A Randomized Study to Evaluate Antibody Response to an Additional Dose of SARS-CoV-2 Vaccination With and Without Immunosuppression Reduction in Kidney and Liver Transplant Recipients
Phase: PHASE2
Conditions: Kidney Transplant Recipients, Liver Transplant Recipients
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)



COVID19-TB-03 
Confidential 
Page 2 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
NIAID Pharmaceutical Specialist  
 
 
 
 
 
  
 
 
Confidentiality Statement 
The information contained within this document is not to be disclosed in any way without the prior permission of the Division 
of Allergy, Immunology, and Transplantation, National Insitututes of Allergy and Infectious Diseases, National Institutes of 
Health. 
 
 
 
 
 

COVID19-TB-03 
Confidential 
Page 4 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
Protocol Synopsis 
Title 
A randomized study to evaluate antibody response to an additional dose of SARS-
CoV-2 vaccination with and without immunosuppression reduction in kidney and 
liver transplant recipients 
Short Title 
COVID Protection After Transplant-Immunosuppression Reduction (CPAT-ISR) 
Clinical Phase 
Phase 2 
Number of Sites 
15 U.S. Transplant Centers 
IND Sponsor/Number  
IND Exempt 
Study Objectives 
To elicit a more robust antibody response to vaccination against SARS-CoV-2 in 
kidney and liver transplant recipients who have had a suboptimal (≤2500 U/mL) 
response to a completed primary series of an mRNA COVID-19 vaccine.  
Study Design 
A randomized, open-label multi-site trial designed to induce an enhanced 
antibody response to SARS-CoV-2 in kidney and liver transplant recipients who 
have ≤ 2500 U/mL anti-spike antibody (as measured by the Roche Elecsys® anti-
SARS-CoV-2 S assay) after a minimum of three mRNA COVID-19 vaccine doses.  
Participants will be randomized to two 2 groups: Group One will undergo a 
temporary, prescribed reduction in their maintenance immunosuppressive 
regimen and receive a dose of mRNA-based COVID-19 vaccine while Group Two 
will receive a dose of mRNA-based COVID-19 vaccine with no change in their 
maintenance immunosuppressive regimen.  
Primary Endpoint(s) 
The primary endpoint is the -fold increase in antibody titer (using the Roche 
Elecsys® anti-SARS-CoV-2 S assay) from before receiving the study dose of vaccine 
to 30 days after the study dose.  
Safety, Secondary, and 
Exploratory Endpoint(s)  
Secondary Safety Endpoints:  
 
Local and systemic vaccine reactogenicity and/or allergy 
 
Serious adverse events occurring during the 30 days following the 
additional dose of vaccine 
 
Treated acute cell-mediated and/or antibody-mediated allograft 
rejection (clinical or biopsy-proven) within 60 days following the 
additional dose of vaccine 
 
Development of de novo donor-specific anti-HLA antibody within 90 days 
of the vaccine 
 
Graft loss within 60 days of the vaccine 
 
Death within 60 days of the vaccine 
Secondary Efficacy Endpoints:  
 
Duration of anti-SARS-CoV-2 S antibody titers and neutralizing capacity in 
the year following the additional dose of vaccine 

COVID19-TB-03 
Confidential 
Page 5 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
 
SARS-CoV-2 PCR positivity 
 
Symptomatic COVID-19 
 
COVID-19 requiring hospitalization 
 
Log SARS-CoV-2 antibody titer at 30 days post-vaccine 
 
Longitudinal changes in log SARS-CoV-2 antibody titer during the study 
Exploratory Mechanistic Endpoints: 
 
Anti-S1 and anti-RBD serology 
 
Detection of SARS-CoV-2 spike protein in blood after the additional dose 
of vaccine 
 
Additional serological panels and correlates of neutralizing antibody 
 
SARS-CoV-2 virology, diagnostics, and sequencing, including novel 
variants of concern  
 
Oral fluid anti-N and anti-S immunoglobulin levels (IgA (total and 
secretory), IgM, IgG) 
 
Antigen-specific B cell response  
 
Antigen-specific T cell response 
 
Evidence of immune activation, transcriptomics and cytokine signaling 
 
Durability of de novo donor-specific anti-HLA antibody 
Accrual Objective 
400 transplant kidney and liver transplant recipients with negative or low (≤ 2500 
U/mL) antibody titers using the Roche Elecsysâ anti-SARS-CoV-2 S assay after an 
authorized or licensed mRNA based anti-COVID-19 vaccination regimen.  
Study Duration 
Accrual: 4 months 
Screening, Vaccination and Follow-up: 13 months 
Total Duration: 17 months 
Treatment Description  
Participants will be randomized to an additional dose of COVID-19 vaccine only 
OR immunosuppression (IS) reduction plus an additional dose of COVID-19 
vaccine. IS reduction will be based on the participant’s IS regimen upon study 
entry, as described in Section 6.3.  
Inclusion Criteria 
Individuals must meet all the following criteria to be eligible: 
1. 
Able to understand and provide informed consent.  
2. 
Individual ³ 18 years of age.  
3. 
Recipient of a kidney or liver transplant ³12 months prior to enrollment, 
without allograft rejection in the 6 months preceding enrollment. 
4. 
Negative for anti-donor HLA antibodies at screening (central lab). 
5. 
Currently taking one of the following tacrolimus-based immunosuppressive 
regimens: 
 
Tacrolimus plus MMF or MPA, with or without a corticosteroid 
 
Tacrolimus with trough level ³ 5 ng/mL , with or without ≤ 5 mg of 
prednisone or equivalent 
6. 
Received a minimum of 3 doses of either the Moderna COVID-19 vaccine or 
Pfizer-BioNTech COVID-19 vaccine. 

COVID19-TB-03 
Confidential 
Page 6 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
7. 
Participant must be ³ 60 days after completion of primary vaccination or 
receipt of the most recent booster dose with any authorized or approved 
monovalent or bivalent COVID-19 vaccine at the time of study vaccine. 
8. 
Serum antibody negative or low (titer ≤ 2500 U/mL) at ³ 30 days from the 
last dose of mRNA COVID-19 vaccine and ³ 30 days following receipt of a 
monoclonal antibody product or convalescent plasma for COVID-19, 
measured using the Roche Elecsys® anti-SARS-CoV-2 S assay.  
9. 
Participant’s transplant physician must confirm the participant’s eligibility 
based on medical history and concur with the plan for immunosuppression 
modification.  
Exclusion Criteria 
 
Individuals who meet any of the following criteria will not be eligible: 
1. 
Currently on an IS regimen different from the two regimens described in the 
Inclusion Criteria, for example (but not limited to) those including sirolimus, 
everolimus, belatacept, or azathioprine. 
2. 
Recipient of any allograft other than a kidney or liver. 
3. 
Participant is pregnant. 
4. 
Any past history of Donor Specific Antibody (DSA) by local site standards. 
5. 
Currently taking any systemic immunosuppressive agent, other than their 
prescribed transplant immunosuppression. 
6. 
Known history of severe allergic reaction to any component of an authorized 
or licensed COVID-19 vaccine.  
7. 
Thrombotic events, myocarditis, or pericarditis temporally associated with a 
prior dose of COVID-19 vaccine. 
8. 
History of heparin-induced thrombocytopenia. 
9. 
Any change in transplant immunosuppression regimen (drug or dose) in 
response to suspected or proven rejection within the last 6 months.  
10. Significant graft dysfunction (see study definitions).  
11. Receipt of any cellular depleting agent (e.g. ATG, rituximab, alemtuzumab, 
Cyclophosphamide) within 12 months preceding enrollment.  
12. Concurrent autoimmune disease at risk for exacerbation with 
immunosuppression reduction.  
13. Any untreated active infection including BK viremia >104 copies. 
14. Infection with HIV. 
15. Recent (within one year) or ongoing treatment for malignancy with the 
exception of (1) non-melanomatous skin cancer definitively treated by local 
therapy, and (2) definitively treated carcinoma-in-situ of the cervix (Stage 0 
cervical cancer)  
16. Receipt of a monoclonal antibody product or convalescent plasma within the 
last 30 days. 
17. Any past or current medical problems, treatments, or findings which, in the 
opinion of the investigator, may pose additional risks from participation in 
the study, may interfere with the candidate’s ability to comply with study 
requirements or may impact the quality or interpretation of the data 
obtained from the study. 

COVID19-TB-03 
Confidential 
Page 7 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
Pausing Rules 
Pausing rules will include: 
If the following occur, relevant study interventions will be temporarily halted 
pending a DSMB review and recommendation as to whether the study may 
proceed. 
1. 
Any Grade 4 or 5 event that is definitely or possibly attributed to the study 
dose of vaccine or to immunosuppression reduction. 
2. 
Any probable or confirmed case of either acute myocarditis or acute 
pericarditis that occurs within 6 weeks of the study vaccine.  
3. 
Excess incidence of acute rejection (clinically treated or biopsy-proven).  
4. 
Excess incidence of graft loss.  
5. 
Excess mortality. 
See Section 11.5 for further details and specific event rates triggering a pause in 
enrollment.  
 
 
 

COVID19-TB-03 
Confidential 
Page 8 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
 
Table of Contents 
Protocol Synopsis .............................................................................................................................................. 4 
Glossary of Abbreviations ................................................................................................................................ 14 
Study Definitions Page ..................................................................................................................................... 15 
1. 
Background and Rationale ....................................................................................................................... 17 
1.1 
Background and Scientific Rationale ................................................................................... 17 
1.2 
Preclinical Experience .......................................................................................................... 18 
1.3 
Clinical Studies ..................................................................................................................... 18 
2. 
Study Hypotheses/Objectives ................................................................................................................. 21 
2.1 
Hypotheses .......................................................................................................................... 21 
2.2 
Primary Objective(s) ............................................................................................................ 21 
2.3 
Secondary Safety Objective(s) ............................................................................................. 21 
2.4 
Secondary Efficacy Objectives ............................................................................................. 21 
2.5 
Secondary Immunogenicity Objectives ............................................................................... 21 
2.6 
Exploratory Objectives ......................................................................................................... 21 
3. 
Study Design ............................................................................................................................................ 23 
3.1 
Description of Study Design ................................................................................................. 23 
3.2 
Primary Endpoint ................................................................................................................. 23 
3.3 
Secondary Endpoints ........................................................................................................... 23 
3.3.1 
Secondary Safety Endpoints ................................................................................................ 24 
3.3.2 
Secondary Efficacy Endpoints .............................................................................................. 24 
3.3.3 
Exploratory Endpoints ......................................................................................................... 24 
3.4 
Stratification, Randomization, and Blinding/Masking ......................................................... 24 
4. 
Selection of Participants and Clinical Sites/Laboratories ........................................................................ 25 
4.1 
Rationale for Study Population ............................................................................................ 25 
4.2 
Inclusion Criteria .................................................................................................................. 25 
4.3 
Exclusion Criteria ................................................................................................................. 25 
4.4 
Selection of Clinical Sites ..................................................................................................... 26 
5. 
Known and Potential Risks and Benefits to Participants ......................................................................... 27 
5.1  
Risks of the Investigational Products as cited in the Full FDA EUA Prescribing Information
 
27 

COVID19-TB-03 
Confidential 
Page 9 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
5.1.1 
Risks of Moderna COVID-19 Vaccine (includes original, bivalent, and 2023-2024 formula)27 
5.1.2 
Risks of Pfizer-BioNTech COVID-19 Vaccine (includes original, bivalent, and 2023-2024 
formula) 
27 
5.2 
Risks of Moderna COVID-19 Vaccine and Pfizer-BioNTech Vaccine in adults as cited in 
Medical Literature (includes original, bivalent, and 2023-2024 formulas) ................................................. 27 
5.3 
Risks Associated with IS Reduction ...................................................................................... 28 
5.4 
Potential Risks to Study Population ..................................................................................... 28 
5.5 
Risks of Other Protocol Specified Medications .................................................................... 28 
5.6 
Risks of Study Procedures .................................................................................................... 28 
5.6.1 
Risk of Blood Draw ............................................................................................................... 28 
5.6.2 
Risks Associated with Nasal Mid-Turbinate Swab Collection .............................................. 28 
5.6.3 
Risks Associated with Oral Fluid Collection ......................................................................... 28 
5.6.4 
Risk of Internet Based Data Collection ................................................................................ 29 
5.7 
Potential Benefits ................................................................................................................ 29 
6. 
Investigational Agents ............................................................................................................................. 30 
6.1 
Investigational Agent #1: Moderna COVID-19 Monovalent Vaccine (Protocol v1.0-5.0) .... 30 
6.2 
Investigational Agent #2: Pfizer-BioNTech COVID-19 Monovalent Vaccine (Protocol v1.0-
5.0) 
30 
6.3 
Investigational Product #3: Moderna Bivalent COVID-19 Vaccine (Protocol v6.0-7.0) ....... 30 
6.4 
Investigational Product #4: Pfizer-BioNTech Bivalent COVID-19 Vaccine (Protocol v6.0-7.0)
 
30 
6.5 
Investigational Product #5: Moderna COVID-19 Vaccine, SpikevaxÒ 2023-2024 Formula 
(Protocol v8.0 and beyond) ......................................................................................................................... 30 
6.5.1 
Formulation, Packaging, and Labelling ................................................................................ 30 
6.5.2 
Dosage, Preparation, and Administration ........................................................................... 30 
6.6 
Investigational Product #4: Pfizer-BioNTech COVID-19 Vaccine, ComirnatyÒ 2023-2024 
Formula (Protocol v8.0 and beyond) ........................................................................................................... 31 
6.6.1 
Formulation, Packaging, and Labelling ................................................................................ 31 
6.6.2 
Dosage, Preparation, and Administration ........................................................................... 31 
6.7 
Immunosuppression Reduction ........................................................................................... 31 
6.7.1 
Immunosuppression (IS) Reduction ..................................................................................... 31 
6.8 
Drug Accountability ............................................................................................................. 32 
6.9 
Assessment of Participant Compliance with Investigational Agent ..................................... 32 
6.10 
Toxicity Prevention and Management ................................................................................. 32 

COVID19-TB-03 
Confidential 
Page 10 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
6.11 
Premature Discontinuation of Investigational Agent .......................................................... 32 
6.12 
Premature Discontinuation of IS Reduction ........................................................................ 32 
7. 
Other Medications ................................................................................................................................... 34 
7.1 
Concomitant Medications ................................................................................................... 34 
7.1.1 
Protocol-mandated .............................................................................................................. 34 
7.1.2 
Other permitted concomitant medications ......................................................................... 34 
7.2 
Prophylactic Medications .................................................................................................... 34 
7.3 
Pre-Exposure Prophylaxis or Treatment of COVID-19 Infection .......................................... 34 
7.4 
COVID-19 Vaccine Booster Doses ........................................................................................ 34 
7.5 
Rescue Medications ............................................................................................................. 34 
8. 
Study Procedures .................................................................................................................................... 35 
8.1 
Enrollment ........................................................................................................................... 35 
8.2 
Screening Period .................................................................................................................. 35 
8.3 
Study Visits or Study Assessments ....................................................................................... 35 
8.3.1 
Day -5 (IS Reduction Arm) .................................................................................................... 35 
8.3.2 
Vaccination Visit: Day 0 (All Participants) ............................................................................ 35 
8.3.3 
Follow-up Visits (All Participants) ........................................................................................ 36 
8.4 
Unscheduled Visits ............................................................................................................... 36 
8.5 
Suspected or Confirmed Myocarditis or Pericarditis ........................................................... 36 
8.6 
Suspected or Confirmed Cases of COVID-19 Infection ........................................................ 37 
8.7 
Visit Windows ...................................................................................................................... 37 
9. 
Mechanistic Assays .................................................................................................................................. 38 
9.1 
Introduction ......................................................................................................................... 38 
9.2 
Objective 1: To quantify spike protein production in serum or plasma after vaccination. . 39 
9.3 
Objective 2: To provide a detailed kinetic characterization of the vaccine-induced antibody 
repertoire (specificity, isotype, titer, neutralization capacity). ................................................................... 39 
9.4 
Objective 3: To perform a kinetic phenotypic and functional analysis of antigen-specific 
Bmem (frequency, antigen specificity, surface markers, metabolomics, gene expression patterns, single 
cell sequencing) and PC. .............................................................................................................................. 39 
9.5 
Objective 4: To perform a kinetic, analysis of antigen-specific CD4+ and CD8+ T cells 
(frequency, epitope specificity, surface markers, metabolomics, gene expression patterns single cell 
sequencing). 
39 
9.6 
Objective 5: To assess phenotypic, functional and gene expression patterns of innate 
immune DC, monocyte/macrophage and NK cell subsets in peripheral blood. .......................................... 40 

COVID19-TB-03 
Confidential 
Page 11 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
9.7 
Objective 6: Exploration of molecular biomarkers of early responders to vaccination ...... 40 
10. 
Biospecimen Storage ........................................................................................................................... 41 
11. 
Criteria for Participant and Study Completion and Premature Study Termination ............................. 42 
11.1 
Participant Completion ........................................................................................................ 42 
11.2 
Participant Stopping Rules and Withdrawal Criteria ........................................................... 42 
11.3 
Participant Replacement ..................................................................................................... 42 
11.4 
Follow-up after Early Study Withdrawal .............................................................................. 42 
11.5 
Study Pausing Rules ............................................................................................................. 42 
12. 
Safety Monitoring and Reporting ........................................................................................................ 45 
12.1 
Overview .............................................................................................................................. 45 
12.2 
Definitions ........................................................................................................................... 45 
12.2.1 
Adverse Event (AE) .............................................................................................................. 45 
12.2.2 
Solicited Adverse Events ...................................................................................................... 45 
12.2.3 
Unsolicited Adverse Events ................................................................................................. 46 
12.2.4 
Adverse Events of Special Interest (AESI) ............................................................................ 46 
12.2.5 
Suspected Adverse Reaction (SAR) ...................................................................................... 46 
12.2.6 
Unexpected Adverse Event .................................................................................................. 46 
12.2.7 
Serious Adverse Event (SAE) ................................................................................................ 46 
12.3 
Grading and Attribution of Adverse Events ......................................................................... 47 
12.3.1 
Grading Criteria ................................................................................................................... 47 
12.3.2 
Attribution Definitions ......................................................................................................... 48 
12.4 
Collection and Recording of Adverse Events ....................................................................... 48 
12.4.1 
Collection Period ................................................................................................................. 48 
12.4.2 
Collecting Adverse Events .................................................................................................... 49 
12.4.3 
Recording Adverse Events ................................................................................................... 49 
12.5 
Reporting of Serious Adverse Events and Adverse Events .................................................. 49 
12.5.1 
Reporting of Serious Adverse Events to DAIT/NIAID ........................................................... 49 
12.5.2 
Reporting of Adverse Events to IRBs/IECs ........................................................................... 50 
12.5.3 
Mandatory reporting to Vaccine Adverse Event Reporting System .................................... 50 
12.6 
Reporting of Other Safety Information ................................................................................ 50 
12.7 
Review of Safety Information .............................................................................................. 50 
12.7.1 
Medical Monitor Review ..................................................................................................... 50 

COVID19-TB-03 
Confidential 
Page 12 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
12.7.2 
DSMB Review ....................................................................................................................... 50 
12.7.2.1 
Planned DSMB Reviews ....................................................................................................... 50 
12.7.2.2 
Ad hoc DSMB Reviews ......................................................................................................... 50 
12.7.2.2.1 
Temporary Suspension of enrollment for ad hoc DSMB Safety Review .............................. 51 
13. 
Statistical Considerations and Analytical Plan ..................................................................................... 52 
13.1 
Overview .............................................................................................................................. 52 
13.2 
Endpoints/Outcomes ........................................................................................................... 52 
13.3 
Measures to Minimize Bias .................................................................................................. 52 
13.4 
Analysis Plan ........................................................................................................................ 52 
13.4.1 
Analysis Populations. ........................................................................................................... 52 
13.4.2 
Primary Analysis of Primary Endpoint(s)/Outcome(s) ......................................................... 52 
13.4.3 
Analyses of Secondary and Other Endpoint(s)/Outcome(s) ................................................ 52 
13.4.4 
Analyses of Exploratory Objectives ..................................................................................... 53 
13.4.5 
Descriptive Analyses ............................................................................................................ 53 
13.5 
Interim Analyses .................................................................................................................. 53 
13.5.1 
Interim Analysis of Efficacy Data ......................................................................................... 53 
13.5.2 
Interim Analysis of Safety Data ............................................................................................ 53 
13.6 
Statistical Hypotheses .......................................................................................................... 53 
13.7 
Sample Size Considerations ................................................................................................. 53 
14. 
Identification and Access to Source Data ............................................................................................ 55 
14.1 
Source Data ......................................................................................................................... 55 
14.2 
Access to Source Data .......................................................................................................... 55 
15. 
Quality Assurance and Quality Control ............................................................................................... 56 
16. 
Protocol Deviations ............................................................................................................................. 57 
16.1 
Protocol Deviation Definitions ............................................................................................. 57 
16.2 
Reporting and Managing Protocol Deviations ..................................................................... 57 
17. 
Ethical Considerations and Compliance with Good Clinical Practice ................................................... 58 
17.1 
Statement of Compliance .................................................................................................... 58 
17.2 
Informed Consent Process ................................................................................................... 58 
17.3 
Privacy and Confidentiality .................................................................................................. 58 
18. 
Publication Policy ................................................................................................................................ 59 
19. 
References ........................................................................................................................................... 60 

COVID19-TB-03 
Confidential 
Page 13 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
Appendix 1: Screening (All Participants) ......................................................................................................... 65 
Appendix 2: Schedule of Events (COVID-19 Vaccine Dose Alone) ................................................................... 66 
Appendix 3: Schedule of Events (IS Reduction plus COVID-19 Vaccine Dose) ................................................. 67 
 

COVID19-TB-03 
Confidential 
Page 14 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
Glossary of Abbreviations 
ATG 
Anti-thymocyte globulin  
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DAIT 
Division of Allergy, Immunology, and Transplantation 
dnDSA 
De novo Donor Specific Antibody 
DSA 
Donor Specific Antibody 
EUA 
Emergency Use Authorization  
DSMB 
Data Safety Monitoring Board 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonization 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IS  
Immunosuppression  
MOP 
Manual of Procedures 
NIAID 
National Institute of Allergy and Infectious Diseases 
PI 
Principal Investigator 
PrEP 
Pre-Exposure Prophylaxis 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAR 
Suspected Adverse Reaction 
SOP 
Standard Operating Procedure 
SOT 
Solid Organ Transplant 
SUSAR 
Serious Unexpected Suspected Adverse Reaction 
ULN 
Upper Limit of Normal  
 

COVID19-TB-03 
Confidential 
Page 15 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
Study Definitions Page  
Acute Rejection  
Acute Cell-Mediated Rejection, Biopsy Proven: Rejection (including 
borderline) graded according to 2019 Banff Criteria. 
Antibody-Mediated Rejection: A clinical and histologic event that meets the 
Banff 2019 criteria for antibody mediated rejection. 
Clinically Diagnosed and Treated Rejection: Any clinical event, with or without 
supporting evidence from a biopsy, which the treating physician diagnoses as 
“rejection” AND for which the patient is treated with steroids, lytic therapy, or 
an increase in dose or number of immunosuppressive medications. 
Acute Myocarditis / Acute 
Pericarditis 
Myocarditis is inflammation of the heart muscle. Pericarditis is inflammation of 
the lining outside the heart. In this study, the definition of suspected or 
confirmed acute myocarditis or acute pericarditis is the Centers for Disease 
Control and Prevention (CDC) case definition criteria: 
https://www.cdc.gov/mmwr/volumes/70/wr/mm7027e2.htm 
Basic Metabolic Panel  
Includes sodium, potassium, chloride, carbon dioxide (CO2) total, blood urea 
nitrogen, creatinine, glucose, calcium, anion gap and BUN/creatinine ratio. 
Comprehensive Metabolic 
Panel  
Includes sodium, potassium, chloride, carbon dioxide (CO2) total, blood urea 
nitrogen, creatinine, glucose, calcium, total protein, albumin, total bilirubin, 
alkaline phosphatase (Alk Phos), aspartate aminotransferase (AST), alanine 
aminotransferase (ALT), anion gap, BUN/creatinine ratio, and AST/ALT ratio. 
Donor Specific Antibodies 
(DSA) 
Antibodies directed at donor human leukocyte antigens (HLA) by central lab 
assessment.  
Graft Failure  
Kidney: Any of the following events: renal dialysis of more than 3 months 
duration; listing for re-transplantation; death from kidney failure. 
Liver: Re-listing for transplantation or death from liver failure.  
IS Reduction Failure 
Participant resumes baseline IS per the criteria outlined in Section 6.7 
Premature Discontinuation of IS Reduction but does not receive definitive 
treatment for rejection e.g. thymoglobulin, steroids, or a sustained increase in 
dose or number of immunosuppressive medications. 
Lost to Follow-up 
Missing primary endpoint assessment and/or final study visit.   
Medical Monitor 
The physician who is responsible for Sponsor oversight of safety aspects of the 
trial. The medical monitor will determine the attribution of Serious Adverse 
Events after considering all investigator input.  
Significant Graft 
Dysfunction for Study 
Eligibility  
Kidney: eGFR <35mL/min/1.73m2. 
Liver: INR >ULN (in patients not on anticoagulation), direct bilirubin >1. 
Negative or indeterminate 
Antibody Titer 
A measurement of <0.8 U/mL using the Roche Elecsys® anti-SARS-CoV-2 S 
assay. 

COVID19-TB-03 
Confidential 
Page 16 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
NIAID Project Manager 
NIAID assigned project manager who is responsible for all day to day 
administrative protocol-related issues, including version control, consent 
review, etc. 
Principal Investigator 
The physician responsible for supervising the conduct of the 
clinical investigation and for protecting the rights, safety, and welfare of 
participants consistent with 21 CFR Part 312. 
Participant Premature 
Termination  
Participants who are lost to follow up, withdraw consent, or die during the 
study. Data and specimens will no longer be expected from participants who 
are terminated from the study. 
Program Officer 
NIAID official who oversees the programmatic and budgetary aspects of the 
grant. 
Protocol Mandated 
Procedures 
A procedure or intervention that is a study requirement at the specified time 
point in the protocol. 
Regulatory Affairs Officer 
NIAID-assigned officer responsible for regulatory aspects of the study. 
Site Principal Investigator 
Lead investigator listed on the Investigator of Record Agreement at a particular 
clinical site who is responsible for the conduct of the study at that site. 
Investigational Product 
The investigational product is an additional dose of the Moderna or Pfizer-
BioNTech COVID-19 vaccine 
Immunosuppression 
Reduction 
Protocol-mandated reduction in immunosuppression, determined by the 
participant’s baseline regimen. See Section 6.3. 

COVID19-TB-03 
Confidential 
Page 17 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
1. 
Background and Rationale  
1.1 
Background and Scientific Rationale 
COVID-19 disproportionately affects vulnerable populations, including those with impaired immune 
defenses. Organ transplant recipients are particularly at risk as a result of both the need for life-long 
immunosuppressive therapy to prevent rejection and a high prevalence of other risk factors for severe 
COVID-19 including cardiovascular disease, hypertension, and diabetes. The consequences of COVID-19 are 
severe in organ transplant recipients; in one study of a large (n=482) cohort of patients who had a 
confirmed diagnosis of COVID-19 by polymerase chain reaction, 78% were hospitalized, and of those, 39% 
required ICU care and 31% required mechanical ventilation. Mortality at 28 days from diagnosis was 17.8% 
overall and 20.5% among those who were hospitalized. Risk factors for mortality included age >65 years, 
congestive heart failure, chronic lung disease and obesity.1-5  
SARS-CoV-2 vaccines are highly immunogenic and effective in the general population. Transplant recipients 
were excluded from landmark trials, but it has become evident during the post-Emergency Use 
Authorization (EUA) experience that the response to vaccination is substantially lower among organ 
transplant recipients as compared to the general population: in a survey of 436 transplant recipients who 
had received two doses of either the Moderna COVID-19 vaccine or the Pfizer-BioNTech COVID-19 Vaccine, 
a positive anti-SARS-CoV-2 S response was detectable in only 17% after the first dose and 30-60% after two 
doses in multiple studies. Associations with suboptimal vaccine response include treatment with 
antimetabolite therapies such as mycophenolate or azathioprine, which are known to impair lymphocyte 
function and response to new antigens (such as influenza vaccination).10-14 
It is critical to understand risk stratification for vaccine failure given mounting reports of serious 
breakthrough infections in fully vaccinated SOT recipients.35 Persistent knowledge gaps include 
characterization of humoral vaccine responses (e.g., level and durability of neutralizing antibody, including 
versus novel variants), B cell memory responses, and antigen-specific T cell responses in transplant 
recipients.15,16 Strategies to improve vaccine response to viral antigens in immunocompromised persons are 
largely based on experiences with influenza and hepatitis B vaccines; these include administration of 
additional vaccinations, higher antigen dosing, and mixing of vaccine platforms such as those containing 
immunostimulatory adjuvants.17,18 Development of a strategy for eliciting an antibody response to COVID-
19 vaccines in transplant recipients is complex as the pharmacologic immunosuppression that prevents 
response to the vaccine also prevents rejection of a life-sustaining allograft. Potential interventions include 
administration of an additional dose of vaccine; alternate vaccine strategies including higher doses of 
vaccine or the use of adjuvanted vaccines; and, most high risk, transient modification of a patient’s 
immunosuppressive regimen before and after vaccine administration. A decision algorithm for an individual 
patient must consider the likelihood of success of a low risk intervention (i.e. a third dose of vaccine), the 
type of transplant (e.g. kidney, heart or lung), the likelihood and consequences of allograft rejection if the 
patient’s immunosuppressive regimen is modified (e.g. the low likelihood of permanent injury after an 
episode of liver rejection versus the high likelihood of permanent injury after an episode of lung rejection), 
and the individual’s risk for severe disease or death from COVID-19 if they remain without antibody 
protection. 

COVID19-TB-03 
Confidential 
Page 18 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
This study will investigate the effect of an additional dose of either the Moderna or Pfizer-BioNTech COVID-
19 vaccine, with or without a reduction in immunosuppression, in participants who demonstrate a negative 
or low (≤ 2500 U/mL) anti-RBD titer after a completed mRNA COVID-19 vaccine series. Response will be 
assessed using the Roche Elecsys® anti-SARS-CoV-2 S assay which has an approximate 1:1 conversion to 
World Health Organization binding antibody units (BAU) Anti-S1/RBD levels are well correlated with 
neutralizing antibody against SARS-CoV-2 and with vaccine sero-protection in the general population.37,38 
The precise cutoff that connotes protection from infection is not established for immunocompromised 
persons. Early studies, however, indicated anti-S1/RBD levels of 15-144 BAU40 are correlated with live virus 
neutralization of ancestral variants in convalescent persons. Subsequent analyses of vaccine efficacy across 
trials indicated a level 2-4-fold higher for vaccine-evoked neutralization (compared to convalescents) best 
correlates with vaccine efficacy.41 Consistent with this, several studies in transplant recipients have 
suggested anti-S1/RBD levels of 100-250 BAU after vaccination as associated with in vitro neutralization; 
below this level, neutralizing capacity against SARS-CoV-2 variants is not reliable and suggests higher risk of 
infection. Notably, variants of concern, particularly the Omicron variant and its sublineages demonstrate 
significant immune evasion and need for 10-20-fold higher levels of antibody to neutralize than required for 
ancestral variants.52-55 Version 6.0 of the protocol increases the SARS-CoV-2 S titer for eligibility from 250 
U/mL to 2500 U/mL to account for the findings that suggest the antibody levels needed to neutralize 
Omicron are significantly higher.58 
Rationale for Selection of Investigational Product or Intervention 
This study will utilize the mRNA-based Moderna and Pfizer-BioNTech COVID-19 Vaccines and will enroll 
kidney or liver recipients who demonstrate a persistently low anti-SARS-CoV-2 S titer after completing at 
least three doses of an mRNA based primary vaccine series for immunocompromised patients. Participants 
will receive a dose of COVID-19 vaccine, with or without concurrent reduction of their transplant 
immunosuppression regimen. These vaccines have been shown to be safe and highly immunogenic in the 
general population, with publication of large Phase III trials data supporting FDA EUA and/or licensure.19,20 
The additional dose of vaccine was chosen due to demonstrated safety of the authorized or licensed 
COVID-19 vaccines and experience with the efficacy of additional dosing strategies of other vaccines (e.g., 
hepatitis and influenza vaccines)17,18 in immunocompromised people.21-23 
1.2 
Preclinical Experience 
Studies performed in murine models in the 1970s and 1980s showed that the repeated immunization of up 
to 4 doses continues to have a positive impact on the titer, isotype, and affinity of the induced antibody 
responses.24,25 Similarly, preclinical murine data indicate that immunization schedules that include third 
doses markedly increase the frequency and functional properties of antigen specific T cell immune 
responses.26 
There are no specific preclinical studies addressing whether and how these effects of immunization 
schedule on vaccine-induced immunity are affected by the immunosuppressant medications used in 
transplantation. 
1.3 
Clinical Studies 
The Moderna and Pfizer-BioNTech COVID-19 Vaccines are known to have excellent immunogenicity in the 
general adult population, even against some of the recently identified SARS-CoV-2 variants.27,28 These 

COVID19-TB-03 
Confidential 
Page 19 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
vaccines are well-tolerated, with mostly mild-to-moderate local and systemic reactogenicity that is more 
pronounced after the second dose.29,30 However, organ transplant recipients have recently been shown to 
have much less reliable and robust responses to these vaccines.10,12 In a large (N=658) prospective cohort 
study of U.S. transplant recipients, only 15% of patients had a positive anti-SARS-CoV-2 S response after a 
first dose of either the Moderna or the Pfizer vaccine, with improvement to only 54% by four weeks after 
the second dose of vaccine. Patients who had a positive response after the first dose of vaccine had higher 
titers of anti-SARS-CoV-2 S after dose two as compared with those who had a negative or indeterminate 
response after dose one but did have a measurable response after dose two. In those with a positive anti-
SARS-CoV-2 S response after dose two, antibody levels were substantially lower than in immunocompetent 
vaccine recipients. Associations with lack of vaccine response included older age, use of antimetabolite 
therapies, history of kidney transplantation (versus other organ transplant), more recent transplantation, 
and receipt of the Pfizer-BioNTech vaccine (versus the Moderna mRNA-1273 vaccine). In a study of 101 
kidney transplant recipients maintained on belatacept-based immunosuppression, only 6% of patients had 
measurable anti-SARS-CoV-2 S after 2 doses of the Pfizer-BioNTech vaccine. In that study, SARS-CoV-2-
specific T-cell responses by EliSpot were present in 30% of those tested (N=23) after two doses of vaccine.15 
Several observational series and one randomized trial have evaluated antibody response to a third dose of 
SARS-CoV-2 vaccination in solid organ transplant (SOT) recipients, predominately following a third mRNA 
vaccination, using a variety of anti-spike antibody assays.42-46  
In observational series focusing on those with negative antibody levels after a two-dose mRNA series, 
seroconversion rates were 27-44%, generally to lower titers. Additionally, preliminary data from Johns 
Hopkins indicate that fully one third of SOT recipients who receive a third vaccine dose continue to 
demonstrate zero neutralizing antibody versus the delta variant.47 In contrast, among those with low, but 
detectable antibody after a two-dose series, seroconversion rates above threshold were 80-100% and to a 
level approximately 5-fold higher than that observed in seronegative participants.42-45 Notably, one cohort 
series of patients on maintenance belatacept therapy showed poor seroconversion rates after a third 
mRNA dose (increasing from 6% to 37%), noting a 5% clinical COVID-19 breakthrough rate with 50% 
mortality.  
In the randomized trial of a third dose of Moderna vaccine given to 60 SOT recipients (20 kidney recipients), 
irrespective of anti-RBD antibody level, median fold-change in anti-RBD antibody level of approximately 40x 
in the vaccination group, and 75x higher than seen in the placebo group (median post intervention level 
314 vs 1.2 u/mL). Additionally, surrogate plasma neutralization capacity versus “wildtype”/vaccine strain 
SARS-CoV-2 increased from 37% at baseline to 60% after a third dose. SARS-CoV-2-specific, polyfunctional 
CD4 and CD8 T cell responses were assessed via intracellular cytokine staining (IFN-y and IL-2) in a subset of 
patients demonstrating higher median counts (432 vs 67 cells/106 CD4+ T cells).45 In this trial, however, 
<20% of participants had any neutralizing capacity versus the Omicron variant following a third dose. This 
emphasizes the need to increase peak binding antibody responses in vulnerable transplant recipients, 
including those with low-level, positive antibody after standard vaccination series, in an effort to reduce the 
risk period for infection during expected antibody wane.56,57 
Reassuringly, in these collective series with limited follow up, reactogenicity was similar after a third dose 
as that described in two-dose mRNA series, with no serious or medically-attended adverse events reported. 

COVID19-TB-03 
Confidential 
Page 20 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
One case of mild rejection was noted in a heart transplant recipient after a third dose of Pfizer-BioNTech 
vaccine (negative DSA), uncertain if related to vaccination.42-46 
Given a significant subset of SOT recipients, particularly kidney recipients on multiple immunosuppressive 
agents, maintain negative or low sero-response after three vaccine doses, alternative strategies to augment 
immune response are needed. In particular, temporary immunosuppressive reduction peri-vaccination, 
particularly of anti-metabolite medications, is attractive potential intervention for those with low 
alloimmune risk. In persons with autoimmune disease, temporary hold of immunosuppressives does 
increase vaccine responses;48,49 this approach is currently recommended by the American College of 
Rheumatology surrounding COVID-19 vaccination in select persons.50 It is not known, however, the degree 
to which short-term immunosuppressive reduction will improve sero-response in transplant recipients and 
whether it is associated with events such as rise in donor-specific antibody or rejection. In light of the above 
data, withholding mycophenolate mofetil around the time of Pfizer-BioNTech COVID-19 vaccination is 
actively being pursued in the randomized trial setting by international investigators.51  

COVID19-TB-03 
Confidential 
Page 21 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
2. 
Study Hypotheses/Objectives  
2.1 
Hypotheses 
 
Kidney and liver transplant recipients who had a negative or low (≤ 2500 U/mL) anti-SARS-CoV-2 S 
response (using the Roche Elecsys® assay) to a completed primary series of the Moderna COVID-19 
Vaccine or the Pfizer-BioNTech COVID-19 Vaccine will develop an enhanced SARS-CoV-2 antibody 
response after receiving a dose of study vaccine, with or without reduction of their maintenance 
transplant immunosuppression regimen.  
 
Temporary reduction of maintenance immunosuppression as directed in this protocol will result in 
higher fold increase in antibody titer than achieved in those who do not have IS reduction, without 
an increased risk of alloimmune events (rejection or development of dnDSA). 
2.2 
Primary Objective(s) 
The primary objective of this study is to elicit a more robust anti-SARS-CoV-2 S level in kidney and liver 
transplant recipients who had an undetectable or low (≤ 2500 U/mL) level of antibody after completing a 
primary series of mRNA COVID-19 vaccine. Antibody titers in response to the study dose of vaccine will be 
evaluated 30 days following vaccine administration and will be measured using the Roche Elecsysâ anti-
SARS-CoV-2 S. All participants with measurable SARS-CoV-2 antibody titers will also have neutralizing 
antibody titers and further quantification and characterization of antibody using the best available assay(s).  
2.3 
Secondary Safety Objective(s)  
 
To determine the incidence of adverse events (AEs) and serious adverse events (SAEs), including 
reactogenicity, following the additional dose of vaccine.  
 
To determine the incidence of alloimmune events (e.g., allograft rejection and development of de 
novo DSA) following the immunosuppression reduction and/or the additional dose of vaccine.  
2.4 
Secondary Efficacy Objectives 
 
To determine the incidence of symptomatic or asymptomatic SARS-CoV-2 infection in the 12 
months following the additional dose of vaccine.  
2.5 
Secondary Immunogenicity Objectives  
 
To assess whether responses to additional doses of COVID-19 vaccine are improved by temporary 
reduction or withholding of immunosuppressive medications around the time of vaccine. 
 
To assess whether response to an additional dose of COVID-19 vaccine is associated with clinical 
phenotype (e.g., age, organ type, time post-transplant, immunosuppressive regimen).  
 
To evaluate durability of response over 1-year in those who have an antibody response to the 
additional dose of vaccine.  
2.6 
Exploratory Objectives 
 
To identify immunologic correlates of vaccine response.  
 
To evaluate immune activation in response to the vaccine.  
 
To assess whether timing between vaccine doses is associated with differential antibody response 
to vaccination. 

COVID19-TB-03 
Confidential 
Page 22 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
 
To assess whether there is a difference in antibody levels among those receiving additional doses of 
Pfizer versus Moderna vaccination. 

COVID19-TB-03 
Confidential 
Page 24 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
3.3.1 
Secondary Safety Endpoints  
 
Local and systemic vaccine reactogenicity and/or allergy 
 
Serious adverse events occurring during the 30 days following the additional dose of vaccine 
 
Treated acute cell-mediated and/or antibody-mediated allograft rejection (clinical or biopsy-
proven) within 60 days following the additional dose of vaccine 
 
Development of de novo donor-specific anti-HLA antibody within 90 days of the vaccine 
 
Graft loss within 60 days of the vaccine 
 
Death within 60 days of the vaccine 
3.3.2 
Secondary Efficacy Endpoints  
 
Duration of anti-SARS-CoV-2 S antibody titers and antibody neutralization in the year following the 
additional dose of vaccine 
 
SARS-CoV-2 PCR positivity 
 
Symptomatic COVID-19 
 
COVID-19 requiring hospitalization 
 
Longitudinal changes in log SARS-CoV-2 antibody titer during the study 
3.3.3 
Exploratory Endpoints 
 
Anti-S1 and anti-RBD serology 
 
Detection of SARS-CoV-2 spike protein in blood after the additional dose of vaccine  
 
Additional serological panels and correlates of neutralizing antibody 
 
SARS-CoV-2 virology, diagnostics, and sequencing, including novel variants of concern  
 
Oral fluid anti-N and anti-S immunoglobulin levels (IgA, IgM, IgG) 
 
Antigen-specific B cell response  
 
Antigen-specific T cell response 
 
Evidence of immune activation, transcriptomics and cytokine signaling 
 
Durability of de novo donor-specific anti-HLA antibody 
3.4 
Stratification, Randomization, and Blinding/Masking  
This is an open-label study.  
 

COVID19-TB-03 
Confidential 
Page 25 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
4. 
Selection of Participants and Clinical Sites/Laboratories 
4.1 
Rationale for Study Population 
This study will enroll individuals who have completed primary series of mRNA COVID-19 vaccine and have a 
negative or low (≤ 2500 U/mL) antibody response measured at least 30 days after the last dose of vaccine. 
This group of patients is at high risk for severe COVID-19 disease due to pharmacologic immunosuppression 
and a high prevalence of non-transplant risk factors such as obesity and diabetes.  
4.2 
Inclusion Criteria 
Individuals who meet all the following criteria are eligible for enrollment as study participants:  
1. 
Able to understand and provide informed consent.  
2. 
Individual ³ 18 years of age.  
3. 
Recipient of a kidney or liver transplant ³ 12 months prior to enrollment, without allograft rejection in 
the 6 months preceding enrollment. 
4. 
Negative for anti-donor HLA antibodies at screening (central lab).  
5. 
Currently taking one of the following CNI-based immunosuppressive regimens: 
 
Tacrolimus plus MMF or MPA, with or without a corticosteroid 
 
Tacrolimus with trough ³ 5ng/mL) with or without ≤ 5 mg of prednisone or equivalent 
6. 
Received a minimum of 3 doses of either the Moderna COVID-19 Vaccine or Pfizer-BioNTech COVID-19 
Vaccine. 
7. 
Participant must be ³ 60 days after completion of primary vaccination or receipt of the most recent 
booster dose with any authorized or approved monovalent or bivalent COVID-19 vaccine at the time of 
study vaccine. 
8. Serum antibody negative or low (titer ≤ 2500 U/mL) at ³ 30 days from the last dose of mRNA COVID-19 
vaccine and ³30 days following receipt of a monoclonal antibody product or convalescent plasma for 
COVID-19, measured using the Roche Elecsys® anti-SARS-CoV-2 S assay.  
9. 
Participant’s transplant physician or midlevel practitioner who is clinically licensed to prescribe and 
manage immunosuppression must confirm the participant’s eligibility based on medical history. 
4.3 
Exclusion Criteria 
Individuals who meet any of these criteria are not eligible for enrollment as study participants:  
1. 
Currently on an IS regimen different from the two regimens described in the Inclusion Criteria, for 
example (but not limited to) those including sirolimus, everolimus, belatacept, or azathioprine. 
2. 
Recipient of any allograft other than a kidney or liver. 
3. 
Participant is pregnant. 
4. 
Any past history of Donor Specific Antibody (DSA) using local site standards. 
5. 
Currently taking any systemic immunosuppressive agent, other than their prescribed transplant 
immunosuppression. 
6. 
Known history of severe allergic reaction to any component of an authorized or licensed COVID-19 
vaccine.  
7. 
Thrombotic events, myocarditis, or pericarditis temporally associated with a prior dose of COVID-19 
vaccine. 
8. 
History of heparin-induced thrombocytopenia. 

COVID19-TB-03 
Confidential 
Page 26 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
9. 
Any change in transplant immunosuppression regimen (drug or dose) in response to suspected or 
proven rejection within the last 6 months.  
10. 
Significant graft dysfunction (see study definitions).  
11. 
Receipt of any cellular depleting agent (e.g. ATG, rituximab, alemtuzumab, Cyclophosphamide) 
within 12 months preceding enrollment.  
12. 
Concurrent autoimmune disease at risk for exacerbation with immunosuppression reduction.  
13. 
Any untreated active infection including BK viremia >104 copies. 
14. 
Infection with HIV. 
15. 
Recent (within one year) or ongoing treatment for malignancy with the exception of (1) non-
melanomatous skin cancer definitively treated by local therapy, and (2) definitively treated 
carcinoma-in-situ of the cervix (Stage 0 cervical cancer)  
16. 
Receipt of a monoclonal antibody product or convalescent plasma within the last 30 days. 
17. 
Any past or current medical problems, treatments, or findings which, in the opinion of the 
investigator, may pose additional risks from participation in the study, may interfere with the 
candidate’s ability to comply with study requirements or may impact the quality or interpretation 
of the data obtained from the study. 
4.4 
Selection of Clinical Sites  
This study will be conducted at approximately 15 clinical sites across the United States that have transplant 
programs with the population described in the protocol and which are able to comply with the 
requirements of the protocol. Sites may be added or withdrawn to meet the accrual goals outlined in the 
protocol.  

COVID19-TB-03 
Confidential 
Page 27 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
5. 
Known and Potential Risks and Benefits to Participants 
The risks cited below reflect the information currently included in the Moderna and Pfizer-BioNTech 
Package Inserts and Emergency Use Authorizations. The safety data accrued with the bivalent vaccines 
(Original and Omicron BA.1) and with the original COVID-19 vaccines are relevant to the updated 2023-
2024 formulations because these vaccines are manufactured using the same process.  
5.1  
Risks of the Investigational Products as cited in the Full FDA EUA Prescribing Information  
5.1.1 
Risks of Moderna COVID-19 Vaccine (includes original, bivalent, and 2023-2024 formula) 
The most common side effects reported include injection site reactions (pain, redness and 
swelling), axillary swelling/tenderness, fatigue, headache, myalgia, arthralgia, chills, and 
nausea/vomiting. Severe allergic reactions, including anaphylaxis, have been reported following the 
administration during mass vaccination outside of clinical trials. Severe allergic reactions included 
difficulty breathing, swelling of the face and throat, rash, dizziness, and weakness. Other risks 
include increased risks of myocarditis (inflammation of the heart muscle) and pericarditis 
(inflammation of the tissue surrounding the heart) following vaccination.  
Additional adverse reactions, some of which may be serious, may become apparent with post-
authorization use of the vaccine. 
5.1.2 
Risks of Pfizer-BioNTech COVID-19 Vaccine (includes original, bivalent, and 2023-2024 formula) 
The most common side effects reported include non-severe allergic reactions (rash, itching, hives 
and facial swelling), injection site reactions (pain, redness and swelling), fatigue, headache, myalgia, 
arthralgia, chills, fever, lymphadenopathy, vomiting, diarrhea, arm pain and general malaise. Severe 
allergic reactions that include difficulty breathing, swelling of the face and throat, rash and dizziness 
or weakness have been reported post authorization but are less common. Other risks include 
increased risks of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of 
the tissue surrounding the heart) following vaccination. 
Additional adverse reactions, some of which may be serious, may become apparent with post-
authorization use of the vaccine. 
5.2 
Risks of Moderna COVID-19 Vaccine and Pfizer-BioNTech Vaccine in adults as cited in Medical 
Literature (includes original, bivalent, and 2023-2024 formulas) 
The Moderna COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine are being administered under an 
Emergency Use Authorization. Adverse Events that occur outside of clinical trials as a result of the mass 
vaccination effort are reported to each manufacturer and included in a Fact Sheet for Healthcare 
Providers.33,34 
In a recent cohort of 741 organ transplant recipients who received two doses of either the Moderna or 
Pfizer-BioNTech vaccine, reactogenicity was similar to what has been reported in immunocompetent 
people: pain at injection site, fatigue, and headache were common. Severe reactogenicity (defined as 
preventing daily activity) occurred in 1-2% of study participants. Systemic reactogenicity was more common 
after the second dose of vaccine. There was an increased risk of local reactogenicity among recipients who 

COVID19-TB-03 
Confidential 
Page 28 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
were maintained on an immunosuppressive regimen that included corticosteroids or mTOR inhibitors, and 
also among those who received the Moderna vaccine. There were no cases of anaphylaxis. There was one 
case of acute allograft rejection after the second dose of vaccine.36 
Infrequent cases of myocarditis or pericarditis have been reported after the use of COVID-19 vaccines 
containing the SARS-CoV-2 S-antigen. Myocarditis and pericarditis have been reported in greatest numbers 
in males under the age of 40 years following a second dose of mRNA vaccines, but cases have been 
reported in older males and in females as well, and also following other doses, and other vaccine platforms, 
including after doses of an adjuvanted protein vaccine. The observed risk is highest in males 12 to 17 years 
of age. While some cases required intensive care support, available data from short-term follow-up suggest 
that symptoms resolve in most individuals with conservative management. Information is not yet available 
about potential long-term sequelae. The risk in children younger than 12 years old is currently being 
assessed, and both the size of the database and length of follow-up in this population are relatively smaller 
than that of those older than 12 years old. Therefore, the characterization of the risk in children younger 
than 12 years old is not as well-known as in adolescents and adults.  
5.3 
Risks Associated with IS Reduction  
Any decrease in dose or frequency of immunosuppressive medications in a transplant recipient carries the 
risk of alloimmune activation leading to acute cellular rejection, subclinical rejection, acute or chronic 
antibody-mediated rejection, and/or the formation of de novo DSA. The inclusion criteria and the specific 
immunomodulatory strategies have been designed to minimize, but do not eliminate, this risk. Study 
participants undergoing IS reduction will be closely monitored for evidence of graft injury and will be 
returned to their baseline immunosuppressive regimen should graft injury be evident. In addition, subjects 
will be monitored for the development of de novo DSA throughout the study period. 
5.4 
Potential Risks to Study Population  
There may be an increased risk of low-to-moderate reactogenicity to trial participants who receive an 
additional dose of vaccine. Based on currently available information, the risk of serious allergic events is 
likely to be extremely low, equal to or less than has been seen in the immunocompetent population. There 
is no evidence that the COVID-19 vaccine will result in new alloimmune events, and none are expected. 
5.5 
Risks of Other Protocol Specified Medications 
Not Applicable 
5.6 
Risks of Study Procedures  
5.6.1 
Risk of Blood Draw 
Collection of blood may cause slight discomfort, pain, bleeding or bruising at the injection site. 
Rarely, fainting or infection may occur. 
5.6.2 
Risks Associated with Nasal Mid-Turbinate Swab Collection 
Nasal mid-turbinate swab collection may cause localized discomfort. Rarely, mild epistaxis may 
occur.  
5.6.3 
Risks Associated with Oral Fluid Collection 

COVID19-TB-03 
Confidential 
Page 29 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
 Oral fluid collection may result in mild irritation where the gums are swabbed.  
5.6.4 
Risk of Internet Based Data Collection  
Data from this study will be entered into a computerized database through a secured web site. All 
information will be saved and transmitted in a coded form. Only authorized personnel requiring a 
password will be permitted to enter data. There is risk, although minimal, of unauthorized persons 
obtaining confidential information. 
5.7 
Potential Benefits 
There might be no benefit to participants in this study. If a participant achieves an increased level of 
antibody against SARS-CoV-2 as a result of participating in this study, there might be associated benefit. 
However, whether any participant will achieve this is unknown.  

COVID19-TB-03 
Confidential 
Page 31 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
Vaccine preparation and administration details will follow the package insert and be recorded on 
the appropriate eCRF.  
6.6 
Investigational Product #4: Pfizer-BioNTech COVID-19 Vaccine, ComirnatyÒ 2023-2024 Formula 
(Protocol v8.0 and beyond) 
The updated Pfizer-BioNTech COVID-19 Vaccine, ComirnatyÒ 2023-2024 Formula, hereafter referred to as 
Pfizer-BioNTech COVID-19 Vaccine 2023-2024 is being used in the study to provide an FDA approved dose 
to eligible participants.  
6.6.1 
Formulation, Packaging, and Labelling  
Pfizer-BioNTech COVID-19 Vaccine 2023-2024 is supplied in single dose vials and single dose 
prefilled syringes. It is supplied as a frozen suspension that does not contain preservative. Clinical 
sites will be provided with the formulation available to the study. 
Each 0.3 mL dose of Pfizer-BioNTech COVID-19 Vaccine 2023-2024 is formulated to contain 30 mcg 
of a nucleoside modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of 
SARS-CoV-2 Omicron variant lineage XBB.1.5 (Omicron XBB.1.5). 
Each 0.3 mL dose of Pfizer-BioNTech COVID-19 Vaccine 2023-2024 also includes the following 
ingredients: lipids (0.43 mg ((4- hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 
0.05 mg 2-(polyethylene glycol 2000)-N,N-ditetradecylacetamide, 0.09 mg 1,2-distearoyl-sn-
glycero-3-phosphocholine, and 0.19 mg cholesterol), 0.06 mg tromethamine, 0.4 mg tromethamine 
hydrochloride, and 31 mg sucrose. 
6.6.2 
Dosage, Preparation, and Administration  
The Pfizer-BioNTech COVID-19 Vaccine 2023-2024 dose used in this study will be a single dose of 30 
mcg (0.3 mL) administered intramuscularly in the deltoid muscle.  
Vaccine preparation and administration details will follow the package insert and be recorded on 
the appropriate eCRF.  
6.7 
Immunosuppression Reduction 
6.7.1 
Immunosuppression (IS) Reduction  
Participants on a tacrolimus-based regimen that includes MMF (or equivalent), with or without 
corticosteroid: 
 
MMF (or equivalent) will be withheld for five days prior to and 2 weeks following vaccine 
administration. During the interval that MMF is withheld, no adjustments will be made to 
the CNI or corticosteroid dose.  
Participants on a tacrolimus based regimen with a trough level ³ 5 ng/mL, with or without ≤5mg 
Prednisone (or equivalent) and no MMF or other antimetabolite 

COVID19-TB-03 
Confidential 
Page 32 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
 
Reduce CNI by 25% of starting dose for 5 days prior to and 2 weeks following vaccine 
administration. 
6.8 
Drug Accountability 
Under Title 21 of the Code of Federal Regulations (21CFR §312.62) the investigator will maintain adequate 
records of the disposition of the investigational agent, including the date and quantity of the drug received, 
to whom the drug was dispensed (participant-by-participant accounting), and a detailed accounting of any 
drug accidentally or deliberately destroyed. 
Records for receipt, storage, use, and disposition will be maintained by the study site. A drug-dispensing log 
will be kept current for each participant. This log will contain the identification of each participant and the 
date and quantity of drug dispensed. 
All records regarding the disposition of the investigational product will be available for inspection. 
6.9 
Assessment of Participant Compliance with Investigational Agent 
Not applicable due to the fact that the assigned COVID-19 vaccine will be a single dose administered by 
qualified personnel at the study site.  
6.10 
Toxicity Prevention and Management 
The vaccine will be administered by qualified personnel in dedicated observation rooms. Participants will be 
monitored for allergic reactions or other intolerance for 30 minutes following vaccine administration. 
Appropriate medications to address allergic reactions will be supplied by the investigational pharmacy (i.e., 
epinephrine, anti-histaminergic medications) and there is access to local rapid response team support in 
case of serious adverse events.  
6.11 
Premature Discontinuation of Investigational Agent 
Not applicable due to the fact that the additional dose of COVID-19 vaccine that will be administered under 
this protocol is a single dose.  
6.12 
Premature Discontinuation of IS Reduction  
Monitoring for evidence of rejection during IS reduction is described in Section 8.3.3. A persistent increase 
in creatinine (for kidney recipients) or of ALT (for liver recipients) will be cause for return to baseline IS, as 
follows:  
For kidney transplant recipients: A finding of a 0.3mg/dL or 25% elevation (whichever is higher) of serum 
creatinine over baseline (pre-reduction in IS) will be repeated in 1-3 days. If the elevation persists or 
increases, the subject will return to his/her baseline immunosuppression regimen. Further management 
will be determined by the treating transplant physician. If the serum creatinine returns to baseline without 
further treatment, the event will not be recorded as rejection. If the participant requires more than 
baseline levels of IS or receives specific treatment for rejection, the event will be recorded as rejection. 
For liver transplant recipients: A finding of an elevation of an ALT >2X baseline (pre-reduction in IS) or >60 
IU/L if the baseline ALT is <30 IU/L will be repeated in 1-3 days. If the elevation persists or increases, the 
subject will return to his/her baseline immunosuppression regimen. Further management will be 
determined by the treating transplant physician. If the ALT returns to baseline without further treatment, 

COVID19-TB-03 
Confidential 
Page 33 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
the event will not be recorded as rejection. If the participant requires more than baseline levels of IS or 
receives specific treatment for rejection, the event will be recorded as rejection. 

COVID19-TB-03 
Confidential 
Page 34 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
7. 
Other Medications 
7.1 
Concomitant Medications 
7.1.1 
Protocol-mandated 
Not applicable  
7.1.2 
Other permitted concomitant medications 
Not applicable  
7.2 
Prophylactic Medications 
Infectious disease prophylaxis will be determined by the treating transplant physician.  
7.3 
Pre-Exposure Prophylaxis or Treatment of COVID-19 Infection  
Per the Emergency Use Authorization, the participants in this study should not receive any pre-exposure 
prophylaxis (PrEP) e.g. tixagevimab plus cilgavimab (Evusheld™, AztraZeneca) during the 2-week period 
following any dose of COVID-19 vaccine. From a study perspective, it would be best to delay administration 
of any PrEP until after the Day 30 post-vaccine visit, when the primary endpoint is collected. If the 
participant or his/her treating physician feels it is in the patient’s best interest to administer PrEP before 
Day 30 following the study dose of vaccine, we ask that the study team be informed since this will impact 
subsequent study evaluations, in particular antibody testing.  
If a participant has a known exposure to COVID-19 and/or develops COVID-19 infection, treatment should 
be prescribed as clinically indicated by the participant’s primary provider.  
Administration of PrEP or any treatment of COVID-19 will be captured in the clinical database.  
7.4 
COVID-19 Vaccine Booster Doses 
Participants should consult with the study team regarding non-study COVID-19 booster doses in order to 
maintain compliance with current CDC recommendations, while not compromising participation in the 
research study. Current CDC recommendations can be found at the following link:  
https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-
us.html#immunocompromised  
Current recommendations may change over the course of the CPAT-ISR study. 
7.5 
Rescue Medications  
Not applicable 

COVID19-TB-03 
Confidential 
Page 35 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
8. 
Study Procedures 
8.1 
Enrollment 
Potential study participants may be identified by medical chart review and initially contacted by a member 
of the study team in person or over the phone. During this initial contact, the potential participant will be 
provided information on the study and asked about their interest in study participation. If they elect to 
continue, they will be consented to the SARS-CoV-2 S antibody testing using the Roche Elecsys® assay. 
Potential participants with eligible SARS-CoV-2 antibody results will receive a concise and focused 
presentation of key information about the clinical trial, verbally and with a written consent form. The 
research study will be explained in lay terms to each potential research participant. The potential 
participant will sign an informed consent form before undergoing any study procedures.  
8.2 
Screening Period 
The purpose of screening is to confirm eligibility prior to the study intervention.  
Initial Screen  
 
Chart review for eligibility 
 
Blood drawn locally for anti-SARS-CoV-2 S (using Roche Elecsys® assay). A prior result may be used for 
eligibility if it was obtained at least 30 days following the last dose of mRNA COVID-19 vaccine 
administration and ≥ 30 days following receipt of a monoclonal antibody product or convalescent 
plasma for COVID-19. 
Screening Procedures (Appendix 1) 
The following procedures, assessments, and laboratory measures will be conducted to determine 
participant eligibility: 
 
Review medical history and immunosuppression medications. 
 
Blood drawn for detection of de novo DSA (central lab). 
 
Research blood (central lab) 
 
Serum creatinine, eGFR (for kidney recipients)  
 
Hepatic panel, direct bilirubin, and INR (for liver recipients)  
 
Confirm with the patient’s transplant physician that they are eligible for IS reduction based on medical 
history, and that their physician concurs with the plan for IS reduction. 
8.3 
Study Visits or Study Assessments  
8.3.1 
Day -5 (IS Reduction Arm) 
Participants randomized to the IS reduction arm will have a Day -5 visit. A study physician will 
discuss what IS medication will be withheld or reduced based on the participant’s IS regimen at 
study entry (see Section 6.3 for further details).  
8.3.2 
Vaccination Visit: Day 0 (All Participants)  
All participants will be scheduled for a vaccination visit.  

COVID19-TB-03 
Confidential 
Page 36 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
Participants will have baseline research blood, oral fluid, and nasal samples collected on Day 0 per 
the Schedule of Events (Appendix 2 (COVID-19 Vaccine Dose Alone) and Appendix 3 (IS Reduction 
plus COVID-19 Vaccine Dose)). Following sample collection, the participant will proceed to the 
administration location and receive the assigned dose of COVID-19 vaccine (see Section 6 for 
vaccine details).  
Participants will be observed for 30 minutes post vaccine administration.  
8.3.3 
Follow-up Visits (All Participants)  
Follow-up will occur at weeks 1, 2, 3, 4, 5, 6 and Months 3, 6, 9, and 12 following vaccine 
administration. Participants will have additional blood tests to monitor their graft function during 
the time they are on a reduced level of immunosuppression and for 1 month following resumption 
of their original regimen of immunosuppression. Identical blood testing schedules will take place 
for both the COVID-19 vaccine dose group and the IS reduction plus COVID-19 vaccine dose group. 
Kidney recipients will have their serum creatinine levels measured at the weekly visits. Liver 
recipients will have a hepatic panel (AST, ALT, alk phos, bilirubin, direct bilirubin) at the weekly 
visits.  
The Week 4 visit is the primary endpoint visit. During these visits, participants will be asked about 
their general health, any new events, immunosuppression medications and their transplanted 
organ per the Schedule of Events in Appendix 2.  
Blood and nasal swabs will be collected for assessments to be run in the clinical and research 
laboratories per the Schedule of Events in Appendix 2 or Appendix 3 based on group assignment. 
Nasal mid-turbinate swabs for SARS-CoV-2 PCR testing will be collected at baseline and Months 1, 
3, 6, 9 and 12 following vaccine administration. 
Participants will be instructed to contact the study team if they receive any COVID-19 testing at an 
outside lab during the course of the study. All instances of COVID-19 infection will be reported on 
the applicable electronic case report form.  
A subset of participants will have a study visit on Day 3 to have blood drawn for a research 
laboratory study to detect the presence of SARS-CoV-2 spike protein generated in response to the 
vaccine. 
8.4 
Unscheduled Visits  
If there is a change in immunosuppressive medications, new medical events or a diagnosis of rejection 
between regularly scheduled visits, participants will be instructed to contact study personnel and may be 
asked to return to the study site for an “unscheduled” visit.  
8.5 
Suspected or Confirmed Myocarditis or Pericarditis 
Participants will be instructed to seek prompt medical attention if they develop symptoms of myocarditis or 
pericarditis, such as including chest pain, shortness of breath, or palpitations. Participants will also be 
instructed to notify the study site team. Participants diagnosed with acute myocarditis or acute pericarditis 
within 6 weeks of any COVID-19 vaccine will be referred to a cardiologist for evaluation and management. 

COVID19-TB-03 
Confidential 
Page 37 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
Cases of study-defined probable or definite acute myocarditis or acute pericarditis will be followed until 
resolution of symptoms and abnormal test findings. 
8.6 
Suspected or Confirmed Cases of COVID-19 Infection 
If participants suspect they have contracted COVID-19 infection, they will be directed to follow-up with 
their local transplant physician or primary care provider to obtain the appropriate clinical care. Information 
related to their illness will be collected for the study and reported in the clinical database.  
8.7 
Visit Windows 
Study visits should take place within the time limits specified below: the designated visit windows (i.e. +/- n 
days) for each scheduled visit are also indicated on the Table of Events.  
Screening  
 
-30 days for screening clinical laboratory assessments 
 
SARS-CoV-2 S antibody at least 30 days following last dose of 
COVID-19 vaccine 
 
-90 days for dnDSA 
Day 3, Week 1 
+/- 1 day 
Weeks 2, 3, 4, 5, and 6 
+/- 3 days 
Months 3, 6, 9, and 12 
+/- 2 weeks 

COVID19-TB-03 
Confidential 
Page 38 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
9. 
Mechanistic Assays 
9.1 
Introduction 
Effective vaccinations induce potent protective humoral and cellular immunity and promote development 
of robust T and B cell memory, together preventing infection and accelerating viral clearance following 
pathogen exposure. Current concepts are that vaccination results in activation of both T cells and B cells. 
Vaccine antigen-activated B cells can differentiate into low affinity IgG- or IgM-secreting plasma cells (PCs). 
Alternatively, vaccine antigen-activated B cells can interact with antigen-activated CD40+ CD4+ (Th1) helper 
T cells to undergo an isotype switch and enter germinal center (GC) reactions wherein they undergo affinity 
maturation. Positive selection of the highest affinity B cells in the GC requires cognate interactions with 
antigen specific IL-21-producing follicular helper CD4+ T cells (Tfh). The positively selected high affinity B 
cells then can differentiate into long lived antibody-secreting PCs, can become memory B cells (Bmem), or 
can reenter the GC to undergo further affinity maturation. Crucial features of the antibody repertoire 
relevant to pathogen clearance include antibody specificity, affinity, titer, isotype class, and glycosylation 
patterns, among others. Antigen-reactive CD4+ and CD8+ T cells that expand and differentiate following 
vaccination are also crucial mediators of pathogen clearance independent of their functions as helper cells 
for effective humoral immune responses. Important characteristics of these induced T cell responses 
include epitope specificity, cytokine secretion patterns, and cytotoxic function, among others. Effective 
anti-pathogen immunity also involves activation of innate immune cells, including dendritic cells, 
macrophages, and natural killer cells that can interact with an enhance the adaptive immune responses and 
have been recently shown to exhibit cellular and molecular features consistent with memory.  
As noted in the background section, emerging evidence indicates that the majority of transplant recipients 
taking immunosuppressant medications do not produce effective antibody responses to SARS-CoV-2 spike 
protein mRNA vaccinations. Whether these patients develop and maintain protective T cell responses after 
the same vaccines is not known. A detailed kinetic analysis of innate and adaptive immunity following SARS-
CoV-2 mRNA vaccination, particularly comparing responders to non-responders, is thus essential in order to 
interpret the clinical trial outcome and to guide design of follow up studies aimed at overcoming identified 
defects. Moreover, if it were possible to identify an early post vaccine molecular signature that correlates 
with vaccine success vs failure, such a biomarker could be used to guide subsequent strategies aimed at 
enhancing induction protective immunity in each transplant patient. 
Thus, the overall goals of the proposed mechanistic studies are to a) characterize the vaccine-induced 
innate and adaptive immune responses in each study subject, b) compare the induced immune responses 
among participants in the various treatment arms. c) define the durability of the responses over 1-year post 
vaccination, d) provide insight into immune mechanisms that prevent formation and/or durability of the 
induced responses within each and among treatment arms, d) identify molecular markers of successful 
vaccination.  
To this end we will serially collect serum, plasma, PBMC, and oral fluid samples over the entire study 
period. Using these samples we will a) quantify spike protein production in serum, b) provide a detailed 
kinetic characterization of the vaccine induced antibody repertoire (specificity, isotype, titer, neutralization 
capacity), c) perform a kinetic phenotypic and functional analysis of antigen specific Bmem (frequency, 
antigen specificity, surface markers, metabolomics, gene expression patterns, single cell sequencing) and 

COVID19-TB-03 
Confidential 
Page 39 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
PC, d) perform a kinetic, analysis of antigen specific CD4+ and CD8+ T cells (frequency, epitope specificity, 
surface markers, metabolomics, gene expression patterns single cell sequencing), e) assess phenotypic, 
functional and gene expression patterns of innate immune DC, monocyte/macrophage and NK cell subsets 
in peripheral blood, and f) perform genomic profiling of peripheral blood cells that will provide a biomarker 
for an effective response. 
9.2 
Objective 1: To quantify spike protein production in serum or plasma after vaccination. 
Transient expression of a modified spike protein using mRNA vaccines (Moderna and Pfizer-BioNTech) has 
been crucial in the global effort to control the SARS-CoV-2 pandemic. This platform offers the flexibility for 
rapid modification to control variants. Given the requirement for effective protein expression of 
immunogen, the extremely poor responses of transplant recipients, particularly those on mycophenolate 
mofetil raises the question whether the anti-metabolite properties of MMF may impair the transient 
expression of spike protein thereby contributing to the impaired vaccine response of transplant patients. 
Using a recently developed ultrasensitive molecular assay to detect spike protein in plasma we will assess 
expression in a subset of antibody negative study participants at baseline (pre-vaccine) and 3 days post-
vaccination. 
9.3 
Objective 2: To provide a detailed kinetic characterization of the vaccine-induced antibody 
repertoire (specificity, isotype, titer, neutralization capacity). 
While relative contributions of vaccine induced humoral and T cell immunity in the protection from severe 
SARS-CoV-2 disease are not fully understood, the development of a critical level of SARS-CoV-2 Ab are 
emerging as a correlate of protection. A detailed understanding of the profile of Ab responses in transplant 
recipients after vaccination is crucial step toward understanding what population benefits from an 
additional dose of vaccine. This objective will provide a deeper mechanistic characterization of to support 
hypothesis generating observations to understand the mechanisms underlying vaccine failure and to 
identify candidate humoral biomarkers to predict vaccine response. This includes surrogate and live virus 
neutralization titers including versus novel variants of concern. 
9.4 
Objective 3: To perform a kinetic phenotypic and functional analysis of antigen-specific Bmem 
(frequency, antigen specificity, surface markers, metabolomics, gene expression patterns, single 
cell sequencing) and PC. 
To identify and characterize SARS-CoV-2 memory B cells we will use fluorescently labeled multimerized 
probes for targets of the vaccine (spike receptor-binding and ectodomain) and as well as non-vaccine 
expressed SARS-CoV-2 antigens (e.g. Nucleocapsid). The magnitude and differentiation of anti-specific IgM+ 
and IgG+ memory B cells will be assessed at each time point. We will use flow cytometry, CyTOF, single B 
cell multi-omics (cell surface CITE-seq profiling using tagged antibody and multimerized probes for vaccine 
targets), transcriptomics, and B cell receptor VDJ repertoire analysis to characterize antigen specific B cells. 
We will perform in vitro ELISPOT assays to determine frequencies of antigen specific PCs in peripheral 
blood.  
9.5 
Objective 4: To perform a kinetic, analysis of antigen-specific CD4+ and CD8+ T cells (frequency, 
epitope specificity, surface markers, metabolomics, gene expression patterns single cell 
sequencing). 

COVID19-TB-03 
Confidential 
Page 40 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
While the requirements for sustained protection against SARS-CoV-2 are not yet known, effective control of 
viral pathogens often depends on the development of both humoral and cellular immunity.  
We will assess the strength, breadth and character of the anti-spike T cell response in study participants 
using flow-cytometry based, ELISPOT, and single cell-multi-omics assays. Antigen-specific cells will be 
interrogated using a rapidly evolving set of peptide and MHC multimer reagents using flow-cytometry, 
CyTOF, and or ELISPOT readouts. For flow-based analysis we will utilize 1) antigen specific functional assays 
(activation-induced marker (AIM), intracellular cytokine secretion assays and novel T cell metabolic profiling 
assays and, 2) phenotypic characterization of spike-specific T cells MHC-peptide multimer staining. We will 
use single T cell multi-omics (cell surface CITE-seq profiling using tagged antibody and tetramers, 
transcriptomics, and T cell receptor VDJ repertoire analysis.  
Exploratory immune profiling assessments will include:  
9.6 
Objective 5: To assess phenotypic, functional and gene expression patterns of innate immune DC, 
monocyte/macrophage and NK cell subsets in peripheral blood. 
We will characterize the kinetics of peripheral blood immune landscape of mononuclear leukocyte lineage 
and phenotypic markers to broadly assess the immunological cellular profile of transplant recipients before 
and after vaccination, focusing on the absolute and relative frequency of T, B, NK and APC subsets.  
We will characterize these cells types in peripheral blood using flow cytometry and or CyTOF assays. We will 
test function using in vitro assays that include in vitro stimulation of DC subsets with TLR ligands (cytokine 
and surface marker readouts as measures of activation), in vitro stimulation of macrophages with LPS 
(cytokine readouts as a measure of trained immunity, which would then be followed up with epigenetic 
analyses), in vitro functional analyses of NK cells. 
9.7 
Objective 6: Exploration of molecular biomarkers of early responders to vaccination 
We will collect serial blood samples for RNA profiling (RNAseq) and/or proteomics in addition to 
characterization of cytokine signaling early after vaccine intervention. 
 

COVID19-TB-03 
Confidential 
Page 41 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
10. 
Biospecimen Storage 
Biological specimens obtained under this protocol may be used in future assays to reevaluate biological 
responses as additional research tests are developed over time. These may include, but are not limited to, 
tests examining aspects of host immunology, cell biology, or human genetics as it relates to any of these 
aspects. Appropriate informed consent will be obtained for both the collection and storage of samples. The 
specimens from these evaluations will be labeled with a coded ID and may be stored beyond the funding 
period. 

COVID19-TB-03 
Confidential 
Page 42 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
11. 
Criteria for Participant and Study Completion and Premature Study Termination 
11.1 
Participant Completion 
All participants will be followed for 12 months following the COVID-19 vaccine administration.  
11.2 
Participant Stopping Rules and Withdrawal Criteria 
Participants may be prematurely terminated from the study for the following reasons: 
1. 
The participant elects to withdraw consent from all future study activities, including follow-up. 
2. 
The participant is “lost to follow-up” (i.e., no further follow-up is possible because attempts to 
reestablish contact with the participant have failed).  
3. 
The participant dies.  
4. 
The Investigator no longer believes participation is in the best interest of the participant. 
11.3 
Participant Replacement 
Participants who withdraw or are withdrawn will not be replaced. 
11.4 
Follow-up after Early Study Withdrawal 
If a participant is withdrawn from the study for any reason, the participant may be asked to complete a final 
visit and/or final assessments.  
11.5 
Study Pausing Rules 
If the following occur, relevant study interventions will be temporarily halted pending a DSMB review and 
recommendation as to whether the study may proceed. 
1. 
Any Grade 4 or 5 event that is definitely or possibly attributed to the study dose of vaccine or to 
immunosuppression reduction. 
2. 
Any probable or confirmed case of either acute myocarditis or acute pericarditis that occurs within 
6 weeks of the study vaccine. 
3. 
Excess incidence of acute rejection (clinically treated or biopsy-proven): Based on registry data, 
approximately 5-6 rejection events would be expected over the course of the study, independent of 
any effect of the study interventions. A pausing rule has been constructed such that the study 
would be paused if there is a >50% chance that the observed event rate exceeds three times the 
expected rate. The pausing rule will be applied to the study by group: (1) COVID-19 vaccine dose 
alone (2) MMF withdrawal (3) CNI reduction. Event rates triggering a pause are shown below:  
 
Number of participants 
Number of events 
required to trigger a pause 
Event rate 
required to trigger a pause 
10 
3 
30% 
20 
3 
15% 
30 
3 
10% 
40 
4 
10% 
50 
4 
8% 
75 
4 
5% 
100 
5 
5% 
150 
6 
4.0% 

COVID19-TB-03 
Confidential 
Page 43 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
200 
7 
3.5% 
250 
8 
3.2% 
300 
9 
3.0% 
350 
10 
2.9% 
400 
11 
2.8% 
 
4. 
Excess incidence of graft loss: Based on registry data, it is expected that there will be 
approximately 6-7 graft losses over the course of the study, independent of any effect of the study 
interventions. A pausing rule has been constructed such that the study would be paused if there is 
a >50% chance that the observed event rate exceeds three times the expected rate. The pausing 
rule will be applied to the study by group: (1) COVID-19 vaccine dose alone (2) MMF withdrawal (3) 
CNI reduction. Event rates triggering a pause are shown below:  
 
Number of participants 
Number of events 
required to trigger a pause 
Event rate 
required to trigger a pause 
10 
3 
30% 
20 
3 
15% 
30 
3 
10% 
40 
4 
10% 
50 
4 
8% 
75 
4 
5% 
100 
5 
5% 
150 
6 
4.0% 
200 
7 
3.5% 
250 
8 
3.2% 
300 
9 
3.0% 
350 
10 
2.9% 
400 
11 
2.8% 
 
 
 

COVID19-TB-03 
Confidential 
Page 44 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
 
5. 
Excess Mortality: Based on registry data, it is expected that there will be approximately 5 deaths 
over the course of the study, independent of any effect of the study interventions. A pausing rule 
has been constructed such that the study would be paused if there is a >50% chance that the 
observed event rate exceeds three times the expected rate AND is determined to be possibly, 
probably or definitely related to a study intervention. The pausing rule will be applied to the study 
overall and by group: (1) COVID-19 vaccine dose alone (2) MMF withdrawal (3) CNI reduction. Event 
rates triggering a pause are shown below:  
 
Number of participants 
Number of events 
required to trigger a pause 
Event rate 
required to trigger a pause 
10 
3 
30% 
20 
3 
15% 
30 
3 
10% 
40 
4 
10% 
50 
4 
8% 
75 
4 
5% 
100 
5 
5% 
150 
5 
3.3% 
200 
6 
3.0% 
250 
7 
2.8% 
300 
8 
2.7% 
350 
9 
2.6% 
400 
10 
2.5% 
 
 

COVID19-TB-03 
Confidential 
Page 45 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
12. 
Safety Monitoring and Reporting 
12.1 
Overview 
This section defines the types of safety data that will be collected under this protocol and outlines the 
procedures for appropriately collecting, grading, recording, and reporting those data. Adverse events that 
are classified as serious according to the definition of health authorities must be reported promptly (per 
Section 12.5, Reporting of Serious Adverse Events and Adverse Events) to the sponsor, DAIT/NIAID. 
Appropriate notifications will also be made to site principal investigators, Institutional Review Boards (IRBs), 
and health authorities.  
Information in this section complies with ICH Guideline E2A: Clinical Safety Data Management: Definitions 
and Standards for Expedited Reporting, ICH Guideline E-6: Guideline for Good Clinical Practice, 21CFR Parts 
312 and 320, and applies the standards set forth in the National Cancer Institute (NCI), Common 
Terminology Criteria for Adverse Events (CTCAE), Version [enter 5.0 or correct version applicable to trial] : 
http://ctep.cancer.gov/reporting/ctc.html. 
12.2 
Definitions 
12.2.1 Adverse Event (AE) 
Any untoward or unfavorable medical occurrence associated with the subject’s participation in the 
research, whether or not considered related to the subject’s participation in the research (modified 
from the definition of adverse events in the 1996 International Conference on Harmonization E-6 
Guidelines for Good Clinical Practice) (from OHRP "Guidance on Reviewing and Reporting 
Unanticipated Problems Involving Risks to Subjects or Others and Adverse Events (1/15/07)" 
http://www.hhs.gov/ohrp/policy/advevntguid.html#Q2 )  
For this study, adverse events will be considered for association with the additional dose of COVID-
19 vaccine and study mandated procedures as follows:  
Vaccine Administration (Moderna COVID-19 Vaccine (monovalent, bivalent, and 2023-2024 formula 
as per protocol version), Pfizer-BioNTech COVID-19 Vaccine (monovalent, bivalent, and 2023-2024 
formula as per protocol version) 
 
All AEs occurring within 30 days following a single COVID-19 vaccine dose and SAEs up 
to 6 months post vaccine administration.  
Study mandated procedures:  
 
Any AE occurring within 24 hours of a protocol mandated blood draw 
 
Any AE occurring within 24 hours of a protocol mandated nasal swab 
 
Any AE occurring within 24 hours of an oral fluid collection 
 
Any AE occurring during the period from the onset of immunosuppression reduction 
until 30 days after return to full immunosuppression and SAEs up to 6 months post 
return to full immunosuppression.  
12.2.2 Solicited Adverse Events 

COVID19-TB-03 
Confidential 
Page 46 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
For the purposes of this study, the following specific local and systemic reactogenicity events, as 
well as symptoms of a potential allergic reaction, will be solicited from the participant through a 
remote contact on Day 7 post-vaccination. Any other adverse events reported during the course of 
this remote contact will be reported on the AE eCRF. Study clinicians will follow all adverse events 
to resolution. 
• 
Local reactions at the injection site including erythema/redness, swelling/induration (hardness), 
and pain. 
• 
Systemic reactions including fever, myalgia, arthralgia, fatigue, headache, nausea, vomiting, 
diarrhea, and chills. 
• 
Potential allergic reaction, which includes the following symptoms: 
• 
Skin: hives, swelling other than injection site, itching, redness other than injection site, rash 
• 
Respiratory: wheezing, shortness of breath, coughing, tightness in the throat or chest, sneezing, 
nasal stuffiness or congestion 
• 
Gastrointestinal: trouble swallowing, abdominal cramps, diarrhea, nausea, vomiting 
• 
Dizziness or lightheadedness 
12.2.3 Unsolicited Adverse Events  
Participants will be instructed to contact the study site and report any adverse events up to 30 days 
post vaccine administration. This will include any delayed onset local reactions.  
12.2.4 Adverse Events of Special Interest (AESI) 
Any case of myocarditis or pericarditis within 6 weeks after study vaccination will be reported as an 
AESI. Regardless of seriousness, these events will be reported to DAIT/NIAID within 24 hours of 
awareness on the Serious Adverse Event case report form.  
For myocarditis and pericarditis events, any relevant laboratory information, imaging 
(echocardiography, cardiac MRI) and/or pathology (cardiac biopsy) results will be reported on case 
report forms. The DAIT medical monitor may require that appropriately deidentified copies of 
studies, including but not limited to EKG, imaging, cardiac biopsies digital images, or other follow-
up results (stress tests results) be made available for medical monitor or ad hoc DSMB review. 
12.2.5 Suspected Adverse Reaction (SAR)  
Any adverse event for which there is a reasonable possibility that the SARS-CoV-2 vaccine caused 
the adverse event. For the purposes of safety reporting, ‘reasonable possibility’ means there is 
evidence to suggest a causal relationship between the drug and the adverse event. A suspected 
adverse reaction implies a lesser degree of certainty about causality than adverse reaction, which 
means any adverse event caused by a drug (21 CFR 312.32(a)). 
12.2.6 Unexpected Adverse Event  
An adverse event or suspected adverse reaction is considered “unexpected” if it is not consistent 
with the risk information described in Vaccine-specific FDA EUA Full Prescribing Information)     (21 
CFR 312.32(a) and 310.305) 
12.2.7 Serious Adverse Event (SAE) 

COVID19-TB-03 
Confidential 
Page 47 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
An adverse event or suspected adverse reaction is considered “serious” if, in the view of either the 
investigator or Sponsor DAIT/NIAID, it results in any of the following outcomes (21 CFR 312.32(a)): 
1. 
Death. 
2. 
A life-threatening event: An AE or SAR is considered “life-threatening” if, in the view of either 
the investigator or Sponsor [DAIT/NIAID], its occurrence places the subject at immediate risk of 
death. It does not include an AE or SAR that, had it occurred in a more severe form, might have 
caused death.  
3. 
Inpatient hospitalization or prolongation of existing hospitalization. 
4. 
Persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions. 
5. 
Congenital anomaly or birth defect.  
6. 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the subject and may require medical or surgical intervention to prevent 
one of the outcomes listed above. 
Elective hospitalizations or hospital admissions for the purpose of conduct of protocol mandated 
procedures are not to be reported as an SAE unless hospitalization is prolonged due to 
complications. 
12.3 
Grading and Attribution of Adverse Events 
12.3.1 Grading Criteria 
The study site will grade the severity of adverse events experienced by the study subjects according 
to the criteria set forth in the National Cancer Institute’s Common Terminology Criteria for Adverse 
Events (CTCAE) Version 5.0. This document (referred to herein as the NCI-CTCAE manual) provides a 
common language to describe levels of severity, to analyze and interpret data, and to articulate the 
clinical significance of all adverse events. The NCI-CTCAE has been reviewed by the NIAID Medical 
Monitor and Protocol Chair and has been deemed appropriate for the subject population to be 
studied in this protocol.  
Adverse events will be graded on a scale from 1 to 5 according to the following standards in the 
NCI-CTCAE manual: 
Grade 1 = Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.  
Grade 2 = Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate  
instrumental activities of daily living (ADL: Instrumental ADL refer to preparing meals, shopping for 
groceries or clothes, using the telephone, managing money, etc. ) 
Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living  
(ADL: Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet,  
taking medications, and not bedridden.)  
Grade 4 = Life-threatening consequences; urgent intervention indicated.  

COVID19-TB-03 
Confidential 
Page 48 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
Grade 5 = Death related to AE.  
For grading an abnormal value or result of a clinical or laboratory evaluation (including, but not 
limited to, a radiograph, an ultrasound, an electrocardiogram etc.), a treatment-emergent adverse 
event is defined as an increase in grade from baseline or from the last post-baseline value that 
doesn’t meet grading criteria. Changes in grade from screening to baseline will also be recorded as 
adverse events but are not treatment-emergent. If a specific event or result from a given clinical or 
laboratory evaluation is not included in the NCI-CTCAE manual, then an abnormal result would be 
considered an adverse event if changes in therapy or monitoring are implemented as a result of the 
event/result. 
12.3.2 Attribution Definitions 
The relationship, or attribution, of an adverse event to the study therapy regimen or study 
procedure(s) will initially be determined by the site investigator and recorded on the appropriate 
AE/SAE eCRF. Final determination of attribution for safety reporting will be determined by 
DAIT/NIAID. The relationship of an adverse event to study therapy regimen or procedures will be 
determined using the descriptors and definitions provided in Table 12.3.2.  
For additional information and a printable version of the NCI-CTCAE manual, consult the NCI-CTCAE 
web site: http://ctep.cancer.gov/reporting/ctc.html. 
    
Table 12.3.2 Attribution of Adverse Events 
Code 
Descriptor 
Relationship (to primary investigational product 
and/or other concurrent mandated study therapy or 
study procedure) 
UNRELATED CATEGORY 
1 
Not 
Related 
The adverse event is clearly not related: there is 
insufficient evidence to suggest a causal relationship. 
 RELATED CATEGORIES 
2 
Possibly 
Related 
The adverse event has a reasonable possibility to be 
related; there is evidence to suggest a causal 
relationship. 
3 
Related 
The adverse event is clearly related. 
 
12.4 
Collection and Recording of Adverse Events 
12.4.1 Collection Period 
Adverse Events temporally associated (24 hours) with the research blood draws and nasal swabs 
will be collected from the time of the screening visit until a subject completes study participation. 

COVID19-TB-03 
Confidential 
Page 49 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
COVID-19 Vaccine Dose Alone: Adverse Events as defined in Section 12.2.1 will be collected for 30 
days following COVID-19 vaccine administration. Serious Adverse Events will be collected for 6 
months following vaccine administration.  
COVID-19 Vaccine Dose plus IS Reduction: All Adverse Events will be collected in those who 
undergo immunosuppression reduction occurring from the onset of IS reduction until 30 days after 
return to full immunosuppression. Serious Adverse Events will be collected for 6 months post onset 
of IS reduction.  
12.4.2 Collecting Adverse Events 
Adverse events (including SAEs) may be discovered through any of these methods: 
• 
Observing the subject. 
• 
Interviewing the subject [e.g., using a checklist, structured questioning, diary, etc.]. 
• 
Receiving an unsolicited complaint from the subject. 
• 
In addition, an abnormal value or result from a clinical or laboratory evaluation can also indicate an 
adverse event, as defined in Section 12.3, Grading and Attribution of Adverse Events. 
12.4.3 Recording Adverse Events 
Throughout the study, the investigator will record adverse events and serious adverse events as 
described previously (Section 12.2, Definitions) on the appropriate electronic case report form 
regardless of the relationship to study therapy regimen or study procedure. 
Once recorded, an AE/SAE will be followed until it resolves with or without sequelae, or until the 
end of study participation, or until 30 days after the subject prematurely withdraws (without 
withdrawing consent)/or is withdrawn from the study, whichever occurs first. 
12.5 
Reporting of Serious Adverse Events and Adverse Events 
12.5.1 Reporting of Serious Adverse Events to DAIT/NIAID 
This section describes the responsibilities of the site investigator to report serious adverse events 
to the sponsor via the AE/SAE eCRF. Timely reporting of adverse events is required by 21 CFR and 
ICH E6 guidelines.  
Site investigators will report all serious adverse events (see Section 12.2.3, Serious Adverse Event), 
regardless of relationship or expectedness within 24 hours of discovering the event. 
For serious adverse events, all requested information on the AE/SAE eCRF provided. However, 
unavailable details of the event will not delay submission of the known information. As additional 
details become available, the AE/SAE eCRF will be updated and submitted. Initial SAE eCRFs should 
include as much information as possible, but at a minimum: 
• 
AE term 
• 
Relationship to study vaccination  
• 
Relationship to study procedure 
• 
Reason why the event is serious 

COVID19-TB-03 
Confidential 
Page 50 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
• 
Supplementary eCRF pages that are current at the time of the SAE reporting e.g. medical 
history and vaccine administration 
12.5.2 Reporting of Adverse Events to IRBs/IECs 
All investigators shall report adverse events, including expedited reports, in a timely fashion to their 
respective IRBs/IECs in accordance with applicable regulations and guidelines.  
12.5.3 Mandatory reporting to Vaccine Adverse Event Reporting System 
Per the FDA EUA for the Moderna COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine, 
reporting of the following to the Vaccine Adverse Event Reporting System (VAERS): 
 
vaccine administration errors whether or not associated with an adverse event, 
 
serious adverse events (irrespective of attribution to vaccination), 
 
cases of myocarditis, 
 
cases of pericarditis,  
 
cases of Multisystem Inflammatory Syndrome in adults, and  
 
cases of COVID-19 that result in hospitalization or death. 
The site investigator, or designee, is also responsible for recording vaccination information in the 
state/local jurisdiction’s Immunization Surveillance System or other designated system.  
12.6 
Reporting of Other Safety Information 
An investigator shall promptly notify the site IRB as well as the SACCC when an “unanticipated problem 
involving risks to subjects or others” is identified, which is not otherwise reportable as an adverse event. 
12.7 
Review of Safety Information 
12.7.1 Medical Monitor Review 
The NIAID Medical Monitor shall receive monthly reports from the SACCC compiling new and 
accumulating information on AEs and SAEs recorded by the study site(s) on appropriate eCRFs. 
In addition, the Medical Monitor shall review and make decisions on the disposition of the SAE and 
pregnancy reports received by the SACCC (See Sections 12.5.1, Reporting of Serious Adverse Events 
to Sponsor, and 12.6, Pregnancy Reporting).  
12.7.2 DSMB Review  
12.7.2.1 Planned DSMB Reviews  
The Data and Safety Monitoring Board (DSMB) shall review safety data one month after all study 
participants have received study vaccine, unless a safety event requires earlier review. They will 
review the study again when the database is locked after the last patient’s last visit. Interim DSMB 
reviews may occur at any time at the discretion of the medical monitor or the protocol chair. Data 
for the planned safety reviews will include, at a minimum, a listing of all reported AEs and SAEs.  
12.7.2.2 Ad hoc DSMB Reviews  

COVID19-TB-03 
Confidential 
Page 51 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
In addition to the pre-scheduled data reviews and planned safety monitoring, the DSMB may be 
called upon for ad hoc reviews. The DSMB will  review any event that potentially impacts safety at 
the request of the protocol chair or DAIT/NIAID. In addition, the following events will trigger an ad 
hoc comprehensive DSMB Safety Review:  
 
Any death that occurs in the study which is possibly or definitely related to study treatment 
regimen. 
 
A Pausing Rule (outlined in Section 11.2) is met. 
After review of the data, the DSMB will make recommendations regarding study conduct and/or 
continuation. 
12.7.2.2.1 
Temporary Suspension of enrollment for ad hoc DSMB Safety Review  
See Section 11.2 for Participant Stopping Rules and Withdrawal Criteria 

COVID19-TB-03 
Confidential 
Page 52 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
13. 
Statistical Considerations and Analytical Plan 
13.1 
Overview  
This is a two-arm, open-label randomized trial with the goals of comparing efficacy of additional COVID-19 
vaccine doses for solid organ transplant recipients with a prior weak immune response, with vs without 
immunoreduction. The study population will consist of solid organ transplant recipients who had a negative 
or low response to a licensed or authorized COVID-19 vaccine regimen, who otherwise meet inclusion 
criteria. 
13.2 
Endpoints/Outcomes  
The primary endpoint is the proportional increase in antibody titer U/mL (using the Roche Elecsys® anti-
RBD assay) at 30 days after the study dose of vaccine. Negative or very low antibody responses (<10 U/mL) 
will be imputed to 10 U/mL, to reduce the influence of measurement error on the proportional increase 
calculation among individuals with very low titers. Secondary safety endpoints include: local and systemic 
vaccine reactogenicity and/or allergy; serious adverse events occurring during the 30 days following the 
additional COVID-19 vaccine dose; treated acute cell-mediated and/or antibody-mediated allograft 
rejection (clinical or biopsy-proven) within 60 days following the COVID-19 vaccine dose; development of 
de novo donor-specific anti-HLA antibody within 90 days of the vaccine; graft loss within 60 days of the 
vaccine; and death within 60 days of the vaccine. Secondary efficacy endpoints include: SARS-CoV-2 PCR 
positivity; symptomatic COVID-19; COVID-19 requiring hospitalization; and longitudinal changes in SARS-
CoV-2 antibody response during the study. 
13.3 
Measures to Minimize Bias  
All participants will be randomized to receive immunoreduction or no immunoreduction prior to receipt of 
the vaccine. Randomization will be clustered by study site, and stratified by pre-dose titer (<50 vs ≥50 
U/mL). Treatment group assignment will be unmasked to participants and clinical study staff.  
All laboratory staff will be masked to treatment assignment. 
13.4 
Analysis Plan 
13.4.1 Analysis Populations. 
For the primary outcome and each secondary outcome, the analysis population will consist of all 
individuals with a measurement for that outcome, in an intent-to-treat framework.  
13.4.2 Primary Analysis of Primary Endpoint(s)/Outcome(s) 
The primary endpoint is a continuous measurement. All individuals whose primary endpoint is 
measured will be included in the analysis population.  
 
For the comparison of immunoreduction vs no immunoreduction, we will reject the null hypothesis 
if the two-sided rank-sum p value comparing the -fold increase between the two groups falls below 
0.05. 
13.4.3 Analyses of Secondary and Other Endpoint(s)/Outcome(s) 

COVID19-TB-03 
Confidential 
Page 53 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
All binary secondary endpoints will be analyzed using a Fisher exact test. Severe adverse events will 
be analyzed by calculating the incidence rate difference with a two-sided 95% confidence interval 
for immunoreduction vs no immunoreduction participants. 
13.4.4 Analyses of Exploratory Objectives 
To assess whether timing between vaccine doses is associated with differential antibody response 
to vaccination, we will calculate the median value of time from last pre-study vaccine dose to study 
dose, and then repeat the analysis of antibody response, stratified by the timing between doses 
(above vs below the median). To assess whether there is a difference in antibody levels among 
those receiving additional doses of Pfizer versus Moderna vaccination, we will repeat the analysis of 
antibody response, stratified by type of dose. 
13.4.5 Descriptive Analyses  
Baseline and demographic characteristics will be compared between groups using a ranksum test 
for continuous variables and a Fisher exact test for binary/categorical variables. The relationship 
between demographic and other characteristics and antibody levels will be explored.  
13.5 
Interim Analyses  
13.5.1 Interim Analysis of Efficacy Data 
An interim efficacy analysis is not planned for this trial, because (1) It is extremely unlikely that a 
definitive difference between arms would emerge at a time when it is still possible to stop 
enrollment, and (2) it is desirable to be able to evaluate safety outcomes in the full cohort, 
assuming that no safety stopping rules are met. However, at the time of the safety interim 
analyses, the DSMB will be provided concurrent SARS-CoV-2 antibody results in each arm to aid in 
evaluating the risk/benefit calculus. 
13.5.2 Interim Analysis of Safety Data 
Excess incidence of dnDSA in kidney transplant recipients: An interim analysis will be performed to 
look for evidence of an excess incidence of dnDSA in the IS reduction groups (those undergoing 
withdrawal of MMF; and those undergoing a decrease in CNI dose) as compared with those 
receiving an additional dose of vaccine alone. When fifteen subjects in each of these groups have 
reached day 30 in the study (study visit 4), the core HLA lab will determine whether de novo DSA is 
present. We will perform a similar analysis when fifty subjects in each group have reached day 30. 
At each of these two time points, the proportion with Class II dnDSA in each IS reduction group will 
be compared with the COVID-19 vaccine dose alone group using a one-sided Fisher exact test to 
determine if there is an excess incidence of Class II dnDSA, and the results presented to the DSMB 
for review 
13.6 
Statistical Hypotheses  
All analyses are superiority framework; the null hypotheses are that there is no difference in outcome rates 
between participants who do / do not receive immunoreduction. The alternative hypotheses for both 
safety and efficacy outcomes is that the outcome occurs more frequently in the immunoreduction group.  
13.7 
Sample Size Considerations  

COVID19-TB-03 
Confidential 
Page 55 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
14. 
Identification and Access to Source Data 
14.1 
Source Data 
Source documents and source data are the original documentation where subject information, visits 
consultations, examinations and other information are recorded. Documentation of source data is 
necessary for the reconstruction, evaluation and validation of clinical findings, observations, and other 
activities during a clinical trial.  
14.2 
Access to Source Data 
The site investigators and site staff will make all source data available to the DAIT/NIAID and their 
representatives as well as to relevant health authorities (Food and Drug Administration). Authorized 
representatives as noted above are bound to maintain the strict confidentiality of medical and research 
information that may be linked to identified individuals. 

COVID19-TB-03 
Confidential 
Page 56 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
15. 
Quality Assurance and Quality Control 
Quality control (QC) procedures will be implemented beginning with the data entry system and data QC 
checks. Any missing data or data anomalies will be communicated to the site for clarification/resolution. 
 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical trial is 
conducted, data are generated, and biological specimens are collected, documented (recorded), and 
reported in compliance with the protocol, International Conference on Harmonisation Good Clinical 
Practice (ICH GCP), and applicable regulatory requirements. 
 
The investigational site will provide direct access to all trial related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory 
authorities. 

COVID19-TB-03 
Confidential 
Page 57 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
16. 
Protocol Deviations 
16.1 
Protocol Deviation Definitions 
Protocol Deviation – The investigators and site staff will conduct the study in accordance with the protocol; 
no deviations from the protocol are permitted. Any change, divergence, or departure from the study design 
or procedures constitutes a protocol deviation. As a result of any deviation, corrective actions will be 
developed by the site and implemented promptly. 
 
Major Protocol Deviation (Protocol Violation) - A Protocol Violation is a deviation from the IRB approved 
protocol that may affect the subject's rights, safety, or well-being and/or the completeness, accuracy and 
reliability of the study data. In addition, protocol violations include willful or knowing breaches of human 
subject protection regulations, or policies, any action that is inconsistent with the NIH Human Research 
Protection Program’s research, medical, and ethical principles, and a serious or continuing noncompliance 
with federal, state, local or institutional human subject protection regulations, policies, or procedures.  
 
Non-Major Protocol Deviation - A non-major protocol deviation is any change, divergence, or departure 
from the study design or procedures of a research protocol that does not have a major impact on the 
subject's rights, safety or well-being, or the completeness, accuracy, and reliability of the study data. 
16.2 
Reporting and Managing Protocol Deviations 
The study site principal investigator has the responsibility to identify, document and report protocol 
deviations as directed by the study Sponsor. However, protocol deviations may also be identified during 
site monitoring visits or during other forms of study conduct review.  

COVID19-TB-03 
Confidential 
Page 58 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
17. 
Ethical Considerations and Compliance with Good Clinical Practice 
17.1 
Statement of Compliance 
This clinical study will be conducted using good clinical practice (GCP), as delineated in Guidance for 
Industry: E6 Good Clinical Practice Consolidated Guidance, and according to the criteria specified in this 
study protocol. Before study initiation, the protocol and the informed consent documents will be reviewed 
and approved by the Sponsor and Institutional Review Board (IRB). Any amendments to the protocol or to 
the consent materials will also be approved by the Sponsor and IRB before they are implemented. 
17.2 
Informed Consent Process 
The consent process will provide information about the study to a prospective participant and will allow 
adequate time for review and discussion prior to his/her decision. The principal investigator or designee 
listed on the Investigator of Record Agreement will review the consent and answer questions. The 
prospective participant will be told that being in the trial is voluntary and that he or she may withdraw from 
the study at any time, for any reason. All participants will read, sign, and date a consent form before 
undergoing any study procedures. Consent materials will be presented in the participants’ primary 
language. A copy of the signed consent form will be given to the participant. 
The consent process will be ongoing, and any new findings will be communicated to the participants. The 
consent form will be revised when important new safety information is available, the protocol is amended, 
and/or new information becomes available that may affect participation in the study.  
17.3 
Privacy and Confidentiality 
A participant’s privacy and confidentiality will be respected throughout the study. Each participant will be 
assigned a unique identification number and these numbers rather than names will be used to collect, 
store, and report participant information. Site personnel will not transmit documents containing personal 
health identifiers (PHI) to the study sponsor or their representatives. 

COVID19-TB-03 
Confidential 
Page 59 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
18. 
Publication Policy 
The publication guidelines and policies stipulated in the grant will apply to this protocol.  
 
 
 

COVID19-TB-03 
Confidential 
Page 60 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
19. 
References 
1. 
Fava A, Cucchiari D, Montero N, Toapanta N, Centellas FJ, Vila-Santandreu A, Coloma A, Meneghini M, 
Manonelles A, Sellares J, Torres I, Gelpi R, Lorenzo I, Ventura-Aguiar P, Cofan F, Torregrosa JV, Perello M, 
Facundo C, Seron D, Oppenheimer F, Bestard O, Cruzado JM, Moreso F, Melilli E. Clinical characteristics and risk 
factors for severe COVID-19 in hospitalized kidney transplant recipients: A multicentric cohort study. Am J 
Transplant. 2020;20(11):3030-41. Epub 2020/08/11. doi: 10.1111/ajt.16246. PubMed PMID: 32777153; PMCID: 
PMC7436908. 
2. 
Hilbrands LB, Duivenvoorden R, Vart P, Franssen CFM, Hemmelder MH, Jager KJ, Kieneker LM, Noordzij M, Pena 
MJ, Vries H, Arroyo D, Covic A, Crespo M, Goffin E, Islam M, Massy ZA, Montero N, Oliveira JP, Roca Munoz A, 
Sanchez JE, Sridharan S, Winzeler R, Gansevoort RT, Collaborators E. COVID-19-related mortality in kidney 
transplant and dialysis patients: results of the ERACODA collaboration. Nephrol Dial Transplant. 
2020;35(11):1973-83. Epub 2020/11/06. doi: 10.1093/ndt/gfaa261. PubMed PMID: 33151337; PMCID: 
PMC7665620. 
3. 
Ravanan R, Callaghan CJ, Mumford L, Ushiro-Lumb I, Thorburn D, Casey J, Friend P, Parameshwar J, Currie I, 
Burnapp L, Baker R, Dudley J, Oniscu GC, Berman M, Asher J, Harvey D, Manara A, Manas D, Gardiner D, 
Forsythe JLR. SARS-CoV-2 infection and early mortality of waitlisted and solid organ transplant recipients in 
England: A national cohort study. Am J Transplant. 2020;20(11):3008-18. Epub 2020/08/12. doi: 
10.1111/ajt.16247. PubMed PMID: 32780493; PMCID: PMC7436919. 
4. 
Raja MA, Mendoza MA, Villavicencio A, Anjan S, Reynolds JM, Kittipibul V, Fernandez A, Guerra G, Camargo JF, 
Simkins J, Morris MI, Abbo LA, Natori Y. COVID-19 in solid organ transplant recipients: A systematic review and 
meta-analysis of current literature. Transplant Rev (Orlando). 2021;35(1):100588. Epub 2020/11/28. doi: 
10.1016/j.trre.2020.100588. PubMed PMID: 33246166; PMCID: PMC7666542. 
5. 
Wadei HM, Gonwa TA, Leoni JC, Shah SZ, Aslam N, Speicher LL. COVID-19 infection in Solid Organ Transplant 
Recipients after SARS-CoV-2 vaccination. Am J Transplant. 2021. Epub 2021/04/24. doi: 10.1111/ajt.16618. 
PubMed PMID: 33890410. 
6. 
Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Perez Marc G, Moreira ED, Zerbini 
C, Bailey R, Swanson KA, Roychoudhury S, Koury K, Li P, Kalina WV, Cooper D, Frenck RW, Jr., Hammitt LL, Tureci 
O, Nell H, Schaefer A, Unal S, Tresnan DB, Mather S, Dormitzer PR, Sahin U, Jansen KU, Gruber WC, Group CCT. 
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383(27):2603-15. Epub 
2020/12/11. doi: 10.1056/NEJMoa2034577. PubMed PMID: 33301246; PMCID: PMC7745181. 
7. 
Thompson MG, Burgess JL, Naleway AL, Tyner HL, Yoon SK, Meece J, Olsho LEW, Caban-Martinez AJ, 
Fowlkes A, Lutrick K, Kuntz JL, Dunnigan K, Odean MJ, Hegmann KT, Stefanski E, Edwards LJ, Schaefer-
Solle N, Grant L, Ellingson K, Groom HC, Zunie T, Thiese MS, Ivacic L, Wesley MG, Lamberte JM, Sun X, 
Smith ME, Phillips AL, Groover KD, Yoo YM, Gerald J, Brown RT, Herring MK, Joseph G, Beitel S, Morrill 
TC, Mak J, Rivers P, Harris KM, Hunt DR, Arvay ML, Kutty P, Fry AM, Gaglani M. Interim Estimates of 
Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 
Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers - 
Eight U.S. Locations, December 2020-March 2021. MMWR Morb Mortal Wkly Rep. 2021 Apr 
2;70(13):495-500. doi: 10.15585/mmwr.mm7013e3. PMID: 33793460; PMCID: PMC8022879. 
8. 
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, 
McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, 
Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, 
Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T, Group CS. Efficacy and Safety of the mRNA-1273 
SARS-CoV-2 Vaccine. N Engl J Med. 2021;384(5):403-16. Epub 2020/12/31. doi: 10.1056/NEJMoa2035389. 
PubMed PMID: 33378609; PMCID: PMC7787219. 
9. 
Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz MA, Hernan MA, Lipsitch M, Reis B, Balicer RD. BNT162b2 
mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. N Engl J Med. 2021;384(15):1412-23. Epub 
2021/02/25. doi: 10.1056/NEJMoa2101765. PubMed PMID: 33626250; PMCID: PMC7944975. 

COVID19-TB-03 
Confidential 
Page 61 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
10. Benotmane I, Gautier-Vargas G, Cognard N, Olagne J, Heibel F, Braun-Parvez L, Martzloff J, Perrin P, Moulin B, 
Fafi-Kremer S, Caillard S. Low immunization rates among kidney transplant recipients who received two doses 
of the mRNA-1273 SARS-CoV-2 vaccine. Kidney Int. 2021. Epub 2021/04/23. doi: 10.1016/j.kint.2021.04.005. 
PubMed PMID: 33887315; PMCID: PMC8055921. 
11. Boyarsky BJ, Werbel WA, Avery RK, Tobian AAR, Massie AB, Segev DL, Garonzik-Wang JM. Immunogenicity of a 
Single Dose of SARS-CoV-2 Messenger RNA Vaccine in Solid Organ Transplant Recipients. JAMA. 2021. Epub 
2021/03/16. doi: 10.1001/jama.2021.4385. PubMed PMID: 33720292; PMCID: PMC7961463. 
12. Boyarsky BJ, Werbel WA, Avery RK, Tobian AAR, Massie AB, Segev DL, Garonzik-Wang JM. Antibody Response to 
Two-Dose SARS-CoV-2 Messenger RNA Vaccine Series in Solid Organ Transplant Recipients. JAMA. Accepted 26 
April 2021. 
13. Marinaki S, Adamopoulos S, Degiannis D, Roussos S, Pavlopoulou ID, Hatzakis A, Boletis IN. Immunogenicity of 
SARS-CoV-2 BNT162b2 vaccine in solid organ transplant recipients. Am J Transplant. 2021. Epub 2021/04/18. 
doi: 10.1111/ajt.16607. PubMed PMID: 33864722. 
14. Grupper A, Rabinowich L, Schwartz D, Schwartz IF, Ben-Yehoyada M, Shashar M, Katchman E, Halperin T, Turner 
D, Goykhman Y, Shibolet O, Levy S, Houri I, Baruch R, Katchman H. Reduced humoral response to mRNA SARS-
Cov-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus. Am J Transplant. 
2021. Epub 2021/04/19. doi: 10.1111/ajt.16615. PubMed PMID: 33866672. 
15. Chavarot N, Ouedrani A, Marion O, Leruez-Ville M, Villain E, Baaziz M, Del Bello A, Burger C, Sberro-Soussan R, 
Martinez F, Chatenoud L, Abravanel F, Anglicheau D, Izopet J, Couat C, Zuber J, Legendre C, Lanternier F, Kamar 
N, Scemla A. Poor Anti-SARS-CoV-2 Humoral and T-cell Responses After 2 Injections of mRNA Vaccine in Kidney 
Transplant Recipients Treated with Belatacept. Transplantation. 2021. Epub 2021/04/09. doi: 
10.1097/TP.0000000000003784. PubMed PMID: 33831941. 
16. Rincon-Arevalo H, Choi M, Stefanski AL, Halleck F, Weber U, Szelinski F, Jahrsdörfer B, Schrezenmeier H, Ludwig 
C, Sattler S, Kotsch K, Potekhin A, Chen Y, Burmester GR, Eckardt KU, Guerra GM, Durek P, Heinrich F, Ferreira-
Gomes M, Radbruch A, Budde K, Lino AC, Mashreghi MF, Schrezenmeier E, Dörner T. Impaired antigen-specific 
memory B cell and plasma cell responses including lack of specific IgG upon SARS-CoV-2 BNT162b2 vaccination 
among Kidney Transplant and Dialysis patients. medRxiv 2021.04.15.21255550; doi: 
https://doi.org/10.1101/2021.04.15.2125555017. 
17. Natori Y, Shiotsuka M, Slomovic J, Hoschler K, Ferreira V, Ashton P, Rotstein C, Lilly L, Schiff J, Singer L, Humar A, 
Kumar D. A Double-Blind, Randomized Trial of High-Dose vs Standard-Dose Influenza Vaccine in Adult Solid-
Organ Transplant Recipients. Clin Infect Dis. 2018;66(11):1698-704. Epub 2017/12/19. doi: 10.1093/cid/cix1082. 
PubMed PMID: 29253089. 
18. Nevens F, Zuckerman JN, Burroughs AK, Jung MC, Bayas JM, Kallinowski B, Rivas EF, Duvoux C, Neuhaus P, 
Saliba F, Buti M, Zarski JP, Pons F, Vanlemmens C, Hamtiaux V, Stoffel M. Immunogenicity and safety of an 
experimental adjuvanted hepatitis B candidate vaccine in liver transplant patients. Liver Transpl. 
2006;12(10):1489-95. Epub 2006/09/12. doi: 10.1002/lt.20836. PubMed PMID: 16964595. 
19. Vink P, Ramon Torrell JM, Sanchez Fructuoso A, Kim SJ, Kim SI, Zaltzman J, Ortiz F, Campistol Plana JM, 
Fernandez Rodriguez AM, Rebollo Rodrigo H, Campins Marti M, Perez R, Gonzalez Roncero FM, Kumar D, 
Chiang YJ, Doucette K, Pipeleers L, Aguera Morales ML, Rodriguez-Ferrero ML, Secchi A, McNeil SA, Campora L, 
Di Paolo E, El Idrissi M, Lopez-Fauqued M, Salaun B, Heineman TC, Oostvogels L, Group ZS. Immunogenicity and 
Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal 
Transplant: A Phase 3, Randomized Clinical Trial. Clin Infect Dis. 2020;70(2):181-90. Epub 2019/03/08. doi: 
10.1093/cid/ciz177. PubMed PMID: 30843046; PMCID: PMC6938982. 
20. Boey L, Curinckx A, Roelants M, Derdelinckx I, Van Wijngaerden E, De Munter P, Vos R, Kuypers D, Van 
Cleemput J, Vandermeulen C. Immunogenicity And Safety Of The Nine-Valent Human Papillomavirus Vaccine In 
Solid Organ Transplant Recipients And Hiv-Infected Adults. Clin Infect Dis. 2020. Epub 2020/12/30. doi: 
10.1093/cid/ciaa1897. PubMed PMID: 33373429. 
21. Chapin-Bardales J, Gee J, Myers T. Reactogenicity Following Receipt of mRNA-Based COVID-19 Vaccines. JAMA. 
2021. Epub 2021/04/06. doi: 10.1001/jama.2021.5374. PubMed PMID: 33818592. 

COVID19-TB-03 
Confidential 
Page 62 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
22. Ou MT, Boyarsky BJ, Motter JD, Greenberg RS, Teles AT, Ruddy JA, Krach MR, Jain VS, Werbel WA, Avery RK, 
Massie AB, Segev DL, Garonzik-Wang JM. Safety and Reactogenicity of 2 Doses of SARS-CoV-2 Vaccination in 
Solid Organ Transplant Recipients. Transplantation. 2021. Epub 2021/04/17. doi: 
10.1097/TP.0000000000003780. PubMed PMID: 33859151. 
23. Leuridan E, Van Damme P. Hepatitis B and the need for a booster dose. Clin Infect Dis. 2011 Jul 
1;53(1):68-75. doi: 10.1093/cid/cir270. PMID: 21653306. 
24. Nakashima I, Ota F, Kobayashi T, Kato O, Kato N. The effect of antigen doses and time intervals between 
antigen injections on secondary, tertiary and quaternary antibody responses. Establishment of 
hyperimmunization with bovine serum albumin in mice treated with capsular polysaccharide of 
Klebsiella pneumoniae. Immunology. 1974 Mar;26(3):443-54. PMID: 4137253; PMCID: PMC1423204. 
25. Berek C, Milstein C. Mutation drift and repertoire shift in the maturation of the immune response. 
Immunol Rev. 1987 Apr;96:23-41. doi: 10.1111/j.1600-065x.1987.tb00507.x. PMID: 3298007. 
26. Masopust D, Ha SJ, Vezys V, Ahmed R. Stimulation history dictates memory CD8 T cell phenotype: 
implications for prime-boost vaccination. J Immunol. 2006 Jul 15;177(2):831-9. doi: 
10.4049/jimmunol.177.2.831. PMID: 16818737. 
27. JAMA online head of print May 5, 2021, doi: 10.1001/jama.2021.7489 
28. Chavarot et al, Transplantation online ahead of print, DOI: 10.1097/TP.0000000000003784. 
29. Wu K, Werner AP, Moliva JI, Koch M, Choi A, Stewart-Jones GBE, Bennett H, Boyoglu-Barnum S, Shi W, Graham 
BS, Carfi A, Corbett KS, Seder RA, Edwards DK. mRNA-1273 vaccine induces neutralizing antibodies against spike 
mutants from global SARS-CoV-2 variants. bioRxiv. 2021. Epub 2021/01/28. doi: 10.1101/2021.01.25.427948. 
PubMed PMID: 33501442; PMCID: PMC7836112. 
30. Xie X, Liu Y, Liu J, Zhang X, Zou J, Fontes-Garfias CR, Xia H, Swanson KA, Cutler M, Cooper D, Menachery VD, 
Weaver SC, Dormitzer PR, Shi PY. Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants 
by BNT162b2 vaccine-elicited sera. Nat Med. 2021;27(4):620-1. Epub 2021/02/10. doi: 10.1038/s41591-021-
01270-4. PubMed PMID: 33558724. 
31. Blumenthal KG, Robinson LB, Camargo CA, Jr., Shenoy ES, Banerji A, Landman AB, Wickner P. Acute Allergic 
Reactions to mRNA COVID-19 Vaccines. JAMA. 2021;325(15):1562-5. Epub 2021/03/09. doi: 
10.1001/jama.2021.3976. PubMed PMID: 33683290; PMCID: PMC7941251. 
32. Wu K, Werner AP, Koch M, Choi A, Narayanan E, Stewart-Jones GBE, Colpitts T, Bennett H, Boyoglu-Barnum S, 
Shi W, Moliva JI, Sullivan NJ, Graham BS, Carfi A, Corbett KS, Seder RA, Edwards DK. Serum Neutralizing Activity 
Elicited by mRNA-1273 Vaccine. N Engl J Med. 2021. Epub 2021/03/18. doi: 10.1056/NEJMc2102179. PubMed 
PMID: 33730471. 
33. FACT SHEET FOR HEALTHCARE PROVIDERS ADMINISTERING VACCINE (VACCINATION PROVIDERS) EMERGENCY 
USE AUTHORIZATION (EUA) OF THE MODERNA COVID-19 VACCINE TO PREVENT CORONAVIRUS DISEASE 2019 
(COVID-19). Found at: https://www.fda.gov/media/144637/download.  
34. FACT SHEET FOR HEALTHCARE PROVIDERS ADMINISTERING VACCINE (VACCINATION PROVIDERS) 
EMERGENCY USE AUTHORIZATION (EUA) OF THE PFIZER-BIONTECH COVID-19 VACCINE TO PREVENT 
CORONAVIRUS DISEASE 2019 (COVID-19). Found at: https://www.fda.gov/media/144413/download.  
35. Tsapepas D, Paget K, Mohan S, Cohen DJ, Husain SA, Clinically Significant COVID-19 Following SARS-
CoV-2 Vaccination in Kidney Transplant Recipients, American Journal of Kidney Diseases (2021), doi: 
https://doi.org/10.1053/j.ajkd.2021.05.004. 
36. Ou MT, Boyarsky BJ, Motter JD, Greenberg RS, Teles AT, Ruddy JA, Krach MR, Jain VS, Werbel WA, 
Avery RK, Massie AB, Segev DL, Garonzik-Wang JM. Safety and Reactogenicity of 2 Doses of SARS-CoV-2 
Vaccination in Solid Organ Transplant Recipients. Transplantation. 2021 Apr 9. doi: 
10.1097/TP.0000000000003780. Epub ahead of print. PMID: 33859151. 
37. Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA Vaccine against SARS-CoV-2 - Preliminary 
Report. N Engl J Med. 2020;383(20):1920-1931. 
38. Amanat F, Stadlbauer D, Strohmeier S, et al. A serological assay to detect SARS-CoV-2 seroconversion in 
humans. medRxiv. 2020. 

COVID19-TB-03 
Confidential 
Page 63 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
39. Departments of Research & Development and Product Management, for Roche Diagnostics Solutions, 
Core Lab. Correlation between Elecsys® Anti-SARS-CoV-2 S assay results and the detection of functional 
SARS-CoV-2 neutralizing antibodies. Memo. 8 Feb 2021. 
40. Resman Rus K, Korva M, Knap N, Avsic Zupanc T, Poljak M. Performance of the rapid high-throughput 
automated electrochemiluminescence immunoassay targeting total antibodies to the SARS-CoV-2 spike 
protein receptor binding domain in comparison to the neutralization assay. J Clin Virol. 
2021;139:104820. 
41. Khoury DS, Cromer D, Reynaldi A, et al. Neutralizing antibody levels are highly predictive of immune 
protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021. 
42. Werbel WA, Boyarsky BJ, Ou MT, Massie AB, Tobian AAR, Garonzik-Wang JM, Segev DL. Safety and 
Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case 
Series. Ann Intern Med. 2021 Jun 15:L21-0282. doi: 10.7326/L21-0282. Epub ahead of print. PMID: 
34125572; PMCID: PMC8252023. 
43. Kamar N, Abravanel F, Marion O, Couat C, Izopet J, Del Bello A. Three Doses of an mRNA Covid-19 
Vaccine in Solid-Organ Transplant Recipients. N Engl J Med. 2021 Aug 12;385(7):661-662. doi: 
10.1056/NEJMc2108861. Epub 2021 Jun 23. PMID: 34161700; PMCID: PMC8262620. 
44. Benotmane I, Gautier G, Perrin P, Olagne J, Cognard N, Fafi-Kremer S, Caillard S. Antibody Response 
After a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients With 
Minimal Serologic Response to 2 Doses. JAMA. 2021 Jul 23. doi: 10.1001/jama.2021.12339. Epub ahead 
of print. PMID: 34297036. 
45. Hall VG, Ferreira VH, Ku T, Ierullo M, Majchrzak-Kita B, Chaparro C, Selzner N, Schiff J, McDonald M, 
Tomlinson G, Kulasingam V, Kumar D, Humar A. Randomized Trial of a Third Dose of mRNA-1273 
Vaccine in Transplant Recipients. N Engl J Med. 2021 Aug 11:NEJMc2111462. doi: 
10.1056/NEJMc2111462. Epub ahead of print. PMID: 34379917; PMCID: PMC8385563. 
46. Chavarot N, Morel A, Leruez-Ville M, Villain E, Divard G, Burger C, Serris A, Sberro-Soussan R, Martinez 
F, Amrouche L, Bererhi L, Lanternier F, Legendre C, Zuber J, Anglicheau D, Scemla A. Weak antibody 
response to 3 doses of mRNA vaccine in kidney transplant recipients treated with belatacept. Am J 
Transplant. 2021 Aug 24. doi: 10.1111/ajt.16814. Epub ahead of print. PMID: 34431207. 
47. Karaba AH, Zhu X, Wang KH, Rittenhouse AG, Kinde O, Eby Y, Ruff JE, Blankson JN, Abedon AT, Alejo JL, 
Cox AL, Bailey JR, Thompson EA, Klein SL, Warren DS, Garonzik-Wang JM, Boyarsky BJ, Sitaras I, Pekosz 
A, Segev DL, Tobian AAR, Werbel WA. A Third Dose of SARS-CoV-2 Vaccine Increases Neutralizing 
Antibodies Against Variants of Concern in Solid Organ Transplant Recipients. medRxiv 
2021.08.11.21261914; doi: https://doi.org/10.1101/2021.08.11.21261914 
48. Connolly CM, Chiang TP, Boyarsky BJ, et al. Temporary hold of mycophenolate augments humoral 
response to SARS-CoV-2 vaccination in patients with rheumatic and musculoskeletal diseases: a case 
series. Annals of the Rheumatic Diseases Published Online First: 23 September 
2021. doi: 10.1136/annrheumdis-2021-221252 
49. Park JK, Lee MA, Lee EY, Song YW, Choi Y, Winthrop KL, Lee EB. Effect of methotrexate discontinuation 
on efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical 
trial. Ann Rheum Dis. 2017 Sep;76(9):1559-1565. doi: 10.1136/annrheumdis-2017-211128. Epub 2017 
May 3. PMID: 28468794 
50. Curtis JR, Johnson SR, Anthony DD, Arasaratnam RJ, Baden LR, Bass AR, Calabrese C, Gravallese EM, 
Harpaz R, Kroger A, Sadun RE, Turner AS, Williams A, Mikuls TR. American College of Rheumatology 
Guidance for COVID-19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 
2. Arthritis & Rheumatology. 15 June 2021. https://doi.org/10.1002/art.41877 
51. Yahav D, Rozen-Zvi B, Mashraki T, et al. Immunosuppression reduction when administering a booster 
dose of the BNT162b2 mRNA SARS-CoV-2 vaccine in kidney transplant recipients without adequate 
humoral response following two vaccine doses: protocol for a randomised controlled trial (BECAME 
study) BMJ Open 2021;11:e055611. doi: 10.1136/bmjopen-2021-055611

COVID19-TB-03 
Confidential 
Page 64 of 67 
CPAT-ISR Study  
Version 8.0/September 13, 2023 
52. Karaba AH, Zhu X, Liang T, Wang KH, Rittenhouse AG, Akinde O, Eby Y, Ruff JE, Blankson JN, Abedon AT, 
Alejo JL, Cox AL, Bailey JR, Thompson EA, Klein SL, Warren DS, Garonzik-Wang JM, Boyarsky BJ, Sitaras I, 
Pekosz A, Segev DL, Tobian AAR, Werbel WA. A third dose of SARS-CoV-2 vaccine increases neutralizing 
antibodies against variants of concern in solid organ transplant recipients. Am J Transplant. 2022 
Apr;22(4):1253-1260. doi: 10.1111/ajt.16933. Epub 2022 Jan 18. PMID: 34951746. 
53. Hall VG, Ferreira VH, Ku T, Ierullo M, Majchrzak-Kita B, Chaparro C, Selzner N, Schiff J, McDonald M, 
Tomlinson G, Kulasingam V, Kumar D, Humar A. Randomized Trial of a Third Dose of mRNA-1273 
Vaccine in Transplant Recipients. N Engl J Med. 2021 Sep 23;385(13):1244-1246. doi: 
10.1056/NEJMc2111462. Epub 2021 Aug 11. PMID: 34379917; PMCID: PMC8385563. 
54. Charmetant X, Espi M, Benotmane I, Barateau V, Heibel F, Buron F, Gautier-Vargas G, Delafosse M, 
Perrin P, Koenig A, Cognard N, Levi C, Gallais F, Manière L, Rossolillo P, Soulier E, Pierre F, Ovize A, 
Morelon E, Defrance T, Fafi-Kremer S, Caillard S, Thaunat O. Infection or a third dose of mRNA vaccine 
elicits neutralizing antibody responses against SARS-CoV-2 in kidney transplant recipients. Sci Transl 
Med. 2022 Mar 16;14(636):eabl6141. doi: 10.1126/scitranslmed.abl6141. Epub 2022 Mar 16. PMID: 
35103481; PMCID: PMC8939774. 
55. Kamar N, Abravanel F, Marion O, Esposito L, Hebral AL, Médrano C, Guitard J, Lavayssière L, Cointault 
O, Nogier MB, Bellière J, Faguer S, Couat C, Del Bello A, Izopet J. Anti-SARS-CoV-2 spike protein and 
neutralizing antibodies at 1 and 3 months after three doses of SARS-CoV-2 vaccine in a large cohort of 
solid organ transplant patients. Am J Transplant. 2022 Jan 9. doi: 10.1111/ajt.16950. Epub ahead of 
print. PMID: 35000296. 
56. Carreño JM, Alshammary H, Tcheou J, Singh G, Raskin AJ, Kawabata H, Sominsky LA, Clark JJ, Adelsberg 
DC, Bielak DA, Gonzalez-Reiche AS, Dambrauskas N, Vigdorovich V; PSP-PARIS Study Group, Srivastava 
K, Sather DN, Sordillo EM, Bajic G, van Bakel H, Simon V, Krammer F. Activity of convalescent and 
vaccine serum against SARS-CoV-2 Omicron. Nature. 2022 Feb;602(7898):682-688. doi: 
10.1038/s41586-022-04399-5. Epub 2021 Dec 31. PMID: 35016197. 
57. Kumar D, Hu Q, Samson R, Ferreira VH, Hall VG, Ierullo M, Majchrzak-Kita B, Hardy W, Gingras AC, 
Humar A. Neutralization against Omicron variant in transplant recipients after three doses of mRNA 
vaccine. Am J Transplant. 2022 Mar 10. doi: 10.1111/ajt.17020. Epub ahead of print. PMID: 35266606. 
58. Pajon R, Doria-Rose N, Shen X, et al. SARS-CoV-2 omicron variant neutralization after mRNA-1273 
booster vaccination. N Engl J Med. 2022;386(11):1088-1091. https://www.proquest.com/scholarly-
journals/sars-cov-2-omicron-variant-neutralization-after/docview/2640093333/se-2. doi: 
https://doi.org/10.1056/NEJMc2119912.