who previously received 3 total doses of an mRNA vaccine (Moderna COVID-19 Vaccine OR Pfizer-BioNTech COVID-19 Vaccine) will receive their choice of either the Janssen vector-based COVID 19 vaccine or the other mRNA COVID-19 vaccine, and participants who previously received 2 doses of the Janssen vector-based COVID-19 vaccine will receive the Moderna COVID-19 Vaccine.
Participants in Cohorts D, E, and F will withhold their cohort-defining IS treatment before and after the alternative vaccine dose per protocol instructions.
In the pediatric portion of this study, participants will be assigned to one of 3 cohorts based on their immunosuppressive regimens:
-
Cohort A: Receipt of MMF or MPA (± other rheumatic disease medications, including biologics) --Participants who are taking mycophenolate mofetil (MMF) or mycophenolic acid (MPA), without additional B cell depleting medications or methotrexate (MTX), will be placed in this cohort.
-
Cohort B: Receipt of MTX (± other rheumatic disease medications, including biologics)
--Participants who are taking MTX (without additional B cell depleting medications or MMF/ MPA) will be placed in this cohort.
- Cohort C: Receipt of B cell depletion therapy within the past 12 months (± other rheumatic disease medications) --Participants taking B cell depletion medications, regardless of whether they are also taking MMF orMTX, will be placed in this cohort.
Treatment Arms: Participants in Cohorts A, B, and C will be assigned to receive an additional dose of the same vaccine as their original vaccine series.
Participants in Cohorts A and B will be randomized into two immunosuppressive medication (IS) treatment plans as follows:
-
Participants continue to take their immunosuppressive medications without alterations in schedule and dosing.
-
Participants withhold their immunosuppressive medications before and after the homologous vaccine dose, per protocol.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort A, Arm A1: Moderna mRNA-1273 +IS (MMF or MPA) Participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive 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
Administration: One dose administered intramuscularly.
Other Names:
Drug: IS (MMF or MPA)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort A, Arm A2: BNT162b2 +IS (MMF or MPA) Participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive 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
Administration: One dose administered intramuscularly.
Other Names:
Drug: IS (MMF or MPA)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort A, Arm A3: Ad26.COV2.S + IS (MMF or MPA) Arm closed, effective protocol version 3.0. Participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will receive the Janssen COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing. |
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
Drug: IS (MMF or MPA)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort A, Arm A4: Moderna mRNA-1273 Participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction. |
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
|
| Experimental: Cohort A, Arm A5: BNT162b2 Participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine, per protocol instruction. |
Biological: BNT162b2
Administration: One dose administered intramuscularly.
Other Names:
|
| Experimental: Cohort A, Arm A6: Ad26.COV2.S Arm closed, effective protocol version 3.0. Participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after the Janssen COVID-19 vaccine booster (1 dose), per protocol instruction. |
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
|
| Experimental: Cohort B, Arm B1: Moderna mRNA-1273 + IS (MTX) Participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive 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
Administration: One dose administered intramuscularly.
Other Names:
Drug: IS (MTX)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort B, Arm B2: BNT162b2 + IS (MTX) Participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive 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
Administration: One dose administered intramuscularly.
Other Names:
Drug: IS (MTX)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort B, Arm B3: Ad26.COV2.S + IS (MTX) Arm closed, effective protocol version 3.0. Participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will receive the Janssen COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing. |
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
Drug: IS (MTX)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort B, Arm B4: Moderna mRNA-1273 Participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Moderna COVID-19 vaccine, per protocol instruction. |
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
|
| Experimental: Cohort B, Arm B5: BNT162b2 Participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after receiving an additional dose of the Pfizer-BioNTech COVID-19 vaccine booster, per protocol instruction. |
Biological: BNT162b2
Administration: One dose administered intramuscularly.
Other Names:
|
| Experimental: Cohort B, Arm B6: Ad26.COV2.S Arm closed, effective protocol version 3.0. Participants who are taking methotrexate (without additional B cell depleting medications or MMF/ MPA) for management of their underlying autoimmune disease will withhold their immunosuppressive medications (IS) before and after the Janssen COVID-19 vaccine booster (1 dose), per protocol instruction. |
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
|
| Experimental: Cohort C, Arm C1: Moderna mRNA-1273 +IS (B cell depletion therapy) Participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive 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
Administration: One dose administered intramuscularly.
Other Names:
Biological: IS (B cell depletion therapy)
Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort C, Arm C2: BNT162b2+IS (B cell depletion therapy) Participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive 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
Administration: One dose administered intramuscularly.
Other Names:
Biological: IS (B cell depletion therapy)
Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort C, Arm C3: Ad26.COV2.S +IS (B cell depletion therapy) Arm closed, effective protocol version 3.0. Participants taking B cell depletion medication(s) for management of their underlying autoimmune disease, regardless of whether they are also taking MMF or MTX, will receive the Janssen COVID-19 vaccine booster (1 dose) and continue to take their immunosuppressive medications (IS) without alterations in schedule and dosing. |
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
Biological: IS (B cell depletion therapy)
Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort D, Arm D1: mRNA Vaccine + IS (MMF or MPA) + Ad26.COV2.S 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: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
Biological: BNT162b2
Administration: One dose administered intramuscularly.
Other Names:
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
Drug: IS (MMF or MPA)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort D, Arm D2: mRNA Vaccine + IS (MMF or MPA) + Alternative mRNA Vaccine 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. |
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
Biological: BNT162b2
Administration: One dose administered intramuscularly.
Other Names:
Drug: IS (MMF or MPA)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort D, Arm D3: Ad26.COV2.S + IS (MMF or MPA) + Moderna mRNA-1273 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. |
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
Drug: IS (MMF or MPA)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort E, Arm E1: mRNA Vaccine + IS (MTX) + Ad26.COV2.S 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: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
Biological: BNT162b2
Administration: One dose administered intramuscularly.
Other Names:
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
Drug: IS (MTX)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort E, Arm E2: mRNA Vaccine + IS (MTX) + Alternative mRNA Vaccine 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. |
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
Biological: BNT162b2
Administration: One dose administered intramuscularly.
Other Names:
Drug: IS (MTX)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort E, Arm E3: Ad26.COV2.S + IS (MTX) + Moderna mRNA-1273 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. |
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
Drug: IS (MTX)
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort F, Arm F1: mRNA Vaccine + IS (B cell depletion therapy) + Ad26.COV2.S 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 withhold their immunosuppressive medications (IS) before and after receiving a dose of the Janssen COVID-19 vaccine, per protocol instruction. |
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
Biological: BNT162b2
Administration: One dose administered intramuscularly.
Other Names:
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
Biological: IS (B cell depletion therapy)
Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort F, Arm F2: mRNA Vaccine + IS (B cell depletion therapy) + Alternative mRNA Vaccine 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 MT,, will withhold their immunosuppressive medications (IS) before and after receiving a dose of an alternative COVID-19 vaccine, per protocol instruction. |
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
Biological: BNT162b2
Administration: One dose administered intramuscularly.
Other Names:
Biological: IS (B cell depletion therapy)
Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing.
Other Names:
|
| Experimental: Cohort F, Arm F3: Ad26.COV2.S + IS (B cell depletion therapy) + Moderna mRNA-1273 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 withhold their immunosuppressive medications (IS) before and after receiving a dose of the Moderna COVID-19 vaccine, per protocol instruction. |
Biological: Moderna mRNA-1273
Administration: One dose administered intramuscularly.
Other Names:
Biological: Ad26.COV2.S
Administration: One dose administered intramuscularly.
Other Names:
Biological: IS (B cell depletion therapy)
Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of adult and pediatric participants who have a protective antibody response at Week 4 [Week 4 Status Post Receipt of COVID-19 Vaccination]
Efficacy measure.
Secondary Outcome Measures
- Percentage of Subset Participants Who Seroconverted [Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48]
Efficacy measure, evaluated in subset of participants who are anti-COVID-19 antibody negative at Baseline.
- Fold increase in anti-COVID-19 antibody levels at Week 4, following participant receipt of a booster dose of COVID-19 vaccine [Baseline (prior to receipt of COVID-19 vaccine booster), Week 4 Status Post Receipt of COVID-19 Vaccine Booster Dose]
Efficacy measure, evaluated in subset of participants who are anti-COVID-19 antibody positive at Week 0 (Baseline).
- Change in anti-COVID-19 antibody response [Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48]
Efficacy measure.
- Change in anti-SARS-CoV-2 neutralizing antibody levels [Baseline (prior to receipt of COVID-19 vaccine booster) and Weeks 4, 12, 24, 36, and 48]
Efficacy measure, employing neutralization and pseudo-neutralization assays.
- Change in disease activity after receipt of additional doses of COVID-19 vaccine as measured by the Clinical Global Impression of Change (CGI-C) [Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Dose]
A measure of disease activity and efficacy. CGI-C: Clinician's global impression of a participant's clinical condition in terms of change relative to the start of treatment. Rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). Higher score = more affected.
- Change in disease activity after receipt of additional doses of COVID-19 vaccine as measured by the Physician's Global Assessment [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of disease activity and efficacy.
- Change in disease activity in adult participant subset with Systemic Lupus Erythematosus (SLE) as measured by Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of SLE disease activity and efficacy.
- Change in disease activity in adult participant subset with Systemic Lupus Erythematosus (SLE) as measured by Thanou modified SELENA-SLEDAI Flare Index for Systemic Lupus Erythematosus (SLE) [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48]
A measure of SLE disease activity and efficacy.
- Change in disease activity in adult participant subset with Rheumatoid Arthritis (RA) as measured by Disease Activity Score 28 C-reactive Protein (DAS28-CRP) [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of RA disease activity and efficacy.
- Change in disease activity in adult participant subset with Systemic Sclerosis (SSc) as measured by Disease Flare Activity [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of SSc disease activity and efficacy. SSc disease flare assessments (including participant self- reported flare assessment). A flare is indicative of increased SSc-related disease activity.
- Change in disease activity in adult participant subset with Pemphigus as measured by Disease Area Index (PDAI) for Pemphigus [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of pemphigus disease activity and efficacy. The PDAI is specific cutaneous and mucosal disease activity assessment performed by the physician and is based on evaluation of lesions in well-defined anatomical locations.
- Change in disease activity in adult participant subset with Multiple Sclerosis (MS) as measured by Physician assessed relapse for MS [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of MS disease activity and efficacy.
- Change in disease activity in pediatric participant subset with juvenile idiopathic arthritis (JIA) as measured by JADAS10 [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of JIA disease activity and efficacy.
- Change in disease activity in pediatric participant subset with JIA as measured by Psoriasis Area and Severity Index (PASI) for psoriatic arthritis [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of JIA disease activity and efficacy.
- Change in disease activity in pediatric participant subset with pediatric-onset multiple sclerosis (POMS) as measured by SLEDAI-2K [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of MS disease activity and efficacy.
- Change in disease activity in pediatric participant subset with POMS as measured by childhood-onset SLE Criteria for Global Flare [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of POMS disease activity and efficacy.
- Change in disease activity in pediatric participant subset with juvenile dermatomyositis (JDM) as measured by Childhood Mysositis Assessment Scale [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of JDM disease activity and efficacy.
- Change in disease activity in pediatric participant subset with JDM as measured by JDM Disease Activity Score (DAS) [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of JDM disease activity and efficacy.
- Change in disease activity in pediatric participant subset with Multiple Sclerosis (MS) as measured by Physician assessed relapse for MS (POMS) [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of MS disease activity and efficacy.
- Change in disease activity in adult participants as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS-29) [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of disease activity and efficacy. The Patient-Reported Outcomes Measurement Information System (PROMIS-29) self-report assesses functioning and well-being in physical, mental and social domains of health. The PROMIS-29 consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance.
- Change in disease activity in pediatric participants as measured by the Pediatric Quality of Life Inventory (PedsQL) [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of disease activity and efficacy. The Patient-Reported Outcomes Measurement Information System (PROMIS-29) self-report assesses functioning and well-being in physical, mental and social domains of health. The PROMIS-29 consists of seven health domains with four 5-level items associated with each and a pain intensity assessment using a 0-10 numeric rank. The seven health domains include physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance.
- Change in disease activity as measured by the Patient Global Assessment [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of disease activity and efficacy. The patient global assessment of disease activity is measured using a 100mm Visual Analog Scale (VAS) ranging from 0=very good to 100=very bad. Change=<week status post receipt of booster vaccine> score minus baseline score. A negative score indicates an improvement in disease activity and a positive score indicates worsening.
- Change in disease activity as measured by the Patient Global Impression of Change (PGI-C) [Baseline (prior to receipt of COVID-19 vaccine doses) and Weeks 4, 12, 24, 36, and 48 Status Post Receipt of COVID-19 Vaccine Booster Dose]
A measure of disease activity and efficacy. Participant's Global Impression of Change Reported on PGI-C Scale (1-7 Point Scale Ranging From 1 "Very Much Improved" to 7 "Very Much Worse").
- Proportion of participants who experience any solicited Grade 1 or higher adverse events related to additional doses of the COVID-19 vaccine [Through Day 7 post study vaccination]
Safety measure status post receipt of study vaccination.
- Proportion of participants who experience any unsolicited Grade 1 or higher adverse events related to additional doses of the COVID-19 vaccine [Through Day 28 post study vaccination]
Safety measure status post receipt of study vaccination.
- Proportion of participants who experience any serious adverse events (SAEs) [Up to Week 48 post study vaccination]
Safety measure status post receipt of study vaccination.
- Proportion of participants who experience any medically attended adverse events (MAAEs) [Up to Week 48 post study vaccination]
Safety measure status post receipt of study vaccination.
- Proportion of participants who experience any New Onset Chronic Medical Conditions (NOCMCs) [Up to Week 48 post study vaccination]
Safety measure status post receipt of study vaccination.
- Proportion of participants who experience any Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection [Up to Week 48 post study vaccination]
Efficacy measure.
Eligibility Criteria
Criteria
Inclusion Criteria Adults:
Individuals who meet all the following criteria are eligible for enrollment as study participants-
- Individuals that meet classification criteria for:
-
systemic lupus erythematosus (SLE)
-
systemic sclerosis (SSc)
-
rheumatoid arthritis (RA)
-
multiple sclerosis (MS), or
-
pemphigus
- Participants must meet:
-
the 2019 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) or the 2012 Systemic Lupus International Collaborating Clinics Classification Criteria (SLICC) classification criteria for SLE
-
the 2010 ACR/EULAR classification criteria for RA
-
the 2013 EULAR/ACR classification criteria for SSc
-
the 2017 McDonald criteria for MS, and
-
the international consensus criteria for pemphigus
Note: If a participant has been diagnosed with more than one autoimmune disease, the participant will be assessed based on the disease that is selected for study entry
-
Willing and able to sign informed consent
-
Documented full COVID-19 vaccination (e.g., Centers for Disease Control and Prevention [CDC] vaccination card or documentation in medical records) that was completed ≥ 4 weeks prior and no more than 52 weeks prior to the Screening visit
-
Negative serologic or suboptimal response to initial COVID-19 vaccine regimen- defined as an Elecsys® Anti-Severe Acute Respiratory Syndrome Coronavirus-2 (anti-SARS-CoV-2-spike (S) protein receptor binding domain (RBD)) result ≤ 200 U/mL at Screening visit
-Initial COVID-19 vaccine regimen is defined as either:
-
2 doses of the Pfizer-BioNTech COVID-19 vaccine
-
2 doses of the Moderna COVID-19 vaccine, or
- Must be currently taking one of the following IS medications with or without additional disease related medications:
-
mycophenolate mofetil (minimum of 1,000 mg per day)/mycophenolic acid (minimum of 720 mg per day)
-
methotrexate (minimum of 7.5mg per week), or
-
B cell depleting agents within the past 18 months (such as rituximab, ocrelizumab, or ofatumumab)
-
If taking mycophenolate mofetil (MMF)/mycophenolic acid (MPA) or methotrexate (MTX), the participant must have initiated therapy at least 8 weeks prior to randomization and be taking the same medications (regardless of dose) as at the time of the initial COVID-19 vaccine regimen
-
Participants on B cell depleting therapy may enter the study if they are also taking MMF/MPA or MTX. In this case, the MMF/MPA or MTX would not be withheld for the vaccine booster dose(s)
-
Participants taking both MMF/MPA and MTX will be excluded from the study
- No changes in background IS medications in the 8 weeks prior to Screening, excluding the following:
-
hydroxychloroquine (HCQ)
-
Intraarticular steroids
-
The addition of prednisone at ≤10 mg per day or prednisone at any dose when given for ≤ 3 days, and
-
Corticosteroid bursts for non-autoimmune disease-related conditions, such as asthma or chronic obstructive pulmonary disease (COPD), are permitted
Exclusion Criteria Adults:
Individuals who meet any of these criteria are not eligible for enrollment as study participants-
-
Inability or unwillingness of a participant to give written informed consent or comply with study protocol
-
History of severe allergic reaction to the initial COVID-19 vaccine regimen, or any component of any of the COVID-19 vaccines, or to polyethylene glycol (PEG)
-
Ongoing treatment for a malignancy with chemotherapy or immunotherapy
-
Active disease (per the Investigator's decision) resulting in inability to hold the immunosuppressive therapy in the Mycophenolate Mofetil (MMF)/Mycophenolic Acid (MPA) or Methotrexate (MTX) arms of the study
The potential impact of temporarily holding medication for participants with a recent mild disease flare within 4 weeks should be carefully considered
- Active disease during the Screening period resulting in:
-
an increase/addition of immunosuppressive medications, or
-
a suggestion of multiple sclerosis (MS) relapse per the investigator
- Recent or current Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection defined as:
-
Documented SARS-CoV-2 infection in the past 30 days (from the day the participant is diagnosed by positive test to Screening), or
-
A positive result on a molecular COVID-19 test at Screening
-
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
-
Participants with:
-
a history of autoimmune disease-related myocarditis within 3 years
-
autoimmune disease-related pericarditis within the past year, or
-
inflammatory myocarditis/pericarditis following initial COVID-19 vaccine regimen
- Participants with active bacterial or viral infections who have received antibiotics within the 14 days prior to Screening, including participants with evidence of:
-
Human Immunodeficiency Virus (HIV)
-
Hepatitis B as indicated by surface antigen or hepatitis B core antibody positivity
-
Hepatitis C as indicated by anti-hepatitis C antibody positivity
-
Note: If a participant is Hepatitis C antibody positive, they will be eligible to participate in the study if he/she is negative for viral load at Screening
-
Participants with common variable immunodeficiency disease, as well as any participants currently receiving immune globulin replacement therapy
-
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
-
Participants who are planning a pregnancy during the course of the trial
-
Hemoglobin (Hgb) < 8.0 g/dL (80 g/L)
-
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
-
Other investigational chemical agent within 30 days or other investigational biologic agent within 8 weeks or 5 half-lives (whichever is longer) of enrollment
-
Concurrent treatment with cyclophosphamide, cladribine, alemtuzumab, or mitoxantrone
-
Participants currently on any type of dialysis, or who have received a solid organ transplant
-
Prisoners or participants who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
-
Taking both MMF/MPA and MTX.
-
Receiving other investigational B cell depleting therapy as part of a clinical trial within one year18 months of Screening, unless drug assignment is known and the participant received an anti-CD20 or CD19 drug.
-
Participants with active systemic infections who have received systemic antimicrobials within the 14 days prior to Screening.
Inclusion Criteria Pediatric:
- Individuals 5-17 years of age that meet classification criteria for SLE, JIA, POMS, or
JDM. Note: Juvenile idiopathic arthritis includes the following conditions:
polyarticular JIA (both RF + and-), oligoarticular persistent and oligoarticular extended JIA, psoriatic arthritis, and enthesitis related JIA.
-
Participants must meet the 2017 EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups [8], the International League of Associations for Rheumatology (ILAR) classification for JIA [4], the 2017 McDonald [6] criteria for MS, or the Bohan and Peter criteria or the 2017 EULAR/ACR classification criteria for JDM.
-
If a participant has been diagnosed with more than one autoimmune disease, the participant will beassessed based on the disease that is selected for study entry.
-
Parents/guardians of pediatric participants must be willing and able to sign informed consent. Participants, ages 7-17, must be willing and able to sign assent.
-
Documented full COVID-19 vaccination (CDC card or documentation in medical records) that was completed at least 4 weeks prior and no more than 52 weeks prior to the Screening visit.
-
Negative or suboptimal serologic response to initial COVID-19 vaccine regimen, defined as an Elecsys® Anti-SARS-CoV-2 S result ≤200 U/mL at Screening visit.
-
Initial COVID-19 vaccine regimen is defined as:
-
- 2 doses (as appropriate to age) of the Pfizer-BioNTech COVID-19 Vaccine
The following vaccines have yet to receive EUA in pediatric populations. If EUA occurs for younger ages, the participants receiving age-appropriate regimens of the following
COVID-19 vaccines may be enrolled into the study:
-
- Moderna COVID-19 Vaccine
-
- Janssen COVID-19 Vaccine
- Must be currently taking one of the following IS medications with or without additional disease-related medications: MMF (minimum of 250 mg per day)/MPA (minimum of 360 mg per day), MTX (minimum of 5 mg per week), or B cell depleting agents within the past 18 months (such as rituximab, ocrelizumab, or ofatumumab).
-
If taking MMF/MPA or MTX, the participant must have initiated therapy at least 8 weeks prior to randomization and be taking the same medications (regardless of dose) as at the time of the initial COVID-19 vaccine regimen. Note: Participants who withheld their IS medications around their initial vaccinations are eligible to participate.
-
If enrolling in the B cell depleting therapy cohort, participant must have received an anti-CD20 or an anti-CD19 B cell depleting therapy in the past 18 months.
- No changes in background IS medications, including MMF/MPA or MTX, in the 8 weeks prior to Screening, excluding the following:
-
HCQ,
-
Intraarticular steroids,
-
The addition of prednisone at ≤10mg per day or prednisone at any dose when given for ≤3 days, and
-
Corticosteroid bursts for non-autoimmune disease-related conditions, such as asthma or COPD, are permitted.
Exclusion Criteria Pediatric:
-
Inability or unwillingness of a participant to give assent or of a parent/guardian to give written informed consent, or of either to comply with study protocol.
-
History of severe allergic reaction to the initial COVID-19 vaccine regimen, or any component of any of the COVID-19 vaccines, or to PEG.
-
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.
- 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
- Recent or current SARS-CoV-2 infection defined as:
-
Documented SARS-CoV-2 infection in the past 30 days (from the day the participant is diagnosed by positive test to Screening).
-
Positive result on a molecular COVID-19 test at Screening.
-
Receipt of a COVID-19 vaccine booster prior to Screening.
-
Inflammatory myocarditis/pericarditis following initial COVID-19 vaccine regimen.
-
Participants with active, ongoing chronic infections, including participants with evidence of:
-
HIV.
-
Hepatitis B as indicated by surface antigen.
-
Hepatitis C as indicated by anti-hepatitis C antibody positivity; if a participant is Hepatitis C antibody positive, they will be eligible to participate in the study if he/she is negative for viral load at Screening. Note: Participants are permitted to be on chronic prophylactic antimicrobial therapy.
-
Participants with common variable immunodeficiency disease, as well as any participants currently receiving immune globulin replacement therapy.
-
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 (postmenarchal females must have a negative urine pregnancy test at Screening)
-
Hemoglobin (Hgb) <8.0 g/dL (80 g/L)
-
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.
-
Other investigational chemical agent within 30 days or other investigational biologic agent within 8 weeks or 5 half-lives (whichever is longer) of Screening.
-
Concurrent treatment with cyclophosphamide.
-
Participants currently on any type of dialysis, or who have received a solid organ transplant.
-
Prisoners or participants who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be allowed to participant in this study.
-
Taking both MMF/MPA and MTX.
-
Other investigational B cell depleting therapy as part of a clinical trial within 18 months of Screening, unless drug assignment is known and the participant received an anti-CD20 or CD19 drug.
-
Participants with active systemic infections who have received systemic antimicrobials within the 14 days prior to Screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCLA Medical Center: Division of Rheumatology | Los Angeles | California | United States | 90095 |
| 2 | Yale University School of Medicine: Rheumatology, Allergy & Immunology | New Haven | Connecticut | United States | 06519 |
| 3 | The Emory Clinic: Division of Rheumatology | Atlanta | Georgia | United States | 30322 |
| 4 | Massachusetts General Hospital: Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases | Boston | Massachusetts | United States | 02114 |
| 5 | Boston Children's Hospital: Department of Pediatrics, Rheumatology Program | Boston | Massachusetts | United States | 02115 |
| 6 | Brigham & Women's Hospital: Department of Medicine, Rheumatology, Immunology | Boston | Massachusetts | United States | 02115 |
| 7 | University of Michigan Health System: Department of Internal Medicine, Division of Rheumatology | Ann Arbor | Michigan | United States | 48109 |
| 8 | Washington University School of Medicine in St. Louis: Division of Rheumatology | Saint Louis | Missouri | United States | 63110 |
| 9 | Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases | Manhasset | New York | United States | 11030 |
| 10 | Feinstein Institute for Medical Research | Manhasset | New York | United States | 11030 |
| 11 | New York University Langone Medical Center: Department of Medicine, Division of Rheumatology | New York | New York | United States | 10016 |
| 12 | Columbia University Irving Medical Center: Department of Neurology, Multiple Sclerosis Center | New York | New York | United States | 10032 |
| 13 | University of Rochester Medical Center | Rochester | New York | United States | 14642 |
| 14 | Stony Brook University Hospital | Stony Brook | New York | United States | 11794-8111 |
| 15 | Duke University Medical Center: Division of Rheumatology and Immunology | Durham | North Carolina | United States | 27710 |
| 16 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 17 | Nationwide Children's Hopspital | Columbus | Ohio | United States | 43205 |
| 18 | Oklahoma Children's Hospital-Pediatrics Specialties Clinic | Oklahoma City | Oklahoma | United States | 73104 |
| 19 | Oklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program | Oklahoma City | Oklahoma | United States | 73104 |
| 20 | Temple Health: Rheumatology | Philadelphia | Pennsylvania | United States | 19104 |
| 21 | University of Pennsylvania Perelman Center for Advanced Medicine | Philadelphia | Pennsylvania | United States | 19104 |
| 22 | Medical University of South Carolina, Nexus Research Center | Charleston | South Carolina | United States | 29425 |
| 23 | Medical University of South Carolina, Shawn Jenkins Children's Hospital | Charleston | South Carolina | United States | 29425 |
| 24 | University of Texas Houston Medical School: Division of Rheumatology and Clinical Immunogenetics | Houston | Texas | United States | 77030 |
| 25 | Benaroya Research Institute at Virginia Mason: Internal Medicine | Seattle | Washington | United States | 98101 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Autoimmunity Centers of Excellence
- Rho Federal Systems Division, Inc.
Investigators
- Study Chair: Judith A. James, MD, PhD, Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation
- Study Chair: Meggan C. Mackay, MD, MS, Center of Autoimmune Musculoskeletal and Hematopoietic Diseases, Feinstein Institute for Medical Research
- Study Chair: Dinesh Khanna, MBBS, MSc, University of Michigan Health, Michigan Medicine
- Study Chair: Amit Bar-Or, MD, FRCP, Center for Neuroinflammation and Neurotherapeutics, Perelman School of Medicine, University of Pennsylvania
- 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 Documents (Full-Text)
None provided.More Information
Additional Information:
- Autoimmunity Centers of Excellence (ACE)
- National Institute of Allergy and Infectious Diseases (NIAID)
- Division of Allergy, Immunology, and Transplantation (DAIT)
Publications
None provided.- DAIT ACV01
- NIAID CRMS ID#: 38873