Conditions: Lung Transplant Recipient SARS-CoV-2 Immunosuppression
Keywords: SARS-CoV-2 lung transplant recipient immunosuppression
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 19
Healthy volunteers: no

Brief summary:
Lung transplant recipients have poor outcomes after COVID-19 infection with mortality. Due to the immunosuppression, they have had poor responses to SARS-CoV-2 vaccine and remain at high risk of poor outcomes. This is a Phase I/II clinical trial to evaluate the safety and immune response from a higher dose mRNA-1273 vaccine among lung transplant recipients who have already received three or four doses of the COVID-19 vaccine.

Detailed description:
This is a Phase I/II open-label dose-finding trial among lung transplant recipients who received three or four mRNA vaccine doses (mRNA-1273 or BNT162b2) after lung transplantation to: standard-dose (50 ug), mid-dose (100 ug) or high-dose (200 ug) mRNA-1273 booster vaccine. Sixty participants will be enrolled into three dose groups: 1) Standard-dose - 20 participants, 2) Mid-dose - 20 participants, 3) High-dose - 20 participants. The first 2 participants in both the mid-dose and high dose groups will be considered the 'sentinel' group. Participants in the sentinel group will receive the vaccine and undergo a 7-day observation period for safety and reactogenicity before additional participants are enrolled into that dose group.

Overall study enrollment will begin with the mid-dose sentinel group (n=2). During the observation period for the mid-dose sentinel group, we will enroll two participants into the standard-dose group. Once the mid-dose sentinel group completes their 7-day observation period without triggering halting rules and is approved to proceed by the DSMB, we will enroll the next 27 participants (Cohort 1) with a 2:1 randomization into the mid-dose (n=18) and standard-dose (n=9) groups.

Once all 20 participants have received their mid-dose vaccine without triggering halting rules and is approved to proceed by the DSMB, we will enroll the high-dose sentinel group (n=2). Once the high-dose sentinel group completes their 7-day observation period without triggering halting rules and is approved to proceed by the DSMB, we will enroll the next 27 participants (Cohort 2) with a 2:1 randomization into the high-dose (n=18) and standard-dose (n=9) groups. All 20 participants in the mid-dose group will be enrolled prior to the enrollment of the high-dose group.

We will perform stratified randomization for the two cohorts based on: 1) the number of prior doses, and 2) prior receipt of any BNT162b2 vaccines. Randomization with be done by the UCLA Clinical and Translational Science Institute (CTSI) statistics team based on scheduled participants prior to the study visit. The 6 participants in the sentinel (n=4) and initial (n=2) groups (Table 1) will be assigned into the 3 groups based on their scheduled visit day.

Arms:
arm 1: mRNA-1273 (Moderna COVID-19 vaccine) 50 ug arm 2: mRNA-1273 (Moderna COVID-19 vaccine) 100 ug arm 3: mRNA-1273 (Moderna COVID-19 vaccine) 200 ug

Interventions: intervention 1: mRNA-1273 (Moderna COVID-19 vaccine)
Intervention descriptions: intervention 1: Study Drug will be administered via intramuscular injection (IM). Only one dose of study drug will be administered for the study.

Protocol document:
Prot_SAP_000.pdf: 
Phase I/II, Open-label Dose-finding Trial of High-Dose mRNA-1273 Booster for Lung Transplant 
Recipients 
 
 
 
 
 
 
 
 
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University of California, Los Angeles 
Clinical Research Protocol 
Phase I/II, Open-Label Dose-Finding Trial of High-Dose mRNA-1273 Booster for Lung Transplant 
Recipients 
 
Protocol Number: 
COVID-19  
NCT Number: 
NCT05280158 
Version Date: 
4/9/22 
Investigational Product: 
Moderna mRNA-1273 vaccine 
IND Number: 
28260 
Development Phase: 
Phase I/II 
Sponsor/Investigator: 
Yusaku Michael Shino, MD 
Funding Organizations: 
Pending 
Principal Investigator: 
Yusaku Michael Shino, MD 
Department of Medicine – Pulmonary Disease  
University of California, Los Angeles 
Box 951690, 43-229 CHS 
Los Angeles, CA 90095 
 
Medical Monitors: 
Yusaku Michael Shino, MD 
Department of Medicine – Pulmonary Disease  
University of California, Los Angeles 
Box 951690, 43-229 CHS 
Los Angeles, CA 90095 
 
Name: S. Sam Weigt, MD 
Department of Medicine – Pulmonary Disease  
University of California, Los Angeles 
Box 951690, 43-229 CHS 
Los Angeles, CA 90095 
 
This confidential information about an investigational product is provided for the exclusive 
use of investigators of this product and is subject to recall at any time.  The information in 
this document may not be disclosed unless federal or state law or regulations require such 
disclosure.  Subject to the foregoing, this information may be disclosed only to those 
persons involved in the study who have a need to know, with the obligation not to further 
disseminate this information.   
 


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Principal Investigator               Yusaku Michael Shino, MD 
 
Associate Professor, Division of Pulmonary and Critical Care 
Co- Investigator   
 
Otto Yang, MD  
Professor, Division of Infectious Disease 
Co- Investigator   
 
Stephen Samuel Weigt, MD 
 
Associate Professor, Division of Pulmonary and Critical Care  
Co- Investigator   
 
Jesse Lawton Clark, MD 
 
Associate Professor in Residence, Department of Infectious 
Diseases 
Co- Investigator   
 
Name: John A. Belperio, MD 
 
Professor, Division of Pulmonary and Critical Care 
Co- Investigator   
 
Name: David Elashoff, PhD 
Professor, Department of Biostatistics 
 
 
PROTOCOL AGREEMENT 
I have read the protocol specified below. In my formal capacity as Investigator, my duties include 
ensuring the safety of the study participants enrolled under my supervision and providing complete and 
timely information, as outlined in the protocol.  It is understood that all information pertaining to the 
study will be held strictly confidential and that this confidentiality requirement applies to all study staff at 
this site. Furthermore, on behalf of the study staff and myself, I agree to maintain the procedures required 
to carry out the study in accordance with accepted GCP principles and to abide by the terms of this 
protocol. 
 
Protocol Title:  Phase I/II, Open-label Dose-finding Trial of High-Dose mRNA-1273 Booster for Lung 
Transplant Recipients 
 
Protocol Date:  4/9/2022 
 
 
 
 
 
 


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TABLE OF CONTENTS 
Table of contents ............................................................................................................................. 2 
1 
BACKGROUND .................................................................................................................. 15 
1.1 
Overview of Non-Clinical Studies ................................................................................. 16 
1.2 
Overview of Clinical Studies ......................................................................................... 16 
2 
STUDY RATIONALE ......................................................................................................... 16 
2.1 
Risk / Benefit Assessment .............................................................................................. 17 
3 
STUDY OBJECTIVES ......................................................................................................... 18 
3.1 
Primary Objective .......................................................................................................... 18 
3.2 
Secondary Objectives ..................................................................................................... 18 
4 
STUDY DESIGN.................................................................................................................. 19 
4.1 
Study Overview .............................................................................................................. 19 
5 
CRITERIA FOR EVALUATION ........................................................................................ 21 
5.1 
Primary Safety Endpoint ................................................................................................ 21 
5.2 
Secondary Immunogenicity Endpoints .......................................................................... 21 
5.3 
Safety Evaluations .......................................................................................................... 22 
6 
PARTICIPANT SELECTION .............................................................................................. 22 
6.1 
Study Population ............................................................................................................ 22 
6.2 
Inclusion Criteria ............................................................................................................ 22 
6.3 
Exclusion Criteria ........................................................................................................... 23 
7 
CONCURRENT MEDICATIONS ....................................................................................... 24 
7.1 
Allowed Medications and Treatments............................................................................ 24 
7.2 
Prohibited Medications and Treatments ......................................................................... 24 
8 
STUDY TREATMENTS ...................................................................................................... 25 
8.1 
Method of Assigning Participants to Treatment Groups ................................................ 25 
8.2 
Formulation .................................................................................................................... 25 
8.3 
Packaging and Labeling ................................................................................................. 26 
8.4 
Supply of Study Drug at the Site .................................................................................... 26 
8.4.1 
Dosage/Dosage Regimen ........................................................................................ 26 
8.4.2 
Dispensing............................................................................................................... 26 
8.4.3 
Administration Instructions .................................................................................... 26 


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8.5 
Supply of Study Drug at the Site .................................................................................... 26 
8.5.1 
Storage .................................................................................................................... 26 
8.6 
Measures of Treatment Compliance .............................................................................. 27 
9 
STUDY PROCEDURES AND GUIDELINES .................................................................... 27 
9.1 
Clinical Assessments ...................................................................................................... 27 
9.1.1 
Concomitant Medications ....................................................................................... 27 
9.1.2 
Demographics ......................................................................................................... 27 
9.1.3 
Medical History ...................................................................................................... 27 
9.1.4 
Physical Examination.............................................................................................. 27 
9.1.5 
Vital Signs ............................................................................................................... 27 
9.1.6 
Adverse Events ....................................................................................................... 28 
9.2 
Clinical Laboratory Measurements ................................................................................ 28 
 
Research Labs ......................................................................................................... 28 
9.2.1 
28 
9.2.2 
Clinical Labs ........................................................................................................... 28 
10 EVALUATIONS BY VISIT................................................................................................. 28 
10.1 Screening/Enrollment Day -30 to 0 (Phone) .................................................................. 28 
10.2 Visit 1 Day 1 (Clinic): Booster Day Vaccine #4 ............................................................ 28 
10.3 Visit 2 Day 3 +/-1 Day (Phone - 2 days post booster): .................................................. 29 
10.4 Visit 3 Day 7 +/-2 Days (Clinic Visit – 6 days post booster:) ....................................... 29 
10.5 Visit 4 Day 30 +/- 7 Days (Clinic – 29 days post booster): ........................................... 30 
10.6 Visit 5 Day 90 +/- 7 Days (Phone - 89 days post booster): ............................................ 30 
10.7 Visit 6 Day 180 +/- 7 Days (Phone – 179 days post booster): End of study ................. 30 
10.8 Unscheduled Additional Visit as needed ....................................................................... 30 
11 ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION ............................. 30 
11.1 Adverse Events ............................................................................................................... 30 
11.2 Serious Adverse Experiences (SAE) .............................................................................. 35 
11.2.1 Serious Adverse Experience Reporting .................................................................. 35 
11.3 Adverse Events of Special Interest................................................................................. 35 
11.4 Medical Monitoring........................................................................................................ 38 
12 DISCONTINUATION AND REPLACEMENT OF PARTICIPANTS............................... 38 


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12.1 Screen Failures ............................................................................................................... 38 
12.2 Halting Criteria for Sentinel Group ................................................................................ 38 
12.3 Halting Criteria for Full Group ...................................................................................... 39 
12.4 Early Discontinuation of Study ...................................................................................... 39 
12.5 Withdrawal of Participants from the Study .................................................................... 40 
12.6 Lost to Follow-up ........................................................................................................... 40 
12.7 Replacement of Participants ........................................................................................... 41 
13 PROTOCOL VIOLATIONS ................................................................................................ 41 
14 STATISTICAL METHODS AND CONSIDERATIONS.................................................... 41 
14.1 General Considerations .................................................................................................. 41 
14.2 Demographic and Baseline Characteristics .................................................................... 42 
14.3 Analysis of Primary Endpoint ........................................................................................ 42 
14.4 Analysis of Secondary Endpoints .................................................................................. 42 
14.5 Analysis of Safety .......................................................................................................... 43 
14.6 Sample Size Justification ............................................................................................... 43 
14.7 Interim Analysis ............................................................................................................. 43 
15 DATA COLLECTION, RETENTION AND MONITORING ............................................ 44 
15.1 Data Collection Instruments ........................................................................................... 44 
15.2 Data Management Procedures ........................................................................................ 44 
15.3 Data Quality Control and Reporting .............................................................................. 44 
15.4 Archival of Data ............................................................................................................. 44 
15.5 Availability and Retention of Investigational Records .................................................. 44 
15.6 Monitoring ...................................................................................................................... 45 
15.7 Participant Confidentiality ............................................................................................. 45 
15.8 Protocol Amendments .................................................................................................... 45 
15.9 Institutional Review Boards and Independent Ethics Committees ................................ 45 
15.10 Informed Consent Form ................................................................................................. 46 
15.11 Publications .................................................................................................................... 46 
15.12 Investigator Responsibilities .......................................................................................... 46 
Appendix 1: Schedule of events ................................................................................................... 47 
Appendix 2: Adverse Events of Special Interest (AESI) Terms................................................... 49 


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Appendix 3: Table of Laboratory abnormalities ........................................................................... 52 
Appendix 4: Claim for Categorical Exclusion .............................................................................. 53 
REFERENCES ............................................................................................................................. 54 
 
 
LIST OF ABBREVIATIONS 
 
AE 
adverse event 
AESI 
adverse event of special interest 
AR 
adverse reaction 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
BNP 
aspartate aminotransferase 
brain naturetic peptide 
Bid 
twice a day 
BMI 
body mass index 
BP 
blood pressure 
BUN 
blood urea nitrogen 
C 
CK 
CKMB 
cm 
cMRI 
CONSORT 
Celsius  
creatinine kinase 
creatinine kinase myocardial band 
centimeter 
cardiac magnetic resonance imaging 
Consolidated Standard of Reporting Trials 
COVID-19 
Cr 
coronavirus disease 2019 
creatinine 
CrCL 
CRF 
creatinine clearance 
case report form 
CTSI 
Clinical & Translational Science Institute 
DHHS 
Department of Health and Human Services 
DMC 
Data Monitoring Committee 
DMF 
drug master file 
EC 
European Commission 
ECG 
electrocardiogram 
eCRF 
EKG 
EOS 
EU 
electronic case report form 
electrocardiogram 
end of study 
European Union 
F 
Fahrenheit 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 


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GMC 
geometric mean concentrations 
GMT 
geometric mean titers 
HEENT 
head, ears, eyes, nose, throat 
Hg 
Mercury 
Hgb 
Hemoglobin 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
human immunodeficiency virus 
HTN 
Hypertension 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IgA 
immunoglobulin A 
IgG 
immunoglobulin G 
IgM 
immunoglobulin M 
IM 
Intramuscular 
IND 
investigational new drug 
IRB 
Institutional Review Board 
ITT 
intent to treat 
IU 
international unit 
IV 
Intravenous 
IVIG 
intravenous immune globulin 
Kg 
LLOQ 
LNP 
LOA 
Kilogram 
Lower limit of quantification 
lipid non-particle 
letter of authorization 
LTOS 
long term outcome study 
MAAE 
MD 
mg 
mL 
mm 
medically attended adverse event 
medical doctor 
milligram 
milliliter 
millimeter 
mRNA 
m2 
NaCl 
messenger RNA 
square meter 
sodium chloride 
Ng 
NOCM 
Nanogram 
new onset chronic medical condition 
NP 
nurse practitioner 
ORA 
Office of Regulatory Affairs 
PA 
Physician’s assistant 
PBMC 
peripheral blood mononuclear cell 
PI 
Principal Investigator 
Plt 
PP 
platelet 
per protocol 


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PT 
prothrombin time 
PTT 
partial prothrombin time 
RBD 
receptor binding domain 
RN 
registered nurse 
SAE 
serious adverse experience 
SARS-CoV-2 
SD 
severe acute respiratory syndrome coronavirus 2 
standard deviation 
S-2P 
T Bili 
UCLA 
spike protein 
total Bilirubin 
University of California, Los Angeles 
ug 
USP 
microgram 
United States Pharmacopeia 
WBC 
white blood cells 
 
 


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PROTOCOL SYNOPSIS 
TITLE 
Phase I/II, Open-label Dose-Finding Trial of High-Dose mRNA-1273 
Booster for Lung Transplant Recipients 
 
 
SPONSOR/INVESTIGAT
OR 
Yusaku Michael Shino, MD 
 
Department of Medicine – Pulmonary Disease  
University of California, Los Angeles 
Box 951690, 43-229 CHS 
Los Angeles, CA 90095 
Telephone:  310-866-6327 
Fax: 
 310-206-8622 
E-mail: MShino@mednet.ucla.edu 
 
 
FUNDING 
ORGANIZATIONS 
Departmental funding 
NUMBER OF SITES 
Single site  
 
 
RATIONALE 
Lung transplant recipients have poor outcomes after COVID-19 infection 
with case fatality rates ranging between 14-39% (1–4). In contrast to 
immunocompetent participants in vaccine trials, solid organ transplant 
recipients have had poor responses to SARS-CoV-2 vaccines with several 
studies reporting anti-SARS-CoV-2 antibody detection in only 34-54% after 
the second dose (5–7). Lung transplant recipients generally require higher 
levels of immunosuppression due to the allograft’s exposure to the external 
environment and active immune surveillance. Thus, vaccine responses have 
been even weaker for lung transplant recipients with several studies 
reporting antibody responses in less than 20% after the second dose (5, 8–
10). Booster vaccines (3rd dose) appear to improve immune responses for 
solid organ recipients (11–13), but has not been studied specifically for lung 
transplant recipients. 
 
 
STUDY DESIGN 
This is a Phase I/II open-label dose-finding trial among lung transplant 
recipients who received three or four mRNA vaccine doses (mRNA-1273 or 
BNT162b2) after lung transplantation to: standard-dose (50 ug), mid-dose 
(100 ug) or high-dose (200 ug) mRNA-1273 booster vaccine. Sixty 
participants will be enrolled into three dose groups: 1) Standard-dose – 20 
participants, 2) Mid-dose – 20 participants, 3) High-dose – 20 participants. 
The first 2 participants in both the mid-dose and high dose groups will be 
considered the ‘sentinel’ group. Participants in the sentinel group will 
receive the vaccine and undergo a 7-day observation period for safety and 
reactogenicity before additional participants are enrolled into that dose 
group.  


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Overall study enrollment will begin with the mid-dose sentinel group (n=2). 
During the observation period for the mid-dose sentinel group, we will 
enroll two participants into the standard-dose group. Once the mid-dose 
sentinel group completes their 7-day observation period without triggering 
halting rules and is approved to proceed by the DSMB, we will enroll the 
next 27 participants (Cohort 1) with a 2:1 randomization into the mid-dose 
(n=18) and standard-dose (n=9) groups.  
 
Once all 20 participants have received their mid-dose vaccine without 
triggering halting rules and is approved to proceed by the DSMB, we will 
enroll the high-dose sentinel group (n=2). Once the high-dose sentinel group 
completes their 7-day observation period without triggering halting rules 
and is approved to proceed by the DSMB, we will enroll the next 27 
participants (Cohort 2) with a 2:1 randomization into the high-dose (n=18) 
and standard-dose (n=9) groups. All 20 participants in the mid-dose group 
will be enrolled prior to the enrollment of the high-dose group.   
  
We will perform stratified randomization for the two cohorts based on: 1) 
the number of prior doses, and 2) prior receipt of any BNT162b2 vaccines. 
Randomization with be done by the UCLA Clinical and Translational 
Science Institute (CTSI) statistics team based on scheduled participants prior 
to the study visit. The 6 participants in the sentinel (n=4) and initial (n=2) 
groups (Table 1) will be assigned into the 3 groups based on their scheduled 
visit day. 
 
 
 
PRIMARY OBJECTIVE 
1. Evaluate safety of high-dose mRNA-1273 vaccine among lung 
transplant recipients measured by incidence of adverse events.  
2. Evaluate reactogenicity of high-dose mRNA-1273 vaccine among lung 
transplant recipients measured by FDA Toxicity Grading scale. 
 
 
SECONDARY 
OBJECTIVES 
1. Evaluate humoral immunogenicity measured by anti-RBD and anti-
spike (S-2P) IgG levels at Day 30.  
2. Evaluate humoral immunogenicity measured by neutralizing antibody 
titers from a pseudovirus neutralization assay at Day 30.   
3. Evaluate cellular immunogenicity measured by cellular response assays 
including flow cytometry with intracellular staining at Day 30.  
 
 


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NUMBER OF 
PARTICIPANTS 
60 Total: 
 
The following numbers of participants will be enrolled:  
1A) Standard-dose – Initial Group 
2 
50 ug 
1B) Standard-dose – Full Group 
18 
50 ug 
 
 
 
2A) Mid-dose – Sentinel Group 
2 
100 ug 
2B) Mid-dose – Full Group 
18 
100 ug 
 
 
 
3A) High-dose – Sentinel Group 
2 
200 ug 
3B) High-dose – Full Group 
18 
200 ug 
 
 
 
PARTICIPANT 
SELECTION 
CRITERIA 
Inclusion Criteria: 
1. All adult lung transplant recipients (age ≥ 18 at the time of consent) 
who received all of their COVID-19 vaccines after lung 
transplantation. 
2. Received three or four doses of either the Moderna mRNA-1273 or 
Pfizer BNT162b2 vaccine with the last dose received at least 4 
months prior to study enrollment.  
3. Currently receiving standard regimen of three drug 
immunosuppression with prednisone, tacrolimus and mycophenolate 
mofetil (cellcept, minimum 250 mg bid) or mycophenolate sodium 
(myfortic, minimum 180 mg bid). 
4. Agrees not to receive other investigational agents for prophylaxis 
against COVID-19 including Evusheld monoclonal antibodies for at 
least 30 days after the study vaccine. 
5. Understands and agrees to comply with the study procedures and 
provides written informed consent. 
6. Is in stable health without any new or worsening medical conditions 
in the opinion of the Investigator. 
7. Female participants of childbearing potential (<1 year since start of 
menopause) may be enrolled in the study if the participant fulfills all 
the following criteria: 
a. Has a negative pregnancy test at Visit 1 Day 1. 
b. Has practiced adequate contraception or has abstained from 
all activities that could result in pregnancy for at least 28 
days prior to the first injection (Day 1). 
c. Has agreed to continue adequate contraception or practice 
abstinence through 3 months following the booster injection 
(Day 90). 


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d. Is not currently breastfeeding. 
e. Adequate female contraception is defined as consistent and 
correct use of a Food and Drug Administration (FDA) 
approved contraceptive method in accordance with the 
product label. For example: 
i. Barrier method (such as condoms, diaphragm, or 
cervical cap) used in conjunction with spermicide 
ii. Intrauterine device 
iii. Prescription hormonal contraceptive taken or 
administered via oral (pill), transdermal (patch), 
subdermal, or IM route 
iv. Sterilization of a female participant’s monogamous 
male partner prior to entry into the study 
v. Note: periodic abstinence (e.g., calendar, ovulation 
methods) and withdrawal are not acceptable 
methods of contraception. 
Exclusion Criteria: 
1. Previous documented COVID-19 infection. 
2. Use of investigational agents for prophylaxis against COVID-19 within 
90 days of the start of the study, including Evusheld monoclonal 
antibodies.  
3. Ongoing therapy for acute cellular or antibody mediated rejection. 
4. Intravenous immunoglobulins (IVIG) administration within the prior 3 
months or ongoing IVIG therapy.   
5. Anaphylaxis or allergic reaction to any prior vaccines. 
6. History of anaphylaxis or other significant adverse reaction requiring 
medical intervention after receipt of a vaccine. 
7. Is acutely ill or febrile 24 hours prior to or at the Day 1 visit. Fever is 
defined as a body temperature ≥ 38.0°C/100.4°F. Participants meeting 
this criterion may be rescheduled within the relevant window periods. 
Afebrile participants with minor illnesses can be enrolled at the 
discretion of the investigator. 
8. Pregnant or breastfeeding. 
9. Has a medical, psychiatric, or occupational condition that may pose 
additional risk as a result of participation, or that could interfere with 
safety assessments or interpretation of results according to the 
investigator’s judgment. 
10. Known history of hypertension (HTN) with systolic blood pressure (BP) 
> 180 mm Hg at the Day 1 visit.  


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11. Known history of hypotension with systolic blood pressure < 85 mm Hg 
at the Day 1 visit.  
12. Bleeding disorder considered a contraindication to IM injection or 
phlebotomy. 
13. Active malignancy diagnosed within previous 4 years (excluding non-
melanoma skin cancer). 
14. Received a major surgery including lung transplantation in the past 3 
months.  
 
 
TEST PRODUCT, DOSE, 
AND ROUTE OF 
ADMINISTRATION 
1.   mRNA-1273 is an LNP dispersion containing an mRNA that encodes for 
the pre-fusion stabilized spike protein 2019-nCoV. 
2.   mRNA-1273 will be received at a concentration of 0.2 mg/ml. The 
investigational pharmacy will prepare doses of 50 ug (0.25 ml) standard-
dose, 100 ug (0.5 ml) mid-dose and 200 ug (1 ml) high-dose.     
 
CONTROL PRODUCT, 
DOSE AND ROUTE OF 
ADMINISTRATION 
The mRNA-1273 vaccine, provided as a sterile liquid at a concentration of 
0.2 mg per milliliter, will be administered by injection into the deltoid 
muscle in a volume of 0.25 ml (50 ug), 0.5 ml (100 ug) or 1.0 ml (200 ug). 
Vaccine mRNA-1273 will be stored at 2° to 8°C (35.6° to 46.4°F) at clinical 
sites before preparation and vaccination. No dilution was required. Doses 
could be held in syringes for up to 8 hours at room temperature before 
administration. 
DURATION OF 
PARTICIPANT 
PARTICIPATION AND 
DURATION OF STUDY 
Treatment: Day 1 intramuscular injection  
Follow-up: 6 months 
Participants will be on study for up to 7 months. 
The total duration of the study for recruitment and completion of 
participants is expected to be up to 12 months. 
CONCOMMITANT 
MEDICATIONS 
Based on inclusion criteria, participants will be required to be on a regimen 
of triple immunosuppression including prednisone, mycophenolate mofetil 
(minimum 250 mg bid) or mycophenolate sodium (minimum 180 mg bid), 
and tacrolimus at the Day 1 study visit. Participants receiving IVIG or 
augmented immunosuppression for treatment of acute cellular rejection or 
antibody mediated rejection will be excluded from the study.  
EFFICACY 
EVALUATIONS 
 
PRIMARY ENDPOINT 
1. Frequency and grade of each solicited local and systemic reactogenicity 
AE will be recorded on a daily diary using the FDA Toxicity Grading 
Scale and collected from Day 1 until Day 7.   
2. Frequency and grade of each unsolicited adverse events will be recorded 
on a daily diary and collected from Day 1 until Day 30. 


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3. Frequency of any serious adverse experiences (SAEs) and adverse 
events of special interests (AESIs) will be collected from Day 1 until 
Day 180.  
SECONDARY 
ENDPOINTS 
1. Humoral immunogenicity measured by anti-RBD and anti-spike (S-2P) 
IgG levels at Day 30.  
2. Humoral immunogenicity measured by neutralizing antibody titers from 
a pseudovirus neutralization assay at Day 30.   
3. Cellular immunogenicity measured by cellular response assays 
including flow cytometry with intracellular staining at Day 30. 
SAFETY 
EVALUATIONS 
The study will use a Data and Safety Monitoring Board (DSMB). DSMB 
reviews are required for study halting and restarting. Reporting to regulatory 
bodies (IRB, FDA) will only be required for serious adverse events judged 
by the treating physician and study investigators to be potentially related to 
the administration of the study drug. All other adverse events will be 
reviewed by the study investigators and reported per FDA and IRB 
regulations. The study will be overseen by CTSI Data and Safety monitoring 
Board. By allowing CTSI DSMB to oversee the study, the PI agrees to abide 
by the CTSI DSMB’s policies and procedures as outlined in the DSMB 
charter. 
PLANNED INTERIM 
ANALYSES  
Interim analysis of the secondary immunogenicity endpoints (humoral and 
cellular immunogenicity) may be conducted once all study participants have 
completed their Day 30 visit and blood draw.   
Statistical Analysis Plan 
Primary Objective Analysis:  
1. Safety: will be measured by the frequency and grade of AEs 
(solicited and unsolicited), SAEs, AESIs, MAAEs.  
2. Reactogenicity: will be measured by the occurrence of solicited 
injection site and systemic reactions.  Simple descriptive statistics 
will be used to summarize toxicities in terms of type, severity and 
minimum or maximum values for laboratory measures, time of 
onset, duration, and reversibility or outcome. Tables will be created 
to summarize these toxicities and side effects. Safety Analyses will 
be performed on Safety Analysis Set. 
 
Secondary Objective Analysis: 
1. Binding antibody: The anti-RBD and anti-spike (S-2P) IgG 
concentrations (log10 and geometric mean concentrations (GMC)) 
at Day 30 will be evaluated with comparisons between the standard-
dose versus high-dose groups. T-tests with two-sided p<0.05 
significance will be used (overall α level of 0.1). Changes in the 
anti-RBC and anti-spike IgG concentrations at Day 30 will be 
compared between the standard-dose versus high-dose groups using 
two sample T-tests with two-sided p<0.05 significance (overall α 
level of 0.1). The percent of participants with detectable antibody 


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levels (greater than the LLOQ) at Day 30 will also be evaluated 
using Fisher’s exact tests. Pairwise comparisons of binding 
antibodies will also be evaluated between the standard-dose versus 
mid-dose groups. 
 
2. Neutralizing antibody: Neutralizing antibody titers (geometric 
mean titers (GMT)) from a pseudovirus neutralization assay at Day 
30 will be compared between the standard-dose versus high-dose 
groups using T-tests with two-sided p<0.05 significance (overall α 
level of 0.1). Changes in the neutralizing antibody titers at Day 30 
will be compared between the standard-dose versus high-dose 
groups using two sample T-tests with two-sided p<0.05 significance 
(overall α level of 0.1). The percent of participants with detectable 
neutralizing antibody levels (greater than the LLOQ) at Day 30 will 
also be evaluated using Fisher’s exact tests. Pairwise comparisons of 
neutralizing antibodies will also be evaluated between the standard-
dose versus mid-dose groups. 
 
3. Cellular immunogenicity: The change in the frequency of target 
cytokine producing T-cells by flow cytometry with intracellular 
staining at Day 30 will be compared using the Kruskal-Wallis Test 
for the standard-dose versus high-dose groups. A comparison of T-
cell frequencies between the standard-dose versus high-dose groups 
will be evaluated using the Wilcoxon rank-sum test. Pairwise 
comparisons of cellular immunogenicity will also be evaluated 
between the standard-dose versus mid-dose groups. 
Rationale for Number of 
Participants 
The overall mean log10 IgG increase after the third (100 ug) vaccine dose 
was 0.46 with standard deviation (SD) 0.63. Assuming participants have a 
50% lower response to the 50 ug fourth-dose, the expected mean log10 IgG 
increase is 0.23. Assuming participants have a 100% higher response to the 
200 ug fourth-dose, their expected mean log10 IgG increase is 0.91. For 
80% power to detect this difference between high-dose and standard-dose 
groups with a SD of 0.63 for a two-sample t-test with two-sided α<0.05 
significance, the minimum required sample size is 15 per group. Thus, we 
will enroll 20 participants into each group. The first 2 participants in the mid 
and high-dose groups will be enrolled as the sentinel group to ensure an 
acceptable safety profile before the full group is enrolled.  
 
1 
BACKGROUND 
The Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) emerged in December 2019 and has caused a 
global pandemic of unparalleled proportion with a respiratory illness named Coronavirus Disease 2019 
(Covid-19). The urgent need for interventions to reduce the high morbidity and mortality associated with 
Covid-19 has led to numerous vaccine candidates based on traditional and new platforms. mRNA-1273 is 


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a lipid-nanoparticle (LNP) encapsulated mRNA vaccine encoding a pre-fusion stabilized form of the 
SARS-CoV-2 spike protein (S-2P).  
1.1 
Overview of Non-Clinical Studies 
Non-clinical studies have demonstrated the immunogenicity, safety and vaccine efficacy of the mRNA-
1273 vaccine. Early studies in non-human primates showed robust SARS-CoV-2 neutralizing activity 
with rapid protection from high-dose SARS-CoV-2 challenge (1). Subsequent non-human primate studies 
showed a dose-response relationship between increasing mRNA-1273 doses and both serum anti-S-2P 
IgG levels as well as protection from viral challenge (2). No animals with anti-S-2P IgG > 645  
international units (IU)/mL had nasal swab positivity > 100,000 copies/swab. Furthermore, passive 
transfer of vaccine-induced IgG from non-human primates to naïve hamsters was protective against 
infection (2).  
1.2 
Overview of Clinical Studies 
Efficacy of the mRNA-1273 vaccine was demonstrated in a phase 3 randomized trial of 30,420 
participants in the COVE Study (3, 4). Vaccine efficacy in was 94.1% at preventing COVID-19 illness, 
including severe disease. Local and systemic reactions to the vaccine were common and included pain at 
injection site, headache, fatigue, myalgias and arthralgias. However, these reactions were transitory and 
there were no serious adverse events, episodes of thrombosis or myocarditis associated with the vaccine 
(3, 4). Hypersensitivity reactions were reported in 1.5% and 1.1% of participants in the vaccine and 
placebo groups, respectively.  
Several medical conditions have been reported in temporal association with COVID-19 vaccines. 
Thrombosis with thrombocytopenia syndrome (TTS) and Guillain-Barre syndrome (GBS) have been 
reported after the Johnson & Johnson Janssen vaccine (5), although these conditions have not been 
associated with the mRNA vaccines (Pfizer-BioNTech and Moderna). The mRNA vaccines have been 
associated with an increased risk of myocarditis and pericarditis, particularly among young males after 
the second dose (6–9). The incidence of myocarditis/pericarditis is low and estimated at 3.5 cases per 
million doses after second dose mRNA among all adults, and 24.3 cases per million among individuals 12 
to 29 years of age (10). Most reported cases of myocarditis/pericarditis occurred within the first 7 days of 
vaccination (7–9). Despite the potential for these rare but serious conditions, the benefit-risk assessment 
for Covid-19 vaccination remains strongly in favor of vaccination for those over age 5.     
The phase 1 mRNA-1273 clinical trial evaluated three doses: 25 ug, 100 ug and 250 ug. There was a 
dose-response relationship between increasing mRNA-1273 doses and serum anti-S-2P antibody levels. 
Systemic adverse reactions including fatigue, chills, headache, myalgia and injection site pain occurred in 
more than half the participants, and occurred more frequently with the 250 ug dose. Thus, the 100 ug dose 
was eventually chosen for the phase 3 clinical trial. 
 
 
2 
STUDY RATIONALE 
In contrast to immunocompetent participants in vaccine trials, solid organ transplant recipients have poor 
responses to SARS-CoV-2 vaccines with studies reporting anti-S-protein antibody detection in only 34-


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54% after the second dose (11–13). Lung transplant recipients in particular have weak responses to the 
vaccine with antibody responses observed in less than 20% after the second dose (11, 14–16). Due to the 
allograft’s exposure to the external environment and active immune surveillance, lung transplant 
recipients generally require higher levels of immunosuppression. Lung transplantation is also unique 
among the solid organ transplants in the direct infection and injury of the allograft by SARS-CoV-2.  
Thus, lung transplant recipients have had poor outcomes after COVID-19 infection with case fatality rates 
ranging between 14-39% (17–20). Third vaccine doses appear to improve immune responses for solid 
organ recipients (21–23), but has not been studied specifically for lung transplant recipients.  
The objectives of this study are to determine the safety, reactogenicity and immunogenicity of a mid-dose 
(100 ug) and high-dose (200 ug) booster mRNA-1273 vaccine among lung transplant recipients who 
previously received three or four mRNA-1273 vaccine doses.  
A single-center observational cohort study of 165 pts at UCLA found that only 35% of lung transplant 
recipients mounted an anti-RBD IgG antibody response after the second mRNA vaccine dose (Pfizer or 
Moderna), with an increase to 59% after the third dose. In contrast, lung transplant recipients who were 
either: 1) infected with COVID-19 or 2) received at least one vaccine dose before transplant, had higher 
antibody levels approaching those of healthy participants. This suggests that lung transplant recipients 
may be able to mount a stronger immune response to higher antigen exposure, and may be able to retain 
their antibody response afterwards. Importantly, we found that reactogenicity was significantly less for 
lung transplant recipients after both the second and third dose of the vaccine compared with healthy 
vaccine recipients. The frequency of any systemic adverse reaction (fever, fatigue, headache, myalgia, 
arthralgia, chills or nausea) was 46% after the third dose for lung transplant recipients compared with 
80% for healthy vaccine recipients.  
In summary, lung transplant recipients have weak antibody responses to the mRNA-1273 vaccine and 
remain at high risk for morbidity and mortality due to Covid-19. The 100 ug third dose was associated 
with significantly less systemic adverse reactions compared with healthy vaccine recipients. Thus, we 
hypothesize that we can safely improve the immunogenicity of the mRNA-1273 vaccine by administering 
a 100 ug or 200 ug booster dose to lung transplant recipients, instead of the currently recommended 50 ug 
booster dose. We will conduct the study as an open-label dose-finding trial comparing: standard-dose (50 
ug) booster, mid-dose (100 ug) and high-dose (200 ug) mRNA-1273 booster as described below.  
 
2.1 
Risk / Benefit Assessment 
Efficacy of the mRNA-1273 vaccine was demonstrated in a phase 3 randomized trial of 30,420 
participants in the COVD Study (3, 4). Vaccine efficacy in was 94.1% at preventing COVID-19 illness, 
including severe disease. Local and systemic reactions to the vaccine were common and included pain at 
injection site, headache, fatigue, myalgias and arthralgias. However, these reactions were transitory and 
there were no serious adverse events, episodes of thrombosis or myocarditis associated with the vaccine 
(3, 4). Hypersensitivity reactions were reported in 1.5% and 1.1% of participants in the vaccine and 
placebo groups, respectively.  
Rare episodes of myocarditis and pericarditis have been reported after the mRNA vaccines (Pfizer-
BioNTech and Moderna), particularly among young males after the second dose (9, 24, 25). The 
incidence of myocarditis/pericarditis is low and estimated at 3.5 cases per million doses after second dose 
mRNA among all adults, and 24.3 cases per million among individuals 12 to 29 years of age (10) . Most 


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reported cases of myocarditis/pericarditis occurred within the first 7 days of vaccination (7–9). Despite 
the potential for these rare but serious conditions, the benefit-risk assessment for Covid-19 vaccination 
remains strongly in favor of vaccination for those over age 5. Of note, myocarditis has also been 
associated with COVID-19 infection at a higher incidence than with the mRNA vaccines (6, 26). Analysis 
of a large national database found the risk ratio of myocarditis after vaccination to be 3.2 (95% CI 1.6-
12.4) compared with those who were unvaccinated (6). After COVID-19 infection, the risk ratio of 
myocarditis was 18.3 (95% CI 4.0-25.1) compared with those who were unvaccinated.   
The phase 1 mRNA-1273 clinical trial evaluated three doses: 25 ug, 100 ug and 250 ug. There was a 
dose-response relationship between increasing mRNA-1273 doses and serum anti-S-2P antibody levels. 
Systemic adverse reactions including fatigue, chills, headache, myalgia and injection site pain occurred in 
more than half the participants, and occurred more frequently with the 250 ug dose. Thus, the 100 ug dose 
was eventually chosen for the phase 3 clinical trial. 
Lung transplant recipients, due to their immune suppression medicines, have had weak responses to the 
COVID-19 vaccines with antibody responses noted in less than 20% after the second vaccine dose (16–
18). Lung transplantation is also unique among the solid organ transplants in the direct infection and 
injury of the allograft by SARS-CoV-2. Thus, lung transplant recipients have poor outcomes following 
COVID-19 infection with a high mortality rate. Third dose vaccines appear to improve immune responses 
for solid organ recipients, but has not been studied specifically for lung transplant recipients.  
The current CDC guidance is for moderately or severely immunocompromised patients to receive a 50 ug 
booster: 1) At least 3 months after 3rd dose (first booster), and 2) At least 4 months after 4th dose (2nd 
booster). We believe that this dosing will be insufficient for many lung transplant recipients, particularly 
in those who did not receive any vaccine doses prior to their lung transplant, and leave them at high risk 
of poor COVID-19 outcomes. Importantly, due to their immunosuppression, lung recipients appear to 
have decreased side effects and reactogenicity to the SARS-CoV-2 vaccine.  
We hypothesize that a 100 ug mid-dose and 200 ug high-dose mRNA-1273 booster dose can be safely 
administered to lung transplant recipients who previously received all of their vaccine doses after their 
lung transplant. We further hypothesize that the higher dose boosters will induce a stronger immune 
response to SARS-COV-2 as measured by humoral and cellular response assays. The objectives of this 
study are to test these two hypotheses.  
 
 
3 
STUDY OBJECTIVES 
3.1 
Primary Objective 
1. Evaluate safety of high-dose mRNA-1273 booster vaccine among lung transplant recipients measured 
by incidence of adverse events.  
2. Evaluate reactogenicity of high-dose mRNA-1273 booster vaccine among lung transplant recipients 
measured by the FDA Toxicity Grading scale. 
3.2 
Secondary Objectives 
1. Evaluate humoral immunogenicity measured by anti-RBD and anti-spike (S-2P) IgG levels at Day 30. 


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2. Evaluate humoral immunogenicity measured by neutralizing antibody titers from a pseudovirus 
neutralization assay at Day 30.   
3. Evaluate cellular immunogenicity measured by cellular response assays including flow cytometry 
with intracellular staining at Day 30. 
 
4 
STUDY DESIGN 
4.1 
Study Overview 
This is a Phase I/II open-label dose-finding trial among lung transplant recipients who received three or 
four mRNA vaccine doses (mRNA-1273 or BNT162b2) after lung transplantation to: standard-dose (50 
ug), mid-dose (100 ug) or high-dose (200 ug) mRNA-1273 booster vaccine. Participants will be enrolled 
into three dose groups: 1) Standard-dose (50 ug) – 20 participants, 2) Mid-dose (100 ug) – 20 participants, 
3) High-dose (200 ug) – 20 participants. The first 2 participants in both the mid-dose and high dose 
groups will be considered the ‘sentinel’ group. Participants in the sentinel group will receive the vaccine 
and undergo a 7-day observation period for safety and reactogenicity before additional participants are 
enrolled into that dose group.  
Overall study enrollment will begin with the mid-dose sentinel group (n=2). During the observation 
period for the mid-dose sentinel group, we will enroll two participants into the standard-dose group. Once 
the mid-dose sentinel group completes their 7-day observation period without triggering halting rules and 
is approved to proceed by the DSMB, we will enroll the next 27 participants (Cohort 1) with a 2:1 
randomization into the mid-dose (n=18) and standard-dose (n=9) groups.  
Once all 20 participants have received their mid-dose vaccine without triggering halting rules and is 
approved to proceed by the DSMB, we will enroll the high-dose sentinel group (n=2). Once the high-dose 
sentinel group completes their 7-day observation period without triggering halting rules and is approved 
to proceed by the DSMB, we will enroll the next 27 participants (Cohort 2) with a 2:1 randomization into 
the high-dose (n=18) and standard-dose (n=9) groups. Thus, all 20 participants in the mid-dose group will 
be enrolled prior to enrollment of the high-dose group.  
We will perform stratified randomization for the two cohorts based on: 1) the number of prior doses, and 
2) prior receipt of any BNT162b2 vaccines. Randomization with be done by the UCLA Clinical and 
Translational Science Institute (CTSI) statistics team based on scheduled participants prior to the study 
visit. The 6 participants in the sentinel (n=4) and initial (n=2) groups (Table 1) will be assigned into the 3 
groups based on their scheduled visit day. 
This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of mid and high-
dose mRNA-1273 vaccine among lung transplant recipients who have received three or four prior mRNA 
vaccines. 
In-person visits will occur on Days 1 (booster vaccine), 7 and 30. Telephone visits will occur on Days 3, 
90 and 180.  Adverse events will be assessed in person (Days 1, 7 and 30) and by telephone calls (Days 3, 
90 and 180). All follow-up visits will include a detailed review for serious adverse experiences (SAEs), 
adverse events of special interest (AESIs) and medically attended adverse events (MAAEs).  
 


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Table 1: Treatment Arms: 
 
Groups will be enrolled as follows:           n                  Dose 
1) Mid-dose – Sentinel group 
2 
100 ug 
2) Standard-dose – Initial group 
2 
50 ug 
 
 
 
3) Cohort 1: 2:1 Randomization into 
 
 
           Mid-dose group 
18 
100 ug 
           Standard-dose group 
9 
50 ug 
 
 
 
4) High-dose – Sentinel group 
2 
200 ug 
     
 
 
5) Cohort 2: 2:1 Randomization into 
 
 
           High-dose group 
18 
200 ug 
           Standard-dose group 
9 
50 ug 
 
Cohorts 1 and 2 will be randomized to their dose and considered the full group.  
 
 
 
 
 
 
Mid-dose Sentinel Group (n=2)
Standard-dose Initial Group (n=2)
Cohort 1:    2:1 Randomization into  
Mid-dose (n=18) versus Standard-dose (n=9) Groups
High-dose Sentinel Group (n=2)
Once mid-dose sentinel group (n=2) clears 
7-day observation period
Once mid-dose full group (n=18) clears 
observation period
Cohort 2:     2:1 Randomization into: 
High-dose (n=18) versus Standard-dose (n=9)
Figure 1. Study enrollment flow diagram
Once high-dose sentinel group (n=2) clears 
7-day observation period


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5 
CRITERIA FOR EVALUATION 
5.1 
Primary Safety Endpoint 
Safety will be measured by the frequency and grade of solicited and unsolicited adverse events (AEs), 
SAEs, AESIs and MAAEs. Reactogenicity will be measured by the occurrence of solicited injection site 
and systemic reactions.   
1. Frequency and grade of each solicited local and systemic reactogenicity AE will be recorded on a 
daily diary using the FDA Toxicity Grading Scale and collected from Day 1 until Day 7.   
2. Frequency and grade of each unsolicited AEs will be recorded on a daily diary and collected from 
Day 1 until Day 30. 
3. Frequency of any SAEs, AESIs and MAAEs will be collected from Day 1 until Day 180.  
Simple descriptive statistics will be used to summarize toxicities in terms of type, severity and minimum 
or maximum values for laboratory measures, time of onset, duration, and reversibility or outcome. Tables 
will be created to summarize these toxicities and side effects. Safety Analyses will be performed on the 
Safety Analysis Set. 
5.2 
Secondary Immunogenicity Endpoints 
1. Binding antibody: The anti-RBD and anti-spike (S-2P) IgG concentrations (log10 and geometric 
mean concentrations (GMC)) at Day 30 will be evaluated with comparisons between the 
standard-dose versus high-dose groups. T-tests with two-sided p<0.05 significance will be used 
(overall α level of 0.1). Changes in the anti-RBC and anti-spike IgG concentrations at Day 30 will 
be compared pairwise between the standard-dose versus high-dose groups using two sample T-
tests with two-sided p<0.05 significance (overall α level of 0.1). The percent of participants with 
detectable antibody levels (greater than the LLOQ) at Day 30 will also be evaluated using 
Fisher’s exact tests. Pairwise comparisons of binding antibodies will also be evaluated between 
the standard-dose versus mid-dose groups.  
 
2. Neutralizing antibody: Neutralizing antibody titers (geometric mean titers (GMT)) from a 
pseudovirus neutralization assay at Day 30 will be compared between the standard-dose versus 
high-dose groups using T-tests with two-sided p<0.05 significance (overall α level of 0.1). 
Changes in the neutralizing antibody titers at Day 30 will be compared between the standard-dose 
versus high-dose groups using two sample T-tests with two-sided p<0.05 significance (overall α 
level of 0.1). The percent of participants with detectable neutralizing antibody levels (greater than 
the LLOQ) at Day 30 will also be evaluated using Fisher’s exact tests. Pairwise comparisons of 
neutralizing antibodies will also be evaluated between the standard-dose versus mid-dose groups. 
 
3. Cellular immunogenicity: The change in the frequency of target cytokine producing T-cells by 
flow cytometry with intracellular staining at Day 30 will be compared using the Kruskal-Wallis 
Test for standard-dose versus high-dose groups. A comparison of T-cell frequencies between the 
standard-dose versus high-dose groups will be evaluated using the Wilcoxon rank-sum test. 
Pairwise comparisons of cellular immunogenicity will also be evaluated between the standard-
dose versus mid-dose groups. 


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5.3 
Safety Evaluations 
The study will use a Data and Safety Monitoring Board (DSMB). DSMB reviews are required for study 
halting and restarting. Reporting to regulatory bodies (IRB, FDA) will only be required for serious 
adverse events judged by the treating physician and study investigators to be potentially related to the 
administration of the study drug, including suspected, unexpected, serious adverse reactions (SUSAR, 
Section 11). All other adverse events will be reviewed by the study investigators and reported per FDA 
and IRB regulations. The study will be overseen by CTSI Data and Safety monitoring Board. By allowing 
CTSI DSMB to oversee the study, the PI agrees to abide by the CTSI DSMB’s policies and procedures as 
outlined in the DSMB charter. 
 
Safety evaluations:  
1. Visit 1: Day 1 (booster day): informed consent, med history, inclusion criteria review, physical 
exam, blood draw, administration of booster, 30-minute observation.  
2. Telephone visit Day 3: Review for AEs, SAEs, AESIs and MAAEs.   
3. Visit 2: Day 7 - blood draw, physical exam and review for AEs, SAEs, AESIs and MAAEs.  
4. Visit 3: Day 30 - blood draw, physical exam and review for AEs, SAEs, AESIs and MAAEs. 
5. Telephone visit Day 90: Review for AEs, SAEs, AESIs and MAAEs.  
6. Telephone visit Day 180: Review for AEs, SAEs, AESIs and MAAEs. 
 
The following labs will be collected at baseline and clinic follow-up visits.  
1. Serum collected for antibody levels. 
2. PBMCs collected for cellular response assays including flow cytometry with intracellular 
staining. 
3. Whole blood collected for cellular response assays.  
4. Troponin, CK and cytokines banked from Day 0, 7 and 30. 
 
6 
PARTICIPANT SELECTION 
6.1 
Study Population 
Participants post lung transplant who previously received three or four mRNA-1273 or BNT162b2 
COVID-19 vaccines who meet the inclusion and exclusion criteria will be eligible for participation in this 
study.   
6.2 
Inclusion Criteria 
1. All adult lung transplant recipients (age ≥ 18 at the time of consent) who received all of their 
COVID-19 vaccines after lung transplantation. 
2. Received three or four doses of either the Moderna mRNA-1273 or Pfizer BNT162b2 vaccine 
with the last dose received at least 4 months prior to study enrollment.  
3. Currently receiving standard regimen of three drug immunosuppression with prednisone, 
tacrolimus and mycophenolate mofetil (minimum 250 mg bid) or mycophenolate sodium 
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4. Agrees not to receive other investigational agents for prophylaxis against COVID-19 including 
Evusheld monoclonal antibodies for at least 30 days after the study vaccine. 
5. Understands and agrees to comply with the study procedures and provides written informed 
consent. 
6. Is in stable health without any new or worsening medical conditions in the opinion of the 
Investigator. 
7. Female participants of childbearing potential (<1 year since start of menopause) may be enrolled 
in the study if the participant fulfills all the following criteria: 
a. Has a negative pregnancy test at Visit 1 Day 1. 
b. Has practiced adequate contraception or has abstained from all activities that could result 
in pregnancy for at least 28 days prior to the first injection (Day 1). 
c. Has agreed to continue adequate contraception or practice abstinence through 3 months 
following the booster injection (Day 90). 
d. Is not currently breastfeeding. 
e. Adequate female contraception is defined as consistent and correct use of a Food and 
Drug Administration (FDA) approved contraceptive method in accordance with the 
product label. For example: 
i. Barrier method (such as condoms, diaphragm, or cervical cap) used in 
conjunction with spermicide 
ii. Intrauterine device 
iii. Prescription hormonal contraceptive taken or administered via oral (pill), 
transdermal (patch), subdermal, or IM route 
iv. Sterilization of a female participant’s monogamous male partner prior to entry 
into the study 
v. Note: periodic abstinence (e.g., calendar, ovulation methods) and withdrawal are 
not acceptable methods of contraception. 
6.3 
Exclusion Criteria 
1. Previous documented COVID-19 infection. 
2. Use of investigational agents for prophylaxis against COVID-19 within 90 days of the start of the 
study, including Evusheld monoclonal antibodies.  
3. Ongoing therapy for acute cellular or antibody mediated rejection. 
4. Intravenous immunoglobulins (IVIG) administration within the prior 3 months or ongoing IVIG 
therapy.   
5. Anaphylaxis or allergic reaction to any prior vaccines. 
6. History of anaphylaxis or other significant adverse reaction requiring medical intervention after 
receipt of a vaccine. 
7. Is acutely ill or febrile 24 hours prior to or at the Day 1 visit. Fever is defined as a body 
temperature ≥ 38.0°C/100.4°F. Participants meeting this criterion may be rescheduled within the 


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relevant window periods. Afebrile participants with minor illnesses can be enrolled at the 
discretion of the investigator. 
8. Pregnant or breastfeeding. 
9. Has a medical, psychiatric, or occupational condition that may pose additional risk as a result of 
participation, or that could interfere with safety assessments or interpretation of results according 
to the investigator’s judgment. 
10. Known history of hypertension (HTN) with systolic blood pressure (BP) > 180 mm Hg at the Day 
1 visit.  
11. Known history of hypotension with systolic blood pressure < 85 mm Hg at the Day 1 visit.  
12. Bleeding disorder considered a contraindication to IM injection or phlebotomy. 
13. Active malignancy diagnosed within previous 4 years (excluding non-melanoma skin cancer). 
14. Received a major surgery including lung transplantation in the past 3 months.  
 
Exclusion of Specific Populations:  
Because the effects on the fetus are not known, pregnant women will not be eligible for the trial. Women 
of childbearing potential (<1 year since start of menopause) must utilize a highly effective method of 
contraception and will be required to have a negative urine or serum pregnancy test within 24 hours prior 
to the vaccination. Children will not be included in this trial as presently there are no children receiving 
lung transplantation at UCLA.  Should the outcome of this trial be deemed acceptable, additional trials 
may be initiated, including those in other populations. 
 
 
 
7 
CONCURRENT MEDICATIONS 
This trial design allows for participants in all study arms to receive other investigational drugs for 
COVID-19 after Day 45 of the study.  
7.1 
Allowed Medications and Treatments 
Standard therapy for COVID-19 is allowed except for treatments noted in the exclusion criteria described 
above and as noted in the prohibited medications section below. Based on inclusion criteria, participants 
will be required to be on a regimen of triple immunosuppression including prednisone, mycophenolate 
mofetil (minimum 250 mg bid) or mycophenolate sodium (minimum 180 mg bid), and tacrolimus at the 
Day 1 study visit. Participants receiving IVIG or augmented immunosuppression for treatment of acute 
rejection or antibody mediated rejection will be excluded from the study. 
7.2 
Prohibited Medications and Treatments 
Use of investigational agents for prophylaxis against COVID-19 within 90 days of the start of the study, 
including Evusheld monoclonal antibodies. Use of investigational agents for prophylaxis including 
Evusheld against COVID-19 for at least 30 days after study vaccination, since this will affect the 
antibody-based secondary endpoints.  
 


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8 
STUDY TREATMENTS 
8.1 
Method of Assigning Participants to Treatment Groups 
This is a Phase I/II open-label dose-finding trial among lung transplant recipients who received three or 
four mRNA vaccine doses (mRNA-1273 or BNT162b2) after lung transplantation to: standard-dose (50 
ug), mid-dose (100 ug) or high-dose (200 ug) mRNA-1273 booster vaccine. Participants will be enrolled 
into three dose groups: 1) Standard-dose – 20 participants, 2) Mid-dose – 20 participants, 3) High-dose – 
20 participants. The first 2 participants in both the mid-dose and high dose groups will be considered the 
‘sentinel’ group. Participants in the sentinel group will receive the vaccine and undergo a 7-day 
observation period for safety and reactogenicity before additional participants are enrolled into that dose 
group.  
Overall study enrollment will begin with the mid-dose sentinel group (n=2). During the observation 
period for the mid-dose sentinel group, we will enroll two participants into the standard-dose group. Once 
the mid-dose sentinel group completes their 7-day observation period without triggering halting rules and 
is approved to proceed by the DSMB, we will enroll the next 27 participants (Cohort 1) with a 2:1 
randomization into the mid-dose (n=18) and standard-dose (n=9) groups.  
Once all 20 participants have received their mid-dose vaccine without triggering halting rules and is 
approved to proceed by the DSMB, we will enroll the high-dose sentinel group (n=2). Once the high-dose 
sentinel group completes their 7-day observation period without triggering halting rules and is approved 
to proceed by the DSMB, we will enroll the next 27 participants (Cohort 2) with a 2:1 randomization into 
the high-dose (n=18) and standard-dose (n=9) groups. All 20 participants in the mid-dose group will be 
enrolled prior to enrollment of the high-dose group.  
We will perform stratified randomization for the two cohorts based on: 1) the number of prior doses, and 
2) prior receipt of any BNT162b2 vaccines. Randomization with be done by the UCLA Clinical and 
Translational Science Institute (CTSI) statistics team based on scheduled participants prior to the study 
visit. The 6 participants in the sentinel (n=4) and initial (n=2) groups (Table 1) will be assigned into the 3 
groups based on their scheduled visit day. 
If the halting criteria is triggered for the high-dose group and further enrollment of this group is not 
recommended by the study investigators, DSMB or IRB, the study will continue randomized enrollment 
into the mid-dose and standard-dose groups with a 1:2 ratio to complete the enrollment of 60 participants 
total. Since the expected immunogenicity difference between the mid-dose and standard-dose group is 
smaller, we will require more participants to detect a difference between these two groups. The 1:2 
enrollment ratio into the mid-dose and standard-dose groups will even the distribution of participants into 
these two groups. The primary endpoint analysis for safety and reactogencity will not be affected by a 
restriction of participants into the mid-dose and standard-dose groups. 
 
8.2 
Formulation   
mRNA-1273 is provided as a sterile liquid for injection, white to off white dispersion in appearance, at a 
concentration of 0.2 mg/ml. Please refer to letter of authorization (LOA) from to cross-reference the drug 
master file (DMF).  


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8.3 
 Packaging and Labeling 
Each of the study products will be labeled according to manufacturer specifications and include the 
statement “Caution: New Drug Limited by Federal Law to Investigational Use.” Sterile empty vials will 
be provided with latex-free stoppers. 
8.4 
Supply of Study Drug at the Site 
mRNA-1273 will be stored as per manufacturer guidelines, dispensed, and accounted for by the 
investigational pharmacy.  
8.4.1 
Dosage/Dosage Regimen 
Investigational product mRNA-1273 will be administered via intramuscular injection (IM) at three doses: 
standard-dose (50 ug), mid-dose (100 ug) or high-dose (200 ug).  
 
Table 2: Dosing and Administration 
 
Group 
Sample Size 
Dose 
Route 
Frequency 
1 Standard 
20 
50 ug 
IM 
Day 1 
2 Mid-dose 
20 
100 ug 
IM 
Day 1 
3 High-dose 
20 
200 ug 
IM 
Day 1 
8.4.2 
Dispensing 
Investigational product mRNA-1273 will be received at 0.2 mg/ml concentration and dispensed by the 
investigational pharmacy undiluted at three dosages: 50 ug (0.25 ml), 100 ug (0.5 ml) and 200 ug (1 ml).  
8.4.3 
Administration Instructions  
 Each dose will be administered via IM injection into the deltoid muscle on Day 1.  
8.5 
Supply of Study Drug at the Site 
Study drug will be supplied by Moderna and stored at the UCLA investigational pharmacy as per 
manufacturer guidelines, dispensed, and accounted for by the investigational pharmacy.  
8.5.1 
Storage 
Vaccine mRNA-1273 will be stored at 2° to 8°C (35.6° to 46.4°F) at clinical sites before preparation and 
vaccination. No dilution will be required. Doses could be held in syringes for up to 8 hours at room 
temperature before administration.  
The number of study drug dispensed will be recorded on the Investigational Drug Accountability Record.  
The UCLA Clinical & Translational Science Institute - Office of Regulatory Affairs (CTSI ORA) will 
verify these documents throughout the course of the study. 


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8.6 
Measures of Treatment Compliance 
Not applicable  
 
 
9 
STUDY PROCEDURES AND GUIDELINES 
A Schedule of Events representing the required testing procedures to be performed for the duration of the 
study is diagrammed in Appendix 1. 
Prior to conducting any study-related activities, written informed consent and the Health Insurance 
Portability and Accountability Act (HIPAA) authorization must be signed and dated by the participant or 
participant’s legal representative.  If appropriate, assent must also be obtained prior to conducting any 
study-related activities. 
9.1 
Clinical Assessments 
9.1.1 
Concomitant Medications 
Based on inclusion criteria, participants will be required to be on a regimen of triple immunosuppression 
including prednisone, mycophenolate mofetil (minimum 250 mg bid) or mycophenolate sodium 
(minimum 180 mg bid), and tacrolimus at the Day 1 study visit. Participants receiving IVIG or 
augmented immunosuppression for treatment of acute rejection, antibody mediated rejection or chronic 
rejection will be excluded from the study.  
9.1.2 
Demographics 
Demographic information will be recorded at enrollment including race, ethnicity, sex, age, BMI, 
medication history, co-morbidities including cardiovascular disease, risk factors for cardiovascular 
disease, and immunosuppressive agents. 
9.1.3 
Medical History 
Relevant medical history, including history of current disease, other pertinent respiratory history, and 
information regarding underlying risk factors will be recorded at screening. 
9.1.4 
Physical Examination  
A complete physical examination will be performed by either the investigator or a sub-investigator who is 
a physician or a qualified member (NP) of the study team at Day 1. Qualified members of the study team 
(MD, NP, RN and PA) will perform a symptom directed physical exam on Days 7 and 30. New abnormal 
physical exam findings will be documented and will be followed by a physician or other qualified staff at 
the next scheduled visit. 
9.1.5 
Vital Signs 
Body temperature, blood pressure, pulse oximetry, and respiratory rate will be performed and recorded. 


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9.1.6 
Adverse Events 
Information regarding occurrence of adverse events will be captured throughout the study. Duration (start 
and stop dates and times), severity/grade, outcome, treatment and relation to study drug will be recorded 
on the case report form (CRF). 
9.2 
Clinical Laboratory Measurements 
9.2.1 
Research Labs 
Blood will be obtained and sent to the research lab for:   
1. Total immunoglobulins: IgG, IgA, IgM. 
2. Anti-RBD, anti-spike binding and neutralizing antibody levels  
3. PBMCs collected for cellular response assays including flow cytometry with intracellular 
staining. 
4. Whole blood collected for cellular response assays. 
5. Troponin / CK and cytokines for storage on Days 0, 7 and 30.  
9.2.2 
Clinical Labs 
The following may be checked for any unscheduled visits: Complete blood count with differential, 
comprehensive metabolic panel, tacrolimus / sirolimus level, C-reactive protein, erythrocyte 
sedimentation rate (ESR), total immunoglobulins (IgG, IgA, IgM), anti-RBD, anti-spike and neutralizing 
antibody levels, PBMCs collected for cellular response assays including flow cytometry with intracellular 
staining, whole blood collected for cellular response assays, troponin / CK, cytokines, PT, PTT, INR (16 
mL of venous blood).    
 
10 
EVALUATIONS BY VISIT 
10.1 Screening/Enrollment Day -30 to 0 (Phone) 
1. Pre-screen participants via chart review using HIPAA waiver. 
2. Invite eligible participants by phone to participate in study. 
3. A qualified member of the study team will review study and provide ICF form. Participants will 
be asked to sign consent at Visit 1 prior to initiating any study-related procedures. 
4. Assign the participant a unique screening number. 
10.2 Visit 1 Day 1 (Clinic): Booster Vaccine Day 
1. For participants who meet inclusion/exclusion criteria, the investigator team will again review the 
study with the participant (or participant’s legal representative) in person and obtain written 
informed consent and HIPAA authorization. 
2. Record demographic data. 
3. Record medical history. 
4. Review of birth control history with female participants of childbearing potential (<1 year since 
start of menopause). 


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5. For women of childbearing potential, counsel participants to use adequate birth control methods 
required during the trial to avoid pregnancy. 
6. For women of childbearing potential, urine pregnancy test will be checked prior to study drug 
administration on Visit 1 (Day 1).  
7. Confirmation participants meet all inclusion criteria and no exclusion criteria review. 
8. Review pre-study concomitant medications and therapies and record on the appropriate CRF.  
9. Review of influenza and any all 2019-CoV vaccinations or other experimental coronavirus 
vaccines. 
10. Vital signs (HR, BP, temperature, oximetry), and height and weight for determination of BMI. 
11. Full physical exam will include assessments of the following organs and organ systems: skin, 
head, ears, eyes, nose, and throat (HEENT), neck, lungs, heart, liver, spleen, abdomen, 
extremities, lymph nodes (axillary and cervical), and nervous system. 
12. Obtain blood samples for baseline: Total immunoglobulins (IgG, IgA, IgM), anti-RBD, anti-spike 
binding and neutralizing antibody levels, PBMCs collected for cellular response assays including 
flow cytometry with intracellular staining, whole blood collected for cellular response assays, 
troponin / CK and cytokines for storage.  
13. Confirm group assignment: standard-dose, mid-dose or high-dose group.   
14. Inform participants of their designated dose. 
15. Administration of booster vaccine. 
16. Participants will be observed for 30-minutes post injection administration.  
17. Dispense daily diary of symptoms for first 7 days after injection dispensed to participant 
measuring FDA Toxicity Grading Scale and adverse events.  
10.3 Visit 2 Day 3 +/-1 Day (Phone – 2 days post booster): 
1. All participants will complete a daily diary of solicited and unsolicited AEs from the vaccination 
until 7 days post-vaccination. Reactogenicity will be measured by the occurrence of solicited 
injection site and systemic reactions for the first 7 days post-vaccination utilizing the FDA 
Toxicity Grading Scale. 
2. Participants will be contacted by telephone to query for safety events and review daily diaries. 
Based on the information collected, participants may be asked to return to the clinic for 
evaluation for an unscheduled visit. 
3. Review daily diaries, AEs (solicited and unsolicited), SAEs, AESIs and MAAEs.  
4. Participants will contact their primary care doctor, lung transplant pulmonologist or study 
principal investigator with any SAEs, AESIs or MAAEs.  
10.4 Visit 3 Day 7 +/-2 Days (Clinic Visit – 6 days post booster): 
1. Vital signs (HR, BP, temperature, oximetry), and height and weight for determination of BMI. 
2. Symptom-directed (targeted) physical exam. Targeted physical examinations should also include 
an assessment for signs suggestive of AEs and AESIs. Interim or unscheduled physical 
examinations will be performed at the discretion of the PI or appropriate sub-investigator, if 
necessary, to evaluate AEs or abnormal clinical laboratory test results. 
3. Obtain blood samples for follow-up: Total immunoglobulins (IgG, IgA, IgM), anti-RBD, anti-
spike binding and neutralizing antibody levels, PBMCs collected for cellular response assays 
including flow cytometry with intracellular staining, whole blood collected for cellular response 
assays, troponin / CK and cytokines for storage. 


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5. Review daily diaries, AEs (solicited and unsolicited), SAEs, AESIs and MAAEs.  
10.5 Visit 4 Day 30 +/- 7 Days (Clinic – 29 days post booster): 
1. Vital signs (HR, BP, temperature, oximetry), and height and weight for determination of BMI. 
2. Symptom-directed (targeted) physical exam. Targeted physical examinations should also include 
an assessment for signs suggestive of AEs and AESIs. Interim or unscheduled physical 
examinations will be performed at the discretion of the PI or appropriate sub-investigator, if 
necessary, to evaluate AEs or abnormal clinical laboratory test results. 
3. Obtain blood samples for follow-up:  Total immunoglobulins (IgG, IgA, IgM), anti-RBD, anti-
spike binding and neutralizing antibody levels, PBMCs collected for cellular response assays 
including flow cytometry with intracellular staining, whole blood collected for cellular response 
assays, troponin / CK and cytokines for storage. 
4. Review daily diaries, AEs (solicited and unsolicited), SAEs, AESIs and MAAEs.  
10.6 Visit 5 Day 90 +/- 7 Days (Phone – 89 days post booster): 
1. Participants will be contacted by telephone to query for safety events. AEs (solicited and 
unsolicited), SAEs, AESIs and MAAEs will be reviewed. Based on the information collected, 
participants may be asked to return to the clinic for evaluation. 
10.7 Visit 6 Day 180 +/- 7 Days (Phone – 179 days post booster): End of study 
1. Participants will be contacted by telephone to query for safety events. AEs (solicited and 
unsolicited), SAEs, AESIs and MAAEs will be reviewed. Based on the information collected, 
participants may be asked to return to the clinic for evaluation. 
10.8 Unscheduled Additional Visit as needed 
1. Clinical evaluation for symptoms to include physical exam and ECG as needed.  
2. Obtain blood samples for evaluation: Complete blood count with differential, comprehensive 
metabolic panel, tacrolimus / sirolimus level, C-reactive protein, erythrocyte sedimentation rate 
(ESR), total immunoglobulins (IgG, IgA, IgM), anti-RBD, anti-spike and neutralizing antibody 
levels, PBMCs collected for cellular response assays including flow cytometry with intracellular 
staining, whole blood collected for cellular response assays, troponin / CK, cytokines, PT, PTT, 
INR (16 mL of venous blood).    
3. AEs (solicited and unsolicited), SAEs, AESIs and MAAEs will be reviewed. Based on the 
information collected, participants may be asked to return to the clinic for evaluation. 
 
 
11 
ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION 
11.1 Adverse Events 
An adverse event (AE) is any untoward medical occurrence in a clinical investigation of a participant 
administered a pharmaceutical product and that does not necessarily have a causal relationship with the 
treatment.  An AE is therefore any unfavorable and unintended sign (including an abnormal laboratory 


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finding), symptom or disease temporally associated with the administration of an investigational product, 
whether or not related to that investigational product.  Any medical condition that is present at the time 
that the subject is screened will be considered as baseline and not reported as an AE. However, if the 
severity of any pre-existing medical condition increases, it will be recorded as an AE. 
AEs can be further divided into solicited AEs and unsolicited AEs. Solicited AEs are those for which the 
study team will specifically query the subject whether they occurred. Unsolicited AEs are those events 
that the subject report occurring without being queried about the specific event.  
A suspected adverse event is one for which there is a ‘reasonable possibility’ that the drug caused the 
adverse event. A ‘reasonable possibility’ means there is evidence to suggest a causal relationship between 
the drug and the adverse event, but implies a lesser degree of certainty about causality compared with an 
adverse event. An unexpected AE is one of a type not identified in nature, severity, or frequency in the 
current Investigator’s Brochure or of greater severity or frequency than expected based on the information 
in the Investigator’s Brochure. All AEs will be assessed for severity and relationship to study intervention 
(Tables 3 and 4). Suspected, Unexpected, Serious Adverse Reactions (SUSAR) is an adverse event where 
a causal relationship with the study drug is at least possible but not listed in the Investigator Brochure 
(IB), Package Insert, and/or Summary of Product Characteristics and includes any of the following: 
suspected AE, unexpected AE and serious adverse experience (SAE). Episodes of myocarditis or 
pericarditis occurring in temporal association with vaccination will be reported as a SUSAR. Medically 
attended adverse event (MAAE) is defined as hospitalization, an emergency room visit or an otherwise 
unscheduled visit to or from medical personnel for any reason.  
Frequency and grade of each solicited AE (local and systemic reactogenicity) will be collected until Day 
7 using the FDA Toxicity Grading Scale to be recorded on a daily diary. Frequency and grade of each 
unsolicited AEs will be collected until Day 30. Frequency of any SAEs, AESIs and MAAEs will be 
collected until Day 180. After Day 30 through the end of study on Day 180, only SAEs, AESIs and 
MAAEs will be reported as AEs. All AEs, solicited and unsolicited, will be captured on the appropriate 
CRF. Information to be collected for AEs includes event description, date of onset, assessment of 
severity, relationship to study product and alternate possible etiology, date of resolution, seriousness, and 
outcome. AEs occurring during the study-collection and reporting period will be documented 
appropriately regardless of relationship. AEs will be followed to resolution or stabilization. 
 
Solicited Adverse Events: 
Solicited AEs are anticipated local and systemic AEs for which consistent collection of 
information is desired. Study clinicians will follow and collect resolution information for any 
reactogenicity symptoms that are not resolved within 7 days. Solicited AEs (i.e., reactogenicity) will be 
collected using a daily diary and recorded on the appropriate CRF from the time of the vaccination until 7 
days post vaccination (Days 1-7). For this study, solicited AEs will be defined and graded as follows 
(Tables 3): 
 
 
Table 3: Solicited Adverse Reactions and Grading 
 


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Reaction 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Injection site pain 
None 
Does not 
interfere with 
activity  
Repeated use of over-
the-counter pain reliever 
> (greater than) 24 hours 
or interferes with activity  
Any use of 
prescription pain 
reliever or prevents 
daily activity 
Requires emergency 
room visit or 
hospitalization 
Injection site 
erythema 
(redness) 
< (less than) 
25 mm or 
 < 2.5 cm 
25 - 50 mm or 
2.5 - 5 cm 
51 - 100 mm or 
5.1 - 10 cm 
> 100 mm or 
> 10 cm 
Necrosis or exfoliative 
dermatitis (severe skin 
rash causing skin 
discoloration or 
peeling) 
Injection site 
swelling/induration 
(hardness) 
< 25 mm or 
< 2.5 cm 
25 - 50 mm or 
2.5 - 5 cm 
51 - 100 mm or 
5.1 - 10 cm  
> 100 mm or 
> 10 cm 
Necrosis (severe 
swelling with skin 
discoloration, 
blistering, or peeling) 
Axillary 
(underarm) 
swelling or 
tenderness 
ipsilateral to the 
side of injection 
None 
No interference 
with activity 
Repeated use of over-
the-counter (non-
narcotic) pain reliever > 
24 hours or some 
interference with activity 
Any use of 
prescription (narcotic) 
pain reliever or 
prevents daily activity 
Requires emergency 
room visit or 
hospitalization 
Headache 
None 
No interference 
with activity 
Repeated use of over-
the-counter pain reliever 
> 24 hours or some 
interference with activity 
Significant; any use of 
prescription pain 
reliever or prevents 
daily activity 
Requires emergency 
room visit or 
hospitalization 
Fatigue 
None 
No interference 
with activity  
Some interference with 
activity 
Significant; prevents 
daily activity  
Requires emergency 
room visit or 


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Reaction 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
hospitalization 
Myalgia (muscle 
aches all over 
body) 
None 
No interference 
with activity  
Some interference with 
activity 
Significant; prevents 
daily activity  
Requires emergency 
room visit or 
hospitalization 
Arthralgia (joint 
aches in several 
joints) 
None 
No interference 
with activity  
Some interference with 
activity 
Significant; prevents 
daily activity  
Requires emergency 
room visit or 
hospitalization 
Nausea/vomiting 
None 
No interference 
with activity or 1-
2 episodes/ 
24 hours 
Some interference with 
activity or 
> 2 episodes/24 hours 
Prevents daily activity, 
requires outpatient 
intravenous hydration 
(fluids given through 
blood veins) 
Requires emergency 
room visit or 
hospitalization for low 
blood pressure 
Chills 
None 
No interference 
with activity 
Some interference with 
activity not requiring 
medical intervention 
Prevents daily activity 
and requires medical 
intervention 
Requires emergency 
room visit or 
hospitalization 
Fever  
< 38.0°C 
< 100.4°F 
38.0 – 38.4°C 
100.4 – 101.1°F 
38.5 – 38.9°C 
101.2 – 102.0°F 
39.0 – 40.0°C 
102.1 – 104.0°F 
> 40.0°C 
> 104.0°F 
Rash 
No rash 
Localized rash, 
without 
associated 
symptoms 
Maculopapular rash 
(bumpy and red rash) 
covering < 50% body 
surface area 
Generalized urticarial 
rash (hives or itchy 
rash) covering > 50% 
body surface area 
Generalized 
exfoliative, ulcerative 
or bullous dermatitis 
(severe skin rash 
causing skin 
discoloration, peeling 
or blistering) 


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Reaction 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
If you experience any grade 4 symptom from your daily diary, or any other severe symptoms that prevents your daily 
activity AND requires you to see a doctor, please call Dr. Michael Shino immediately at 310-206-6766. The operator 
will answer the call, please tell them that you would like to "page Dr Shino". Dr Shino or another covering Dr will call 
you back.  
Source: Guidance for industry – Toxicity Grading Scale for Heathy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials; tables for clinical abnormalities (DHHS 2007).  
 
Unsolicited Adverse Events 
All AEs spontaneously reported by the subject and/or in response to an open question from study 
staff or revealed by observation, physical examination or other diagnostic procedures must be 
recorded on the appropriate CRF. Unsolicited AEs of all severities will be reported from the time of study 
product administration through Day 30. After Day 30, only SAEs and AESIs will be reported through the 
end of the study (Day 180).  
 
AE Severity 
”Table 3: Solicited Adverse Reactions and Grading” will be used to assess and grade solicited AE 
severity. “Appendix 3: Table of Laboratory Abnormalities” will be used to grade any laboratory 
abnormalities observed. If the adverse event is not covered in Table 3 and Appendix 3, the guidelines 
shown in Table 4 below should be used to grade severity. It should be pointed out that the term “severe” 
is a measure of intensity and that a severe AE is not necessarily serious. 
Table 4.  AE Severity Grading 
Severity (Toxicity Grade) 
Description 
Mild (1) 
These events do not interfere with the participant’s daily activities. 
Moderate (2) 
These events cause some interference with the participant’s daily activities 
and require limited or no medical intervention. 
Severe (3) 
These events prevent the participant’s daily activity and require intensive 
therapeutic intervention.  
 
 
AE Relationship to Study Drug 
The relationship of an AE to the study drug should be assessed using the following guidelines in Table 5. 
Table 5.  AE Relationship to Study Drug 
Relationship 
to Drug 
Comment 


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Definitely 
Previously known toxicity of agent; or an event that follows a reasonable temporal 
sequence from administration of the drug; that follows a known or expected response 
pattern to the suspected drug; that is confirmed by stopping or reducing the dosage 
of the drug; and that is not explained by any other reasonable hypothesis. 
Probably 
An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to the suspected drug; that is 
confirmed by stopping or reducing the dosage of the drug; and that is unlikely to be 
explained by the known characteristics of the participant’s clinical state or by other 
interventions. 
Possibly 
An event that follows a reasonable temporal sequence from administration of the 
drug; that follows a known or expected response pattern to that suspected drug; but 
that could readily have been produced by a number of other factors. 
Unrelated 
An event that can be determined with certainty to have no relationship to the study 
drug. 
 
11.2 
Serious Adverse Experiences (SAE) 
An SAE is defined as any AE occurring at any dose that results in any of the following outcomes: 
1. death 
2. a life-threatening adverse experience 
3. inpatient hospitalization or prolongation of existing hospitalization 
4. a persistent or significant disability/incapacity 
5. a congenital anomaly/birth defect  
Other important medical events may also be considered an SAE when, based on appropriate medical 
judgment, they jeopardize the participant or require intervention to prevent one of the outcomes listed.  
Participants will be instructed to call a study team line (attended 24-hours per day) if they experience any 
grade 4 symptom from the “Solicited Adverse Reactions and Grading” table (Table 3), any severe 
unsolicited AE (Table 4), or any SAE. The study team member will interview, document and triage the 
participant for further evaluation.  
11.2.1 
Serious Adverse Experience Reporting 
All SAEs that occur (whether or not related to study drug) will be reported per UCLA OHRPP IRB 
guidelines and policy. The collection period for all SAEs will begin after informed consent is obtained 
and end after procedures for the final study visit have been completed. 
In accordance with the standard operating procedures and policies of the local Institutional Review Board 
(IRB), the site investigator will report SAEs to the IRB and FDA.   
11.3 
Adverse Events of Special Interest 
An AESI is an AE (serious or nonserious) of scientific and medical topic of interest, for which ongoing 
monitoring and immediate notification by the investigator is required and documentation is in the form of 
a case narrative. Such events may require further investigation to characterize and understand them. Refer 
to Appendix 2 for a list of AESIs pertinent to this study. All AESIs will be collected through the entire 


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study period and must be reported immediately and in all circumstances within 7 days of becoming aware 
of the event. AESIs were identified as immunologically driven sequelae of COVID-19 and thus topics of 
interest/AESIs for all COVID vaccines. 
 
Anaphylaxis 
All suspected cases of anaphylaxis should be recorded and reported as an SAE and AESI, based on 
criteria for a medically important event, unless the event meets other serious criteria. For reporting 
purposes, a participant who displays signs/symptoms consistent with anaphylaxis as shown below should 
be reported as a potential case of anaphylaxis. This is provided as general guidance for investigators and 
is based on the Brighton Collaboration case definition (27). 
Anaphylaxis is an acute hypersensitivity reaction with multi-organ-system involvement that can 
present as, or rapidly progress to, a severe life-threatening reaction. It may occur following 
exposure to allergens from a variety of sources. Anaphylaxis is a clinical syndrome characterized 
by: 
1. Sudden onset AND 
2. Rapid progression of signs and symptoms AND 
3. Involving 2 or more organ systems, as follows: 
a. Skin/mucosal: urticaria (hives), generalized erythema, angioedema, generalized pruritus 
with skin rash, generalized prickle sensation, red and itchy eyes 
b. Cardiovascular: measured hypotension, clinical diagnosis of uncompensated shock, loss 
of consciousness or decreased level of consciousness, evidence of reduced peripheral 
circulation 
c. Respiratory: bilateral wheeze (bronchospasm), difficulty breathing, stridor, upper airway 
swelling (lip, tongue, throat, uvula, or larynx), respiratory distress, persistent dry cough, 
hoarse voice, sensation of throat closure, sneezing, rhinorrhea 
d. Gastrointestinal: diarrhea, abdominal pain, nausea, vomiting 
 
Acute Myocarditis and/or Pericarditis 
All suspected cases of probable or confirmed myocarditis, pericarditis, or myopericarditis should be 
recorded as an AESI, and reported as an SAE, if the event meets seriousness criteria. As an SAE, the 
event should be reported immediately and in all circumstances within 72 hours. The investigator will 
submit any updated myocarditis, pericarditis, or myopericarditis case data within 72 hours of it being 
available. For reporting purposes, a participant who displays signs/symptoms consistent with the CDC 
case definitions as described below (27), should be reported as a potential case of confirmed or probable 
myocarditis, pericarditis, or myopericarditis. 
The CDC case definitions are intended to serve as a guide to help in the diagnosis and reporting 
of suspected cases of myocarditis and/or pericarditis; however, the diagnosis of suspected cases is left to 
the investigator’s clinical judgement. 
 
Acute Myocarditis Case Definition 
Presence of ≥ 1 new or worsening of the following clinical symptoms (persons who lack the listed 
symptoms but who meet other criteria may be classified as subclinical myocarditis [probable or 
confirmed]): 
1. Chest pain/pressure/discomfort 


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2. Dyspnea/shortness of breath/pain with breathing 
3. Palpitations 
4. Syncope 
AND 
For PROBABLE CASE: 
Presence of ≥ 1 new finding of the following: 
1. Troponin level above upper limit of normal (any type of troponin) 
2. Abnormal electrocardiogram (ECG or EKG) or rhythm monitoring findings consistent 
with myocarditis 
To meet the ECG or rhythm monitoring criterion, a probable case must include at least one of the 
following: 
a. ST segment or T-wave abnormalities 
b. Paroxysmal or sustained atrial, supraventricular, or ventricular arrhythmias 
c. AV nodal conduction delays or intraventricular conduction defects 
 
       3. Abnormal cardiac function or wall motion abnormalities on echocardiogram 
4. Cardiac magnetic resonance imaging (cMRI) finding consistent with myocarditis (28). 
AND  
1. No other identifiable cause of the symptoms and findings 
 
For CONFIRMED CASE: 
1. Histopathologic confirmation of myocarditis (using Dallas criteria (29)) 
OR 
2. cMRI findings consistent with myocarditis in the presence of troponin level above 
upper limit of normal (any type of troponin). 
AND 
1. No other identifiable cause of the symptoms and findings 
 
Acute Pericarditis Case Definition 
Presence of ≥ 2 new or worsening of the following clinical features (30): 
1. Acute chest pain (Typically described as pain made worse by lying down, deep 
inspiration, or cough; and relieved by sitting up or leaning forward, although other 
types of chest pain may occur) 
2. Pericardial rub on examination 
3. New ST-elevation or PR-depression on EKG 
4. New or worsening pericardial effusion on echocardiogram or magnetic resonance 
imaging 
 
Myopericarditis Case Definition 
Participants who meet criteria for both myocarditis and pericarditis may be described under 
myopericarditis. 


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11.4 
Medical Monitoring 
Michael Shino, MD or S. Sam Weigt, MD should be contacted directly at these numbers to report medical 
concerns or questions regarding safety. 
Yusaku Michael Shino, MD 
Telephone:  310-866-6327 
Pager: 310-206-6766 Pgr#24405 
 
S. Sam Weigt, MD 
Telephone: 310-825-8599 
Pager: 310-206-6766 Pgr#20928 
 
 
12 
DISCONTINUATION AND REPLACEMENT OF PARTICIPANTS 
12.1 
Screen Failures 
Screen failures are defined as participants who consent to participate in the study but are not subsequently 
assigned to study intervention. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants to meet the Consolidated Standards of Reporting Trials 
(CONSORT) publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any SAE. 
 
After the screening assessments have been completed, the PI or qualified designee is to review the 
inclusion and exclusion criteria and determine the participant’s eligibility for the study. Only the 
following information will be collected on screen failures: demographics (age, screen number, sex, 
ethnicity, and race, BMI, medication history, co-morbidities including cardiovascular disease, risk factors 
for cardiovascular disease, and immunosuppressive agents) and reason for ineligibility. Participants who 
are found to be ineligible will be told the reason for ineligibility. 
 
12.2 
Halting Criteria for Sentinel Group 
The study will be paused if any of the following events occur in the mid-dose (n=2) or high-dose (n=2) 
sentinel groups and enrollment may resume only after the DSMB reviews the events and permits the 
study to continue.  
1. Any grade 4 (Table 3) solicited local or systemic reaction considered to be at least possibly 
related to vaccination within 7 days after administration of the vaccine. 
2. Two or more grade 3 (Table 3) solicited local or systemic reaction in the same dose group 
considered to be at least possibly related to vaccination that lasted at least 48 hours within 7 days 
after administration of the vaccine.  
3. Any severe allergic reaction that is at least possibly related to vaccination within 24 hours after 
administration of the vaccine.  


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4. Any SAE within 28 days after administration of the vaccine considered to be at least possibly 
related to vaccination.  
5. Any episode of myocarditis / pericarditis within 28 days after administration of the vaccine.  
6. Any new episodes of elevated troponin, ECG and physical exam findings concerning for 
myocarditis / pericarditis within 28 days after administration of the vaccine.  
7. Any death unless determined to be definitely not related to vaccination within 90 days after 
administration of the vaccine.  
12.3 
Halting Criteria for Full Group (Cohorts 1 and 2) 
The study will be paused if any of the following events occur in the full group (standard (n=18), mid 
(n=18) and high dose (n=18) groups) and enrollment may resume only after the DSMB reviews the events 
and permits the study to continue.  
1. Any grade 4 (Table 3) solicited local or systemic reaction in the mid or high-dose groups 
considered to be at least possibly related to vaccination within 7 days after administration of the 
vaccine. 
2. Three or more grade 3 (Table 3) solicited local or systemic reaction in the same dose group 
considered to be at least possibly related to vaccination that lasted at least 48 hours within 7 days 
after administration of the vaccine. 
3. Any three participants with severe allergic reaction that is at least possibly related to vaccination 
within 24 hours after administration of the vaccine.  
4. Any SAE within 28 days after administration of the vaccine considered to be at least possibly 
related to vaccination.  
5. Any episode of myocarditis / pericarditis within 28 days after administration of the vaccine.  
6. Any new episodes of elevated troponin, ECG and physical exam findings concerning for 
myocarditis / pericarditis within 28 days after administration of the vaccine.  
7. Any death unless determined to be definitely not related to vaccination within 90 days after 
administration of the vaccine. 
If the halting criteria is triggered for the high-dose group and further enrollment of this group is not 
recommended by the study investigators, DSMB or IRB, the study will continue randomized enrollment 
into the mid-dose and standard-dose groups with a 1:2 ratio to complete the enrollment of 60 participants 
total. Since the expected immunogencity difference between these two groups will be smaller, we will 
require more participants to detect a difference between these two groups. The 1:2 enrollment ratio into 
the mid-dose and standard-dose groups will even the distribution of participants into these two groups. 
The primary endpoint analysis for safety and reactogencity will not be affected by a restriction of 
participants into the mid-dose and standard-dose groups. 
 
12.4 
Early Discontinuation of Study  
A participant may be discontinued from study treatment at any time if the participant or study team 
determines that it is not in the participant’s best interest to continue.  The following is a list of possible 
reasons for study treatment discontinuation:  


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1. Participant withdrawal of consent  
2. Participant is not adherent with study procedures 
3. Adverse event that in the opinion of the investigator would be in the best interest of the 
participant to discontinue study treatment 
4. Protocol violation requiring discontinuation of study treatment 
5. Loss to follow-up 
If a participant is withdrawn from treatment due to an adverse event, the participant will be followed and 
treated by the Investigator until the abnormal parameter or symptom has resolved or stabilized.   
All participants are free to withdraw from participation at any time, for any reason, specified or 
unspecified, and without prejudice. 
Reasonable attempts will be made by the investigator to provide a reason for participant withdrawals.  
The reason for the participant’s withdrawal from the study will be recorded in the study. 
12.5 
Withdrawal of Participants from the Study 
A participant may be withdrawn from the study at any time if the participant, the sponsor/investigator, or 
the study team determines that it is not in the participant’s best interest to continue.   
All participants are free to withdraw from participation at any time, for any reason, specified or 
unspecified, and without prejudice. 
Reasonable attempts will be made by the investigator to provide a reason for participant 
withdrawals.  The reason for the participant’s withdrawal from the study will be specified in the 
participant’s source documents.  As noted above, participants who discontinue study early (i.e., they 
withdraw prior to the last visit) should have an early discontinuation visit if they have been discharged 
from the hospital. Participants who withdraw should be encouraged to come in for a final laboratory visit. 
When a participant withdraws or is withdrawn from the study, the reason(s) for withdrawal will be 
recorded by the investigator on the relevant page of the eCRF. These participants will be requested to 
complete the EOS assessments scheduled for end of participation. 
12.6 
Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for scheduled visits 
without stating an intention to withdraw consent and is unable to be contacted by the study site. The 
following actions must be taken if a participant fails to return to the study site for a required study visit: 
1. The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible, counsel the participant on the importance of maintaining the assigned visit schedule, and 
ascertain whether the participant wishes to and/or should continue in the study. 
2. Before a participant is deemed lost to follow-up, the investigator or designee must make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if necessary, a 
certified letter to the participant’s last known mailing address or local equivalent methods). These 
contact attempts (e.g., dates of telephone calls and registered letters) should be documented in the 
participant’s study source document. 


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3. Should the participant continue to be unreachable, he/she will be considered to have withdrawn 
from the study. 
4. A participant should not be considered lost to follow-up until due diligence has been completed. 
Date of withdrawal/lost to follow-up should be the date of last contact with the participant where 
safety status of the participant was assessed (e.g., study site visit, telephone call). 
12.7 
Replacement of Participants 
Any participant who is withdrawn or who is lost to follow-up from the study may be replaced at the 
principal investigator’s discretion. 
13 PROTOCOL VIOLATIONS 
A protocol violation occurs when the participant, investigator, or Sponsor fails to adhere to significant 
protocol requirements affecting the inclusion, exclusion, participant safety and primary endpoint criteria.  
Protocol violations for this study include, but are not limited to, the following: 
1. Failure to meet inclusion/exclusion criteria 
2. Use of a prohibited concomitant medication 
Failure to comply with Good Clinical Practice (GCP) guidelines will also result in a protocol violation. 
The Investigator will determine if a protocol violation will result in withdrawal of a participant. 
When a protocol violation occurs, it will be discussed with the investigator and a Protocol Violation Form 
detailing the violation will be generated. This form will be signed by the Investigator. The form will be 
sent to the IRB and a copy will be filed in the site’s regulatory binder.  
 
 
14 STATISTICAL METHODS AND CONSIDERATIONS 
14.1 
General Considerations 
Data collected in this study will be presented using summary tables and participant data listings. 
Continuous variables will be summarized using descriptive statistics, specifically the mean, median, 
standard deviation, minimum, and maximum. Categorical variables will be summarized by frequencies 
and percentages. Data Sets Analyzed: 
• 
Intent-to-Treat (ITT) Analysis Set 
The ITT analysis set includes all participants who are enrolled into a treatment (dose) group regardless of 
whether participants receive any study drug(s), or receive a different regimen from the regimen they were 
randomized to. Participants will be assigned into a dose group as described above.  
• 
Safety Analysis Set 
A safety analysis set will include data from participants who receive at least one dose of study treatment, 
with treatment assignments designated according to the actual treatment received. This analysis set will 
be used in the analyses of safety variables (primary endpoint) as well as study treatment administration. 
• 
Per-Protocol (PP) Analysis Set 


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The PP analysis set includes data from participants in the ITT analysis set who meet the general criteria 
defining the target population for this study, are adherent to the protocol, are compliant with study drug 
treatment, and are evaluable for relevant efficacy endpoints. Treatment assignment will be designated 
according to the actual treatment received. The PP analysis set will be used in the analyses of the 
secondary endpoints. The PP analysis set will only include participants randomized to the dose-group 
(Cohorts 1 and 2, Figure 1). The PP analysis set will exclude participants in the sentinel mid-dose (n=2), 
sentinel high-dose (n=2) and initial standard-dose groups (n=2) who were not randomized to their dose-
group. Participants who are found to have detectable anti-N-protein IgG antibody levels (representing 
prior infection) at their Day 1 (baseline) visit will be excluded from the PP analysis set.  
14.2 
Demographic and Baseline Characteristics 
The following demographic variables at screening will be included: race, ethnicity, sex, age, BMI, 
medication history, co-morbidities including cardiovascular disease, risk factors for cardiovascular 
disease, and immunosuppressive agents.   
14.3 
Analysis of Primary Endpoint 
Safety will be measured by the frequency and grade of AEs (solicited and unsolicited), SAEs, AESIs, 
MAAEs. Reactogenicity will be measured by the occurrence and severity of solicited injection site and 
systemic reactions. Simple descriptive statistics will be used to summarize toxicities in terms of type, 
severity and minimum or maximum values for laboratory measures, time of onset, duration, and 
reversibility or outcome. Tables will be created to summarize these toxicities and side effects. Safety 
Analyses will be performed on Safety Analysis Set. 
14.4 
Analysis of Secondary Endpoints 
1. Binding antibody: The anti-RBD and anti-spike (S-2P) IgG concentrations (log10 and geometric 
mean concentrations (GMC)) at Day 30 will be evaluated with comparisons between the standard-
dose versus high-dose groups. T-tests with two-sided p<0.05 significance will be used (overall α level 
of 0.1). Changes in the anti-RBC and anti-spike IgG concentrations at Day 30 will be compared 
between the standard-dose versus high-dose groups using two sample T-tests with two-sided p<0.05 
significance (overall α level of 0.1). The percent of participants with detectable antibody levels 
(greater than the LLOQ) at Day 30 will also be evaluated using Fisher’s exact tests. Pairwise 
comparisons of binding antibodies will also be evaluated between the standard-dose versus mid-dose 
groups. 
 
2. Neutralizing antibody: Neutralizing antibody titers (geometric mean titers (GMT)) from a 
pseudovirus neutralization assay at Day 30 will be compared between the standard-dose versus high-
dose groups using T-tests with two-sided p<0.05 significance (overall α level of 0.1). Changes in the 
neutralizing antibody titers at Day 30 will be compared between the standard-dose versus high-dose 
using two sample T-tests with two-sided p<0.05 significance (overall α level of 0.1). The percent of 
participants with detectable neutralizing antibody levels (greater than the LLOQ) at Day 30 will also 
be evaluated using Fisher’s exact tests. Pairwise comparisons of neutralizing antibodies will also be 
evaluated between the standard-dose versus mid-dose groups. 
 


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3. Cellular immunogenicity: The change in the frequency of target cytokine producing T-cells by flow 
cytometry with intracellular staining at Day 30 will be compared using the Kruskal-Wallis Test for 
the standard-dose versus high-dose groups. A comparison of T-cell frequencies between the standard-
dose versus high-dose groups will be evaluated using the Wilcoxon rank-sum test. Pairwise 
comparisons of cellular immunogenicity will also be evaluated between the standard-dose versus 
mid-dose groups. 
14.5 
Analysis of Safety 
Safety is the primary endpoint and described above. Simple descriptive statistics will be used to 
summarize frequency and grade of AEs (solicited and unsolicited), SAEs, AESIs and MAAEs. Safety 
Analyses will be performed on Safety Analysis Set. 
14.6 
Sample Size Justification 
The overall mean log10 IgG increase after the third (100 ug) vaccine dose was 0.46 with standard 
deviation (SD) 0.63. Assuming participants have a 50% lower response to the 50 ug fourth-dose, the 
expected mean log10 IgG increase is 0.23. Assuming participants have a 100% higher response to the 200 
ug fourth-dose, their expected mean log10 IgG increase is 0.91. For 80% power to detect this difference 
between high-dose and standard-dose groups with a SD of 0.63 for a two-sample t-test with two-sided 
α<0.05 significance, the minimum required sample size is 15 per group. Thus, we will enroll 20 
participants in each group. The first 2 participants in the mid and high-dose groups will be enrolled as the 
sentinel group to ensure an acceptable safety profile before the full group is enrolled.  
If the halting criteria is triggered for the high-dose group and further enrollment of this group is not 
recommended by the study investigators, DSMB or IRB, the study will continue randomized enrollment 
into the mid-dose and standard-dose groups with a 1:2 ratio to complete the enrollment of 60 participants 
total. Since the expected immunogenicity difference between the mid-dose and standard-dose group is 
smaller, we will require more participants to detect a difference between these two groups. The 1:2 
enrollment ratio into the mid-dose and standard-dose groups will even the distribution of participants into 
these two groups. The primary endpoint analysis for safety and reactogencity will not be affected by a 
restriction of participants into the mid-dose and standard-dose groups. 
 
14.7 
Interim Analysis 
Interim analysis of the secondary immunogenicity endpoints (humoral and cellular immunogenicity) may 
be conducted once all study participants have completed their Day 30 visit and blood draw.   
 
 
 


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15 DATA COLLECTION, RETENTION AND MONITORING 
15.1 
Data Collection Instruments 
The Investigator will prepare and maintain adequate and accurate source documents designed to record all 
observations and other pertinent data for each participant treated with the study drug.   
Study personnel will enter data from source documents corresponding to each participant into the 
protocol-specific electronic Case Report Form (eCRF) OR paper CRF when the information 
corresponding to that visit is available.  Participants will not be identified by name in the study database 
or on any study documents to be collected by the Sponsor (or designee), but will be identified by a 
participant number. 
The Investigator is responsible for all information collected on participants enrolled in this study.  All 
data collected during the course of this study must be reviewed and verified for completeness and 
accuracy by the Investigator.  A copy of the CRF will remain at the Investigator’s site at the completion 
of the study. 
15.2 
Data Management Procedures 
The data will be entered into a secure, de-identified, database.  The study coordinators will be responsible 
for data processing, in accordance with procedural documentation.  Database lock will occur once quality 
assurance procedures have been completed. 
All procedures for the handling and analysis of data will be conducted using good computing practices 
meeting FDA guidelines for the handling and analysis of data for clinical trials. 
15.3 
Data Quality Control and Reporting 
After data have been entered into the study database, a system of computerized data validation checks 
will be implemented and applied to the database on a regular basis. The study database will be updated in 
accordance with the resolved queries.  All changes to the study database will be documented. 
15.4 
Archival of Data 
The database is safeguarded against unauthorized access by established security procedures; appropriate 
backup copies of the database and related software files will be maintained.  Databases are backed up by 
the database administrator in conjunction with any updates or changes to the database.   
At critical junctures of the protocol (e.g., production of interim reports and final reports), data for analysis 
is locked and cleaned per established procedures. 
15.5 
Availability and Retention of Investigational Records 
The Sponsor/Investigator must make study data accessible to the monitor, IRB/ and Regulatory Agency 
(e.g., FDA) inspectors upon request.  A file for each participant must be maintained that includes the 
signed Informed Consent, HIPAA Authorization and Assent Form and copies of all source documentation 
related to that participant.  The Investigator must ensure the reliability and availability of source 
documents from which the information on the CRF was derived. 


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All study documents (participant files, signed informed consent forms, copies of CRFs, Study File 
Notebook, etc.) must be kept secured for a period of two years following marketing of the investigational 
product or for two years after centers have been notified that the IND has been discontinued.  There may 
be other circumstances for which the Sponsor/Investigator is required to maintain study records. 
15.6 
Monitoring 
This study will be monitored by the UCLA Clinical & Translational Science Institute – Office of 
Regulatory Affairs (CTSI ORA). Monitoring visits will be conducted according to the U.S. CFR Title 21 
Parts 50, 56, and 312 and ICH Guidelines for GCP (E6). By signing this protocol, the 
Sponsor/Investigator grants permission to the appropriate regulatory authorities to conduct on-site 
monitoring and/or auditing of all appropriate study documentation.  
15.7 
Participant Confidentiality 
In order to maintain participant confidentiality, only a participant number will identify all study 
participants on CRFs and other documentation.  
 
 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS 
The study will be conducted according to the Declaration of Helsinki, Protection of Human Volunteers 
(21 CFR 50), Institutional Review Boards (21 CFR 56), and Obligations of Clinical Investigators (21 
CFR 312). 
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other records will be 
identified by a coded number and initials only.  All study records will be kept in a locked file cabinet and 
code sheets linking a participant’s name to a participant identification number will be stored separately in 
another locked file cabinet.  Clinical information will not be released without written permission of the 
participant, except as necessary for monitoring by the FDA.  The Investigator must also comply with all 
applicable privacy regulations (e.g., Health Insurance Portability and Accountability Act of 1996, EU 
Data Protection Directive 95/46/EC). 
15.8 
Protocol Amendments 
Any amendment to the protocol will be written by the Sponsor/Investigator. Protocol amendments cannot 
be implemented without prior written IRB approval except as necessary to eliminate immediate safety 
hazards to participants. A protocol amendment intended to eliminate an apparent immediate hazard to 
participants may be implemented immediately, provided the IRBs are notified within five working days. 
15.9 
Institutional Review Boards and Independent Ethics Committees 
The protocol and consent form will be reviewed and approved by the IRB.  Serious adverse experiences 
regardless of causality will be reported to the IRB in accordance with the standard operating procedures 
and policies of the IRB, and the Investigator will keep the IRB informed as to the progress of the study.  
The Investigator will obtain assurance of IRB compliance with regulations. 
Any documents that the IRB may need to fulfill its responsibilities (such as protocol, protocol 
amendments, Investigator’s Brochure, consent forms, information concerning participant recruitment, 
payment or compensation procedures, or other pertinent information) will be submitted to the IRB. The 


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IRB unconditional approval of the study protocol and the informed consent form will be in the possession 
of the Investigator before the study is initiated. This approval must refer to the study by exact protocol 
title and number and should identify the documents reviewed and the date of review. 
Protocol and/or informed consent modifications or changes may not be initiated without prior written IRB 
approval except when necessary to eliminate immediate hazards to the participants or when the change(s) 
involves only logistical or administrative aspects of the study.  Such modifications will be submitted to 
the IRB and written verification that the modification was submitted and subsequently approved should 
be obtained.   
The IRB must be informed of revisions to other documents originally submitted for review; serious and/or 
unexpected adverse experiences occurring during the study in accordance with the standard operating 
procedures and policies of the IRB; new information that may affect adversely the safety of the 
participants of the conduct of the study; an annual update and/or request for re-approval; and when the 
study has been completed. 
15.10 Informed Consent Form  
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH GCP, US Code of 
Federal Regulations for Protection of Human Subjects (21 CFR 50.25[a,b], CFR 50.27, and CFR Part 56, 
Subpart A), the Health Insurance Portability and Accountability Act (HIPAA, if applicable), and local 
regulations. 
The Investigator will prepare the informed consent form, and HIPAA authorization and provide the 
documents to the IRB/.  The consent form generated by the Investigator must be approved by the IRB.  
The written consent document will embody the elements of informed consent as described in the 
International Conference on Harmonisation and will also comply with local regulations. The Investigator 
will include the IRB/ -approved copy of the Informed Consent Form in the study file. 
A properly executed, written, informed consent will be obtained from each participant prior to entering 
the participant into the trial.  Information should be given in both oral and written form and participants 
(or their legal representatives) must be given ample opportunity to inquire about details of the study.  If a 
participant is unable to sign the informed consent form (ICF) and the HIPAA authorization, a legal 
representative may sign for the participant.   A copy of the signed consent form) will be given to the 
participant or legal representative of the participant and the original will be maintained with the 
participant’s records. 
15.11 Publications  
The publication or presentation of any study results shall comply with all applicable privacy laws, 
including, but not limited to, the Health Insurance Portability and Accountability Act of 1996.  
15.12 Investigator Responsibilities 
By signing the Agreement of Investigator form, the Investigator agrees to: 
1. 
Conduct the study in accordance with the protocol and only make changes after notifying the 
Sponsor (or designee), except when to protect the safety, rights or welfare of participants. 
2. 
Personally, conduct or supervise the study (or investigation). 


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3. 
Ensure that the requirements relating to obtaining informed consent and IRB review and approval 
meet federal guidelines, as stated in § 21 CFR, parts 50 and 56. 
4. 
Report to the Sponsor or designee any AEs that occur in the course of the study, in accordance with 
§21 CFR 312.64. 
5. 
Ensure that all associates, colleagues and employees assisting in the conduct of the study are 
informed about their obligations in meeting the above commitments. 
6. 
Maintain adequate and accurate records in accordance with §21 CFR 312.62 and to make those 
records available for inspection with the Sponsor (or designee). 
7. 
Ensure that an IRB that complies with the requirements of §21 CFR part 56 will be responsible for 
initial and continuing review and approval of the clinical study. 
8. 
Promptly report to the IRB and the Sponsor (or designee) all changes in the research activity and all 
unanticipated problems involving risks to participants or others (to include amendments and IND 
safety reports). 
9. 
Seek IRB approval before any changes are made in the research study, except when necessary to 
eliminate hazards to the participants. 
10. Comply with all other requirements regarding the obligations of clinical investigators and all other 
pertinent requirements listed in § 21 CFR part 312. 
 
APPENDIX 1.  SCHEDULE OF EVENTS 
 
Screening 
Day -30 to 
Day 0 
Visit 1 
Day 1 
Clinic 
Visit 2 
Day 3 
Phone 
+/-1 
day 
Visit 3 
Day 7 
Clinic 
+/-2 
days 
Visit 4 
Day 30 
Clinic 
+/-7 
days 
Visit 5 
Day 90 
Phone 
+/-7 
days 
Visit 6 
Day 180 
Phone 
+/-7 
days 
Unscheduled 
visit as 
needed 
Informed 
Consent 
 
X 
 
 
 
 
 
 
Demographic 
data 
 
X 
 
 
 
 
 
 
Medical History 
 
X 
 
 
 
 
 
 
Eligibility 
review 
X 
X 
 
 
 
 
 
 
Con meds 
 
X 
 
 
 
 
 
 
Pre-study meds 
 
X 
 
 
 
 
 
 
Review CoV 
vaccinations 
 
X 
 
 
 
 
 
 
Height 
 
X 
 
 
 
 
 
 
Weight 
 
X 
 
X 
X 
 
 
 
Vital Signs (HR, 
BP, temperature, 
oximetry) 
 
X 
 
X 
X 
 
 
 
Full physical 
exam 
 
X 
 
 
 
 
 
X 


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Targeted 
physical exam 
 
 
 
X 
X 
 
 
 
Blood draw* 
 
X 
 
X 
X 
 
 
X 
Group 
assignment 
 
X 
 
 
 
 
 
 
IP administration 
 
X 
 
 
 
 
 
 
30-minute post-
dose observation 
 
X 
 
 
 
 
 
 
Review AEs, 
SAEs, AESIs, 
MAAEs 
 
 
X 
X 
X 
X 
X 
X 
Review 
myocarditis and 
pericarditis 
symptoms 
 
 
X 
X 
X 
X 
X 
X 
Dispense daily 
diary 
 
X 
 
 
 
 
 
 
Diary review 
 
 
X 
X 
 
 
 
 
Pregnancy test 
(women of child-
bearing 
potential) 
 
X 
 
 
 
 
 
 
Birth control 
history (women 
of child-bearing 
potential) 
 
X 
 
 
 
 
 
 
Review 
participants’ use 
of  appropriate 
birth control (if 
applicable) 
 
X 
 
 
 
 
 
 
 
*Baseline labs must be drawn before vaccine dose. Day 7 must be drawn +/- 2 days. All other 
labs can be drawn +/- 7 days.   
 
 
 
 


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APPENDIX 2: ADVERSE EVENTS OF SPECIAL INTEREST (AESI) TERMS 
The Investigator’s medical judgement must be applied to assess an event as an AESI, as most 
AESIs are based on medical concepts. The table below does not provide a comprehensive list of 
terms.  
 
The following table describes events/medical concepts that are of interest in COVID-19 vaccine safety 
surveillance. Some are specific to vaccines; however, some are of interest due to their occurrence in the 
context of concurrent or recent COVID-19. Events falling into the descriptions below should be reported 
as AESIs, per protocol, even when they occur during/following COVID infection.  
 
Please note: COVID-19 itself is not an AESI. 
 
Medical Concept 
Medical Concept Descriptions/Guidance 
0. Not an AESI 
 
1. Anosmia, Ageusia 
 
• New onset of anosmia or ageusia associated with COVID-19 or idiopathic 
etiology  
• DOES NOT INCLUDE anosmia or ageusia associated with sinus/nasal 
congestion, congenital, or traumatic etiologies  
2. Subacute thyroiditis 
 
• Acute inflammatory disease of the thyroid (immune-mediated or 
idiopathic) 
• DOES NOT INCLUDE new onset of chronic thyroiditis 
3. Acute pancreatitis 
 
• New onset of pancreatitis in the absence of a clear, alternate etiology, 
such as alcohol, gallstones, trauma, recent invasive procedure, etc. 
4. Appendicitis  
• Any event of appendicitis  
5. Rhabdomyolysis 
 
• New onset of rhabdomyolysis in the absence of a clear, alternate etiology, 
such as drug/alcohol abuse, excessive exercise, trauma, etc. 
6. Acute respiratory 
distress syndrome 
(ARDS) 
• New onset of ARDS/respiratory failure due to acute inflammatory lung 
injury 
• DOES NOT INCLUDE non-specific symptoms of shortness of breath or 
dyspnea, nor events with underlying etiologies of heart failure or fluid 
overload 
7. Coagulation disorders 
• New onset of thrombosis, thromboembolic event, or non-traumatic 
hemorrhage/bleeding disorder (ex. stroke, DVT, pulmonary embolism, 
disseminated intravascular coagulation (DIC), etc.) 
8. Acute cardiovascular 
injury 
• New onset of clinically confirmed, acute cardiovascular injury, such as 
myocarditis, pericarditis, arrhythmia confirmed by ECG (ex. atrial 
fibrillation, atrial flutter, supraventricular tachycardia), stress 
cardiomyopathy, heart failure, acute coronary syndrome, myocardial 
infarction, etc. 
• DOES NOT INCLUDE transient sinus tachycardia/bradycardia, non-specific 
symptoms such as palpitations, racing heart, heart fluttering or pounding, 
irregular heartbeats, shortness of breath, chest pain/discomfort, etc. 


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Medical Concept 
Medical Concept Descriptions/Guidance 
9. Acute kidney injury 
• New onset of acute kidney injury or acute renal failure in the absence of a 
clear, alternate etiology, such as urinary tract infection/urosepsis, trauma, 
tumor, nephrotoxic medications/substances, etc.; 
• Increase in serum creatinine by ≥ 0.3 mg/dl (or ≥26.5 µmol/l) within 48 
hours; OR 
• Increase in serum creatinine to ≥ 1.5 times baseline, known or presumed 
to have occurred within prior 7 days 
10. Acute liver injury 
• New onset in the absence of a clear, alternate etiology, such as trauma, 
tumor, hepatotoxic medications/substances, etc.: 
• >3-fold elevation above the upper normal limit for ALT or AST; OR 
• >2-fold elevation above the upper normal limit for total serum bilirubin or 
GGT or ALP 
11. Dermatologic 
findings  
• Chilblain-like lesions 
• Single organ cutaneous vasculitis 
• Erythema multiforme 
• Bullous rash 
• Severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, 
Toxic epidermal necrolysis, Drug reaction with eosinophilia and systemic 
symptoms (DRESS), fixed drug eruptions, and necrotic or exfoliative 
reactions 
12 Systemic 
inflammatory syndromes  
• Multisystem inflammatory syndrome in adults (MIS-A) or children (MIS-C) 
• Kawasaki’s disease 
• Hemophagocytic lymphohistiocytosis (HLH) 
13. Thrombocytopenia 
• Platelet count < 150 x10^9/L (thrombocytopenia) 
• New clinical diagnosis, or worsening, of thrombocytopenic condition, such 
as immune thrombocytopenia, thrombocytopenic purpura, or HELLP 
syndrome 
14. Acute aseptic 
arthritis  
 
Clinical syndrome characterized by acute onset of signs and symptoms of 
joint inflammation without recent trauma for a period of no longer than 
6 weeks, synovial increased leukocyte count and the absence of 
microorganisms on Gram stain, routine culture and/or PCR. 
• DOES NOT INCLUDE new onset of chronic arthritic conditions 
15. New onset, or 
worsening, of 
neurological disease 
• Immune-mediated neurological disorders 
• Guillain-Barre Syndrome 
• Acute disseminated encephalomyelitis (ADEM) 
• Peripheral facial nerve palsy (Bell’s palsy)  
• Transverse myelitis 
• Encephalitis/Encephalomyelitis 
• Aseptic meningitis 
• Seizures/convulsions/epilepsy 
• Narcolepsy/hypersomnia 
16. Anaphylaxis  
• Anaphylaxis associated with study drug administration 


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Medical Concept 
Medical Concept Descriptions/Guidance 
17. Other syndromes 
 
• Fibromyalgia  
• Postural Orthostatic Tachycardia Syndrome  
• Chronic Fatigue Syndrome  
• Myalgic encephalomyelitis  
• Post viral fatigue syndrome 
• Myasthenia gravis 
 
 
 
 
 


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APPENDIX 3: TABLE OF LABORATORY ABNORMALITIES 
 
Test
Mild             
(Grade 1)
Moderate        
(Grade 2)
Severe           
(Grade 3)
Potentially Life 
Threatening      
(Grade 4)
Sodium (Hyponatremia) mEq/L
132 - 134
130 - 131
125 - 129
< 125
Sodium (Hypernatremia) mEq/L
144 - 145
146 - 147
148 - 150 
> 150
Potassium (Hyperkalemia) mEq/L
5.4 - 5.6
5.6 - 5.8
5.8 - 6.0
> 6.0
Potassium (Hypokalemia) mEq/L
3.2 - 3.5
3.0 - 3.1
2.8 - 2.9
< 2.8
Glucose (Hypoglycemia) mg/dL
65 - 69
55 - 64
45 - 54
< 45
Glucose (Hyperglycemia) mg/dL
        Fasting
110 - 110
111 - 125
> 125
Requires insulin
        Random
110 - 125
126 - 200
> 200
Requires insulin
Blood Urea Nitrogen (BUN) mg/dL
30 - 35
35 - 40
> 40
Requires dialysis
Creatinine (Cr) mg/dL
1.8 - 2.3
2.4 - 2.8
2.9 - 3.2
> 3.2 or Requires 
dialysis
Calcium (Hypocalcemia) mg/dL
8.0 - 8.4
7.5 - 7.9
7.0 - 7.4
< 7.0
Calcium (Hypercalcemia) mg/dL
10.5 - 11.0
11.1 - 11.5
11.6 - 12.0
> 12.0
Magnesium (Hypomagnesemia) mg/dL
1.3 - 1.5
1.0 - 1.2
0.7 - 0.9
< 0.7
Phosporus (Hypophosphatemia) mg/dL
2.3 - 2.5
2.0 - 2.2
1.6 - 1.9
< 1.6
CPK
1.25 - 1.5 ULN
1.6 - 3.0 x ULN
3.1 - 10 x ULN
> 10 x ULN
Albumin (Hypoalbuminemia) mg/dL
2.5 - 2.8
2.1 - 2.4
< 2.1
---
Protein (Hypoproteinnemia) mg/dL
5.0 - 5.5
4.4 - 4.9
< 4.4
---
Alkaline Phosphatate - Increase by Factor
1.1 - 2.0 x ULN
1.6 - 3.0  x ULN
3.1 - 10 x ULN
> 10 x ULN
Liver function Tests (ALT, AST) - Increase by 
Factor
1.1 - 2.5 x ULN
2.6 - 5.0 ULN
5.1 - 10 x ULN
> 10 x ULN
Bilirubin - when accompanied by any increase 
in LFTs - Increase by Factor
1.1 - 1.25 x ULN
1.26 - 1.5 x ULN
1.51 - 1.75 x ULN
>1.75 x ULN
Bilirubin - when LFTs are normal - Increase by 
Factor
1.1 - 1.5 x ULN
1.6 - 2.0 x ULN
2.0 - 3.0 x ULN
>3.0 x ULN
Pancreatic enzymes (Amylase, lipase)
1.1 - 1.5 x ULN
1.6 - 2.0 x ULN
2.0 - 5.0 x ULN
>5.0 x ULN
Hemoglobin (Female)
8.6 - 9.1
8.1 - 8.5
7.0 - 8.0
< 7.0
Hemoglobin (Female) change from baseline 
value gm/dL
1.2 - 1.5
1.6 - 2.0
2.1 - 5.0
> 5.0
Hemoglobin (Male)
9.1 - 9.5
8.6 - 9.0
7.5 - 8.5
< 7.5
Hemoglobin (Male) change from baseline 
value gm/dL
1.2 - 1.5
1.6 - 2.0
2.1 - 5.0
> 5.0
WBC (High) cell/mm3 
15,000  - 20,000
20,001 - 25,000
25,001 - 30,000
> 30,000
WBC (Low) cell/mm3
1,501 - 2,000
1,001 - 1,500
500 - 1,000
< 500
Lymphocyte (Low) cell/mm3
601 - 800
401 - 600
200 - 400
< 200
Neutrophil (Low)  cell/mm3
701 - 1,000
501 - 700
401 - 500
< 400
Eosinophils (High)  cell/mm3
650 - 1,500
1,501 - 5,000
> 5,000
Hypereosiniphilic
Platelets (Low)  cell/mm3
60,001 - 80,000
40,001 - 60,000
> 25,000 - 40,000
< 25,000
Prothrombin time (PT) - Increase by Factor
1.11 - 1.2
1.21 - 1.3
1.31 - 1.4 x ULN
>1.4 ULN
Partial thrombinplastin time (PTT) - Increase 
by Factor
1.31 - 1.4
1.41 - 1.5
1.51 - 1.6 x ULN
>1.6 ULN
Fibrinogen (High) mg/dL
400 - 500
501 - 600
> 600
---
Fibrinogen (Low) mg/dL
150 - 200
125 - 149
100 - 124
< 100 or associated with 
gross bleeding or 
disseminated intravascular 
coagulation
[1] ULN - Upper limit of normal. 
[2] Values highlighted in yellow are adjusted from "Guidance for Industry Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers
 Enrolled in Preventitive Vaccine Clinical Trials" to reflect immunosuppressed lung transplant population.


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APPENDIX 4: CLAIM FOR CATEGORICAL EXCLUSION 
 
Per 21 CFR 25.15(d) that, to our knowledge, no extraordinary circumstances exist that would warrant the 
preparation of an environmental assessment (EA). 
 
 
 


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REFERENCES 
 
1. 
Corbett KS, Flynn B, Foulds KE, Francica JR, Boyoglu-Barnum S, Werner AP, Flach B, 
O’Connell S, Bock KW, Minai M, Nagata BM, Andersen H, Martinez DR, Noe AT, 
Douek N, Donaldson MM, Nji NN, Alvarado GS, Edwards DK, Flebbe DR, Lamb E, 
Doria-Rose NA, Lin BC, Louder MK, O’Dell S, Schmidt SD, Phung E, Chang LA, Yap 
C, et al. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman 
Primates. N Engl J Med 2020;383:1544–1555. 
2. 
Corbett KS, Nason MC, Flach B, Gagne M, O’Connell S, Johnston TS, Shah SN, Edara 
VV, Floyd K, Lai L, McDanal C, Francica JR, Flynn B, Wu K, Choi A, Koch M, Abiona 
OM, Werner AP, Moliva JI, Andrew SF, Donaldson MM, Fintzi J, Flebbe DR, Lamb E, 
Noe AT, Nurmukhambetova ST, Provost SJ, Cook A, Dodson A, et al. Immune correlates 
of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. 
Science (80- ) 2021;373:. 
3. 
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, et al. Efficacy and Safety 
of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med 2021;384:403–416. 
4. 
El Sahly HM, Baden LR, Essink B, Doblecki-Lewis S, Martin JM, Anderson EJ, 
Campbell TB, Clark J, Jackson LA, Fichtenbaum CJ, Zervos M, Rankin B, Eder F, 
Feldman G, Kennelly C, Han-Conrad L, Levin M, Neuzil KM, Corey L, Gilbert P, Janes 
H, Follmann D, Marovich M, Polakowski L, Mascola JR, Ledgerwood JE, Graham BS, 
August A, Clouting H, et al. Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at 
Completion of Blinded Phase. N Engl J Med 2021;385:1774–1785. 
5. 
Oliver SE, Wallace M, See I, Mbaeyi S, Godfrey M, Hadler SC, Jatlaoui TC, Twentyman 
E, Hughes MM, Rao AK, Fiore A, Su JR, Broder KR, Shimabukuro T, Lale A, Shay DK, 
Markowitz LE, Wharton M, Bell BP, Brooks O, McNally V, Lee GM, Talbot HK, Daley 
MF. Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine: Updated Interim 
Recommendations from the Advisory Committee on Immunization Practices — United 
States, December 2021. MMWR Morb Mortal Wkly Rep 2022;71:90–95. 
6. 
Barda N, Dagan N, Ben-Shlomo Y, Kepten E, Waxman J, Ohana R, Hernán MA, Lipsitch 
M, Kohane I, Netzer D, Reis BY, Balicer RD. Safety of the BNT162b2 mRNA Covid-19 
Vaccine in a Nationwide Setting. N Engl J Med 2021;385:1078–1090. 
7. 
Simone A, Herald J, Chen A, Gulati N, Shen AYJ, Lewin B, Lee MS. Acute Myocarditis 
following COVID-19 mRNA Vaccination in Adults Aged 18 Years or Older. JAMA 
Intern Med 2021;181:1668–1670. 
8. 
Oster ME, Shay DK, Su JR, Gee J, Creech CB, Broder KR, Edwards K, Soslow JH, 
Dendy JM, Schlaudecker E, Lang SM, Barnett ED, Ruberg FL, Smith MJ, Campbell MJ, 
Lopes RD, Sperling LS, Baumblatt JA, Thompson DL, Marquez PL, Strid P, Woo J, 
Pugsley R, Reagan-Steiner S, DeStefano F, Shimabukuro TT. Myocarditis Cases Reported 


Phase I/II, Open-label Dose-finding Trial of High-Dose mRNA-1273 Booster for Lung Transplant 
Recipients 
 
 
 
 
 
 
 
 
Confidential 
 
 
 
Version Date: 04/09/2022 
Page 55 of 56 
 
 
After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 
2021. Jama 2022;327:331. 
9. 
Larson KF, Ammirati E, Adler ED, Cooper LT, Hong KN, Saponara G, Couri D, Cereda 
A, Procopio A, Cavalotti C, Oliva F, Sanna T, Ciconte VA, Onyango G, Holmes DR, 
Borgeson DD. Myocarditis after BNT162b2 and mRNA-1273 Vaccination. Circulation 
2021;506–508.doi:10.1161/CIRCULATIONAHA.121.055913. 
10. 
Rosenblum HG, Hadler SC, Moulia D, Shimabukuro TT, Su JR, Tepper NK, Ess KC, 
Woo EJ, Mba-Jonas A, Alimchandani M, Nair N, Klein NP, Hanson KE, Markowitz LE, 
Wharton M, McNally V V., Romero JR, Talbot HK, Lee GM, Daley MF, Mbaeyi SA, 
Oliver SE. Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult 
Recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 Vaccines (Pfizer-
BioNTech and Moderna): Update from the Advisory Committee on Immunization 
Practices — United States, July 202. MMWR Recomm Reports 2021;70:1094–1099. 
11. 
Marion O, Del Bello A, Bravanel F. Safety and Immunogenicity of Anti–SARS-CoV-2 
Messenger RNA Vaccines in Recipients of Solid Organ Transplants. Ann Intern Med 
2021;174:1336–1338. 
12. 
Hall VG, Ferreira VH, Ku T. Randomized Trial of a Third Dose of mRNA-1273 Vaccine 
in Transplant Recipients. new engl J Med 2021;385:1244–1246. 
13. 
Boyarsky BJ, Werbel WA, Avery RK, Tobian AAR, Massie AB, Segev DL, Garonzik-
Wang JM. Antibody response to 2-dose sars-cov-2 mrna vaccine series in solid organ 
transplant recipients. JAMA - J Am Med Assoc 2021;325:2204–2206. 
14. 
Schramm R, Costard-Jäckle A, Rivinius R, Fischer B, Müller B, Boeken U, Haneya A, 
Provaznik Z, Knabbe C, Gummert J. Poor humoral and T-cell response to two-dose 
SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients. 
Clin Res Cardiol 2021;110:1142–1149. 
15. 
Shostak Y, Shafran N, Heching M, Rosengarten D, Shtraichman O, Shitenberg D, Amor 
SM, Yahav D, Ben Zvi H, Pertzov B, Kramer MR. Early humoral response among lung 
transplant recipients vaccinated with BNT162b2 vaccine. Lancet Respir Med 2021;9:e52–
e53. 
16. 
Havlin J, Svorcova M, Dvorackova E, Lastovicka J, Lischke R, Kalina T, Hubacek P. 
Immunogenicity of BNT162b2 mRNA COVID-19 vaccine and SARS-CoV-2 infection in 
lung transplant recipients. J Hear Lung Transplant 2021;40:754–758. 
17. 
Messika J, Eloy P, Roux A, Hirschi S, Nieves A, Le Pavec J, Sénéchal A, Saint Raymond 
C, Carlier N, Demant X, Le Borgne A, Tissot A, Debray MP, Beaumont L, Renaud-Picard 
B, Reynaud-Gaubert M, Mornex JF, Falque L, Boussaud V, Jougon J, Mussot S, Mal H. 
COVID-19 in Lung Transplant Recipients. Transplantation 2021;105:177–186. 
18. 
Saez-Giménez B, Berastegui C, Barrecheguren M, Revilla-López E, Los Arcos I, Alonso 
R, Aguilar M, Mora VM, Otero I, Reig JP, Quezada CA, Pérez V, Valle M, Laporta R, 
Deu M, Sacanell J, Bravo C, Gavalda J, Lopez-Meseguer M, Monforte V. COVID-19 in 
lung transplant recipients: A multicenter study. Am J Transplant 2021;21:1816–1824. 
19. 
Aversa M, Benvenuto L, Anderson M, Shah L, Robbins H, Pereira M, Scheffert J, Carroll 
M, Hum J, Nolan M, Reilly G, Lemaitre P, Stanifer BP, D’Ovidio F, Sonett J, Arcasoy S. 


Phase I/II, Open-label Dose-finding Trial of High-Dose mRNA-1273 Booster for Lung Transplant 
Recipients 
 
 
 
 
 
 
 
 
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Version Date: 04/09/2022 
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COVID-19 in lung transplant recipients: A single center case series from New York City. 
Am J Transplant 2020;20:3072–3080. 
20. 
Kamp JC, Hinrichs JB, Fuge J, Ewen R, Gottlieb J. COVID-19 in lung transplant 
recipients—Risk prediction and outcomes. PLoS One 2021;16:1–14. 
21. 
Hall VG, Ferreira VH, Ierullo M, Ku T, Marinelli T, Majchrzak-Kita B, Yousuf A, 
Kulasingam V, Humar A, Kumar D. Humoral and cellular immune response and safety of 
two-dose SARS-CoV-2 mRNA-1273 vaccine in solid organ transplant recipients. Am J 
Transplant 2021;00:1–10. 
22. 
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;385:661–662. 
23. 
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. Ann Intern Med 
2021;15–17. 
24. 
Damluji AA, Christenson RH, Defilippi C. Clinical application of serologic testing for 
coronavirus disease 2019 in contemporary cardiovascular practice. J Am Heart Assoc 
2021;10:1–9. 
25. 
Abu S, Roguin A, Hellou E, Ishai A, Shoshan U, Mahamid L. Since January 2020 
Elsevier has created a COVID-19 resource centre with free information in English and 
Mandarin on the novel coronavirus COVID- 19 . The COVID-19 resource centre is hosted 
on Elsevier Connect , the company ’ s public news and information . 2020; 
26. 
Patone M, Mei XW, Handunnetthi L, Dixon S, Zaccardi F, Shankar-Hari M, Watkinson P, 
Khunti K, Harnden A, Coupland CAC, Channon KM, Mills NL, Sheikh A, Hippisley-Cox 
J. Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 
vaccination or SARS-CoV-2 infection. Nat Med 2021;doi:10.1038/s41591-021-01630-0. 
27. 
Gargano JW, Wallace M, Hadler SC, Langley G. Use of mRNA COVID-19 Vaccine After 
Reports of Myocarditis Among Vaccine Recipients: Update from the Advisory Committee 
on Immunization Practices — United States, June 2021. MMWR 2019;70:977–982. 
28. 
Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, 
Kindermann I, Gutberlet M, Cooper LT, Liu P, Friedrich MG. Cardiovascular Magnetic 
Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. J Am 
Coll Cardiol 2018;72:3158–3176. 
29. 
Thomas Aretz H. Myocarditis: The Dallas criteria. Hum Pathol 1987;18:619–624. 
30. 
Adler Y, Charron P, Imazio M, Badano L, Barón-Esquivias G, Bogaert J, Brucato A, 
Gueret P, Klingel K, Lionis C, Maisch B, Mayosi B, Pavie A, Ristić AD, Tenas MS, 
Seferovic P, Swedberg K, Tomkowski W, Achenbach S, Agewall S, Al-Attar N, Ferrer 
JA, Arad M, Asteggiano R, Bueno H, Caforio ALP, Carerj S, Ceconi C, Evangelista A, et 
al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases. Eur 
Heart J 2015;36:2921–2964. 
 

ICF_001.pdf: 
 
Protocol V4, 04/09/22 
Main Consent Form Version 06/29/22 
Page 1 of 20 
 
University of California, Los Angeles 
Consent to Participate in Research 
Phase I/II, Open-Label Dose-Finding Trial of High-Dose mRNA-1273 Booster for Lung Transplant 
Recipients 
 
Protocol Number: 
COVID-19  
NCT Number: 
NCT05280158 
Version Date: 
4/9/22 
Investigational Product: 
Moderna mRNA-1273 vaccine 
IND Number: 
28260 
Development Phase: 
Phase I/II 
Sponsor/Investigator: 
Yusaku Michael Shino, MD 
Funding Organizations: 
Pending 
Principal Investigator: 
Yusaku Michael Shino, MD 
Department of Medicine – Pulmonary Disease  
University of California, Los Angeles 
Box 951690, 43-229 CHS 
Los Angeles, CA 90095 
Medical Monitors: 
Yusaku Michael Shino, MD 
Department of Medicine – Pulmonary Disease  
University of California, Los Angeles 
Box 951690, 43-229 CHS 
Los Angeles, CA 90095 
 
Name: S. Sam Weigt, MD 
Department of Medicine – Pulmonary Disease  
University of California, Los Angeles 
Box 951690, 43-229 CHS 
Los Angeles, CA 90095 
 
 
 


 
Protocol V4, 04/09/22 
Main Consent Form Version 06/29/22 
Page 2 of 20 
 
UNIVERSITY OF CALIFORNIA LOS ANGELES 
CONSENT TO PARTICIPATE IN RESEARCH 
 
Sponsor / Study Title: 
ModernaTX, Inc / “Phase I/II, Open-Label Dose-Escalation 
Trial of High-Dose mRNA-1273 Booster for Lung Transplant 
Recipients” 
Short Title:  
Evaluation of the Safety and Immune Response of a Higher-
dose mRNA-1273 Vaccine Dose Among Lung Transplant 
Recipients 
Protocol Number: 
   V4, 06/07/22 
Principal Investigator:     Yusaku Michael Shino, MD, MSCr 
Telephone: 
310-206-6766 
Address: 
43-229 Center for Health Sciences 
 
10833 Le Conte Ave 
 
Westwood, CA 90095 
 
INTRODUCTION: 
Dr. Yusaku Michael Shino, and associates from the Departments of Pulmonary and 
Critical Care and Infectious Disease at the University of California, Los Angeles are 
conducting a research study. The study is being funded by the David Geffen School of 
Medicine.  
 
KEY INFORMATION: 
The Moderna mRNA-1273 vaccine has been approved by the U.S. Food and Drug 
Administration (FDA) to help provide protection from a viral infection called “COVID-19” 
caused by the 2019 novel coronavirus (the virus is also called “SARS-CoV-2”) in 
individuals 18 years of age and older and is authorized for a booster dose. The purpose 
of this study is to test the safety of higher booster doses of the Moderna mRNA-1273 
vaccine among lung transplant recipients. The mRNA-1273 study vaccine is intended to 
boost the immune system to produce enough antibodies against SARS-CoV-2; so, in 
case of an exposure, the virus does not cause severe illness. Lung transplant recipients 
have had weaker responses to the vaccine, and we are studying the safety of higher 
vaccine doses that are not FDA approved.  
 
WHY AM I BEING INVITED TO TAKE PART IN THIS RESEARCH STUDY? 
You are being invited to take part in this UCLA clinical research study, conducted in 
partnership with ModernaTX, Inc, because you have received a lung transplantation 
and have received at least three doses of the Moderna mRNA-1273 or Pfizer 
BNT162b2 vaccine after your lung transplantation.  
 
 


 
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WHAT SHOULD I KNOW ABOUT THIS RESEARCH STUDY? 
 Someone will explain this research study to you. 
 Whether or not you take part is up to you. 
 You can choose not to take part. 
 You can agree to take part and later change your mind. 
 Your decision will not be held against you. 
 You can ask all the questions you want before you decide. 
 You can discuss this study with friends and family. 
 You can also discuss it with your health care doctor or request a second opinion. 
  
 
 WHY IS THIS RESEARCH BEING DONE? 
An outbreak of COVID-19 caused by the 2019 novel coronavirus SARS-CoV-2 
began in Wuhan, Hubei Province, China in December 2019 and has spread 
throughout the world, including the United States. Vaccines serve to prepare your 
immune system for fighting infection and preventing illnesses. Certain cells of the 
immune system produce antibodies (special proteins) that recognize viruses and 
other pathogens (things that cause disease) and make them harmless. Moderna’s 
mRNA-1273 vaccine is intended to boost the immune system to produce antibodies 
against SARS-CoV-2; so, in case of an infection, the virus does not cause severe 
illness.  
However, lung transplant recipients, due to their immune suppressing medications, 
have had a weaker response to the COVID-19 vaccines including mRNA-1273 and 
remain at higher risk of severe disease. This study is testing the mRNA-1273 vaccine 
at a higher booster doses of 100 micrograms (ug) and 200 ugs compared with the 
standard booster dose of 50 ug. The FDA has approved the use of the standard 50 ug 
booster dose, but not the 100 ug or 200 ug doses. The main purpose of this study is 
to understand the safety and antibody response after these higher doses of mRNA-
1273 vaccine among lung transplant recipients who previously received at least three 
doses of the Moderna mRNA-1273 or Pfizer BNT162b2 vaccine, with the last dose 
received at least four months prior to study enrollment.  
 
How long will the research last and what will I need to do? 
We expect that you will be in this research study for 6 months. You will be asked to 
complete 3 visits to the clinic and 3 telephone calls. If you chose to participate in this 
study, you will receive 1 booster injection of study vaccine at either the standard-dose, 
mid-dose or high-dose at your first visit at the study center. You will be told which dose 
you will receive but you or your doctor will not be able to choose the dose. You will be 
asked to keep a daily diary to record side effects that you experience for the first 7 days 
after your booster dose. During your 3 in-person visits to the study center, blood samples 
and a short physical exam will be required. More detailed information about the study 
procedures can be found under the section “WHAT WILL HAPPEN IF I TAKE PART IN 
THIS STUDY”.  


 
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Since we are studying antibody responses to vaccine doses, we ask that you do not 
receive any antibody infusions or injections for COVID-19 prophylaxis, including Evusheld 
monoclonal antibodies until 30 days after you receive the study vaccine. The standard of 
care recommendation is that Evusheld can be given 2 weeks after vaccination, but if you 
choose to participate in this study, we will ask you to wait until after your 30 day study 
visit (which includes the last study blood draw) before receiving Evusheld. If you become 
sick with COVID-19, you would not be limited from receiving any treatments including 
antibody infusions but we defer your treatment to your lung transplant or primary care 
doctor.   
 
WHAT KINDS OF RISKS OF DISCOMFORTS COULD I EXPECT? 
The most common side effects associated with receiving the vaccine include: injection 
site pain, swelling of the lymph nodes in the injection arm, fatigue, headache, muscle 
pain, fever, and chills.  In addition to side effects from the study vaccine, you may feel 
faint or have mild pain, bruising, irritation, or redness where the blood samples are 
taken. A very uncommon side effect after vaccination with mRNA-1273 is inflammation 
of the muscle of the heart, called myocarditis, or lining around the heart that is called 
pericarditis. This has been reported more in young men under 30 years of age after the 
second dose of vaccine; however, it has been reported in older males and in females as 
well after the first dose. Symptoms of myocarditis and pericarditis include chest pain, 
shortness of breath, or feelings of having a fast-beating, fluttering, or pounding heart, 
syncope or fainting with onset of symptoms most commonly reported within a few days 
following vaccination. You should seek medical attention and notify study site staff if any 
of these symptoms occur following vaccination. Most cases are mild and the patients 
recover fully. However, long-term follow-up information is limited. It is not known whether 
the risk of myocarditis or pericarditis is increased following additional doses of the 
vaccine. More detailed information about the risks of this study can be found under the 
section “WHAT KINDS OF RISKS OR DISCOMFORTS COULD I EXPECT?  (Detailed 
Description)” on page 9.  
 
ARE THERE ANY BENEFITS IF I PARTICIPATE? 
You may directly benefit if the higher booster dose is effective in preventing COVID-
19 infection or severe disease from COVID-19 infection. Also, by taking part, you will 
help to provide new scientific information that will benefit patients in the future. 
 
WHAT OTHER CHOICES DO I HAVE IF I DON’T WANT TO PARTICIPATE? 
Participation in research is completely voluntary. You can decide to participate or not 
to participate. Your decision to participate or not will not affect your medical care at 
UCLA or your relationship with your doctor. An alternative treatment would be to 
receive the currently FDA approved booster dose (50 ugs) of the mRNA-1273 
vaccine or another vaccine. Another alternative treatment is Evusheld, which is a 
monoclonal antibody for COVID-19 prevention. Evusheld received an FDA 
Emergency Use Authorization for moderate to severely immunocompromised 
individuals, but its efficacy has not yet been well evaluated. 
 
DISCLOSURE STATEMENT: 


 
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Your health care provider may be an investigator of this research protocol, and as an 
investigator, is interested in both your clinical welfare and in the conduct of this study. 
You are not under any obligation to participate in any research project offered by your 
clinician. 
 
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY? 
Sixty participants from UCLA will take part in this study.  
 
WHAT WILL HAPPEN IF I TAKE PART IN THIS STUDY? 
All participants will be assigned to receive either: 50 ug “standard-dose”, 100 ug “mid-
dose” or 200 ug “high-dose” of the mRNA-1273 booster vaccine. There is no placebo 
(inactive) doses given in this study. You will receive either the 50 ug, 100 ug or 200 ug 
dose and will be told which dose you will receive, but you will not be able to choose the 
dose that you receive. The first two participants in the “mid-dose” and “high-dose” groups 
will be observed for 7 days. The remaining participants will only receive these higher 
doses if it is well tolerated in these initial participants.  
 
WHAT PROCEDURES ARE INVOLVED? 
If you decide to participate in this study, you will complete a total of 3 scheduled in-
person visits, and 3 safety telephone calls over 6 months. The first visit where you 
will receive your study vaccine (Visit 1) will take approximately 60 to 90 minutes, 
each follow-up in-person visit will take approximately 30 minutes, and each 
telephone visit will take approximately 10 - 15  minutes. If you experience severe 
symptoms between the time you receive the study vaccine and 6 months after you 
receive the study vaccine, you will be asked to immediately contact your study 
doctor for a telephone “safety check” as soon as possible. As part of the “safety 
check”, you may be asked to come to the study center or your doctor’s office for 
further evaluation and additional blood draw depending on the severity. 
 
 
STUDY PROCEDURES: 
The following activities will be performed as part of the study: 
Demographics, Medical History, and Medications: During your first clinic visit, you 
will be asked to provide information about your medical history. Contact information 
for your primary care and lung transplant doctors and may be requested to provide 
personal medical records from your doctor(s). 
This is really important information for your study doctor to have to ensure the best 
care for you in the event you become sick during the study. The study doctor or 
designee may need to review your medical records for additional information. To 
prepare for this, they will ask you to sign and date a medical release of information so 
we can get your records from your primary care and lung transplant doctors or view 
your hospital records. They will also ask you to provide the name of a person who 
can provide information for you if you are unable to do it yourself, such as if you are 
admitted to the hospital. 


 
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You will be asked about all medications including prescription medications, non-
prescription (over-the-counter) medications, dietary supplements, vitamins, and 
herbal medications that you are currently taking and may have taken recently in the 
past. 
Physical Examination, Height, and Weight: A full physical examination, 
including vital signs, height, and weight will be performed at Screening and Day 1 
(Visit 1) by the study doctor or designated staff. 
A symptom-directed physical examination by the study doctor or designated staff 
will be performed on Day 7 and Day 30 and thereafter at the discretion of the 
study doctor.  
Pregnancy Test: If you are a woman of childbearing potential (WOCBP), that is, a 
woman who can become pregnant, you will be asked to provide a urine sample at 
screening to confirm that you are not pregnant, prior to you receiving the study 
vaccination.  
Your study doctor may choose to do a blood pregnancy test at any of these visits, in 
addition to or in place of the urine pregnancy test. If you are pregnant, you cannot 
receive the study vaccine. 
 
Birth Control: WOCBP who are sexually active will be asked to use birth control for 
at least 28 days prior to the study vaccination and for 3 months afterwards. 
Acceptable forms for birth control include: 
 
Barrier method (condom, diaphragm, or cervical cap) with spermicide 
 
Intrauterine device (IUD) 
 
Hormonal contraceptives in the form of a pill or patch 
 
Medroxyprogesterone injection (Depo-Provera®) 
 
Etonogestrel implant (Nexplanon®) 
 
Sterilization of the male partner of a female subject before entry into the study 
 
Female subject is at least 1 year postmenopausal 
Periodic abstinence for the duration of the study and withdrawal method are not 
acceptable methods of contraception. You should discuss with the study doctor your 
chosen method of birth control to determine whether it is acceptable for your participation 
in this study. 
 
Blood Tests: During your study visits, you will be asked to provide blood samples. 
Blood samples collected during the course of this clinical trial will be sent to the 
clinical and research laboratories for further testing for immune responses (antibody 
levels) to the study vaccine. You will not be told the results of these test of your 
immune system. 
The total amount of blood collected from you during each visit will not exceed 25 mL, 
which is approximately 2 tablespoons. Overall, approximately 75 mL or 6 
tablespoons of blood will be collected over the 3-month duration of the study. This is 
less than a typical blood donation (470 mL taken at one time). 


 
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Nasopharyngeal Swab: During study visits or if you become sick, you may be 
asked to provide nasopharyngeal swabs at the study center. Nasopharyngeal swab 
is a method for collecting a test sample of nasal secretions from the back of the 
nose and throat to test for COVID-19. You may have minor bleeding and you may 
feel discomfort, but this should not be painful. Nasopharyngeal swabs collected 
throughout the study will be sent to the laboratory for SARS-CoV-2 testing to see if 
you are infected. An additional swab will be collected at illness to look for other 
respiratory illnesses such as influenza. Results of the swabs will be shared with you 
when they are available.  
Study Vaccination: You will receive an injection of the study vaccine (“standard-
dose”, “mid-dose” or “high-dose”) that was assigned to you at Visit 1. After the 
injection, you will remain in the clinic for an observation period of approximately 30 
minutes. During this time, the study doctor or his/her staff will assess you for any 
potential reactions to the study vaccine by asking you questions and taking your vital 
signs. The site will also provide you with instructions on what you should do after 
you leave the clinic and information about your next study visit. 
Daily Diary: For the first week after your study vaccine, you will be asked to report 
on symptoms you might experience using a diary notebook. You will be trained on 
how to complete the diary. You will have to complete the diary every day (preferably 
at the same time each day in the evenings) for 7 days after the study vaccinations. 
Completion of the daily symptoms should take about 5-10 minutes each day. 
To fill out the diary, you will also be asked to do the following: 
 
Look at your arm where you received the study vaccine and measure any 
specific reactions you may see (a ruler will be provided to you to measure 
injection site reactions). 
 
Check for underarm gland swelling or tenderness on the same arm where you 
were vaccinated. 
 
Describe reactions that are sometimes seen after vaccination. 
 
Measure your temperature (an oral thermometer will be provided to you). You 
must not eat or drink anything hot or cold within 10 minutes of taking your 
temperature. 
 
Note if you take any medications. 
 
Confirm if you have seen another healthcare provider for any illness or symptoms. 
 
Home Visits: The study visits consist of both in-person and telephone contacts. 
Ideally, all in-person visits will take place at the study site. However, there may be 
circumstances in which you are not able to visit the clinic in person due to travel 
restrictions or other limitations as a result of the COVID-19 pandemic. If this occurs, 
the site study staff may ask if they or a representative may come to your home in 
order to perform the scheduled assessments. If any in-person visits must be 
performed at your home, the site will notify you before the visit takes place. A home 
visit will only take place if verbally agreed upon and approved by you prior to the 
visit. Procedures that may take place during a home visit are outlined in the table 
below; however, study vaccination will only take place on site at the clinic.  


 
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A detailed description of the procedures for each study visit and telephone call is 
presented in the following table: 
 
 
 
Visit
When
What will be done
Screening       
(Telephone) 
Before you enter 
the study 
 
Informed consent review 
 
Medical history review (including any 
medications you take and vaccination 
history). If you choose to move forward 
with enrolling in the study, we will plan 
Visit 1 to be at least 4 months after 
your last dose of an mRNA COVID-19 
vaccine. 
Visit 1        
(in clinic) 
Day 1                
(study        
vaccination) 
 
Informed consent review and signature 
 
Confirmation that you may participate in the study 
after review of inclusion/exclusion criteria 
 
Medication review and discussion of any changes in 
your health since the last visit 
 
Physical examination (including vital signs) 
 
Pregnancy test 
 
Blood sample collection 
 
Study vaccination 
 
A 30-minute observation after study vaccination 
 
Receive daily diary notebook: the diary will be used 
to record any changes in your health starting the 
day of your study vaccination for a total of 7 days 
following your study vaccination.   
 
Receive oral thermometer and ruler 
Safety Call 
(Telephone) 
Day 3            
(Safety Check) 
 
Review any symptoms which may have 
developed from the study vaccine.  
 
Review daily diary.  
 
This telephone call will take 10-15 mins.  
Visit 2         
(in clinic) 
Day 7
 
Review any symptoms which may have 
developed from the study vaccine.  
 
Review daily diary.  
 
Physical examination (including vital signs) 
 
Blood sample collection 


 
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Visit 3        
(in clinic) 
Day 30 
 
Review any symptoms which may have 
developed from the study vaccine.  
 
Physical examination (including vital signs) 
 
Blood sample collection 
Safety Call 
(Telephone) 
Day 90      
(Safety Check) 
 
Review any symptoms which may have 
developed from the study vaccine.  
 
This telephone call will take 10-15 mins.  
 
Safety Call 
(Telephone) / 
End of Study 
Day 180    
(Safety Check) 
 
Review any symptoms which may have 
developed from the study vaccine.  
 
This telephone call will take 10-15 mins.  
If you are not familiar with any of the above procedures, please ask your study doctor to 
explain how they are performed. 
“Safety Check” after study vaccination: During your participation in the 
study you will be asked to monitor your health for possible symptoms 
associated with the vaccine including:  
 
Pain, redness and swelling at injection site. 
 
Pain, redness and swelling in the armpit of the injection arm.  
 
Fatigue 
 
Headache 
 
Muscle pain 
 
Joint pain 
 
Fever (Temperature greater than or equal to 38⁰C/100.4⁰F) 
 
Chills 
 
Nausea and vomiting 
 
Rash 
If these symptoms are severe, you are asked to immediately contact your study 
doctor for a telephone “safety check” as soon as possible. You may be asked to 
come to the study center or your doctor’s office for further evaluation, depending on 
the severity. At your first study visit, you will be given a daily diary notebook listing 
these symptoms with severity rating and thermometer. You will be trained on how to 
use the thermometer and daily diary.  
You will also be asked to monitor your health for symptoms of COVID-19 including:  
 
Fever  (Temperature greater than or equal to 38⁰C/100.4⁰F) 
 
Chills 
 
Sore throat 
 
Nasal congestion or runny nose 
 
Coughing 
 
Chest congestion 
 
Fatigue 
 
Headache 


 
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 
Body aches 
 
Nausea and vomiting 
 
Diarrhea 
 
Loss of smell or taste 
If you develop symptoms that may indicate COVID-19 infection during the 6-month 
study period, we request that you notify your lung transplant and/or primary care 
doctor immediately. We also request that you contact the study team as well. We will 
make sure that your lung transplant doctor and/or primary care doctor are aware of 
your symptoms, and that you can receive testing and medical care under their 
direction. If you become sick or are hospitalized during the first 30 days after the 
study vaccine, a medically qualified site staff may try to obtain additional medical 
records, information, and possibly a blood test at your home or hospital. Your lung 
transplant or primary care doctor will advise you on any additional steps you must 
take with respect to local quarantine requirements and ensure that you understand 
your options for access to medical care.  
 
 
WHAT KINDS OF RISKS OR DISCOMFORTS COULD I EXPECT?  (Detailed 
Description) 
 
Known Risks and Discomforts:  
The mRNA-1273 vaccine has been found to be safe and effective in large clinical trials. 
However, like all medicines and vaccines, the study vaccine may cause side effects, 
although not everyone gets them. The most likely side effects you may have from the 
study vaccine are pain, redness, and swelling where the shot is given, headache, muscle 
pain, joint pain, fever, feeling tired, nausea/vomiting, underarm gland swelling on the 
side of the vaccination, and shivering. In addition to side effects from the study vaccine, 
you may feel faint or have mild pain, bruising, irritation, or redness where the blood 
samples are taken.  
There is a remote chance that the mRNA-1273 Vaccine could cause a severe allergic 
reaction. A severe allergic reaction would usually occur within a few minutes to one hour 
after getting a dose of the Moderna COVID-19 Vaccine. For this reason, your vaccination 
provider may ask you to stay at the place where you received your vaccine for monitoring 
after vaccination. Signs of a severe allergic reaction can include:  
• 
Difficulty breathing  
• 
Swelling of your face and throat  
• 
A fast heartbeat  
• 
A bad rash all over your body  
• 
Dizziness and weakness  
Myocarditis (swelling of the heart) and pericarditis (swellingaround the heart) have 
occurred in some people who have received the Moderna COVID-19 Vaccine, more 
commonly in males under 30 years of age. In most of these people, symptoms began 
within a few days following receipt of the second dose of the Moderna COVID-19 
Vaccine. The chance of having this occur is very low. It is estimated at 3.5 cases per 


 
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million doses after second dose mRNA among all adults, and 24.3 cases per million 
among individuals 12 to 29 years of age. Several studies have also found that the risk of 
myocarditis and pericarditis after vaccination is significantly lower than the risk of 
developing these conditions after COVID-19 infection. However, if you receive the higher 
doses of the vaccine (mid-dose or high-dose) as part of the study, the risk of myocarditis 
and pericarditis (swelling in and around the heart) may be higher, especially for male 
participants under the age of 30. 
You should seek medical attention right away if you have any of the following symptoms 
after receiving the Moderna COVID-19 Vaccine:  
• 
Chest pain 
• 
Shortness of breath 
• 
Feelings of having a fast-beating, fluttering, or pounding heart 
 
Side effects that have been reported during post-authorization use of the Moderna 
COVID-19 Vaccine include: 
• 
Severe allergic reactions 
• 
Myocarditis (inflammation of the heart muscle) 
• 
Pericarditis (inflammation of the lining outside the heart) 
• 
Fainting in association with injection of the vaccine 
These may not be all the possible side effects of the Moderna COVID-19 Vaccine. 
Serious and unexpected side effects may occur. The Moderna COVID-19 Vaccine is still 
being studied in clinical trials. If you choose to take part in this study, you are at risk for 
the side effects listed in this section. If you receive the higher doses of the vaccine (mid-
dose or high-dose), you may be at increased risk for these side effects or more severe 
adverse effects than with the standard dose. You should discuss these with the study 
staff and if you choose, with your regular doctor. You will be monitored for risks and side 
effects throughout your participation in the study. You should contact the study doctor if 
you think you are having side effects or experiencing a change in your medical condition. 
If you had an allergic reaction after being vaccinated in the past or if you are allergic to 
any product(s), then you must tell the study doctor or study staff before you decide to sign 
and date this informed consent form. Some symptoms of allergic reactions are rash; 
wheezing and difficulty breathing; dizziness and fainting; swelling around the mouth, 
throat, or eyes; a fast pulse; or sweating. If you have an allergy to some products, then 
you may not be able to take part in this study. Serious allergic reactions can be life- 
threatening. 
In other studies of people receiving similar study vaccines like mRNA-1273, the most 
common side effects are listed below. You will be asked about these side effects during 
this study. 
 
Fever 
 
Pain at the injection site 
 
Redness and hardness of the skin at the injection site 
 
Headache 
 
Muscle aches or pain 
 
Joint aches or pain 


 
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 
Fatigue (tiredness) 
 
Nausea/vomiting 
 
Chills 
 
Under arm gland swelling on the side of study vaccination 
 
Most of these side effects occurred within the first few days after study vaccination and 
went away within a few days. Not everyone has had these side effects and those who 
experienced them did not necessarily experience them after every dose. These side 
effects were usually reported as mild or moderate and not severe. Brief laboratory tests 
abnormalities including lipase elevation and hemoglobin decrease were noted in previous 
clinical studies with similar mRNA vaccines. These increases were observed without 
physical symptoms or signs, usually within the first week and generally returned to levels 
observed before study vaccination. The significance of these observations is unknown, 
but the major side effects associated with the vaccine are listed above. 
Blood collection may be associated with temporary discomfort, lightheadedness, or a 
bruise at the needle site. Infection may occur at the needlestick site where blood is 
collected, but this is very rare. 
You may have emotional stress if you experience any of the side effects listed above or 
from keeping to the study visit schedule. Some of the questions we will ask you as part of 
this study may make you feel uncomfortable. You may stop taking part in the study at any 
time. 
 
Are there risks if you become infected with the coronavirus after getting study 
vaccine? 
Receipt of this experimental mRNA-1273 study vaccine may affect your response to 
future vaccines against the SARS-CoV-2 virus, as well as a SARS-CoV-2 infection. The 
mRNA-1273 booster vaccine has been shown to be highly effective in protecting against 
severe disease. You will receive either the “standard dose” (50 ug), “mid-dose” (100 ug) 
or “high-dose” (200 ug) vaccine. There will be no placebo (inactive) doses given as part 
of this study. It is not known how long the immune response or COVID-19 protection from 
the study vaccine may last.  
If you develop symptoms concerning for COVID-19 during the 6-month study period, we 
request that you notify your lung transplant and/or primary care doctor immediately. We 
also request that you contact the study team as well. We will make sure that your lung 
transplant doctor and/or primary care doctor are aware of your symptoms, and that you 
can receive testing and medical care under their direction. 
 
 
Unknown Risks and Discomforts: 
The experimental treatments may have side effects that no one knows about yet. The 
researchers will let you know if they learn anything that might make you change your 
mind about participating in the study. 
 
Are there any reproductive risks? 


 
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Women: It is not known if the study treatment may affect an unborn child or nursing 
infant. For this reason, if you are breastfeeding, pregnant, or plan to become 
pregnant, then you may not participate in this study. Please refer to contraception 
requirements in page 5.  
Pregnancy: If you become pregnant during your participation in the trial, then your 
participation in the study may be stopped, but you will be asked to stay in the study 
and be followed-up for safety. You will be asked to sign a separate consent for the 
collection of pregnancy follow up data. It is important that you tell the study doctor 
immediately if you become pregnant during the study. The study doctor will talk with 
you about what you should do. 
 
Could there be any other risks? 
There could be other risks to you (or to a pregnancy, embryo, or fetus, if you or your 
partner become pregnant) that are currently unforeseeable. 
 
 
HOW WILL INFORMATION ABOUT ME AND MY PARTICIPATION BE KEPT 
CONFIDENTIAL?  
The researchers will do their best to make sure that your private information is kept 
confidential. Information about you will be handled as confidentially as possible, but 
participating in research may involve a loss of privacy and the potential for a breach in 
confidentiality. Study data will be physically and electronically secured.  As with any use 
of electronic means to store data, there is a risk of breach of data security.   
Because this study involves the treatment of a medical condition and/or medical 
procedures, a copy of this consent form will be placed in your medical record. This will 
allow the doctors that are caring for you to obtain information about what medications 
and/or procedures you are receiving in the study and treat you appropriately. 
 
Use of personal information that can identify you: 
This research study may be performed only by collecting and using your medical 
information. After completion of the study, your study data and clinical samples 
(including blood, nasopharyngeal / nasal swabs) will only contain a de-identified 
code. UCLA will keep the study code – personal identification link confidential and 
take every precaution to ensure that it remains confidential. All study data will be 
physically and electronically secured. You will not be personally identified in any 
reports or publications that may result from this research study. 
 
People and agencies that will have access to your information: 
There might be circumstances where it is difficult or impossible for study monitors, 
auditors and those other individuals mentioned in the ICF to access the study site to 
check that the study is being performed correctly and that the information collected about 
you is accurate. Remote solutions may be adopted to allow the study to continue in these 
circumstances. Such solutions will involve your personal information collected for the 
study being handled and disclosed in new ways. These solutions may include the 


 
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following: 
 
Information from your medical file may be “redacted” and forwarded by email, 
fax, or secure portal to remote based study monitors, auditors and other 
individuals. Redaction means that your identifying information will be 
removed and replaced with your Subject ID. 
In all cases, the study site and the study monitors, auditors and other individuals will 
implement technical and organizational controls to ensure that your confidential 
personal information is protected from unauthorized access or loss.  
 
Information from this study (without your personal identifying information) may 
be given to authorized study collaborators. “Collaborator” includes any persons or 
companies which are contracted by UCLA to have access to the de-identified 
research information during and after the study. De-identified study information will 
also be given to the U.S. FDA, as well as other governmental agencies in other 
countries where the study drug may be considered for approval.  
The research team, authorized UCLA personnel, ModernaTX Inc (the vaccine 
manufacturer), and regulatory agencies such as the Food and Drug Administration(FDA), 
may have access to study data and records to monitor the study. Research records 
provided to authorized, non-UCLA personnel will not contain identifiable information 
about you. Publications and/or presentations that result from this study will not identify 
you by name. Representatives of ModernaTX and government agencies may also 
observe a study visit to check that the study staff are conducting the study correctly. 
Absolute confidentiality cannot be guaranteed because of the need to give information to 
these parties. 
 
USE OF DATA AND SPECIMENS FOR FUTURE RESEARCH:  
Results of your serum (blood) samples taken throughout the study will be used for 
research purposes only. You will not receive your results of the tests. Your blood samples 
and nasopharyngeal / nasal swabs (if collected) will be sent to special laboratories to test 
the response of your body’s immune system to the study vaccine. Samples obtained in 
the study will be labeled with a code and will not contain any information that could 
identify you. These samples will be stored in a freezer until the tests analyzing your 
immune response to the study vaccine are performed. These samples may be stored for 
up to approximately 15 years by UCLA. 
Additional laboratory tests may be performed in the future to further understand immune 
responses to the study vaccine or for further research. This research may be performed 
at the discretion of the study investigators to further understand the immune response to 
SARS-CoV-2, additional assay (new laboratory tests) development, and the immune 
response across coronaviruses. The future use of your samples may result in new 
discoveries that are important to the understanding of the study vaccine(s) or disease. 
Any leftover samples (including blood, nasopharyngeal / nasal swabs) may be used for 
future research after this study is over. These leftover samples will be labeled with a code 
and will not contain any identifying information. UCLA will keep the study code – personal 


 
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identification link confidential. The samples will remain the property of UCLA and may be 
shared with collaborators including ModernaTX Inc. as long as confidentiality is 
maintained. You are allowing the UCLA to use the information and samples in the 
research and development of mRNA- 1273 and other medicines and diagnostics.  Any 
specimens (e.g., tissue, blood, urine) obtained for the purposes of this study will become 
the property of the University of California. Once you provide the specimens you will not 
have access to them. The University may share your specimens in the future with other 
researchers or outside institutions. Information that identifies you will not be shared with 
anyone outside of UCLA. The specimens will be used for research and such use may 
result in inventions or discoveries that could become the basis for new products or 
diagnostic or therapeutic agents. In some instances, these inventions and discoveries 
may be of potential commercial value and may be patented and licensed by the 
University. You will not receive any money or other benefits derived from any commercial 
or other products that may be developed from use of the specimens. 
 
How long information from the study will be kept? 
The UCLA and the study collaborators may continue using the deidentified study 
data and samples after the study is over for up to approximately 15 years.   
 
 
WHAT IS EXPECTED FROM YOU? 
When deciding whether to participate, consider whether you are able and willing to do the 
following: 
 
To follow the instructions, you are given by your study doctor 
 
To commit the time required to keep appointments 
 
To accurately disclose your complete medical history 
 
To promptly report any new problems, illnesses, or changes in medication 
during the study, including any potential COVID-19 symptoms 
 
To complete your daily diary for 7 days following the study vaccination.  
 
 
WHAT WILL HAPPEN AT THE END OF THE STUDY? 
After completing all of your study-specific visits, you will be discharged from 
the study at the discretion of the study doctor. 
 
WILL YOU BE INFORMED OF NEW INFORMATION THAT BECOMES AVAILABLE 
DURING THE STUDY?  
Your study doctor will inform you in a timely manner of any new information learned 
during the study that may affect your willingness to continue your participation in this 
study. 
 
CAN I SHARE INFORMATION ABOUT THIS STUDY? 
If you participate in this study, you should feel free to discuss the study with your family 
and with other people who are close to you. It is recommended to tell your health care 
provider about your participation in the study. However, to help make sure that the 
information from the study is as accurate and reliable as possible, please do not discuss 


 
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information about the study in public places while the study is in progress. Public places 
include things like social media (Facebook, Instagram, Twitter), blogging, and speaking to 
the media. 
 
ARE THERE ANY COSTS FOR TAKING PART IN THIS STUDY? 
The study will pay for the cost of supplying and administering the study drug, and all 
required study items and services as described in this consent form. 
 
WILL I BE PAID FOR MY PARTICIPATION: 
For your time and inconvenience related to your participation in this study, you will 
be paid up to a total of $300 in the form of Amazon gift cards if you complete this 
study. You will be paid according to the following schedule after each visit. If you do 
not complete the study, you will only be paid for the study visits that you completed. 
The study team will provide parking vouchers for the study visits. 
 
 
 
 
 
 
 
If you have any questions regarding your compensation for participation, please 
contact the study doctor at the telephone number listed on page one of this consent 
document. 
Specimens collected (e.g., blood, nasopharyngeal / nasal swabs (if collected) obtained 
for the purposes of this study may be provided to study collaborators. These specimens 
will not include information that identifies you directly. Once you provide the specimens 
you will not have access to them.  The specimens will be used for research and such 
use may result in discoveries that could become the basis for new products or 
therapeutic agents. In some instances, these discoveries may be of potential 
commercial value. You will not receive any money or other benefits derived from such a 
product. 
 
WHO CAN I CONTACT IF I HAVE QUESTIONS ABOUT THIS STUDY? 
During the study, if you experience any medical problems, suffer a research-related 
injury, or have questions, concerns or complaints about the study, please contact the 
Principal Investigator of the study listed below. If you need emergency care, or 
hospitalization is required, please call 911 and alert the treating physician that you are 
participating in this research study. 
 
Principal Investigator: Yusaku Michael Shino, MD 
Department of Medicine, Division of Pulmonary and Critical Care 
Pager: 310-206-6766 – ask to page Dr Shino 
Email: mshino@mednet.ucla.edu 
 
Visit:
Amount:
Clinic Visit 1: Vaccination 
$100 Amazon gift card 
Clinic Visit 2: Day 7
$100 Amazon gift card
Clinic Visit 3: Day 30
$100 Amazon gift card


 
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Other study contact: S. Sam Weigt, MD 
Department of Medicine, Division of Pulmonary and Critical Care 
Pager: 310-206-6766 – ask to page Dr Weigt 
Email: sweigt@mednet.ucla.edu 
 
An institutional review board (IRB) is an independent committee established to help 
protect the rights of research subjects. If you have any questions about your rights 
as a research subject, and/or concerns or complaints regarding this research study, 
contact: 
 
By mail: 
Office of the Human Research Protection Program (OHRPP) 
10889 Wilshire Blvd, Suite 830 
Los Angeles, CA 90095-1406 
 
or call: 310-825-5344 
 
or by email: webIRBHelp@research.ucla.edu 
 
PUBLIC INFORMATION ABOUT THIS STUDY: 
ClinicalTrials.gov is a website that provides information about federally and privately 
supported clinical trials. A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov as required by U.S. Law. This Web site will not include 
information that can identify you. At most, the Web site will include a summary of 
the results. You can search this Web site at any time. 
 
 
WHAT HAPPENS IF I BELIEVE I AM INJURIED BECAUSE I TOOK PART IN THIS 
STUDY? 
It is important that you promptly tell the researchers if you believe that you have been 
injured because of taking part in this study.  You can tell the researchers in person or 
call them at the number(s) listed above. 
If you are injured as a result of being in this study, UCLA will provide necessary medical 
treatment. The costs of the treatment may be covered by the University of California or 
billed to you or your insurer just like other medical costs, depending on a number of 
factors. The University of California does not normally provide any other form of 
compensation for injury. For more information about this, you may call the UCLA Office 
of the Human Research Protection Program at 310-825-5344 or send an email to 
mirb@research.ucla.edu. 
You will not lose any of your legal rights or release UCLA, the study doctor, the study 
staff, or study site from liability for mistakes or intentional misconduct by signing this 
consent document. The federal government also has a program that may provide 
compensation to you or your family if you experience serious physical injuries or death 
and these costs are not covered by other payors. To find out more about this 
“Countermeasures Injury Compensation Program” go to 
https://www.hrsa.gov/cicp/about/index.html or call 1-855-266-2427. 
Due to the coronavirus public health crisis, the federal government has issued an order 


 
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that may limit your right to sue and recover for losses if you are injured or harmed while 
participating in this COVID-19 clinical study. If the order applies, it limits your right to sue 
and recover for losses from the researchers, healthcare providers, any study sponsor or 
manufacturer or distributor involved with the study. However, the order does not limit your 
right to seek compensation for injuries that result from conduct or activities of the 
researchers, health care providers, study sponsors, manufacturers and distributors that is 
unrelated to the study. 
 
VOLUNTARY PARTICIPATION AND WITHDRAWAL: 
Your participation in the study is voluntary. You may decide not to participate, or you 
can leave the study at any time. You will not be punished if you decide not to 
participate or leave the study before the last study visit. Your decision will not result in 
any penalty or loss of benefits to which you are entitled and will not affect your 
relationship with UCLA or UCLA Medical Center. 
If you decide to leave the study before the last study visit, please notify a member 
of the research team and follow instructions. It may be helpful if you could explain 
your reasons. 
You will receive standard treatment and no prejudice will be shown towards you for 
medical care or participation in future research. 
If you withdraw consent during the study, the study doctor and study staff will not 
collect additional personal information from you. Personal information already 
collected will be retained to ensure that the results of the research project can be 
measured properly and to comply with the law. Data collected by the Sponsor up to 
the time you withdraw will form part of the research project results. 
In addition, your participation in the study can be terminated by your study 
doctor or the Sponsor, even if you wish to continue, for example: 
 
If you experience a severe adverse reaction 
 
If you do not follow the study rules 
 
If it is discovered that you do not meet the study requirements 
 
If the study is cancelled 
 
For administrative reasons, including completion of enrollment 
If your participation in the study is stopped early or you decide to leave the study 
before the last study visit, you may be asked to complete end-of-study procedures 
(such as a final medical examination and laboratory tests) for your safety. 
 
WHAT ARE MY RIGHTS IF I TAKE PART IN THIS STUDY?  
Taking part in this study is your choice. You can choose whether or not you want to 
participate. Whatever decision you make, there will be no penalty to you and you will not 
lose any of your regular benefits. 
 You have a right to have all of your questions answered before deciding whether to 
take part. 
 Your decision will not affect the medical care you receive from UCLA. 


 
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 If you decide to take part, you can leave the study at any time.  
 If you decide to stop being in this study you should notify the research team right away. 
The researchers may ask you to complete some procedures in order to protect your 
safety.  
 If you decide not to take part, you can still get medical care from UCLA. 
 
HOW DO I INDICATE MY AGREEMENT TO PARTICIPATE? 
If you want to participate in this study you should sign and date below. You have been 
given a copy of this consent form and the Research Participant’s Bill of Rights to keep.  
You will be asked to sign a separate form authorizing access, use, creation, or disclosure 
of health information about you.  
 
 


 
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SIGNATURE LINES: 
 
 
 
 
      Participant 
    Printed Name  
 
 
 
    
    Signature                                                            Date (MM/DD/YYYY) 
 
 
 
 
 
 
 
    Consenter 
    Printed Name 
 
 
 
 
    
    Signature                                                           Date (MM/DD/YYYY) 
 
 
Primary health care provider notification option 
I consent to having my family doctor, primary health care provider or lung transplant 
doctor notified by the study site of my participation in this study and/or any significant 
findings related to my health (please check yes or no). 
 YES (If yes, please complete the information below) 
 NO 
Primary Health Care Provider Information: 
Name: 
 
Address: 
 
Telephone: