A Randomized Controlled Study to Assess SARS CoV-2 Infection, Viral Shedding, and Subsequent Potential Transmission in Individuals Immunized With Moderna COVID-19 Vaccine
Phase: PHASE3
Conditions: SARS-CoV-2 Infection
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

 
PROTOCOL 
CoVPN 3006 
A randomized controlled study to assess SARS CoV-2 
infection, viral shedding, and subsequent potential 
transmission in individuals immunized with Moderna 
COVID-19 Vaccine  
DOCUMENT ID 38822 
Non-IND Study 
CLINICAL TRIAL SPONSORED BY 
 
 
National Institute of Allergy and Infectious Diseases (NIAID) 
National Institutes of Health (NIH) 
Department of Health and Human Services (DHHS) 
Bethesda, Maryland, USA 
May 20, 2021 
Final 
CoVPN 3006 
Version 4.0 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 2 of 166 
Contents 
1 Overview ........................................................................................................................5 
1.1 
Protocol Team ................................................................................................8 
2 Background ..................................................................................................................10 
2.1 
Rationale for trial concept ............................................................................10 
2.2 
Measures of vaccine efficacy .......................................................................11 
2.3 
Importance of understanding vaccine effects on infectiousness and 
transmissibility .............................................................................................13 
2.4 
Limitations of the current Phase 3 trials for addressing unanswered 
questions .......................................................................................................16 
2.5 
Burden of SARS-CoV-2 infection and COVID-19 disease among students
 ......................................................................................................................18 
2.6 
Age and Asymptomatic Infection ................................................................19 
2.7 
Evidence for viral load as a predictor of infectiousness ...............................20 
2.8 
Evidence for viral load as a marker of COVID-19 disease severity and 
clinical course ...............................................................................................21 
2.9 
Methods for capturing transmission .............................................................21 
2.10 Moderna COVID-19 Vaccine ......................................................................23 
2.11 Trial design rationale ....................................................................................24 
3 Objectives and endpoints .............................................................................................28 
4 Ethical considerations ..................................................................................................32 
5 IRB/EC review considerations .....................................................................................34 
5.1 
Minimized risks to participants ....................................................................34 
5.2 
Reasonable risk/benefit balance ...................................................................34 
5.3 
Equitable participant selection .....................................................................35 
5.4 
Appropriate informed consent ......................................................................35 
5.5 
Adequate safety monitoring .........................................................................35 
5.6 
Protect privacy/confidentiality .....................................................................36 
6 Statistical considerations ..............................................................................................37 
6.1 
Accrual and sample size calculations ...........................................................39 
6.2 
Role of the Independent Data Monitoring Committee (IDMC) ...................44 
6.3 
Randomization .............................................................................................45 
6.4 
Statistical analyses ........................................................................................45 
7 Selection and withdrawal of participants .....................................................................54 
7.1 
Inclusion criteria for Main Cohort, Immediate Vaccination Group and 
Standard of Care Group ................................................................................54 
7.2 
Exclusion criteria for Main Cohort, Immediate Vaccination Group and 
Standard of Care Group ................................................................................55 
7.3 
Inclusion criteria for Main cohort, Vaccine Declined Group .......................56 
7.4 
Exclusion criteria for Main cohort, Vaccine Declined Group......................56 
7.5 
Inclusion criteria for Prospective Close Contact (PCC) cohort ...................57 
7.6 
Inclusion criteria for Case-ascertained Close Contact (CACC) cohort ........57 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 3 of 166 
8 Study product ...............................................................................................................58 
8.1 
Vaccine regimen ...........................................................................................58 
8.2 
Storage, handling, preparation, and administration ......................................58 
8.3 
Acquisition of Moderna COVID-19 Vaccine ..............................................58 
9 Clinical procedures ......................................................................................................60 
9.1 
Informed consent ..........................................................................................60 
9.2 
Pre-enrollment procedures for Main Cohort ................................................62 
9.3 
Enrollment and vaccination visits for Main Cohort, Immediate Vaccination 
Group ............................................................................................................62 
9.4 
Follow-up procedures for Main Cohort, Immediate Vaccination Group .....63 
9.5 
Enrollment (visit 2) and Month 2 (visit 4) Visits for Main Cohort, Standard 
of Care and Vaccine Declined Groups .........................................................63 
9.6 
Month 4 (visit 5) and Month 5 (visit 6) Visits for Main Cohort, Standard of 
Care Group and Vaccine Declined Group ....................................................64 
9.7 
Procedures for Main Cohort participant diagnosed with a SARS-CoV-2 
infection during the study .............................................................................65 
9.8 
Enrollment and follow-up procedures for Prospective Close Contact (PCC) 
cohort ............................................................................................................65 
9.9 
Enrollment and Follow-up procedures for Case-Ascertained Close Contact 
(CACC) cohort .............................................................................................66 
9.10 Visit windows and missed visits ..................................................................67 
9.11 Discontinuing vaccination for a participant who receives a COVID-19 
Vaccine outside the study .............................................................................67 
9.12 Early termination visit ..................................................................................68 
9.13 Pregnancy for Main Cohort ..........................................................................68 
9.14 SARS-CoV-2 monitoring by schools for Main Cohort, if applicable ..........68 
9.15 COVID-19 symptom surveillance for Main Cohort ....................................68 
9.16 Use of electronic Diary (eDiary) for Clinical Outcomes Assessments ........68 
10 Laboratory ....................................................................................................................71 
10.1 CRS laboratory procedures ..........................................................................71 
10.2 Total blood volume ......................................................................................71 
10.3 Endpoint assays ............................................................................................71 
10.4 Lab assay portfolio .......................................................................................72 
10.5 Exploratory studies .......................................................................................72 
10.6 Specimen storage and other use of specimens .............................................73 
10.7 Biohazard containment .................................................................................73 
11 Safety Reporting ..........................................................................................................74 
11.1 FDA/CDC Vaccine Adverse Event Reporting System (VAERS) ...............74 
11.2 Reporting safety events to v-safe .................................................................75 
12 Protocol conduct ..........................................................................................................76 
12.1 Study termination .........................................................................................76 
12.2 Emergency communication with study participants ....................................77 
13 Version history .............................................................................................................78 
14 Document references (other than literature citations) ..................................................84 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 4 of 166 
15 Acronyms and abbreviations........................................................................................86 
16 Literature cited .............................................................................................................88 
Appendix A Sample informed consent form for Main cohort, Immediate Vaccination and 
Standard of Care Groups ..............................................................................93 
Appendix B Sample informed consent form for Main cohort, Vaccine Declined Group
 112 
Appendix C Sample informed consent form for Prospective Close Contact (PCC) cohort
 135 
Appendix D Sample informed consent form for Case-Ascertained Close Contact 
(CACC) cohort ...........................................................................................147 
Appendix E Procedures for Main Cohort, Immediate Vaccination Group ....................159 
Appendix F Procedures for Main Cohort, Standard of Care and Vaccine Declined 
Groups ........................................................................................................161 
Appendix G Procedures for Prospective Close Contact (PCC) cohort ...........................163 
Appendix H Procedures for Case-Ascertained Close Contact Cohort ............................164 
Appendix I Visit windows .............................................................................................165 
Appendix J Protocol Signature Page .............................................................................166 
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 5 of 166 
1 
Overview 
Title  
A randomized controlled study to assess SARS CoV-2 infection, viral shedding, 
and subsequent potential transmission in individuals immunized with Moderna 
COVID-19 Vaccine 
Primary objective(s) 
Primary objective 1: 
To evaluate the efficacy of Moderna COVID-19 Vaccine against SARS-CoV-2 
infection (ie, to evaluate vaccine efficacy against infection or VES) 
Primary objective 2: 
To evaluate the effect of Moderna COVID-19 Vaccine on peak nasal viral load as 
a measure of infection and a proxy of infectiousness 
Study product and route of administration 
Moderna COVID-19 Vaccine: a lipid nanoparticle (LNP) dispersion of a 
messenger ribonucleic acid (mRNA) encoding the prefusion stabilized S protein 
of SARS-CoV-2 formulated in LNPs composed of 4 lipids (1 proprietary and 3 
commercially available). The Moderna COVID-19 Vaccine, also known as 
mRNA-1273, is a suspension for intramuscular injection administered as a series 
of two doses (0.5 mL each) 1 month apart. 
This vaccine has been issued an Emergency Use Authorization (EUA) by the US 
Food and Drug Administration (FDA) for active immunization to prevent 
COVID-19 in individuals 18 years and older.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 6 of 166 
Table 1-1 Schema for the Main Cohort 
 
 
Injection schedule in months 
Group 
N 
0 
1 
4 
5 
Randomized 
Groups 
 
 
 
 
 
Immediate 
Vaccination1 
Up to 
6000 
Moderna 
COVID-19 
Vaccine 
Moderna 
COVID-19 
Vaccine 
- 
- 
Standard of 
Care2 
Up to 
6000 
- 
- 
Moderna 
COVID-19 
Vaccine3 
Moderna 
COVID-19 
Vaccine3 
Observational 
Group 
 
 
 
 
 
Vaccine 
Declined4 
Up to 
6000 
- 
- 
-4 
-4 
Total 
Up to 18,000 
 
 
1 Immediate Vaccination Group: participants receive Moderna COVID-19 vaccine on enrollment and 
are given recommendations to follow federal, state, and local guidelines on COVID-19 precautions 
following vaccination, such as masking, physical distancing, isolation and quarantine. 
2 Standard of Care Group: participants are given recommendations to follow federal, state, and local 
guidelines on COVID-19 vaccination and COVID-19 precautions, such as masking, physical 
distancing, isolation and quarantine. 
3 Vaccine will be offered if participant has not received vaccine outside of the study. 
4 Vaccine Declined Group includes participants who prefer not to be vaccinated. If requested, 
participant will be offered vaccine if they have not received vaccine outside of the study 
Participants 
Main Cohort (main study participants) 
Up to approximately 18,000 healthy volunteers, aged 18 through 29 years, who 
will be followed for up to 5 months after enrollment; up to 6,000 randomized to 
Immediate Vaccination Group, up to 6,000 randomized to Standard of Care 
Group, and up to 6,000 non-randomized to Vaccine Declined Group. 
Prospective Close Contact (PCC) Cohort  
Up to approximately 36,000 volunteers who are in frequent close physical 
proximity with main study participants  
Case-Ascertained Close Contact (CACC) Cohort  
Approximately 3 contacts per incident case. Actual number dependent on 
incidence rate. Up to approximately 2250 volunteers aged 18 years and older who 
have been in close contact with a SARS-CoV-2 positive case from the Main 
Cohort  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 7 of 166 
Design 
Multicenter, randomized, controlled, open-label trial augmented by an 
observational cohort 
Duration per participant 
Up to 5 months per participant for the Main Cohort and for the Prospective Close 
Contact Cohort. 1 month per participant in Case-Ascertained Close Contact 
Cohort. 
Estimated total study duration 
9 months (includes enrollment and follow-up). 
Core operations 
CoVPN Vaccine leadership Group/Core Operations Center, Fred Hutchinson 
Cancer Research Center (Fred Hutch) (Seattle, Washington, USA) 
PPD, Inc. (Wilmington, North Carolina, USA)  
Statistical and Data Management Center (SDMC) 
Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutch 
(Seattle, Washington, USA) 
Laboratory Center (LC) 
Endpoint assay laboratories  
• University of Washington Virology Laboratory (UW-VL) (Seattle, 
Washington, USA) 
• University of Washington Virology Specialty Laboratory (UW-VSL) (Seattle, 
Washington, USA) 
• Pioneer Hi-Bred International, Inc., a member of the Corteva Agriscience 
group of Companies (Johnston, Iowa, USA) 
• Duke University Medical Center (Durham, North Carolina, USA) 
• CoreMedica Labs (Lee’s Summit, Missouri, USA) 
Study sites 
Clinical research sites (CRSs) across the US  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 8 of 166 
Study monitoring 
Independent Data Monitoring Committee (IDMC)  
 
1.1 
Protocol Team 
Protocol leadership 
Co-chairs 
Kathryn Stephenson 
Harvard University School of 
Medicine 
Beth Israel Deaconess Medical 
Center 
617-735-4556 
kstephen@bidmc.harvard.edu 
 
Audrey Pettifor  
Department of Epidemiology 
Gillings School of Global Public 
Health 
University of North Carolina  
919-966-7439 
apettif@email.unc.edu 
 
Jasmine Marcelin 
Division of Infectious Diseases 
University of Nebraska Medical 
Center 
402-559-8650 
jasmine.marcelin@unmc.edu 
Protocol Lead 
Advisors 
Larry Corey 
CoVPN LOC, Fred Hutch 
206-667-6770 
lcorey@fredhutch.org 
 
Myron Cohen  
University of North Carolina  
919-966-2537 
myron_cohen@med.unc.edu 
 
James Kublin 
CoVPN LOC, Fred Hutch 
206-667-1970 
jkublin@fredhutch.org 
 
Statisticians 
Holly Janes 
CoVPN SDMC, Fred Hutch 
206-667-6353 
hjanes@fredhutch.org 
 
Elizabeth Brown 
CoVPN SDMC, Fred Hutch  
206-667-1731 
erbrown@fredhutch.org 
Laboratory lead 
John Hural 
CoVPN Laboratory Program 
206-667-1683 
jhural@fredhutch.org 
Protocol 
Team leader 
Nicole Grunenberg 
CoVPN LOC, Fred Hutch 
206-667-2043 
ngrunenb@fredhutch.org 
DAIDS Medical 
Officer 
Catherine Yen 
DAIDS, NIAID 
240-292-4783 
catherine.yen@nih.gov 
 
 
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 9 of 166 
Other contributors to the original protocol 
Core medical monitor 
Nicole Grunenberg 
CoVPN LOC, Fred 
Hutch 
CoVPN Physician 
consultant  
Nzeera Ketter  
CoVPN LOC, Fred 
Hutch 
Laboratory consultants 
Alexander Greninger 
Robert Coombs 
University of 
Washington Medical 
Center (UWMC) 
Keith Jerome 
Fred Hutch, UWMC  
Clinical safety 
specialists 
Megan Jones 
Maija Anderson 
CoVPN LOC, Fred 
Hutch 
Laboratory center 
representatives 
Nicole Espy 
Lisa Sanders  
Jen Hanke 
CoVPN Laboratory 
Center, Fred Hutch 
Clinical trials manager 
Julie Hunt 
CoVPN LOC, Fred 
Hutch 
Regulatory affairs 
associate 
Megan Brandon 
CoVPN LOC, Fred 
Hutch 
Clinical data managers 
Melissa Cummings 
Vicky Kim 
CoVPN SDMC, Fred 
Hutch 
Community Advisory 
Board (CAB) members 
John Isaac 
Boston University 
SDMC Associate 
Director of Operations 
Jessica Andriesen 
CoVPN SDMC, Fred 
Hutch 
Statistical research 
associates 
Erika Rudnicki 
Moni Neradilek 
CoVPN SDMC, Fred 
Hutch 
SDMC Associate 
director of lab science 
April Randhawa 
CoVPN SDMC, Fred 
Hutch 
Community engagement 
unit representative 
Francisco E Rentas 
CoVPN LOC, Fred 
Hutch 
Data Management 
Director 
Kristine Donaty 
CoVPN SDMC, Fred 
Hutch 
Project coordinator 
Kylie McCloskey  
CoVPN LOC, Fred 
Hutch 
Protocol development 
managers 
Kajari Mondal 
Meg Trahey 
CoVPN LOC, Fred 
Hutch 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 10 of 166 
2 
Background  
2.1 
Rationale for trial concept 
The United States has the most infections and deaths from SARS-CoV-2 (the 
virus that causes Coronavirus disease 2019 [COVID-19]) of any nation in the 
world (1). Fortunately, there is now hope that the large burden of COVID-19-
related illness may lessen in 2021 due to the discovery that candidate COVID-19 
vaccines, including the Moderna COVID-19 Vaccine, can prevent symptomatic 
COVID-19 and severe disease in adults (2, 3). Ongoing Phase 3 trials are not 
designed to estimate a vaccine’s efficacy against all infections, with a critical gap 
being asymptomatic infections. The current trials are also not designed to evaluate 
vaccine effects on infectiousness as measured by viral shedding or on onward 
transmission of infection. For example, at an individual level, it is currently 
unknown if vaccinated individuals should continue to wear masks or social 
distance, or if they should be quarantined if exposed to COVID-19. At a policy 
level, it is unknown if vaccination should be required for certain settings, such as 
public transit including air travel, places of employment, or school. These 
questions are especially important given that SARS-CoV-2 is highly infectious 
compared to other respiratory illnesses such as the flu. Recent data also 
demonstrate that even individuals with asymptomatic COVID-19 can have high 
titers of nasal viral shedding and thus may be highly infectious. Furthermore, 
many individuals with asymptomatic infection develop low level and transient 
antibodies against SARS-CoV-2 (4), suggesting that trials relying on 
seroconversion as a marker of infection may miss infections.  
While there are many populations at risk for SARS-CoV-2 infection, young 
people are particularly at risk of acquiring and transmitting SARS-CoV-2. 
Between August and September 2020, COVID-19 cases among young people 
aged 18-22 years increased 55% nationally (5) and during June-August 2020, 
young people aged 20-29 years had the highest incidence of disease in the US, 
accounting for >20% of all confirmed cases (6). Further, increases in SARS-CoV-
2 infection among younger adults in the Southern US preceded increases among 
older adults by 4-15 days, which confirms the importance of younger adults 
spreading infection to older, more vulnerable populations (5). At the same time, 
individuals aged 18-29 account for a tiny percentage (0.5%) of all deaths due to 
COVID-19 and are very unlikely to develop severe disease (7). These reasons 
plus the congregate and social living situations of students and that many schools 
are regularly testing their student body make them an excellent population to 
examine. The proposed study is designed to evaluate comprehensively the vaccine 
efficacy profile of the Moderna COVID-19 Vaccine, including its effect on 
acquisition of infection including asymptomatic infection, on disease and severity 
of disease, on measures of infectiousness, and transmission of infection. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 11 of 166 
This study is a 2-arm randomized, open-label trial in adults aged 18 through 29 
years augmented with an observational cohort that will compare those who are 
randomized to receive the Moderna COVID-19 Vaccine upon enrollment 
(Immediate Vaccination Group) to those who are randomized to receive the 
vaccine 4 months later (Standard of Care Group) and those who prefer not to be 
vaccinated (Vaccine Declined Group). The study will capture all incident 
SARS-CoV-2 infections among study participants in real time, by 
establishing real-time testing for SARS-CoV-2 on study and augmenting with 
all available data from school testing or community testing. Study participants 
will be asked to collect daily nasal swabs, to enable ascertainment of the timing of 
acquisition and to capture the full viral load trajectory for incident infections. To 
capture secondary transmission events, very close contacts of study participants 
will be enrolled who may undergo school or other community testing for incident 
infection over the duration of the study (‘prospective contacts’); in addition, 
diagnosis of infection among a study participant will trigger recruitment of 
additional participant contacts (‘case-ascertained close contacts’). When a study 
participant tests positive based on testing of study-collected nasal swabs, school 
testing, or community testing, both prospective contacts and case-ascertained 
close contacts will be asked to collect daily nasal swabs for 14 days to detect 
incident infection and also will have blood collected for serology. At the end of 
the trial, all participants in the Standard of Care and Vaccine Declined Groups 
will be offered vaccine if they have not already been vaccinated in their 
communities. The goal of the study is to report results to inform public policy 
including guidance on masking and physical distancing indoors. 
2.2 
Measures of vaccine efficacy  
Ongoing Phase 3 COVID-19 vaccine trials are designed with the primary 
objective to evaluate vaccine efficacy against COVID-19 disease, written VED, 
and defined as the multiplicative reduction in risk of disease in the vaccine vs. 
placebo groups. COVID-19 disease is defined by a protocol-specified set of signs 
and symptoms of disease coincident with PCR-confirmed SARS-CoV-2 infection. 
While the reduction in risk of disease is arguably the most relevant vaccine effect 
to the individual participant, understanding the population effect of a vaccine 
requires considering the other effects of the vaccine (see Table 2-1) (8). The most 
fundamental effect of a vaccine is to reduce acquisition of infection, sometimes 
referred to as ‘vaccine efficacy against susceptibility’, written VES, and measured 
by the multiplicative reduction in PCR-confirmed infection in the vaccine vs. 
placebo group. A vaccine that reduces acquisition of infection will provide benefit 
to the individual (i.e. direct effects), as well as benefit to the population by 
reducing the number of infected and therefore potentially infectious individuals 
who may expose and infect unvaccinated individuals in the population (i.e. 
indirect effects). Modeling studies suggest that COVID-19 vaccines that reduce 
acquisition are predicted to have considerably greater population impact, not only 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 12 of 166 
reducing disease, hospitalizations, and mortality, but reducing transmission of 
infection and thereby magnifying their effects (9, 10). 
An additional potential indirect effect of a vaccine is its effect on reducing 
secondary transmission of infection, written VEI and defined as the multiplicative 
reduction in the rate of secondary transmission among vaccine vs. placebo 
individuals who become SARS-CoV-2 infected. A vaccine might reduce 
transmission through reducing the magnitude and/or duration of viral shedding, 
by reducing symptoms associated with transmission such as coughing, or by 
selectively blocking infection with less transmissible viral strains. Evaluating the 
effect of a COVID-19 vaccine on transmissibility is critical because a vaccine 
with high efficacy against COVID-19 disease but low efficacy against SARS-
CoV-2 infection would necessarily yield a net increase in the number of 
asymptomatic infections. If individuals who become asymptomatically infected 
despite having received the vaccine are still infectious, and given that 
asymptomatic individuals are less likely to be diagnosed and self-isolate, such a 
vaccine has the potential to increase transmission and prolong the pandemic (2, 
3). 
As we prepare this study, we recognize there are other approaches to measuring 
population level benefit (eg, vaccine effect on infection and transmissibility). 
These approaches include: observational studies, such as those being conducted in 
Israel to examine population benefit of the vaccine and those planned by the CDC 
to examine transmission from vaccinated individuals to household contacts in 
longitudinal cohorts; and ancillary studies with frequent swabbing on a subset of 
participants in Phase 3 studies. However, none of these studies will allow for the 
rigorous capture, through daily nasal swabbing, of the early dynamics of viral 
replication and the capture of transmission events during the acute period of 
infection in a randomized trial.  
All of these vaccine salutatory effects may depend on a variety of individual 
characteristics such as age, prior infection with SARS-CoV-2; on virological 
characteristics; and in the case of VEI which conditions on infection, may depend 
on clinical characteristics such as symptomatology.  
As will be discussed below in detail, the ongoing Phase 3 trials evaluate VED and 
partially identify VES, but do not allow direct estimation of VEI. In contrast, the 
proposed study will collect data to enable evaluation of all three vaccine efficacy 
parameters in the participant population. Importantly, the use of an open-label 
Standard of Care Group as opposed to a blinded placebo arm, implies that the 
various effects evaluated will capture not only biological vaccine effects, but also 
potential behavioral effects associated with vaccination, including potential 
behavioral disinhibition. Behavioral effects most plausibly influence exposure and 
therefore infection, but knowledge of vaccine receipt is viewed as less likely to 
influence disease, viral load, and secondary transmission. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 13 of 166 
Table 2-1 Population measures of vaccine efficacy that will be evaluated using the proposed 
study, where a Standard of Care Group will be used instead of placebo 
Efficacy measure 
Definition 
Vaccine efficacy against 
SARS-CoV-2 infection 
(VES) 
The multiplicative reduction in SARS-CoV-2 infection as 
measured by PCR of nasal swabs, vaccine vs. placebo 
Vaccine efficacy against 
COVID-19 disease (VED) 
The multiplicative reduction in symptomatic COVID-19*, 
vaccine vs. placebo 
Vaccine efficacy against viral 
replication (VEVL) 
The reduction in SARS-CoV-2 viral burden as measured by 
PCR of nasal swabs, vaccine vs. placebo 
Vaccine efficacy against 
transmission (VEI) 
The multiplicative reduction in rate of SARS-CoV-2 
transmission from infected individuals on the vaccine arm 
relative to the placebo arm 
*Defined by a protocol-specific set of signs and symptoms defined in Section 3. 
2.3 
Importance of understanding vaccine effects on infectiousness and 
transmissibility 
The most effective way for a vaccine to prevent onward transmission of infection 
is to prevent acquisition of infection. Vaccine efficacy against infection, VEs, is a 
measure of this effect (8). However, a vaccine that does not completely block 
acquisition of infection may still reduce onward transmission among individuals 
who become infected despite having received the vaccine, as measured by VEI (8, 
11). As discussed above, understanding the effect of a COVID-19 vaccine on 
transmission is critical because a vaccine with high efficacy against COVID-19 
disease but low efficacy against SARS-CoV-2 infection would necessarily yield a 
net increase in the number of asymptomatic infections. If individuals who become 
asymptomatically infected despite having received the vaccine are still infectious, 
and given that asymptomatic individuals are less likely to be diagnosed and self-
isolate, such a vaccine has the potential to increase transmission and prolong the 
pandemic (2, 3).  
If a COVID-19 vaccine did reduce infectiousness, mathematical modeling 
suggests that much greater population impact could be achieved. Deterministic 
compartmental models fit to data from King County, Washington and envisioning 
vaccine rollout starting December 1, 2020 to 18% of the adult population 
proportionally across age groups, suggest that while a vaccine that reduces 
COVID-19 disease by 90% and SARS-CoV-2 infection by 10% reduces total 
infections in 2021 by 18.1% and deaths by 27.5%, if the vaccine additionally 
reduces infectiousness by 50% the impact on infections would more than double 
(to 49.3% reduction) and deaths would be cut in half (to 50.9% reduction) (Swan 
and Dimitrov et al, in preparation; Figure 2-1).  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 14 of 166 
 
Figure 2-1 COVID-19 vaccine that reduces infectiousness by 50% has greater impact on 
infections and deaths. Deterministic compartmental model calibrated to King County, WA 
stratified by age, SARS-CoV-2 infection status, COVID-19 treatment status and vaccination. 
800,000 doses vaccine (for 18% of population) starting Dec 1, 2020, allocated proportionally across 
age groups. Absent vaccination, 20% of infections are asymptomatic; asymptomatic infections are 
28% less infectious than symptomatic infections, but more transmissible due to lower rates of 
diagnosis and quarantine. Both vaccines reduce COVID-19 disease by 90% and SARS-CoV-2 
infection by 10%. While one vaccine (light blue) does not reduce infectiousness among individuals 
who become infected, the other vaccine (dark blue) reduces infectiousness by 50%. As a result, it 
achieves a much greater reduction in both infections and deaths. (Swan, Dimitrov et al, in 
preparation). 
In the context of limited vaccine supply, mathematical modeling also suggests 
that optimal allocation of vaccine depends on how well a vaccine reduces 
infectiousness. Take, for instance, a deterministic compartmental model calibrated 
to Washington State that uses the following assumptions: that, absent vaccination, 
40% of infections are asymptomatic, asymptomatic infections confer equal 
immunity and are equally infectious, and that there is sufficient vaccine supply for 
30% of the population. For a vaccine that reduces COVID-19 disease by 90% but 
has no effect on infection or infectiousness, the limited supply of vaccine should 
be allocated to older adults who have a high burden of disease in order to 
minimize deaths and peak hospitalizations (Figure 2-2). However, if the vaccine 
also reduces infectiousness by 60%, minimizing peak hospitalizations is achieved 
by allocating limited vaccine to the young, while minimizing deaths still requires 
vaccinating older adults. These results again highlight the critical importance of 
understanding vaccine effects on acquisition and infectiousness in order to make 
policy decisions. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 15 of 166 
 
Figure 2-2 Deterministic compartmental model calibrated to Washington State (7.6M people), 
reflecting US demographics. Model assumes 4.56M doses vaccine (for 30% of population) 
assuming 10% of the population is previously infected and immune and there are 1000 current 
infections. Absent vaccination, 40% of infections are asymptomatic; asymptomatic infections confer 
equal immunity (for at least 6 mo. duration) and are equally infectious. (Matrajt et al, in preparation) 
Non-human primate (NHP) data also suggests that elimination of viral shedding 
by a COVID-19 vaccine is not guaranteed. Table 2-2 shows the comparison of 
NHP data between candidate COVID-19 vaccines in current Phase 3 trials. While 
most of the vaccines were shown to prevent viremia within the lower respiratory 
tract (bronchoalveolar lavage fluid), and thus improve markers of disease severity, 
three out of the four platforms tested did not eradicate nasal viral shedding in all 
cases.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 16 of 166 
Table 2-2 Comparison of NHP data between Janssen Ad26, Moderna RNA, AstraZeneca 
ChimpAdOx1 and Novavax COVID-19 vaccines 
 
Ad26 
One dose  
1 x10
11 
mRNA 
(4 weeks 
post-dose 2) 
AstraZeneca/Oxford 
2.5x10
10 
0, 4 weeks 
Novavax 
2 doses 
(0,21)  
5 mcg, 50 
mcg 
Pseudovirus 
neutralization 
(GMT) 
408 
1,862 
5 – 40 
boost 10 - 160 
No 
Live virus assay 
113 
3,481 
 
16,026 
Spike protein 
15,000 
(not 
shown) 
36,186 
(AUC) 
 
335,017 
Lung BAL 
protection 
Complete 
Complete at 
day 7 
75% both prime and 
boost 
Complete 
Nasal protection 
5/6 (83%) 
7/8 
0% 
Complete 
(12/12) 
T-cell immune 
response 
Some 
CD8 
No CD8+ T 
cells 
Not reported 
CD4 and 
CD8 
Finally, not understanding relative infectivity is a huge gap in translating vaccine 
use to public health messaging. The demonstration of reduced infectivity may 
reduce vaccine hesitancy. Public health, medical personnel and organizations may 
embrace vaccination, as well as users, if the vaccine both provides individual as 
well as family/community benefit. For individuals, knowing that a vaccine 
reduces infectivity to household and personal contacts is often a prime motivator 
for vaccination. Data from this trial can facilitate this messaging as well as help 
decision-making among individuals about interactions with household members 
and attending work and school. 
2.4 
Limitations of the current Phase 3 trials for addressing unanswered 
questions 
Currently, none of the current Phase 3 vaccine efficacy trials will enable robust 
estimation of vaccine effects on infectiousness. The primary objectives for all 
trials are to evaluate vaccine efficacy (VE) against COVID-19 disease. Secondary 
objectives include evaluating VE against seroconversion using infrequent 
serology (every 1-6 months over 1 year, with more frequent sampling over the 
first 3 months), but this will not fully capture all infections including those that 
are asymptomatic. Estimates based on acute infection cohorts (12) suggest that 
12-50% of asymptomatic infections might be missed using this sampling, leading 
to an unknown magnitude and direction of bias in the estimate of VES. Data from 
Long et al. found that 40% of individuals with asymptomatic RT-PCR confirmed 
SARS-CoV-2 infections were IgG negative at 8 weeks after the acute phase of 
infection (Figure 2-3) (4). Further, it has been observed that asymptomatic cases 
have lower IgG titers across all antigens (including NP) (Figure 2-4) (13). In 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 17 of 166 
current trials, infectiousness is not captured robustly among those who become 
infected; viral load (VL) is only measured for those who are symptomatic and 
only after the onset of symptoms. Data from the Moderna trial where nasal swabs 
were collected at the time of vaccine administration on days 0 and 28 among all 
participants suggest that the vaccine may reduce the level of nasal carriage of 
virus (14). However, one time point does not robustly capture the full viral 
dynamics of infection, in particular, asymptomatic infections. The data are 
suggestive that the vaccine may reduce viral carriage (15). The level of viral 
shedding prior to the onset of symptoms, when most transmission occurs (16), 
will not be captured for any infected participants. Importantly, no data in current 
trials are collected on onward transmission of infection and therefore VEI cannot 
be evaluated directly.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 18 of 166 
 
Figure 2-3 40% of asymptomatic individuals were IgG negative by 8 weeks post-acute 
infection (Long et al.(4). 
 
Figure 2-4 Asymptomatic Patients with COVID-19 have Lower IgG Titers Across Multiple 
Antigens Among Italian Medical Staff N>600 (13). 
2.5 
Burden of SARS-CoV-2 infection and COVID-19 disease among 
students 
The study will be conducted among eligible adults 18 through 29 years of age 
including students enrolled in post-secondary educational institutions (eg, 
universities, vocational and technical colleges) because these are ideal locations 
for studying SARS-CoV-2 transmission clusters. Large numbers of cases of 
COVID-19 have been reported on numerous campuses throughout the US as 
colleges and universities re-opened in fall 2020. More than 397,000 cases were 
counted at 1,800+ colleges and universities in fall 2020 (17, 18). Over the time 
period July-December 11th, 2020, more than 85 colleges and Universities had 
more than 1,000 cases. Among these 49 campuses the cumulative attack rate from 
July to October was on average 6.2%. These estimates are somewhat uncertain 
given the fact that the number of reported cases for some schools includes faculty, 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 19 of 166 
staff and graduate students; however, the number of such individuals is very small 
in comparison to the number of undergraduates.  
Among 15 Association of American Universities (AAU) universities, and using 
data from the start of semester through September 18, 2020, there was an 
estimated 3.7% 1-month attack rate. The attack rate appeared to decline over time; 
it was 1.7% over September 19 to October 20, 2020. Attack rates may be 
underestimated because the denominator is assumed to be all undergraduates, 
whereas some schools had only a subset of students on campus. These statistics 
suggest that a conservative assumption of SARS-CoV-2 incidence among US 
university students for Fall semester 2020 is 6%. A conservative incidence 
assumption for Spring and Summer 2021semesters, anticipating potential 
improvements in testing, contact tracing, social distancing measures, as well as 
vaccine rollout to priority populations outside the universities, is therefore 3-6%.  
The outbreaks of SARS-CoV-2 infection at college campuses have been reported 
to be associated with students residing in high density housing, socializing off 
campus, and not following social distancing guidelines (19). In the US, it is 
estimated that 45 percent of young adults aged 18-22 years were enrolled in 
colleges and universities in 2019 (16). As such, much of the increase in cases this 
summer and fall are attributed to college students. The college campuses are 
associated with a high rate of SARS-CoV-2 infection and resulting asymptomatic 
carriage due to huge impulse to socialize as well as no fear of severe disease 
among the young students. 
2.6 
Age and Asymptomatic Infection 
For this study, participants will be enrolled who are 18 through 29 years of age. 
This age range is chosen because of the high incidence of asymptomatic infection 
in this population. A considerable body of data suggest that SARS-CoV-2 can be 
spread by individuals with and without symptoms (20-23). VL data among 
individuals with acute SARS-CoV-2 infection also indicate that peak VL usually 
occurs before disease onset (22, 24). This suggests that there is a substantial 
transmission potential before symptom onset. According to the latest Centers for 
Disease Control and Prevention (CDC) estimate 40% of SARS-CoV-2 infections 
are asymptomatic (25). Available data indicate that younger individuals appear 
more likely to remain asymptomatic following infection than older individuals 
(26, 27). A recent study done in the UK showed about 80% of children between 
10-19 years of age remain asymptomatic (28). As infected young students are less 
likely to show clinical symptoms, the number of clinical cases reported among 
young populations would be lower, but the asymptomatic young students could 
still be capable of transmitting the virus to others (29). 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 20 of 166 
2.7 
Evidence for viral load as a predictor of infectiousness 
Mathematical modelling in human immunodeficiency virus (HIV) and 
herpesviruses and now COVID-19 suggests a significant percentage of 
transmission occurs from high peak VL which in all these diseases is during the 
asymptomatic period. Models by Josh Schiffer and Ashish Goyal suggest that a 
person has a 50% chance of infection with exposure to 107 SARS-CoV-2 RNA 
and <5% chance of infection with exposure to 105 SARS-CoV-2 RNA (Figure 
2-5) (21). The model by Goyal et al (21) suggests that vaccine reduction in peak 
VL may reduce infectiousness. A 0.6 log reduction corresponds to ~50% VEI and 
a 2.5 log reduction to ~90% VEI (Figure 2-6). This suggests collecting nasal 
swabs every other day would be required to measure the vaccine effect on peak 
VL and area under the VL curve. Asymptomatic and pre-symptomatic cases of 
SARS-CoV-2 appear to play an important role in the onward transmission of the 
virus.  
 
Figure 2-5 SARS-CoV-2 transmission probability as a function of shedding. A. Optimal 
infectious dose (ID) response curve (infection risk = Pt) and transmission dose (TD) 
response curve (transmission risk = Pt * Pt) curves for SARS-CoV-2. Transmission 
probability is a product of two probabilities, contagiousness and infectiousness. B-D. Three 
simulated viral shedding curves. Heat maps represent risk of transmission at each shedding 
timepoint given an exposed contact with an uninfected person at that time.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 21 of 166 
 
Figure 2-6 Vaccine efficacy against infectiousness versus the change in peak viral load. 
Model by Goyal et al (personal communication).  
2.8 
Evidence for viral load as a marker of COVID-19 disease severity and 
clinical course 
Beyond infectiousness, there is a growing body of evidence supporting a linkage 
between VL and COVID-19 disease outcome. Two Phase 2/3 trials of monoclonal 
antibodies for COVID-19 treatment in outpatient settings found that VL at 
enrollment and early after intervention was associated with future clinical 
outcomes and disease course (30, 31). In the BLAZE-1 trial of intravenous 
infusion of the LY-CoV555 antibody, on day 7 post-infusion the frequency of 
hospitalization among patients with a high VL (Ct value of less than 27.5) was 
12% (7 of 56 patients), as compared to 0.9% (3 of 340 patients) among those with 
a lower VL. Numerous observational studies have also identified associations 
between VL and clinical outcomes (32). The highest quality evidence comes from 
large cohort studies. In a large hospitalized cohort, Pujadas et al (33) estimated a 
highly significant 7% increase in mortality per log10 increase in VL at admission, 
after adjusting for other factors associated with clinical outcomes (p = 0.0014, 
multivariate Cox model). Chen et al (34) confirmed this finding in a larger cohort 
of patients admitted to three New York City hospitals. These data suggest that VL 
at and soon after the time of symptom onset may be a useful measure of disease 
severity.  
2.9 
Methods for capturing transmission  
Reducing transmission is key to ending/controlling the COVID-19 pandemic. Due 
to vaccination, the number of asymptomatic individuals might increase as 
vaccine-induced immune responses may lead to VL reduction. However, it is still 
to be discovered whether those individuals will continue to shed and transmit 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 22 of 166 
virus to others. Hence, it is important to identify secondary transmissions from 
study participants to estimate secondary infections rates by arm and to validate 
VL as a surrogate for transmission risk. Onward transmission of SARS-CoV-2 
infection from study participants can be identified in combination with sequence-
analysis and phylogenetics methods (35).  
Estimating vaccine efficacy in reducing transmission (VEI), requires measuring 
transmission of SARS-CoV-2 from vaccinated and unvaccinated individuals to 
others (36, 37). Measuring transmission of infected individuals to uninfected 
individuals is challenging, especially for transient infections where it may be 
more difficult to ascertain which infection occurred first. For example, because 
HIV is not transient and per-exposure transmission is low, resulting in a 
potentially long time period of exposure, transmission can be studied in sero-
discordant sexual partnerships. In a transient infection, ideally both members of 
the transmission pair are monitored before either is infected so that timing and 
direction of transmission can be easily determined. Prospectively following a 
cohort of vaccinated and unvaccinated individuals and their close contacts to 
observe whether infection is transmitted from study participants to close contacts, 
or from contacts to study participants, based on frequent testing of both allows for 
better quantification of the temporality of events regarding infection transmission, 
if it occurs. To do this, Datta et al. propose augmenting a randomized, controlled 
vaccine trial with a cohort of close contacts of trial participants. Both trial 
participants and the contact cohort are followed prospectively for acquisition, 
allowing for estimation of VEI. Another approach to capturing transmission 
events is a case ascertainment design (38, 39). Under this design, contacts of 
index cases are enrolled and tested as the cases emerge over time. A similar case 
ascertainment design was used for a recent household study for SARS-CoV-2 
prevention. In the HCQ PEP trial, which was a household-randomized, double-
blind, controlled trial of hydroxychloroquine postexposure prophylaxis to prevent 
acquisition of SARS-CoV-2 among close contacts recently exposed to persons 
diagnosed with SARS-CoV-2 infection, individuals were self-referred from 
infected individuals and enrolled online and all study procedures were done 
remotely including informed consent and daily self-nasal swabbing for 14 days 
(40). A case-ascertained approach is more resource-efficient than a prospective 
contact approach which requires enrollment of a large number of contacts, most 
of whom will not become infected nor have an infected index case in the main 
study. Because contacts are only identified and tested after index case diagnosis, 
the case-ascertained approach also enables assessment of secondary transmission 
in contacts not participating in frequent, prospective testing programs. However, 
the case-ascertained approach has the potential to miss or misclassify transmission 
events given the gap between diagnosing an index case and identifying, enrolling, 
and testing a contact. Index cases may also experience stigma when identifying 
contacts at the time of diagnosis, as opposed to when identifying contacts 
prospectively and before infection. The feasibility of recruiting and retaining 
contacts of young adults, and of classifying transmission events among contacts, 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 23 of 166 
using the prospective and case-ascertained designs has yet to be evaluated and 
compared. 
This study will employ both the augmented and case ascertainment approaches to 
studying transmission through enrollment of two contact cohorts, a Prospective 
Close Contact (PCC) cohort and a Case-Ascertained Close Contact (CACC) 
cohort. The PCC Cohort will be identified at enrollment as close and sustained 
contacts of main study participants (eg, roommates or co-workers). Participants in 
the PCC cohort may undergo routine screening for SARS-CoV-2 infection as part 
of their attendance at their school or location of employment, which may allow 
the participant and study team to receive real-time clinical diagnosis of COVID-
19 during the study. Additionally, when a positive case is identified for a main 
study participant, the participant (‘index case’) will identify and refer their recent 
close contacts for enrollment into the CACC cohort. For both cohorts, infection 
diagnosis of the associated main study participant will trigger intensive short term 
sample collection (with a potential delay for the CACC cohort due to the need for 
informed consent and enrollment) including sera followed by daily nasal swabs 
for 14 days. Assessment of viral sequences, viral load trajectories, antibody 
detection and epidemiologic information from the infected participant and any 
positive close contacts in the PCC or CACC will aid in identifying transmission 
events between the participant and the contact. Details of the enrollment and 
procedures for both contact cohorts are described below. 
2.10 
Moderna COVID-19 Vaccine 
This trial will utilize vaccine obtained under EUA by the US Government’s 
COVID-19 Vaccine Response and allocated for this trial. Participants may also 
access Moderna COVID-19 EUA vaccine via other sources (see Section 8.3). 
2.10.1 
Clinical studies of Moderna COVID-19 Vaccine  
Table 2-3 Summary of clinical studies 
ClinicalTrials.go
v Identifier 
Study 
number 
Phase 
N 
Dose 
groups 
Route 
Schedule 
Reference 
NCT04283461 
P101 
1 
120 
25, 50, 
100, or 
250 mcg 
IM 
M0, M1 
(41, 42) 
NCT04405076 
P201 
2 
600 
50 or 100 
mcg 
IM 
M0, M1 
(14, 15, 43) 
NCT04470427 
P301 
3 
30,351 
100 mcg 
IM 
M0, M1 
(14, 15, 43) 
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 24 of 166 
2.10.2 
Potential risks of Moderna COVID-19 Vaccine 
Risks associated with receipt of the Moderna COVID-19 Vaccine are described in 
the “Fact Sheet For Healthcare Providers Administering Vaccine (Vaccination 
Providers) Emergency Use Authorization (EUA) Of The Moderna COVID-19 
Vaccine To Prevent Coronavirus Disease 2019 (COVID-19)”, available at 
https://www.modernatx.com/covid19vaccine-eua/. 
2.11 
Trial design rationale 
We are proposing a 2-arm randomized, controlled, open-label trial, augmented 
with an observational cohort. Individuals indifferent to receipt and timing of 
COVID-19 vaccination will be randomized to immediate vaccination at Months 0 
and 1, or standard of care with vaccination given at Months 4 and 5, if not 
received off-study previously. Individuals who prefer not to be vaccinated will be 
enrolled in an observational ‘Vaccine Declined’ group; all these individuals are 
considered part of the ‘Main cohort’ (Figure 2-7). The design also includes two 
cohorts of contacts of main study cohort participants – the Prospective Close 
Contact (PCC) cohort and the Case-Ascertained Close Contact (CACC) cohort – 
to allow capture of secondary transmission events.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 25 of 166 
 
Figure 2-7 Main cohort study design 
Participants in the main study will self-collect nasal swabs daily in order to 
capture all incident SARS-CoV-2 infection events over 4 months of follow-up 
and to capture the full course of viral shedding – from onset of infection to viral 
clearance – among those with both asymptomatic and symptomatic infection.  
To minimize participant burden and maximize study efficiency, as many study 
procedures as possible will be conducted remotely (not requiring an in-person 
visit) and electronically, such as initial screening and consent. Participants 
diagnosed with SARS-CoV-2 infection will complete daily e-diaries to capture 
symptoms. 
Given that primary analyses will be conducted among baseline seronegative 
participants, the rate of baseline SARS-CoV-2 seropositivity will be monitored 
operationally with an operational target of no more than 10% for the main study 
cohort. 
2.11.1 
Dose and schedule 
The latest information regarding Moderna COVID-19 Vaccine dose and 
administration instructions can be found at 
https://www.modernatx.com/covid19vaccine-eua/. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 26 of 166 
For this study, vaccine will be administered at D1 and D29 for the immediate 
vaccination arm, and at D113 and D141 for the Standard of Care Group (if they 
have not been vaccinated outside the study). Vaccine will also be offered to the 
Vaccine Declined Group at D113 and D141. 
2.11.2 
Choice of Standard of Care Group  
There is no licensed SARS-CoV-2 vaccine currently available to serve as a 
reference control. Currently, there are several SARS-CoV-2 vaccines available in 
the US under Emergency Use Authorization (EUA), including the Moderna 
COVID-19 Vaccine being used in this study. Accordingly, a Standard of Care 
Group has been chosen as an internal control. No placebo will be used, and 
participants will not be blinded to randomization assignment. The open-label 
design has been chosen primarily to achieve operational efficiency and to 
minimize resource utilization. Main study participants will be asked throughout 
the study about the timing and type of any outside vaccination, and contacts in the 
PCC and CACC will be queried about COVID-19 vaccine receipt. Main study 
participants receiving outside vaccination will remain on-study and follow the 
same study procedures after vaccination. Section 6.4.3.1 describes how the 
analysis of vaccine efficacy will take into account outside vaccination. 
Randomized participants will not be blinded to randomization assignment. The 
open-label design has been chosen primarily to achieve operational efficiency and 
to minimize resource utilization. With an open-label design, differences between 
the randomized arms in study endpoints including SARS-CoV-2 infection, viral 
load, and secondary transmission will capture not only biological effects of 
vaccination, but potentially behavioral effects influencing exposure, including 
adherence to study procedures. This is most relevant for the SARS-CoV-2 
infection endpoint: if participants who are randomized to immediate vaccination 
engage in more risk-taking behavior and thus experience higher exposure to 
SARS-CoV-2 relative to participants randomized to delayed vaccination, ie, there 
is behavioral disinhibition, this will be captured in the estimate of vaccine 
efficacy against infection: the biological reduction in incidence of SARS-CoV-2 
infection attributable to vaccination will be offset by an increase in incidence due 
to higher exposure. Therefore, the measure of vaccine efficacy against infection 
that is estimated in this study is in truth a measure of effectiveness. However, we 
retain the terminology “vaccine efficacy” for simplicity. Section 6.4.3.1 discusses 
this issue in greater detail, including how the statistical analysis will attempt to 
control for potential imbalances in SARS-CoV-2 exposure between treatment 
arms when evaluating vaccine efficacy, and how both efficacy and effectiveness 
measures will be evaluated and compared. We note that endpoints measured after 
diagnosis of SARS-CoV-2 infection, including SARS-CoV-2 viral load and 
secondary transmission, are viewed as much less likely to be influenced by 
participant behavior and knowledge of vaccine receipt. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 27 of 166 
2.11.3 
Rationale for Vaccine Declined Group  
A cohort of individuals who prefer not to receive COVID-19 vaccination and 
decline randomization will be enrolled as a second internal control group in 
addition to the Standard of Care arm. The purpose of this group is to provide 
supplementary information on study endpoints, including SARS-CoV-2 
incidence, SARS-CoV-2 viral load, and secondary transmission, absent COVID-
19 vaccination. The ‘Vaccine Declined’ group will be enrolled concurrently with 
the randomized study participants, and at the same study sites, and in this fashion 
variability in the endpoints due to space and time will be minimized. Section 6.4 
and the Statistical Analysis Plan will detail methods that will be used to control 
for other potential differences between participants who are randomized versus 
those in the Vaccine Declined group. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 28 of 166 
3 
Objectives and endpoints 
Primary Objectives  
Primary Endpoints 
1. To evaluate the efficacy of Moderna 
COVID-19 Vaccine against SARS-CoV-2 
infection (ie, to evaluate vaccine efficacy 
against infection or VES). 
SARS-CoV-2 infection diagnosed by PCR 
among participants who were SARS-CoV-2 
seronegative at enrollment  
2. To evaluate the effect of Moderna 
COVID-19 Vaccine on peak nasal viral 
load as a measure of infection and a proxy 
of infectiousness 
Peak viral load in nasal samples from participants 
diagnosed with SARS-CoV-2 infection among 
participants who were SARS-CoV-2 seronegative 
at enrollment  
Secondary Objectives  
Secondary Endpoints 
1. To evaluate the impact of Moderna 
COVID-19 Vaccine on secondary 
transmission of SARS-CoV-2 infection, 
using data for the Prospective Close 
Contact (PCC) cohort and Case-
Ascertained Close Contact (CACC) cohort 
(ie, to evaluate vaccine efficacy against 
infectiousness or VEI) 
Number of adjudicated* secondary transmission 
events in PCC and CACC cohorts from main 
study participants who were SARS-CoV-2 
seronegative at enrollment.  
*based on questionnaire-based epidemiologic 
data, antibody and viral dynamics, and viral 
sequence data 
2. To evaluate the efficacy of Moderna 
COVID-19 Vaccine to prevent 
serologically confirmed SARS-CoV-2 
infection 
SARS-CoV-2 antibodies to the nucleocapsid 
protein post visit 3 (month 1), among 
participants who were SARS-CoV-2 
seronegative at enrollment  
3. To evaluate vaccine efficacy against 
COVID-19 disease, (ie, to evaluate VED) 
using weekly e-diaries and confirmatory 
PCR testing 
SARS-CoV-2 infection confirmed by PCR 
among participants who were SARS-CoV-2 
seronegative at enrollment, coincident with the 
following symptoms: 
• at least TWO of the following 
systemic symptoms: Fever (≥ 38ºC), 
chills, myalgia, headache, sore 
throat,  
OR 
at least ONE of the following signs/symptoms: 
cough, shortness of breath or difficulty 
breathing, new olfactory or taste disorder, 
clinical or radiographical evidence of 
pneumonia, thromboembolic event, myocardial 
infarction, myocarditis, chilblains, or multi-
inflammatory syndrome 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 29 of 166 
4. To evaluate vaccine effect on additional 
measures of magnitude of viral load over 
time, e.g. area under the viral load curve, 
duration of shedding, and time to log10 
viral load above 105 copies/mL 
 
Summary measures of the viral load curve, all 
evaluated among participants diagnosed with 
SARS-CoV-2 infection who were SARS-CoV-2 
seronegative at enrollment: 
• Transmission potential endpoint, defined as 0 
for an individual without SARS-CoV-2 
infection, and peak log10 viral load, for an 
individual with SARS-CoV-2 infection 
• Area under log10 viral load curve (AUC) 
• Duration of viral shedding (viral load above 
assay limit of detection) 
• Area under log10 viral load curve above 105 
copies/mL 
• Duration of viral shedding above 105 
copies/mL 
• Time from enrollment to viral load above 105 
copies/mL 
 
5. To evaluate vaccine efficacy against 
SARS-CoV-2 infection, the vaccine effect 
on viral load, and the vaccine effect on 
secondary transmission in all enrolled 
participants without regard to baseline 
SARS-CoV-2 serostatus 
• 
SARS-CoV-2 infection diagnosed by PCR 
[Primary endpoint 1] 
• 
Peak log10 viral load in nasal samples from 
participants who are diagnosed with SARS-
CoV-2 infection [Primary endpoint 2] 
• 
Number of secondary transmission events in 
the PCC and CACC [Secondary endpoint 1] 
6. To evaluate the immunogenicity of the 
vaccine 
Magnitude and response rate of immune 
responses to vaccination measured at Months 0, 
and 2 stratified by baseline SARS-CoV-2 
serostatus as measured by binding antibody and 
neutralization assays in the case-cohort 
immunogenicity set 
7. To evaluate immune responses 1 month 
post-second vaccination as correlates of 
risk of SARS-CoV-2 acquisition, viral 
load, secondary infection, and COVID-19 
disease among vaccine recipients in the 
Immediate Vaccination Group 
Magnitude and response rate of immune 
responses to vaccination in the Immediate 
Vaccination Group and measured at Months 0 
and 2, stratified by baseline SARS-CoV-2 
serostatus, as measured by binding antibody and 
neutralization assays in the case-cohort 
immunogenicity set 
8. To evaluate vaccine efficacy against 
asymptomatic SARS-CoV-2 infection  
SARS-CoV-2 infection by PCR or periodic 
serology among participants seronegative for 
SARS-CoV-2 at baseline and without any prior 
reporting of symptoms that led to confirmation 
of a COVID-19 disease endpoint 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 30 of 166 
9. To evaluate vaccine efficacy against 
SARS-CoV-2 infection and COVID-19 
disease and the vaccine effect on viral 
load and secondary transmission among 
participants who received all planned 
immunizations at the designated 
immunization visits within specific visit 
windows  
Endpoints evaluated among participants who 
were SARS-CoV-2 seronegative at enrollment  
• 
SARS-CoV-2 infection diagnosed by PCR 
[Primary endpoint 1] 
• 
Peak log10 viral load in nasal samples from 
participants who are diagnosed with SARS-
CoV-2 infection [Primary endpoint 2] 
• 
Number of secondary transmission events in 
the PCC and CACC [Secondary endpoint 1] 
• 
SARS-CoV-2 infection coincident with 
signs and symptoms of COVID-19 listed 
under Secondary endpoint 3 
10. To evaluate the association between 
measures of the magnitude of viral load 
over time and secondary transmission of 
SARS-CoV-2 infection, among 
individuals with incident SARS-CoV-2 
infection in each treatment group, i.e. to 
conduct analyses aimed at evaluating viral 
load measures as surrogates of secondary 
transmission 
• 
Peak log10 viral load [Primary endpoint 2] 
and other viral load summaries [Secondary 
endpoints 4] 
• 
Number of secondary transmission events in 
the PCC cohort and CACC cohort 
[Secondary endpoint 1] 
11. To evaluate vaccine effects on peak viral 
load and on secondary transmission of 
SARS-CoV-2 infection separately among 
individuals with asymptomatic vs. 
symptomatic SARS-CoV-2 infection 
• Peak log10 viral load [Primary endpoint 2] 
and other viral load summaries [Secondary 
endpoints 4] 
• Number of secondary transmission events in 
the PCC cohort and CACC cohort 
[Secondary endpoint 1]  
• SARS-CoV-2 infection diagnosed using 
PCR, with and without signs and symptoms 
of COVID-19 listed under Secondary 
endpoint 3 
Exploratory Objectives 
1. To evaluate the associations between demographic and clinical factors and secondary 
transmission of SARS-CoV-2 infection and COVID-19 disease, among individuals with incident 
SARS-CoV-2 infection in the main study cohort and their contacts in the PCC and CACC 
2. To assess if and how vaccine efficacy against SARS-CoV-2 infection, transmission and COVID-
19 disease depends on baseline demographic, clinical, socio-economic indicators, and/or 
behavioral characteristics of study participants 
3. To assess if and how vaccine efficacy against SARS-CoV-2 infection and COVID-19 disease 
depends on genotypic or neutralization phenotypic characteristics of SARS-CoV-2 (sieve 
analysis)  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 31 of 166 
4. To further evaluate immunogenicity of the vaccine, additional immunogenicity assays may be 
performed such as antibody (Ab) Avidity and Fc Receptor function assays, based on the CoVPN 
Laboratory Center assay portfolio 
5. To conduct analyses related to furthering the understanding of SARS-CoV-2, immunology, 
vaccines, and clinical trial conduct 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 32 of 166 
4 
Ethical considerations 
It is critical that universally accepted ethical guidelines are followed at all sites 
involved in the conduct of clinical trials. The COVID-19 Prevention Network 
(CoVPN) have addressed ethical concerns in the following ways:  
• 
CoVPN trials are designed and conducted to enhance the scientific 
knowledge base necessary to find a preventive vaccine, using methods that 
are scientifically rigorous and valid, and in accordance with International 
Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use (ICH) and/or other Good Clinical Practice (GCP) guidelines. 
• 
CoVPN scientists and operational staff incorporate the philosophies 
underlying major codes (44-46), declarations, and other guidance documents 
relevant to human subjects research into the design and conduct of SARS-
CoV-2 vaccine clinical trials. 
• CoVPN scientists and operational staff are committed to substantive 
community input—into the planning, conduct, and follow-up of its research—
to help ensure that locally appropriate cultural and linguistic needs of study 
populations are met.  
• The CoVPN provides training so that all participating sites similarly ensure 
fair participant selection, protect the privacy of research participants, and 
obtain meaningful informed consent. During the study, participants will have 
their wellbeing monitored, and to the fullest extent possible, their privacy 
protected. Participants may withdraw from the study at any time. 
• Prior to implementation, CoVPN trials are rigorously reviewed by scientists 
who are not involved in the conduct of the trials under consideration. 
• CoVPN trials are reviewed by local and national regulatory bodies and are 
conducted in compliance with all applicable national and local regulations. 
• The CoVPN designs its research to minimize risk and maximize benefit to 
both study participants and their local communities. For example, CoVPN 
protocols provide enhancement of participants’ knowledge of SARS-CoV-2 
and SARS-CoV-2 prevention, as well as counseling, guidance, and assistance 
with any social impacts that may result from research participation. CoVPN 
protocols also include careful medical review of each research participant’s 
health conditions and reactions to study products while in the study. 
• CoVPN research aims to benefit local communities by directly addressing the 
health and SARS-CoV-2 prevention needs of those communities and by 
strengthening the capacity of the communities through training, support, 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 33 of 166 
shared knowledge, and equipment. Researchers involved in CoVPN trials are 
able to conduct other critical research in their local research settings. 
• The CoVPN values the role of in-country Institutional Review Boards (IRBs), 
Ethics Committees (ECs), and other Regulatory Entities (REs) as custodians 
responsible for ensuring the ethical conduct of research in each setting. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 34 of 166 
5 
IRB/EC review considerations 
US Food and Drug Administration (FDA) and other US federal regulations 
require IRBs/ECs/REs to ensure that certain requirements are satisfied on initial 
and continuing review of research (Title 45, Code of Federal Regulations (CFR), 
Part 46.111(a) 1-7; 21 CFR 56.111(a) 1-7). The following section highlights how 
this protocol addresses each of these research requirements. Each CoVPN 
Investigator welcomes IRB/EC/RE questions or concerns regarding these research 
requirements. 
5.1 
Minimized risks to participants 
45 CFR 46.111 (a) 1 and 21 CFR 56.111 (a) 1: Risks to subjects are 
minimized. 
This protocol minimizes risks to participants by (a) correctly and promptly 
informing participants about risks so that they can join in partnership with the 
researcher in recognizing and reporting harms; (b) respecting local/national blood 
draw limits; (c) performing direct observation of participants postvaccination and 
reporting information regarding side effects to the FDA/CDC Vaccine Adverse 
Event Reporting System (VAERS) per EUA guidance; (d) having staff properly 
trained in administering study procedures that may cause physical harm or 
psychological distress, such as blood draws, vaccinations, COVID-19 testing and 
counseling; and (e) providing safety monitoring. 
5.2 
Reasonable risk/benefit balance 
45 CFR 46.111(a) 2 and 21 CFR 56.111(a) 2: Risks to subjects are 
reasonable in relation to anticipated benefits, if any, to subjects, and 
the importance of the knowledge that may reasonably be expected to 
result. 
In all public health research, the risk-benefit ratio may be difficult to assess 
because the benefits to participants in prevention protocols are not as apparent as 
they would be in treatment protocols, where a study participant may be ill and 
may have exhausted all conventional treatment options. However, this protocol is 
designed to minimize the risks to participants while maximizing the potential 
value of the knowledge it is designed to generate. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 35 of 166 
5.3 
Equitable participant selection  
45 CFR 46.111 (a) 3 and 21 CFR 56.111 (a) 3: Subject selection is 
equitable 
This protocol has specific inclusion and exclusion criteria for investigators to 
follow in admitting participants into the protocol. Participants are selected 
because of these criteria and not because of positions of vulnerability or privilege. 
Investigators are required to maintain screening and enrollment logs to document 
volunteers who screened into and out of the protocol and for what reasons. 
5.4 
Appropriate informed consent 
45 CFR 46.111 (a) 4 and 5 and 21 CFR 56.111 (a) 4 and 5: Informed 
consent is sought from each prospective subject or the subject’s 
legally authorized representative as required by 45 CFR 46.116 and 
21 CFR Part 50; informed consent is appropriately documented as 
required by 45 CFR 46.117 and 21 CFR 50.27 
The protocol specifies that informed consent must be obtained before any study 
procedures are initiated and assessed throughout the trial (see Section 9.1). Each 
site is provided training in informed consent by the CoVPN and is required to 
have a Standard Operating Procedure (SOP) on the informed consent process. The 
CoVPN requires a signed consent document for documentation, in addition to 
chart notes or a consent checklist. 
5.5 
Adequate safety monitoring 
45 CFR 46.111 (a) 6 and 21 CFR 56.111 (a) 6: There is adequate 
provision for monitoring the data collected to ensure the safety of 
subjects. 
Vaccination providers are required to report to VAERS the certain adverse events 
after COVID-19 vaccination, under Emergency Use Authorization (EUA) and 
encouraged to report adverse events to ModernaTX 
|(https://www.cdc.gov/vaccines/covid-19/vaccination-provider-support.html, see 
Section 11). Additionally, the use of v-safe will be recommended to vaccine 
recipients (https://www.cdc.gov/coronavirus/2019-
ncov/vaccines/safety/vsafe.html, see Section 11), and an Independent Data 
Monitoring Committee (IDMC) will periodically review study data. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 36 of 166 
5.6 
Protect privacy/confidentiality 
45 CFR 46.111 (a) 7 and 21 CFR 56.111 (a) 7: There are adequate 
provisions to protect the privacy of subjects and maintain the 
confidentiality of data. 
Privacy refers to an individual’s right to be free from unauthorized or 
unreasonable intrusion into his/her private life and the right to control access to 
individually identifiable information about him/her. The term “privacy” concerns 
research participants or potential research participants as individuals whereas the 
term “confidentiality” is used to refer to the treatment of information about those 
individuals. This protocol respects the privacy of participants by informing them 
about who will have access to their personal information and study data (see 
Appendix A, Appendix B, Appendix C and Appendix D ). The privacy of 
participants is protected by assigning unique identifiers in place of the 
participant’s name on study data and specimens. In the United States, research 
participants in CoVPN protocols are protected by a Certificate of Confidentiality 
from the US NIH, which can prevent disclosure of study participation even when 
that information is requested by subpoena. Participants are told of the use and 
limits of the certificate in the study consent form. In addition, each staff member 
at each study site in this protocol signs an Agreement on Confidentiality and Use 
of Data and Specimens with the CoVPN. In some cases, a comparable 
confidentiality agreement process may be acceptable. Each study site participating 
in the protocol is required to have a standard operating procedure on how the staff 
members will protect the confidentiality of study participants. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 37 of 166 
6 
Statistical considerations 
With an overall goal of accruing 48,000 person-months divided evenly between 
vaccinated and unvaccinated follow-up time, we anticipate enrolling up to 18,000 
participants. Up to 12,000 participants will be randomized 1:1 to Immediate 
Vaccination Group (at Months 0 and 1) or Standard of Care Group, with 
vaccination given at Months 4 and 5 if not received off-study previously. Up to an 
additional 6,000 participants will be enrolled into the Vaccine Declined Group 
and will also be offered vaccine at Months 4 and 5. Operational monitoring of 
SARS-CoV-2 incidence, retention, outside COVID-19 vaccination, adherence to 
study procedures, and enrollment and testing of contacts in the PCC and CACC – 
pooled over main study participant groups-- will guide the choice of total number 
randomized and total number in the Vaccine Declined Group. Guidelines will be 
specified in the study SAP. 
Primary analyses of vaccine efficacy against infection (VES) and of the vaccine 
effect on viral load (ΔVL) will be conducted among all main study participants 
SARS-CoV-2 seronegative at enrollment. These analyses will be supported by 
analyses in the “Day 29 Negative Set”--the set of participants without PCR-
confirmed infection on or prior to Day 29—that only count SARS-CoV-2 
infection events diagnosed post-Day 29; see Table 6-1 for a full definition of the 
various analysis sets for the study. Secondary analyses will be conducted among 
all participants who receive both immunizations, ie, the Per-Protocol Set. 
Immunogenicity assessment will be done in the Case-Cohort Immunogenicity 
Set—a subsample of the participants randomized to immediate vaccination and 
sampled on the basis of SARS-CoV-2 infection status and baseline characteristics 
that will be fully described in the study SAP. 
The FAS differs from a full Intention-to-Treat set by excluding randomized 
volunteers who do not enroll. The exclusion of these individuals is justified 
because the effects of the vaccine are unlikely to influence such exclusion. 
Because of the brief length of time between randomization and enrollment 
(ideally these will be on the same day), we expect almost all randomized 
volunteers to be in the FAS. 
All primary and secondary analyses will be done according to enrollment group, 
ie, Immediate Vaccination Group, Standard of Care Group, or Vaccine Declined 
Group.   
Main study participants will be tested using real-time PCR testing of swabs, and 
these data will be used to identify SARS-CoV-2 infection events for primary 
analysis. Some main study participants may also receive SARS-CoV-2 testing 
through university testing systems, or through outside providers, and will be 
asked to report any positive test results to the study team. Any positive SARS-
CoV-2 test results for main study participants – based on PCR testing of study 
swabs or based on other testing systems indicative of acute infection– will trigger 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 38 of 166 
swabbing of contacts in the PCC and enrollment and swabbing of contacts in the 
CACC. Secondary analyses of vaccine efficacy will include SARS-CoV-2 
infection events diagnosed through any testing system – either by PCR testing of 
study swabs or through outside testing. 
The two contact cohorts – the PCC and the CACC – will both be used for 
analyses of the vaccine effect on secondary transmission, as described below. 
The study is “time-driven”, ie, the primary analysis will occur when all 
participants have completed the 4 months follow-up. The number of primary 
endpoint infection events that accrue in the study is random and will depend on 
the level of SARS-CoV-2 incidence in each arm. 
Table 6-1 Study Analysis Sets and Definitions 
Analysis Set 
Definition 
Analyses 
Full Analysis Set (FAS)   
Main Study participants who enroll in the study  
Primary efficacy 
analyses* 
Day 29 Negative (D29-) 
Set 
Participants in the FAS without PCR-confirmed 
infection on or before Day 29¥ 
Primary efficacy 
analyses* 
Per-Protocol (PP) Set 
Participants in the D29- set who received all planned 
immunizations at the designated immunization visits 
within specific visit windows 
Secondary efficacy 
analyses* 
Day 29 Negative 
Transmission Set (D29-TS) 
Participants in the D29- set and their contacts in the 
Prospective and Case Ascertained Contact Cohorts 
Primary analyses 
of secondary 
transmission* 
Case-Cohort 
Immunogenicity Set (ccIS) 
Subset of the FAS that is randomly sampled for 
measurement of immunological markers and fully 
described in study SAP  
Immunology 
marker analyses 
*These analysis sets include participants without regard to baseline SARS-CoV-2 status. However, 
primary  
efficacy analyses will condition on baseline SARS-CoV-2 seronegative status. 
¥ Note that Day 29 is the second vaccination visit (visit 3) for participants on the Immediate 
Vaccination Group. The SAP will specify the definition of Day 29 for participants in the Standard of 
Care Group and in the Vaccine Declined Group. 
Table 6-2 Assumptions underlying study power/sample size calculations, unless otherwise 
specified. Parameters and their assumed values pertain to participants in the main study cohort. 
Parameter   
Assumption   
Enrollment     
Uniform enrollment over 4 weeks   
Baseline seroprevalence in main 
study and PCC and CACC  
10% of enrolled participants are baseline SARS-CoV-2 seropositive. 
This parameter is monitored and controlled operationally (see 
Section 6.3)   
Per-protocol rate  
98% of enrolled participants are in the per-protocol set   
Loss to follow-up rate in the main 
study, the PCC and the CACC  
5% of participants are lost to follow-up over 16 weeks at a constant 
rate   
SARS-CoV-2 incidence absent 
vaccination  
Exponential (constant rate) over 16 weeks; primary assumption 
is 4% over 16 weeks  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 39 of 166 
Secondary transmission 
rate among susceptible contacts 
absent vaccination  
15% transmission rate based on (47-49) 
Vaccine efficacy (VE) against 
SARS-CoV-2 infection and 
transmission   
Constant after 14 days post-first vaccination (calculations do not 
depend on earlier VE); level is varied     
Contact enrollment  
For the PCC: 60% of main study participants enroll contact(s) and 
the average number of contacts enrolled is 2  
For the CACC: 75% of main study participants enroll contact(s) and 
the average number of contacts enrolled is 3  
6.1 
Accrual and sample size calculations 
Sample size calculations were performed assuming that 48,000 person-months of 
follow-up will accrue, evenly divided between vaccinated and unvaccinated 
follow-up time and subject to a small 5% loss-to-follow-up rate. This person-time 
may come entirely from 12,000 participants randomized to Immediate 
Vaccination Group versus Standard of Care Group and followed for 4 months (16 
weeks), or, if there is insufficient unvaccinated follow-up among those 
randomized to Standard of Care, it will be supplemented with unvaccinated 
follow-up for participants in the Vaccine Declined Group. The power calculations 
apply, regardless of where the unvaccinated follow-up comes from. For this 
reason, we refer to the two groups being compared as “vaccinated” and 
“unvaccinated”, where the former group consists of participants randomized to 
immediate vaccination and the latter group may include both participants 
randomized to Standard of Care Group and participants enrolled in the Vaccine 
Declined Group (see Figure 2-7). 
Power calculations also focused conservatively on numbers of infections that 
accrue post-Day 29, although as mentioned above, primary analyses will be 
conducted both in the FAS, counting all follow-up and infection events post-
enrollment; and in the Day 29 negative set, counting only follow-up and infection 
events post-Day 29. 
With 48,000 person-months of follow-up, evenly divided between vaccinated and 
unvaccinated follow-up, there is a high probability that a sufficient number of 
post-Day 29 infection events, ie, SARS-CoV-2 infections among baseline 
seronegative participants in the D29- set and diagnosed after Day 29, will accrue 
to adequately power analyses addressing both primary objectives as well as key 
secondary objectives. Specifically, with 24,000 person-months of vaccinated 
follow-up and 24,000 person-months of unvaccinated follow-up, under a 4% 
SARS-CoV-2 incidence absent vaccination over 16 weeks (a conservative 
assumption for US college campuses, see Section 2.5, and supported by 
unpublished modeling within the CoVPN), assuming VES = 50% and other 
assumptions laid out in Table 6-2, a total of 225 post-Day 29 infection events will 
occur across vaccinated and unvaccinated groups with probability 0.5 and 214 
events will occur with probability 0.8.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 40 of 166 
Table 6-3 shows the expected number of post-Day 29 infection events in the main 
study cohort overall and in the vaccinated group, as the assumed incidence absent 
vaccination varies. As shown, the design ensures a sufficient number of post-Day 
29 infection events to address a variety of objectives that condition on post-Day 
29 infection. For example, with 4% SARS-CoV-2 incidence absent vaccination, 
75 post-Day 29 infection events are expected in the vaccinated group for immune 
correlates analyses. 
Table 6-3 Expected number of post-Day 29 infection events, available for secondary 
analyses that condition on event status. Calculations assume 24,000 person-months of 
vaccinated follow-up and 24,000 person-months of unvaccinated follow-up and other assumptions 
in Table 6-2, VES = 50%, and varying 16-week incidence of SARS-CoV-2 infection absent 
vaccination. 
16-Week SARS-CoV-2 
Background 
(unvaccinated) Incidence 
 Post-Day 29 Infection Events 
Vaccinated and Unvaccinated 
Groups Combined 
Vaccinated Group  
1.5% 
86 
28 
2% 
143 
47 
3% 
170 
56 
3.5% 
198 
66 
4% 
225 
75 
The study provides high power to evaluate the vaccine effect on acquisition 
(VES). Figure 6-1 shows the power of the study to detect a given level of VES, 
rejecting H0: VES ≤ 30%, based on a 1-sided 0.025-level log-rank test and as a 
function of the SARS-CoV-2 incidence absent vaccination. With 4% 16-week 
incidence, the study has 90% power to detect any VES > 57%; with 3% incidence, 
VES > 60% can be detected with 90% power.  
The proposed study also provides adequate precision with which to estimate VES. 
Table 6-4 shows that, with 225 post-Day 29 infection events, the approximate 
95% confidence interval (CI) about an estimated 50% VES is (36.9%, 60.4%). 
More precise inference is obtained under higher VES and higher post-Day 29 
infection totals. 
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 41 of 166 
 
 
Figure 6-1 Power to detect varying vaccine efficacy (VE) against SARS-CoV-2 infection as a 
function of incidence absent vaccination over 16 weeks. Simulation-based power calculations 
assume 24,000 person-months of vaccinated and 24,000 person-months of unvaccinated follow-
upand other assumptions listed in Table 6-2. Power based on 1-sided 0.025-level log-rank test and 
1,000 simulations. 
Table 6-4 Approximate 95% confidence interval around a given estimated VES against SARS-
CoV-2 infection, comparing vaccinated and unvaccinated groups as a function of the 
number of post-Day 29  infection events in the vaccinated and unvaccinated groups. 
Calculations assume 24,000 person-months of follow-up in each group and other assumptions in 
Table 6-2. 
Number of post-Day 29 
infection events 
Approximate 95% CI for 
estimated VE = 50%   
Approximate 95% CI for 
estimated VE = 70%   
200 
(36.0%, 60.9%) 
(60.7%, 77.2%) 
225 
(36.9%, 60.4%) 
(61.1%, 76.9%) 
250 
(37.7%, 59.9%) 
(61.6%, 76.6%) 
6.1.1 
Power and precision for evaluating the vaccine effect on VL 
Emerging data on acute SARS-CoV-2 infection suggest that with an expected 225 
post-Day 29 infection events, the vaccine effect on mean peak log10 viral load 
among post-Day 29 infection events can be estimated with adequate precision. 
Specifically, assuming that peak log10 viral load is normally distributed with a 
1.8 standard deviation in both treatment groups, and assuming 50% VES, a 1-log 
reduction in mean peak viral load can be detected with 96.9% power given 225 
post-Day 29 infection events; power remains high (93.5%) with 70% VES. Table 
6-5 shows power to detect a 1-log reduction in peak log viral load as a function of 
the assumed standard deviation in log peak viral load which is allowed to vary 
between 1.0 and 2.5. The standard deviation in peak log viral load in a cohort of 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 42 of 166 
68 individuals associated with the National Basketball Association who were 
diagnosed with acute SARS-CoV-2 infection was 1.4 to 1.8, depending on the set 
of samples included in the analysis (50). Emerging data from the HCQ-PEP study 
of ~100 acutely infected household members of recently diagnosed COVID-19 
cases suggests a standard deviation in peak log viral load in the range of 2.0-2.2, 
depending on the set of samples included [data not published]. Table 6-6 shows 
the approximate 95% CI about an estimated 1-log reduction in mean peak log 
viral load, demonstrating the precision that is obtained with 225 post-Day 29 
infection events. Modest precision is observed with a 1-1.8 standard deviation in 
the endpoint, with lower precision under a higher standard deviation; precision is 
also lower under increasing VES. 
Table 6-5 Power to detect a 1-log reduction in mean peak log viral load comparing post-Day 
29 infection events between vaccinated and unvaccinated groups, as a function of the 
assumed standard deviation in peak log viral load in both groups and the assumed level of 
VE against SARS-CoV-2 infection. Simulation-based power calculations assume 225 post-Day 
29 infection events across vaccinated and unvaccinated groups. Power based on 1-sided 0.025-
level t-test and 1,000 simulations. 
Std. dev. in peak log viral 
load 
VES = 50% 
VES = 70% 
1 
100% 
100% 
1.5 
99.6% 
97.8% 
1.8 
96.9% 
93.5% 
2 
95.6% 
86.5% 
2.5 
79.9% 
68.7% 
Table 6-6 Approximate 95% confidence interval around an estimated 1-log reduction in 
mean peak log viral load comparing post-Day 29 infection events between vaccinated and 
unvaccinated groups, as a function of the assumed standard deviation in peak log viral load 
in both groups and the assumed level of vaccine efficacy against SARS-CoV-2 infection. 
Calculations assume 225 post-Day 29 infection events across vaccinated and unvaccinated 
groups. 
Std. dev. in peak log viral 
load 
VES = 50% 
VES = 70% 
1 
(0.72, 1.28) 
(0.68, 1.31) 
1.5 
(0.57, 1.41) 
(0.51, 1.46) 
1.8 
(0.50, 1.50) 
(0.44, 1.57) 
2 
(0.46, 1.57) 
(0.36, 1.61) 
2.5 
(0.29, 1.65) 
(0.20, 1.74) 
6.1.2 
Power for evaluating the vaccine effect on secondary transmission 
The study has adequate power to evaluate vaccine efficacy against secondary 
transmission, based on analyses that are conducted among post-Day 29 infection 
events in the Main study cohort and their contacts in the PCC and CACC, ie, 
based on conditional analyses, as long as VE against SARS-CoV-2 infection is 
low. As demonstrated in Figure 6-2, if there is high vaccine efficacy against 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 43 of 166 
SARS-CoV-2 infection, power is low to evaluate secondary transmission using a 
conditional analysis. In this case, an unconditional analysis of VE against 
secondary transmission is planned and is expected to be more powerful, and also 
more appropriate given that it reflects that infections blocked have no 
transmission potential.    
We performed simulation-based calculations to explore the power to evaluate VE 
against secondary transmission based on a conditional analysis that compares 
secondary transmission events among contacts of vaccinated and unvaccinated 
main study participants. In addition to the assumptions in Table 6-2, we assumed: 
equal infection surveillance in the PCC and CACC; that PCC contacts acquire 
infection from outside sources (other than the index case) at the same rate as the 
Standard of Care Group; that only baseline seronegative contacts and those in the 
PCC not infected by outside sources are at risk of secondary transmission; that the 
number of secondary transmission events among at-risk contacts follows a 
Poisson distribution in each arm, with VE against secondary transmission 
reducing the event rate proportionally given vaccination. A one-sided 0.025-level 
likelihood ratio test based on a Poisson regression model was used to evaluate VE 
against secondary transmission. As shown in Figure 6-2, the study has 90% power 
to detect a 59% reduction in secondary transmission if VES = 50%; a higher 69% 
reduction in secondary transmission is detectable if VES = 70%. Table 6-7 helps 
explain the power results: it shows the amount of statistical information on which 
the analysis is based, ie, the median number of post-Day 29 infection events and 
associated secondary transmission events in the vaccinated and unvaccinated 
groups. With 50% VES and 50% VE against secondary transmission, we expect 
15 secondary transmission events in the vaccinated group and 59 in the 
unvaccinated group; the limited number of events is due to the “transmission 
cascade” whereby under our assumptions only some SARS-CoV-2 infected 
participants enroll contacts into the PCC and CACC, only some contacts are 
susceptible and retained, and the transmission rate is low (15%).   

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 44 of 166 
 
Figure 6-2 Power to detect varying vaccine efficacy against secondary transmission as a 
function of vaccine efficacy against SARS-CoV-2 infection. Simulation-based power 
calculations assume 24,000 person-months of vaccinated follow-up and 24,000 person-months of 
unvaccinated follow-up and other assumptions listed in Table 6-2. Power based on 1-sided 0.025-
level likelihood ratio test under Poisson regression model and 1,000 simulations. 
Table 6-7 Number of post-Day 29 infection events and associated secondary transmission 
events in the vaccinated and unvaccinated groups, under varying VE against SARS-CoV-2 
infection and varying VE against secondary transmission, under other assumptions laid out 
in Table 6-2, and based on 1,000 simulations. 
 
VES = 50% 
VES = 70% 
VE against 
secondary 
transmission 
Median no. post-Day 29 
infection events, 
Vaccinated vs. 
Unvaccinated Groups 
(IQR) 
Median no. secondary 
transmissions, 
Vaccinated vs. 
Unvaccinated Groups 
(IQR) 
Median no. post-Day 
29 infection events, 
Vaccinated vs. 
Unvaccinated Groups 
(IQR) 
Median no. secondary 
transmissions, 
Vaccinated vs. 
Unvaccinated Groups 
(IQR) 
VE = 0% 
76 (70-82)  
vs. 150 (142-158) 
29 (25-34)  
vs. 59 (53-66) 
45 (41-50)  
vs. 149 (141-158) 
18 (14-21)  
vs. 59 (53-65) 
VE = 40% 
76 (70-81)  
vs. 150 (142-158) 
18 (15-21)  
vs. 59 (53-64) 
45 (41-50)  
vs. 149 (142-158) 
11 (8-13)  
vs. 59 (53-65) 
VE = 50% 
76 (70-82)  
vs. 150 (143-159) 
15 (12-17)  
vs. 59 (53-66) 
45 (41-50)  
vs. 150 (142-158) 
9 (7-11)  
vs. 59 (53-65) 
VE = 60% 
76 (70-82)  
vs. 150 (142-158) 
12 (9-14)  
vs. 58 (52-65) 
45 (41-50)  
vs. 151 (143-159) 
7 (5-9)  
vs. 59 (53-65) 
VE = 70% 
75 (70-81)  
vs. 150 (142-158) 
9 (7-11)  
vs. 58 (52-65) 
46 (41-50)  
vs. 150 (142-159) 
5 (4-7)  
vs. 59 (53-65) 
6.2 
Role of the Independent Data Monitoring Committee (IDMC)  
The study IDMC will provide study oversight and ensure that the study is on-
target to meeting its objectives in a timely fashion. The IDMC will receive 
summaries of study progress throughout the study. Given the short duration of the 
study and the considerable prior data establishing safety and efficacy of the 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 45 of 166 
vaccine, and the status of the EUA vaccine, there will be no pre-specified interim 
monitoring boundaries for VE or non-efficacy. The IDMC will make 
recommendations to protocol chairs and lead advisors. The set of metrics, 
operational targets for them, and potential remedial actions will be laid out in full 
in the IDMC Charter.  
6.3 
Randomization  
A participant’s randomization assignment will be computer generated and 
provided to the CRS study staff through a Web-based randomization system.  
Randomization will be stratified. The randomization will be done in blocks to 
ensure balance among contemporaneously evaluated Immediate Vaccination and 
Standard of Care arms within levels defined by study site and type of residence. 
6.4 
Statistical analyses 
This section describes the final study analyses which will occur after the last main 
study participant has completed the Month 4 visit. All data from enrolled 
participants will be analyzed according to the initial group assignment regardless 
of how and when in-study and outside-study vaccinations are received. Follow-up 
and endpoints that accrue post-outside-study-vaccination will be censored for 
primary and secondary analyses. In the rare instance that a participant receives 
study vaccination at the wrong time, the Statistical Analysis Plan (SAP) will 
address how to analyze the data. Analyses are modified intent-to-treat in that 
individuals who are randomized but not enrolled do not contribute data and hence 
are excluded. Because of the brief length of time between randomization and 
enrollment, few such individuals are expected. 
The SAP will specify how data from the Vaccine Declined group will contribute 
to assessing primary and secondary objectives. Wherever possible, analyses will 
limit to data collected on randomized participants, and will entail comparing 
outcomes between those randomized to Immediate Vaccination or Standard of 
Care. However, if operational data on enrollment, retention, adherence to study 
procedures suggest that there will be insufficient unvaccinated follow-up for the 
Standard of Care Group to permit a specific analysis, data from the Standard of 
Care Group will be combined with data from the Vaccine Declined Group, with 
methods fully pre-specified in the SAP. 
Analyses for primary endpoints will be performed using SAS and R. All other 
descriptive and inferential statistical analyses will be performed using SAS, 
StatXact, or R statistical software. 
In general, no formal multiple comparison adjustments will be employed for 
multiple secondary endpoints. However, multiplicity adjustments will be made for 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 46 of 166 
certain immunogenicity assays, as discussed below, when the assay endpoint is 
viewed as a collection of hypotheses (eg, testing multiple peptide pools to 
determine a positive response). 
6.4.1 
Analysis variables 
The analysis variables defined for all participants in the main study cohort consist 
of baseline participant characteristics, longitudinal measures of risk of infection, 
SARS-CoV-2 infection and seroconversion and COVID-19 disease status, and 
immune response biomarkers. For individuals diagnosed with SARS-CoV-2 
infection, post-infection variables will include various summaries of VL, the full 
genome sequence of the infecting virus, and the infection status of and 
relationship to each of their contacts enrolled in the PCC and CACC. For contacts 
enrolled in the PCC and CACC, variables consist of baseline participant 
characteristics, SARS-CoV-2 infection and seroconversion status, risk factors 
around time of exposure to main study participant (if infected) and relationship to 
the referring main study participant.   
6.4.2 
Baseline comparability and comparability over study follow-up 
Groups of main study participants will be compared with respect to baseline 
participant characteristics using descriptive statistics. 
Given that the study is open-label, and the associated potential for differences 
between randomized arms with respect to retention, compliance with study 
procedures, ascertainment of endpoints, and variables associated with exposure to 
SARS-CoV-2, these measures will be compared between randomized arms over 
time using methods fully described in the SAP. Given that participants self-select 
into the Vaccine Declined Group, similar methods will be used to evaluate 
potential differences between this group and those randomized to Immediate 
vaccination or Standard of Care. Imbalances between groups will influence the 
analysis choices as described below. 
6.4.3 
Vaccine efficacy (VE) analyses against SARS-CoV-2 infection 
The time origin for all analyses of SARS-CoV-2 infection is enrollment. We 
define the time of diagnosis of the SARS-CoV-2 infection endpoint as the 
collection time of the first daily swab with a positive PCR test. The time of 
diagnosis of lab-confirmed clinical COVID-19 disease is the first time of reported 
qualifying COVID-19 symptoms that occurs simultaneously or after the diagnosis 
of the SARS-CoV-2 infection endpoint. The time of diagnosis of asymptomatic 
SARS-CoV-2 infection is the collection time of the first sample with a positive 
PCR test result or seroconversion without any prior or subsequent reporting of 
symptoms that led to confirmation of a COVID-19 disease endpoint. The time of 
diagnosis of SARS-CoV-2 seroconversion is the collection time of the first 
sample seropositive for SARS-CoV-2, for participants SARS-CoV-2 seronegative 
at baseline; the SAP will specify criteria for defining seroconversion (re-infection) 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 47 of 166 
for individuals SARS-CoV-2 seropositive at baseline. The failure times of 
participants never observed to be diagnosed with a given clinical endpoint will be 
right-censored at the date of last contact at which endpoint status was assessed or 
study termination. The failure times of participants reporting receipt of COVID-
19 vaccination outside the study will be right-censored at the date of first outside 
vaccination. 
6.4.3.1 
Primary VE Analysis 
For the primary analysis, Cox proportional hazards regression will be used to 
estimate vaccine efficacy against SARS-CoV-2 infection among baseline SARS-
CoV-2 seronegative participants, as measured by one minus the hazard ratio (HR) 
in the Immediate Vaccination vs. Standard of Care arms. This analysis that 
restricts attention to randomized participants will be supported by a co-primary 
analysis that combines data from the Standard of Care arm with data from the 
Vaccine Declined Group. An additional supportive analysis will restrict to the 
D29- set, counting only infection events diagnosed post-Day 29. These analyses 
supporting the primary objectives of the study will be detailed in the SAP.To 
improve precision when comparing randomized groups, and to avoid bias when 
including non-randomized participants, primary analyses will adjust for an SAP-
specified set of “risk” variables, or a composite risk score based on them, that are 
potentially associated with SARS-CoV-2 exposure including demographics and 
behaviors captured using the risk assessment tool. Inference will be based on a 2-
sided score-based CI and 2-sided score-test for H0: VE = 0% with a type 1 error 
rate of 0.05, although primary interest is in estimation as opposed to hypothesis 
testing and the study is designed to ensure that the lower limit for the CI will lie 
above 30% with high probability under VE > 60%.The baseline hazard function 
in the Cox model will be stratified by study site and randomization stratum, which 
improves precision of the VE estimate and accounts for the fact that SARS-CoV-2 
infection incidence may vary widely across study sites. Description of the risk 
variables under consideration and of the derivation of a risk score based on them 
will be described in the study SAP. 
The potential impacts of the open-label and observational aspects of the study 
design will be factored into the choice of efficacy analysis. If there is evidence of 
differential retention of study participants across groups, or differential adherence 
to study procedures affecting ascertainment of endpoints such as collection of 
daily swabs, the analyses will adjust for the differential censoring distribution 
across groups- as well as potentially informative censoring- as described in the 
study SAP. At a minimum, these analyses will be performed as sensitivity 
analyses, complementing the primary analyses described above.  
Variables captured using the risk assessment tool and potentially associated with 
exposure will be compared across groups over study follow-up. If there is 
evidence that their distributions differ between groups over time, sensitivity 
analysis will additionally adjust for time-dependent exposure-related variables.   

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 48 of 166 
The proportional hazards assumption will be evaluated using methods of 
Grambsch and Therneau (51).  
6.4.3.2 
Secondary VE Analyses 
The primary analysis of VE against SARS-CoV-2 infection will be repeated in the 
FAS and D29- sets but including baseline seropositive participants [Secondary 
Objective 5]; and in the PP set [Secondary Objective 9]. The same methods also 
apply to evaluating VE against seroconversion [Secondary Objective 2] and VE 
against COVID-19 disease [Secondary Objective 3]. Additional secondary VE 
analyses will be conducted where the time of SARS-CoV-2 infection diagnosis is 
defined as the earliest of the first positive SARS-CoV-2 test result based on either 
PCR testing of nasal swabs or external SARS-CoV-2 testing. 
While the primary analysis of VE against SARS-CoV-2 infection will censor the 
follow-up time of participants who receive outside COVID-19 vaccination at the 
time of first outside vaccination, a secondary analysis will be performed that 
includes infection events and person-time that accrue following outside 
vaccination with the Moderna COVID-19 Vaccine. Participants receiving outside 
vaccination other than Moderna COVID-19 Vaccine will continue to be censored 
at the time of outside vaccination. A time-varying Cox model will be used for 
inference, per methods in the study SAP. 
The asymptomatic SARS-CoV-2 infection endpoint [Secondary Endpoint 8] is 
defined by the PCR tests of daily swabs and serologic diagnostic testing schedule 
at month 0, 2, and 4. The occurrence of a COVID-19 disease event is a competing 
risk because the occurrence of COVID-19 disease precludes the possibility of 
occurrence of a subsequent asymptomatic SARS-CoV-2 infection event. 
Therefore, VE against asymptomatic SARS-CoV-2 infection will be assessed 
using methods accounting for COVID-19 disease as a competing risk. The SAP 
will provide details. 
Vaccine efficacy against the infection and disease endpoints as measured by the 
reduction in the cumulative incidence of the endpoint by Month 4, will also be 
evaluated using the Nelson-Aalen estimator of cumulative incidence. This 
analysis does not rely on the proportional hazards assumption and has a simple 
interpretation that lends itself to understanding of population effects. 
6.4.4 
VL analyses 
Primary analyses of the vaccine effect on VL will focus on the primary VL 
endpoint, peak log10 viral load, and will condition on SARS-CoV-2 infection 
status. Peak log10 viral load will be estimated by the observed maximum log10 
viral load measure; secondary VL analyses will employ parametric models to 
estimate VL at peak. The mean observed log10 viral load will be compared 
between the Immediate Vaccination and Standard of Care arms. This analysis that 
restricts attention to randomized participants will be supported by a co-primary 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 49 of 166 
analysis that combines data from the Standard of Care arm with data from the 
Vaccine Declined Group. Both analyses will use methods that adjust for baseline 
covariates and covariates at the time of SARS-CoV-2 infection diagnosis, per the 
study SAP. The covariate adjustment is used to control for potential post-
randomization selection bias and lack of comparability between randomized 
participants and those in the observed cohort, whereby SARS-CoV-2 infected 
participants in the vaccinated and unvaccinated groups are not comparable in 
ways that are associated with the VL endpoint. Importantly, this bias occurs when 
there are factors that modify VE against SARS-CoV-2 infection and that are 
associated with the VL endpoint. An additional supportive analysis will restrict to 
SARS-CoV-2 infections in the D29- set. Full details around the analysis plan will 
be specified in the study SAP.   
Secondary analyses of vaccine effects on VL will consider a set of other summary 
measures of the VL curve, each of which have merits for further characterizing 
the vaccine effect. These include a model-based estimate of peak log10 viral load, 
duration of detection of virus [estimated empirically or alternatively based on a 
model fit to the viral load curve], area under the log viral load curve [AUC] 
calculated using the trapezoidal rule, and area under the portion of the log viral 
load curve over 105 viral copies/mL. Some mathematical modeling studies 
provide evidence of transmission potential for VL above this threshold (21), but 
there is considerable uncertainty and therefore other thresholds will be 
considered. Analysis methods will be the same as for the primary VL endpoint 
above. 
In addition, the above VL endpoints will be evaluated using unconditional 
analyses, ie, not conditioning on SARS-CoV-2 infection status, among all 
enrolled main study participants. Participants not diagnosed with SARS-CoV-2 
infection will have an endpoint value defined for analysis, typically a value of 
zero. The ‘transmission potential’ endpoint [Secondary endpoint 4] is one such 
endpoint that is defined unconditionally. The merit of unconditional analyses is 
that they are not subject to potential post-randomization selection bias. A 
disadvantage of the unconditional analyses is that they may have lower statistical 
power.   
An additional VL endpoint that will be studied is a censored event-time variable, 
time to VL above 105 copies/mL. This endpoint is defined for all enrolled main 
study participants and will be analyzed using the same methods used to evaluate 
VE against SARS-CoV-2 infection, but only counting infections once VL is 
above 105 copies/mL. Additional methods of analysis that allow for the 
uncertainty in the level of virus that is associated with transmission will be 
considered.  
Sensitivity analyses for VL will include data from all SARS-CoV-2 infected 
participants diagnosed based on PCR testing of study swabs or based on outside 
testing. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 50 of 166 
The study SAP will detail the secondary analysis approaches for the VL 
endpoints. 
6.4.5 
Secondary transmission analyses 
6.4.5.1 
Identifying ‘adjudicated transmission events’ 
An expert adjudication committee will examine and make a primary 
determination to identify ‘adjudicated transmission events’ from a main study 
participant diagnosed with infection (‘index case’) to a contact in the PCC or 
CACC diagnosed with SARS-CoV-2 infection. Note that the close contact could 
also be a main study participant in theory, although this is unlikely given the 
relatively small proportion of each community that will be recruited to the main 
study. The adjudication committee will operate under a charter that lays out a pre-
specified set of criteria for defining the occurrence and direction of transmission 
and will be blinded to the enrollment group of all study participants and contacts. 
The endpoint definition will include criteria that need to be met regarding the 
temporal relationship (eg, evidence that person B’s infection occurred after person 
A’s infection, evidence of compatible incubation period), epidemiologic link 
(evidence of close contact during person A’s infectious period), and relatedness of 
their SARS-CoV-2 viruses. 
The adjudication committee will be provided with all relevant data from the study 
to deduce transmission events from potential transmission pairs. A potential 
transmission pair is a post-baseline SARS-CoV-2- infected main study index case 
and their identified contact(s) in the PCC or CACC who have positive SARS-
CoV-2 test results within a prespecified period (eg, two weeks) of the index case 
diagnosis. This will include the type, frequency, and magnitude (eg, duration and 
setting) of contact between the index case and contact based on risk assessment 
questionnaires given to the index case and the contact; the timing of diagnosis of 
infection by PCR for the index case and the contact (defined as the date of 
specimen collection); the VL trajectories, serology, and symptomatology for the 
index case and the contact; and summaries of the viral sequences for the index 
case and the contact including the number of nucleotide differences in the 
sequences and any clustering and results of phylogenetic analyses (see Section 
6.4.5.3). Adjudication of all potential transmission events will occur within a 
short time frame at the end of the study to ensure decisions are being made using 
the same background research on transmission and to ensure that the adjudication 
can take into account all SARS-CoV-2 infection events captured in the main study 
cohort and both contact cohorts. Primary analyses of the vaccine effect on 
secondary transmission will rely on the determination of this committee and use 
the adjudicated transmission events and outcomes in statistical models. These 
same primary analyses will also only include main study participants diagnosed 
with infection through PCR testing of study swabs. However, sensitivity analyses 
will incorporate data from the full set of main study participants diagnosed with 
infection either through outside testing or through PCR testing of swabs collected 
through the study per methods described in the SAP. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 51 of 166 
6.4.5.2 
Analyses of the vaccine effect on secondary transmission 
Primary analyses of vaccine efficacy against secondary transmission will include 
adjudicated transmission events collected from both the PCC and CACC. Both 
conditional and unconditional analyses will be performed. Conditional analyses 
will compare the expected number of adjudicated transmission events between 
index cases in the Immediate Vaccination Group vs. Standard of Care Group. This 
analysis that restricts attention to randomized participants will be supported by a 
co-primary analysis that combines data from the Standard of Care Group with 
data from the Vaccine Declined Group. An additional supportive analysis will 
restrict to SARS-CoV-2 infection events in the D29- set. These primary analyses 
will use Poisson regression, where goodness of fit tests will be used to determine 
whether an overdispersed Poisson or other alternative distributions fit the data 
better, per the study SAP. Analyses using the observational cohort cannot assume 
balanced mixing with susceptible contacts between vaccinated and unvaccinated 
groups and will adjust for number and type of contacts. The SAP will specify the 
baseline participant characteristics and measurements available at the time of 
SARS-CoV-2 infection diagnosis that are potentially associated with secondary 
transmission to be included as covariates. The conditional analysis may have 
greater power than an unconditional analysis, eg, under low VE against SARS-
CoV-2 infection. However, it is subject to the post-randomization selection bias, 
as discussed in relation to the viral load endpoint. In general, it will be biased if 
there are factors that modify VE against SARS-CoV-2 infection that are also 
associated with onward transmission; or if factors associated with onward 
transmission are modifiers of VE against infection.  
A secondary analysis of this endpoint will measure vaccine efficacy against 
secondary transmission as the percent reduction in the expected number of 
adjudicated transmission events linked to a participant in the Immediate 
Vaccination Group relative to the Standard of Care Group. In contrast to the 
primary transmission analysis that conditions on the main study participant being 
infected, all main study participants will contribute to the analysis including those 
who do not become infected to reflect the fact that SARS-CoV-2-uninfected 
participants do not transmit to others and therefore have 0 transmission events. 
Let N = number of adjudicated transmission events for a given index case which 
is assumed to follow a zero-inflated Poisson distribution with the mean of the 
non-zero point mass component is 𝜇𝑒(𝑉𝛾) , where V indicates randomization 
assignment (1 Immediate Vaccination; 0 Standard of Care). Further let 𝛽 denote 
the log hazard ratio from a Cox proportional hazards model for infection time. 
Then the ratio of the expected number of adjudicated transmission events linked 
to a participant in the Immediate Vaccination Group relative to the Standard of 
Care Group can be expressed as 
𝑒𝜃= 𝑒𝛾𝑒𝛽, 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 52 of 166 
where 𝜃 is a measure of the vaccine’s impact on total onward transmission 
(transmission from participants in main study) and 𝑒𝜃 is the relative reduction in 
the proportion of adjudicated transmission events in the Immediate Vaccination 
Group relative to the Standard of Care Group. This is analogous to the product 
estimator in the proportional means model (53, 54). Note that this formulation 
assumes the time between detection in the index case participant and infection of 
a contact is ignorable. Covariate-adjusted approaches will be detailed in the SAP. 
The analysis that restricts attention to randomized participants will be supported 
by an analysis that combines data from the Standard of Care Group with data 
from the Vaccine Declined Group. 
The unconditional analysis retains high power even if there are few breakthrough 
infections in the Immediate Vaccination Group due to high VE against infection. 
It also properly reflects that a vaccine is successful at reducing secondary 
transmission if it either meaningfully reduces acquisition or reduces onward 
transmission from infected participants. Moreover, by avoiding conditioning on 
SARS-CoV-2 infection, it avoids the post-randomization selection bias issue.  
6.4.5.3 
Processing and phylogenetic analysis of SARS-CoV-2 viral sequence data 
A central sequencing facility will obtain whole-genome sequences from all 
infected participants in the main study cohort and all infected participants in the 
PCC and CACC, based on the nasal swab with the highest viral load (see Section 
10.3.2). Details about the sequencing platform and methodology for QC processes 
will be included in the study SAP. This will include the creation of a global 
alignment, which will be used for the isolation of genes and the sequence analyses 
of local regions. 
A first step in the analysis of the sequence data will be to determine, for each pair 
of sequences among infected participants or contacts within a given study 
community, which are identical. Data from GenBank, Global Initiative on Sharing 
Avian Influenza Data (GISAID), and other public databases suggest that we can 
expect limited variability in genetic sequences, especially those from a single 
common ancestor and constrained within a single study community over a 4-
month time period. Consensus-based whole genomes that differ by more than two 
nucleotides can reasonably be ruled out as being transmission events.  
A second step will be to conduct distance-based analyses of the sequences, 
including phylogenetic analysis, to identify potential lineages of infecting viral 
strains, infection clusters, and potentially linked transmissions. Phylogenetic 
analyses will also include ‘background’ SARS-CoV-2 sequences with 
geographical or temporal relevance from publicly available databases, such as 
GenBank and GISAID. The background sequences will help root the tree and give 
the tree structure and may lend insight into the identification of clusters and into 
potential transmission events during the adjudication process. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 53 of 166 
Details about the phylogenetic and other sequence analyses, including the tree-
building methods and evolutionary models to be used, as well as approaches to 
incorporating data from multiple reads, will be available in the study SAP. 
6.4.6 
Immunogenicity analyses 
6.4.6.1 
Vaccine immunogenicity  
Immunogenicity will be characterized for the immediate vaccination group only, 
using data from the Case-Cohort Immunogenicity Set (ccIS). Data from 
quantitative immunogenicity assays will be summarized using positive response 
rates and geometric means with 95% CIs, for each timepoint for which an 
assessment is performed. Data from qualitative (ie, yielding a positive or negative 
result) assays will be summarized by tabulating the frequency of positive 
responses for each assay at each timepoint that an assessment is performed. 
Analyses focus on the Month 2 time point, the Day 1 time point, and the change 
in marker response between the two time points. The analyses will evaluate 
immunogenicity in all immediate vaccination arm participants and separately in 
subgroups defined by baseline SARS-CoV-2 serostatus. The SAP will describe 
the complete set of immunogenicity analyses.  
6.4.6.2 
Immune response marker correlates of risk 
A separate Trial Marker SAP will describe the statistical methods and data 
analysis implementations for assessing immune response markers as correlates of 
the SARS-CoV-2 infection and peak log viral load study endpoints, as well as 
various types of correlates/surrogates of protection.  
An unblinded statistical analysis by treatment assignment of a primary 
immunogenicity endpoint may be performed when all participants have 
completed the Month 2 visit and data are available for analysis from at least 80% 
of these participants. Similarly, an unblinded statistical analysis by treatment 
assignment of a secondary or exploratory immunogenicity endpoint may be 
performed when all participants have completed the corresponding 
immunogenicity visit and data are available for analysis from at least 80% of 
these participants. The CoVPN Laboratory Center will review the analysis report 
prior to distribution to the protocol chairs, NIAID, study product developer, and 
other key CoVPN members and investigators. Reports for distribution or 
presentation should use PubIDs and not PTIDs for individual responses. 
Distribution of reports will be limited to those with a need to know for the 
purpose of informing future trial-related decisions. The CoVPN leadership must 
approve any other requests for CoVPN immunogenicity analyses prior to the end 
of the scheduled follow-up visits. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 54 of 166 
7 
Selection and withdrawal of participants 
Participants will be generally healthy adults who comprehend the purpose of the 
study and have provided written informed consent. Volunteers will be recruited 
and screened; those determined to be eligible, based on the inclusion and 
exclusion criteria, will be enrolled in the study. Final eligibility determination will 
depend on information available at the time of enrollment, medical history 
questionnaire, physical examinations, and answers to self-administered and/or 
interview questions. 
Investigators should always use good clinical judgment in considering a 
volunteer’s overall fitness for trial participation. Some volunteers may not be 
appropriate for enrollment even if they meet all inclusion/exclusion criteria. 
Medical, psychiatric, occupational, or other conditions may make evaluation of 
safety and/or immunogenicity difficult, and some volunteers may be poor 
candidates for retention. 
Determination of eligibility, taking into account all inclusion and exclusion 
criteria, must be made within 56 days prior to enrollment unless otherwise noted 
below. 
7.1 
Inclusion criteria for Main Cohort, Immediate Vaccination Group and 
Standard of Care Group 
General and Demographic Criteria 
1. Age of 18 through 29 years. 
2. Willingness to be followed for the planned duration of the study. 
3. Agrees to allow study staff to access school SARS-CoV-2 testing data and 
outcomes, if applicable.  
4. Ability and willingness to provide informed consent. 
5. Assessment of understanding: volunteer demonstrates understanding of this 
study; completes a questionnaire with demonstration of understanding of all 
questionnaire items answered incorrectly. 
6. Willing to be randomized to either immediate vaccination or standard of 
care group and comply with planned study procedures. 
7. Agrees not to enroll in another study of an investigational research agent until 
the end of the study. 
8. Access to device and internet for completion of study procedures.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 55 of 166 
7.2 
Exclusion criteria for Main Cohort, Immediate Vaccination Group and 
Standard of Care Group 
General 
1. Acutely ill 72 hours prior to or at screening. Volunteers meeting this criterion 
may be rescheduled within the relevant window periods. Participants with minor 
illnesses can be enrolled at the discretion of the investigator. 
2. Blood products, systemic immunoglobulins, or monoclonal antibodies (including 
against SARS-CoV-2) received within 90 days before first vaccination. 
3. Investigational research agents received within 30 days before first vaccination. 
4. Self-reported known history of SARS-CoV-2 infection. 
Vaccines and other Injections 
5. Prefers to receive COVID-19 vaccination immediately. (These volunteers to be 
referred to community resources for vaccination). 
6. Prior administration of a coronavirus (SARS-CoV-2, SARS-CoV, MERS-
CoV) vaccine or current/planned simultaneous participation in another 
interventional study to prevent or treat COVID-19. 
Immune System  
7. Immunosuppressive medications received within 168 days before first 
vaccination (not exclusionary: [1] corticosteroid nasal spray; [2] inhaled 
corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatologic 
condition; or [4] a single course of oral/parenteral prednisone or equivalent at 
doses < 60 mg/day and length of therapy < 11 days with completion at least 30 
days prior to enrollment). 
Clinically significant medical conditions 
8. Clinically significant medical condition, physical examination findings, or past 
medical history with clinically significant implications for current health. A 
clinically significant condition or process includes but is not limited to: 
• A process that would affect the immune response (well-controlled human 
immunodeficiency virus infection is allowed), or 
• Any condition specifically listed among the exclusion criteria below. 
9. Any medical, psychiatric, occupational, or other condition that, in the 
judgment of the investigator, would interfere with, or serve as a contraindication 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 56 of 166 
to, protocol adherence, assessment of safety or reactogenicity, or a volunteer’s 
ability to give informed consent. 
10. Bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder 
requiring special precautions). 
11. Asplenia: any condition resulting in the absence of a functional spleen. 
12. History of angioedema or anaphylaxis, including to vaccines or vaccine 
components (not exclusionary: angioedema or anaphylaxis with known trigger 
and no episodes within five years.). 
13. History of generalized urticaria within past five years. 
7.3 
Inclusion criteria for Main cohort, Vaccine Declined Group 
General and Demographic Criteria 
1. Age of 18 through 29 years. 
2. Ability and willingness to provide informed consent. 
3. Prefers not to receive COVID-19 vaccine. 
4. Willingness to be followed for the planned duration of the study. 
5. Assessment of understanding: volunteer demonstrates understanding of this 
study; completes a questionnaire with demonstration of understanding of all 
questionnaire items answered incorrectly. 
6. Access to device and internet for completion of study procedures.  
7.4 
Exclusion criteria for Main cohort, Vaccine Declined Group 
1. Prior administration of a coronavirus (SARS-CoV-2, SARS-CoV, MERS-
CoV) vaccine or current/planned simultaneous participation in another 
interventional study to prevent or treat COVID-19 (participation in studies of 
other investigational research agents allowed). 
2. Any medical, psychiatric, occupational, or other condition that, in the 
judgment of the investigator, would interfere with, or serve as a contraindication 
to, protocol adherence, or a volunteer’s ability to give informed consent. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 57 of 166 
7.5 
Inclusion criteria for Prospective Close Contact (PCC) cohort 
1. Age of 18 years or older, at the time of signing the informed consent. 
2. Willing and able to provide informed consent. 
3. Expected to be in frequent close physical proximity with Main Cohort 
participant during the study. 
4. Willing to share results of SARS-CoV-2 testing. 
5. Access to device and internet for completion of study procedures. 
7.6 
Inclusion criteria for Case-ascertained Close Contact (CACC) cohort 
1. Age of 18 years or older, at the time of signing the informed consent. 
2. Willing and able to provide informed consent. 
3. Access to device and internet for completion of study procedures. 
4. Willing to share results of SARS-CoV-2 testing. 
5. Had close contact with Main Cohort participant with known PCR-confirmed 
SARS-CoV-2 infection (eg, index case). Close contacts will have had exposure 
to the index participant, generally within 72 hours of an index diagnosis, and may 
include individuals that meet any of the following guidelines: 
• Prolonged close physical proximity with Main Cohort participant within a 
residence/vehicle/enclosed space without maintaining social distance, 
• Medical staff, first responders, or other care persons who cared for the index 
case without appropriate personal protective equipment. 
Further information on the definition of close contact can be found in the CoVPN 
3006 Study Specific Procedures (SSP). 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 58 of 166 
8 
Study product  
The protocol schema is shown in Table 1-1.  
Definitions of on-study and outside of study COVID-19 vaccination: 
• On-study: occurred as directed by the protocol procedures (i.e. procedures 
occurring within the visit windows) with Moderna COVID-19 vaccine for the 
cohort to which the participant has been randomized or assigned 
• Outside of study: any COVID-19 vaccination that was administered at a time 
outside of protocol-specified visit windows for the cohort to which the 
participant has been randomized or assigned  
Moderna COVID-19 Vaccine provided via the US Government study-allocated 
supply can only be administered to CoVPN 3006 study participants in an on-study 
manner. Exceptions may be made for Main Cohort study participants who become 
infected with SARS-CoV-2 after enrollment. Such exceptions require approval of 
CoVPN 3006 Protocol leadership. 
8.1 
Vaccine regimen 
Immediate Vaccination Group 
Treatment 1 (T1): Moderna COVID-19 Vaccine in 100 mcg dose given as 0.5 
ml IM into the deltoid muscle on Day 1 and Day 29. 
Standard of Care Group and Vaccine Declined Group who accept 
vaccine offer at M4 
Treatment 2 (T2): Moderna COVID-19 Vaccine in 100 mcg dose given as 0.5 
ml IM into the deltoid muscle on Day 113 and Day 141. 
8.2 
Storage, handling, preparation, and administration 
Vaccination providers will refer to EUA vaccine instructions accessed and 
updated at https://www.modernatx.com/covid19vaccine-eua/. 
8.3 
Acquisition of Moderna COVID-19 Vaccine 
Emergency use authorized Moderna COVID-19 Vaccine will be provided by 
Moderna, Inc. through the US Government COVID-19 Vaccine Response and 
allocated for this trial. Participants may also access Moderna COVID-19 EUA 
vaccine via other sources for on-study vaccinations if the administration fee is 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 59 of 166 
either paid for by the study or is not billed to any party. Examples of how 
vaccinations may be administered to study participants includethe following: 
• At the CRS using study-allocated vaccine supply 
• At a non-CRS location using study-allocated vaccine supply with 
administration fees funded by the study 
• At a pharmacy administering EUA Moderna COVID-19 vaccine via Federal 
Retail Pharmacy Partnership (FRPP) supply with administration fees funded 
by the study  
Please see the  CoVPN 3006 SSP for additional examples and details.  
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 60 of 166 
9 
Clinical procedures 
Procedures are in place so that study visits may be conducted remotely, such as 
via phone, text message, email, or other electronic means, in lieu of, or in 
combination with, in-person visits at the clinical research site. Furthermore, some 
visit procedures may be conducted outside the CRS (see CoVPN 3006 SSP for 
additional details). 
The schedules of clinical procedures are shown in Appendix E, Appendix F, 
Appendix G and Appendix H. 
9.1 
Informed consent 
Informed consent is the process of working with participants so that they fully 
understand what will and may happen to them while participating in a research 
study. The CoVPN informed consent form documents that a participant (1) has 
been informed about the potential risks, benefits, and alternatives to participation, 
and (2) is willing to participate in a CoVPN study. Informed consent encompasses 
all written, verbal, and electronic study information CRS staff provide to the 
participant, before and during the trial. CRS staff will obtain informed consent of 
participants according to the CoVPN 3006 SSP. 
If any new information is learned that might affect the participants’ decisions to 
stay in the trial, this information will be shared with trial participants. If 
necessary, participants will be asked to provide revised informed consent forms. 
9.1.1 
Screening consent form 
Without a general screening consent, screening for a specific study cannot take 
place until the site receives protocol registration from NIAID or its designee. 
Some CRSs have approval from their IRB/EC and any applicable RE to use a 
general screening consent form that allows screening for an unspecified SARS-
CoV-2 vaccine trial. In this way, CRS staff can continually screen potential 
participants and, when needed, proceed quickly to obtain protocol-specific 
enrollment consent. Sites conducting general screening or prescreening approved 
by their IRB/EC and any applicable RE may use the results from this screening to 
determine eligibility for this protocol, provided the tests are conducted within the 
time periods specified in the eligibility criteria. 
9.1.2 
Protocol-specific consent forms 
The protocol-specific consent forms describe the study products to be used and all 
aspects of protocol participation, including screening and enrollment procedures. 
Sample protocol-specific consent forms for the Main cohort are located in 
Appendix A and Appendix B. A sample protocol-specific consent form for the 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 61 of 166 
PCC cohort is located in Appendix C. A sample protocol-specific consent form 
for the CACC cohort is located in Appendix D. 
The consent forms for the PCC and CACC cohorts may be managed centrally by 
the CoVPN. This will allow for a streamlined approach to consenting these 
individuals, given the referral mechanism to participate in the study, in addition to 
the remote nature of their study participation. In this instance, the centralized 
consents and consenting process will be approved by the IRB/EC at the protocol-
level.  
For consent forms that the CoVPN does not manage centrally, each CRS is 
responsible for developing protocol-specific consent form(s) for local use, based 
on the sample protocol-specific consent forms. The consent form(s) must be 
developed in accordance with requirements of the following: 
• CRS’s IRB/EC and any applicable REs 
• CRS’s institution 
• Elements of informed consent as described in Title 45, CFR Part 46 and Title 
21 CFR, Part 50, and in ICH E6(R2), Good Clinical Practice: Consolidated 
Guidance 4.8 
Study sites are strongly encouraged to have local community representatives from 
the target population review their sites-specific consent forms. This review should 
include, but should not be limited to, issues of cultural competence, local 
language considerations, and the level of understandability. 
The sample informed consent form(s) include(s) instructions for developing 
specific content. 
9.1.3 
Assessment of Understanding 
Study staff are responsible for ensuring that participants fully understand the 
study before enrolling them. This process involves reviewing the informed 
consent form with the participant, allowing time for the participant to reflect on 
the procedures and issues presented, and answering all questions completely. 
An Assessment of Understanding is used to document the participant’s 
understanding of key concepts in this study. Participants must demonstrate 
understanding of all questions answered incorrectly. This process and the 
participant’s understanding of the key concepts is to be recorded in the eConsent. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 62 of 166 
9.2 
Pre-enrollment procedures for Main Cohort  
Screening may occur over the course of several contacts/visits, up to and 
including before enrollment. All inclusion and exclusion criteria must be assessed 
within 56 days before enrollment, unless otherwise specified in the eligibility 
criteria (or below in this section). Screening results will be reviewed with the 
volunteer. 
After the appropriate informed consent has been obtained and before enrollment, 
the following procedures are performed: 
• Participant will download the electronic diary (eDiary) application to their 
smartphone or tablet and complete an optional application training. Participant 
will use eDiary to enter data. Data collection will include: 
▪ Medical history questionnaire  
▪ Volunteer demographics in compliance with the NIH Policy on Reporting 
Race and Ethnicity Data: Subjects in Clinical Research, Aug. 8, 2001 
(available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-
053.html) 
▪ Baseline SARS-CoV-2 infection risk information 
• Discussion of the eDiary entries done by the participant with the site staff 
• 
Review of materials for possible self-collection of blood by the participant 
9.3 
Enrollment and vaccination visits for Main Cohort, Immediate 
Vaccination Group 
Once a volunteer has consented to trial participation and is found to meet all 
eligibility criteria (see Sections 7.1 and 7.2), the CRS requests the randomization 
assignment via a Web-based randomization system. Enrollment is simultaneous 
with randomization. In general, the time interval between randomization and 
completion of all study activities for Visit 2 should not exceed approximately 7 
working days. However, circumstances may require a participant’s visit to be 
changed. This may exceed the 7-day randomization time limit recommendation. 
At vaccination visits, the following procedures are performed before 
vaccination: 
• 
COVID-19 symptom check, both vaccination visits 
• 
Specimen collection (only at first vaccination visit, see Appendix E) 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 63 of 166 
Following completion of all procedures in the preceding list, and if results 
indicate that vaccination may proceed, vaccination is prepared and administered 
per Moderna EUA Fact Sheet and Full Prescribing Information for Vaccination 
Providers that can be accessed at https://www.modernatx.com/covid19vaccine-
eua/).  
Additionally, the participants will be: 
• Reminded to enter information in eDiary throughout the study  
• Provided with a supply of nasal swabs and shown how to swab both nostrils  
9.4 
Follow-up procedures for Main Cohort, Immediate Vaccination Group 
The following procedures are performed during follow-up per schedule in 
Appendix E: 
• Participants reminded to enter information in eDiary throughout the study (see 
Section 9.16) 
• Nasal swab collection by participant 
• Blood collection by CRS staff, phlebotomist, or participant  
• End of study questionnaire 
9.5 
Enrollment (visit 2) and Month 2 (visit 4) Visits for Main Cohort, 
Standard of Care and Vaccine Declined Groups 
Randomization applies to Standard of Care participants only: Once a volunteer 
has consented to trial participation and is found to meet all eligibility criteria (see 
Sections 7.1 and 7.2), the CRS requests the randomization assignment via a Web-
based randomization system. Enrollment is simultaneous with randomization. 
In general, the time interval between randomization and completion of all study 
activities for Visit 2 should not exceed approximately 7 working days. However, 
circumstances may require a participant’s visit to be changed. This may exceed 
the 7-day randomization time limit recommendation. 
For Vaccine Declined participants: Once a volunteer has consented to trial 
participation and is found to meet all eligibility criteria (see Sections 7.3, and 7.4) 
they are considered enrolled. 
For Standard of Care and Vaccine Declined participants: before leaving the 
clinic, the participants will be: 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 64 of 166 
• Reminded to enter information in eDiary throughout the study  
• Provided with a supply of nasal swabs and shown how to swab both nostrils 
At visits 2 and 4, the following procedures are performed per schedule in 
Appendix F: 
• eDiary entries by participant (see Section 9.16) 
• Nasal swab collection by participant 
• Blood collection by CRS staff, phlebotomist, or participant 
9.6 
Month 4 (visit 5) and Month 5 (visit 6) Visits for Main Cohort, 
Standard of Care Group and Vaccine Declined Group 
For those participants who have not received a COVID-19 vaccine outside 
the study and who request vaccination: 
At vaccination visits the following procedures are performed before 
vaccination: 
• COVID-19 symptom check, both visits  
• Specimen collection (only at Month 4 visit, see Appendix F) 
Following completion of all procedures in the preceding list, and if results 
indicate that vaccination may proceed, vaccination is prepared and administered, 
per Moderna EUA Fact Sheet and Full Prescribing Information for Vaccination 
Providers that can be accessed at https://www.modernatx.com/covid19vaccine-
eua/).  
• End of study questionnaire at Month 5 (Visit 6) 
For participants who have already received COVID-19 vaccination outside of 
study prior to Month 4 (Visit 5) visit or who decline vaccination, the following 
procedures are performed at Visit 5; Visit 6 will not occur (see Appendix F):  
• Specimen collection   
• End of Study questionnaire 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 65 of 166 
9.7 
Procedures for Main Cohort participant diagnosed with a SARS-CoV-
2 infection during the study 
If a participant is diagnosed with a SARS-CoV-2 infection during the course of 
the study, CDC guidelines on administration of vaccination will be followed.  
Main Cohort participants who are clinically diagnosed with SARS-CoV-2 
infection (from any test result indicative of acute infection) are referred to as 
clinically diagnosed index cases. They will be instructed to isolate per local 
guidelines and the following procedures will be performed: 
• eDiary collection of daily symptoms of COVID-19 and assessment of whether 
clinical care was sought or hospitalization occurred (via self-report and/or 
request for medical records) through an eDiary for a period of 14 days or until 
symptoms have resolved, whichever is longer 
• Daily nasal swabbing continued per schedule of procedures (see Appendix E) 
• Blood collection by phlebotomist or participant for SARS-CoV-2 clinical 
serology 
• Close contacts identification (see Section 9.9) 
Following resolution of the isolation period, participants will continue scheduled 
study visits. Follow-up duration for participants diagnosed with moderate or 
severe COVID-19 disease may be adjusted in consultation with the CRS (eg, to 
avoid interference with participant initiation of SARS-CoV-2 treatment).  
9.8 
Enrollment and follow-up procedures for Prospective Close Contact 
(PCC) cohort  
Upon enrollment, participants from the Main Cohort will be asked to invite 
individuals with whom they will be in frequent close physical proximity during 
the study to join the PCC cohort (See Section 7.5 and CoVPN 3006 SSP for 
additional information on PCC cohort). New PCC contacts may also be added 
during the study. 
Prospective close contacts will be given referral codes and information about how 
to enroll in the study as part of the PCC cohort. If they choose to enroll and sign 
an informed consent, they will be asked to: 
• provide access to their routine SARS-CoV-2 testing reports, if applicable 
• enter data weekly through eDiary (see Section 9.16) 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 66 of 166 
If a PCC cohort participant or the Main Cohort participant to whom he/she is 
connected is diagnosed with a SARS-CoV-2 infection during the course of the 
study, the PCC cohort participant will be instructed to perform the following 
procedures (see Appendix G): 
• eDiary collection of daily symptoms of COVID-19 and assessment of whether 
clinical care was sought or hospitalization occurred (via self-report and/or 
request for medical records) through an eDiary for a period of 14 days or until 
symptoms have resolved, whichever is longer 
• provide nasal swab for 14 days 
• self-collect blood samples on day 1 and day 29, relative to the notification of 
infection 
For Main Cohort participants who are also PCC cohort participants related to an 
index case in another Main cohort participant, the following procedures in 
addition to those listed in Appendix E may be performed: 
• one additional blood collection (self-collection) as soon as possible following 
the report of the index case  
• eDiary collection of information regarding exposure to the Index case 
• eDiary collection of daily symptoms of COVID-19 and assessment of whether 
clinical care was sought or hospitalization occurred (via self-report and/or 
request for medical records) through an eDiary for a period of 14 days or until 
symptoms have resolved, whichever is longer 
See CoVPN 3006 SSP for additional information on PCC cohort. 
9.9 
Enrollment and Follow-up procedures for Case-Ascertained Close 
Contact (CACC) cohort 
Participants from the Main Cohort who are clinically diagnosed with SARS-CoV-
2 (referred to as the Index case) during the study will be asked to contact any 
individuals with whom they have been in close contact within about 72 hours of 
the date of the SARS-CoV-2 diagnosis test. See Section 7.6 and CoVPN 3006 
SSP for additional information on case-ascertained close contacts. 
Potential CACC cohort participants will be given referral codes and information 
about how to enroll in the study as part of the CACC cohort, if they choose to, 
and sign an informed consent. 
Once a volunteer has consented to be a part of CACC cohort, the following 
procedures will be performed (see Appendix H): 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 67 of 166 
• eDiary collection of information regarding exposure to the Index case 
• eDiary collection of daily symptoms of COVID-19 and assessment of whether 
clinical care was sought or hospitalization occurred (via self-report and/or 
request for medical records) through an eDiary for a period of 14 days or until 
symptoms have resolved, whichever is longer. 
• Outcomes of SARS-CoV-2 testing performed by the school or other facilities 
• Nasal swab self-collection from day 1-14 
• Blood collection by participant for SARS-CoV-2 clinical serology at day 3 
and at day 29 
If a CACC participant is diagnosed with a SARS-CoV-2 infection during the 
course of the study, they will be instructed to track daily symptoms of COVID-19 
through an eDiary for a period of 14 days or until symptoms have resolved, 
whichever is longer.  
For Main Cohort participants who are also CACC cohort participants, the 
following procedures in addition to those listed in Appendix E may be performed: 
• one additional blood collection (self-collection) as soon as possible  
• eDiary collection of information regarding exposure to the Index case  
• eDiary collection of daily symptoms of COVID-19 and assessment of whether 
clinical care was sought or hospitalization (via self-report and/or request for 
medical records) occurred through an eDiary for a period of 14 days or until 
symptoms have resolved, whichever is longer. 
9.10 
Visit windows and missed visits 
Visit windows are included in Appendix I. The procedures for documenting 
missed visits and out of window visits are described in CoVPN 3006 SSP.  
9.11 
Discontinuing vaccination for a participant who receives a COVID-19 
Vaccine outside the study 
In the event a participant receives an EUA or licensed COVID-19 vaccine outside 
the study, an individual participant’s study vaccinations will be permanently 
discontinued. Participants should be counseled on the importance of continuing 
with the study and strongly encouraged to participate in follow-up visits and 
protocol-related procedures per the protocol for the remainder of the trial, unless 
medically contraindicated.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 68 of 166 
9.12 
Early termination visit 
In the event of early participant termination, site staff should consider if final 
specimen collection is appropriate.  
9.13 
Pregnancy for Main Cohort 
For Main cohort participants who have been vaccinated, pregnancies and 
pregnancy outcomes will be reported via the FDA/CDC Vaccine Adverse Event 
Reporting System (VAERS) (see Section 11.1).  
9.14 
SARS-CoV-2 monitoring by schools for Main Cohort, if applicable 
For participating schools that have SARS-CoV-2 monitoring plans in place, 
monitoring will typically provide approximately twice weekly SARS-CoV-2 
testing for enrolled Main Cohort participants. For any positive test result, the 
institution will inform the student (initiating isolation), will provide the SARS-
CoV-2 test results to the students, and will carry out contact tracing if applicable. 
Participants will be instructed to report positive test results via the eDiary.  
9.15 
COVID-19 symptom surveillance for Main Cohort 
Participants will be monitored for symptoms of COVID-19 throughout the course 
of the study via a weekly eDiary. These symptoms will be used to establish 
whether a participant meets criteria for COVID-19 disease as defined by 
Secondary Endpoint 4. If a participant has symptoms consistent with COVID-19, 
they will be encouraged to seek testing and clinical care through their local testing 
and care facilities. Results of testing will be reported through the eDiary and 
participants who have positive test results will follow procedures described in 
Section 9.7. 
For Immediate Vaccination Group only:due to the overlap of symptoms that can 
result from vaccination and symptoms of COVID-19, monitoring will begin 7 
days following the first study product administration. Symptom monitoring will 
be paused 7 days following the second product administration.  
9.16 
Use of electronic Diary (eDiary) for Clinical Outcomes Assessments 
At the time of consent, participants must confirm they will be willing to complete 
an eDiary collection of study data (see below for details of data to be collected). 
The eDiary will be completed using an application downloaded to their 
smartphone or tablet. This study will utilize the Medidata Patient Cloud 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 69 of 166 
Application as the eDiary software. This application allows for real-time data 
collection directly from participants. 
After participants have signed the informed consent, all participants will be 
instructed to download the eDiary application on their personal smartphone or 
tablet. The eDiary application has a self-training component, enabling immediate 
use. The site staff will perform any retraining as necessary. 
For Main Cohort participants,  
Study participants will record data in the eDiary throughout the study as described 
in Appendix E and Appendix F, following the prompts provided for data 
collection. eDiary data collection areas may include: 
• Medical history questionnaire  
• Volunteer demographics  
• Risk assessment for SARS-CoV-2 infection (see Appendix E and Appendix F) 
• Surveillance for symptoms of COVID-19 (see Section 9.15) 
• Self-collection of samples (eg, nasal swabs) (see Appendix E and Appendix F) 
• Outcomes of SARS-CoV-2 testing performed by the school or other facilities 
(see Appendix E and Appendix F) 
• COVID-19 symptom tracking upon incident diagnosis of SARS-CoV-2 
infection, including assessments of whether clinical care was sought or 
hospitalization occurred via self-report and/or request for medical records (see 
Section 9.7) 
Additionally, participants will be reminded through the eDiary of the need to 
continue practices for reducing acquisition and transmission of SARS-Cov-2 
regardless of their vaccination status. 
For Prospective Close Contact (PCC) cohort participants,  
PCC participants record data in the eDiary as described in Appendix G, following 
the prompts provided for data collection. eDiary data collection areas may 
include: 
• Collection of demographic information 
• Collection of information regarding exposure to the main study participant 
• Outcomes of SARS-CoV-2 testing performed by the school or other facilities 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 70 of 166 
• Self-collection of samples (eg, nasal swabs) (see Appendix G) 
• COVID-19 symptom tracking upon incident diagnosis of SARS-CoV-2 
infection in PCC or main study participant, including assessments of whether 
clinical care was sought or hospitalization occurred via self-report and/or 
request for medical records  
• Recording of any COVID-19 vaccines received outside of the study  
For Case-Ascertained Close Contact (CACC) cohort participants,  
CACC participants will record data in the eDiary as described in Appendix H, 
following the prompts provided for data collection. eDiary data collection areas 
may include: 
• Collection of demographic information 
• Collection of information regarding exposure to the Index case 
• Outcomes of SARS-CoV-2 testing performed by the school or other facilities 
• COVID-19 symptom tracking, including assessments of whether clinical care 
was sought or hospitalization occurred via self-report and/or request for 
medical records  
• Self-collection of samples (eg, nasal swabs) (see Appendix H) 
• Recording of any COVID-19 vaccines received outside of the study  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 71 of 166 
10 
Laboratory 
10.1 
CRS laboratory procedures 
The CoVPN 3006 SSP and other study materials provide further guidelines for 
operational issues concerning the clinics and laboratories. These documents 
include special considerations for phlebotomy and guidelines for general 
specimen collection, specimen labeling and specimen processing. 
Tube types for blood collection are specified in CoVPN 3006 SSP. 
Of note, all assays described below, with the exception of SARS-CoV-2 PCR, are 
performed as research assays to evaluate the ability of the SARS-CoV-2 virus to 
induce immune responses in the context of the participants’ genetic background 
and are not approved for use in medical care. Results from these research assays 
are not made available to participants or medical professionals to guide treatment 
decisions. 
10.2 
Total blood volume 
Required blood collections per visit are shown in Appendix E, Appendix F, 
Appendix G and Appendix H. The total blood volume drawn for each participant 
will not exceed 500 mL in any 56-day (8-week) period.  
10.3 
Endpoint assays  
10.3.1 
SARS-CoV-2 PCR 
Real-time reverse transcription polymerase chain reaction (RT-PCR) assays to 
detect SARS-CoV-2 will be run on nasal samples collected from study 
participants. After RNA extraction, specimens will be analyzed by a laboratory 
developed test using the World Health Organization’s E/RdRp primer set, the 
N1/N2 primer set from the Centers for Disease Control and Prevention, or tests 
from Hologic (Panther Fusion), DiaSorin (Simplexa), or Roche (cobas). Novel 
methods to detect SARS-CoV-2 may also be used if applicable. 
10.3.2 
SARS-CoV-2 viral sequencing 
Genome sequencing of SARS-CoV-2 virus may be performed on nasal samples 
from study participants using a metagenomic approach. RNA from positive 
specimens is converted to a cDNA library by reverse transcription and the library 
is sequenced. Resulting consensus sequences are assembled against a SARS-CoV-
2 reference genome.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 72 of 166 
10.3.3 
Neutralizing antibody assay (nAb) 
SARS-CoV-2–specific nAb assays may be performed on serum samples from 
study participants. The assay will test neutralization of S-pseudotyped and/or full-
genome recombinant viruses as measured by a reduction in luciferase (Luc) 
reported gene expression after infection in ACE-2 positive cells. 
10.3.4 
Binding antibody multiplex assay (BAMA) 
SARS-CoV-2 specific total IgG and IgM binding antibodies may be assessed in 
serum samples. In addition, SARS-CoV-2–specific serum IgA and IgG subclass 
(IgG1, IgG2, IgG3, and IgG4) antibodies may also be assessed. Epitope 
specificity by ACE-2 blocking assay and responses to endemic coronavirus 
proteins may also be assessed. 
10.3.5 
Antibody avidity (BioLayer Interferometry and BAMA avidity index) 
SARS-CoV-2-specific polyclonal serum antibody and IgG subclass avidity may 
be measured using BAMA with the addition of a dissociation step to calculate the 
antibody avidity index (BAMA-AI). BLI and/or SPR technologies may also be 
used to measure antibody avidity.  
10.3.6 
Fc-Mediated Antibody Function 
Additional assays to measure SARS-CoV-2-specific antibody Fc functions may 
be performed (ie, antibody dependent cellular cytotoxicity [ADCC], antibody-
dependent cellular phagocytosis [ADCP], antibody-dependent neutrophil 
phagocytosis [ADNP], binding antibody FcR array, and S-protein-Expressing Cell 
Antibody Binding Assay [SECABA]). 
10.4 
Lab assay portfolio 
Additional assays may be performed per the Laboratory Center assay portfolio, 
which includes immune assessments such as those for cellular, humoral, and 
innate immune responses, and host genetics. The assay portfolio will be updated 
periodically to include new assays and adjust qualification levels of existing 
assays. 
10.5 
Exploratory studies 
Samples may be used for other testing and research related to furthering the 
understanding of SARS-CoV-2 immunology, virology, or vaccines. In addition, 
cryopreserved samples may be used to perform additional assays to support 
standardization and validation of existing or newly developed methods. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 73 of 166 
10.6 
Specimen storage and other use of specimens 
The CoVPN stores specimens from all study participants indefinitely, unless a 
participant requests that specimens be destroyed or if required by IRB/EC, or RE. 
Other use of specimens is defined as studies not covered by the protocol or the 
informed consent forms for the study (see Appendix A, Appendix B, Appendix C, 
and Appendix D). 
This research may relate to SARS-CoV-2, vaccines, coronaviruses, the immune 
system, and other diseases. This could include genetic testing and, potentially, 
genome-wide studies. This research is done only to the extent authorized in each 
study site’s informed consent form, or as otherwise authorized under applicable 
law. Other research on specimens (“other use”) will occur only after review and 
approval by the CoVPN, the IRB/EC of the researcher requesting the specimens, 
and the IRBs/ECs/REs of the CRSs if required. 
As part of consenting for the study, participants document their initial decision to 
allow or not allow their specimens to be used in other research, and they may 
change their decision at any time. The participant’s initial decision about other 
use of their specimens, and any later change to that decision, is recorded by their 
CRS in a Web-based tool that documents their current decisions for other use of 
their specimens. The CoVPN will only allow other research to be done on 
specimens from participants who allow such use. 
CRSs must notify CoVPN Regulatory Affairs if institutional or local 
governmental requirements pose a conflict with or impose restrictions on 
specimen storage or other use of specimens. 
10.7 
Biohazard containment 
The transmission of blood-borne pathogens can occur through contact with 
contaminated needles, blood, and blood products, and the transmission of SARS-
CoV-2 and other respiratory pathogens may occur through contact with 
contaminated respiratory droplets, aerosols, and other biological materials. 
Appropriate precautions will be employed by all personnel in the collection, 
shipping, and handling of all specimens for this study, as currently recommended 
by local health authorities, the CDC, the NIH, or other applicable agencies. 
All dangerous goods materials, including Biological Substances, Category A or 
Category B, must be transported according to instructions detailed in the 
International Air Transport Association Dangerous Goods Regulations. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 74 of 166 
11 
Safety Reporting  
11.1 
FDA/CDC Vaccine Adverse Event Reporting System (VAERS) 
The Vaccine Adverse Event Reporting System (VAERS) is co-managed by the 
U.S. CDC and FDA and serves as the reporting mechanism for adverse events 
occurring from licensed and EUA vaccines, including the Moderna COVID-19 
vaccine being used in this trial. VAERS accepts and analyzes reports of adverse 
events (AEs) after a person has received a vaccination. It is accessed at 
https://vaers.hhs.gov/reportevent.html. 
Risks associated with receipt of the Moderna COVID-19 Vaccine and AE 
reporting requirements are described in the “Fact Sheet For Healthcare Providers 
Administering Vaccine (Vaccination Providers) Emergency Use Authorization 
(EUA) Of The Moderna COVID-19 Vaccine To Prevent Coronavirus Disease 
2019 (COVID-19)”, available at https://www.modernatx.com/covid19vaccine-
eua/. 
All vaccination providers, including those at the CRS, are required to report to 
VAERS the following adverse events after COVID-19 vaccination, under 
Emergency Use Authorization (EUA), and other adverse events if later revised by 
CDC |(https://www.cdc.gov/vaccines/covid-19/vaccination-provider-support.html 
and https://vaers.hhs.gov/faq.html): 
• Vaccine administration errors, whether or not associated with an adverse 
event (AE) 
• Serious AEs regardless of causality. Serious AEs per FDA are defined as: 
▪ Death; 
▪ A life-threatening AE; 
▪ Inpatient hospitalization or prolongation of existing hospitalization; 
▪ A persistent or significant incapacity or substantial disruption of the ability 
to conduct normal life functions; 
▪ A congenital anomaly/birth defect; 
▪ An important medical event that based on appropriate medical judgement 
may jeopardize the individual and may require medical or surgical 
intervention to prevent one of the outcomes listed above. 
• Cases of Multisystem Inflammatory Syndrome 
• Cases of COVID-19 that result in hospitalization or death 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 75 of 166 
CRS vaccination providers are encouraged to report to VAERS any additional 
clinically significant AEs following vaccination, even if they are not sure if 
vaccination caused the event; and are to report any additional select AEs and/or 
any revised safety reporting requirements per FDA’s conditions of authorized use 
of vaccine(s) throughout the duration of any COVID-19 Vaccine being authorized 
under an EUA.   
CRS vaccination providers will complete and submit reports to VAERS online at 
https://vaers.hhs.gov/reportevent.html. Further assistance with reporting to 
VAERS is accessed by calling 1-800-822-7967. The reports should include the 
words “Moderna COVID- 19 Vaccine EUA” in the description section of the 
report.  
As indicated in the “Fact Sheet For Healthcare Providers Administering Vaccine 
(Vaccination Providers) Emergency Use Authorization (EUA) Of The Moderna 
COVID-19 Vaccine To Prevent Coronavirus Disease 2019 (COVID-19)”, 
vaccination providers (including those at the CRS) are encouraged, to the extent 
feasible, to report adverse events to Moderna. 
11.2 
Reporting safety events to v-safe 
An additional source of VAERS reports will be through a program administered 
by the CDC known as v-safe (https://www.cdc.gov/coronavirus/2019-
ncov/vaccines/safety/vsafe.html). V-safe is a smartphone-based opt-in program 
that uses text messaging and web surveys from CDC to check in with vaccine 
recipients for health problems following COVID-19 vaccination. The system also 
will provide telephone follow-up to anyone who reports medically significant 
(important) adverse events. Responses indicating missed work, inability to do 
normal daily activities, or that the recipient received care from a doctor or other 
healthcare professional will trigger the VAERS Call Center to reach out to the 
participant and collect information for a VAERS report, if appropriate. CRS 
vaccination providers will encourage the study participants receiving the Moderna 
COVID-19 vaccine to use v-safe. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 76 of 166 
12 
Protocol conduct 
This protocol and all actions and activities connected with it will be conducted in 
compliance with the principles of GCP (ICH E6 (R2)), and according to NIAID 
and CoVPN policies and procedures as specified in the CoVPN 3006 SSP, NIAID 
Clinical Research Policies and Standard Procedures Documents including 
procedures for the following: 
• Protocol registration, activation, and implementation; 
• Informed consent, screening, and enrollment; 
• Study participant reimbursement; 
• Clinical and safety assessments; 
• Safety monitoring and reporting; 
• Data collection, documentation, transfer, and storage; 
• Participant confidentiality; 
• Study follow-up and close-out; 
• Unblinding of staff and participants; 
• Quality control; 
• Protocol monitoring and compliance; 
• Specimen collection, processing, and analysis; 
• Exploratory and ancillary studies and sub-studies, and 
• Destruction of specimens. 
Any policies or procedures that vary from NIAID and CoVPN standards or 
require additional instructions (eg, instructions for randomization specific to this 
study) will be described in the CoVPN 3006 SSP. 
12.1 
Study termination 
NIAID reserves the right to terminate or curtail a clinical study for any reason, 
including but not limited to the following (reference: 
https://grants.nih.gov/grants/guide/rfa-files/RFA-AI-12-012.html ): 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 77 of 166 
• risk to subject safety 
• the scientific question is no longer relevant or the objectives will not be met 
(ie, slow accrual) 
• failure to comply with GCP, U.S. Federal regulations, or Terms and 
Conditions of Award 
• occurrence of unforeseen drug safety issues or data from preclinical studies 
indicate a presence of unanticipated toxicity 
• risks that cannot be adequately quantified 
• ethical concerns raised by the local community or local medical care/health 
care authorities 
• failure to remedy deficiencies identified through site monitoring 
• substandard data 
• reaching a major study endpoint substantially before schedule with persuasive 
statistical significance. 
This study may also be terminated early by the determination of the FDA, the 
United States Department of Health and Human Services Office for Human 
Research Protections (OHRP). In addition, the conduct of this study at an 
individual CRS may be terminated by the determination of the IRB/EC and any 
applicable RE. 
12.2 
Emergency communication with study participants 
As in all clinical research, this study may generate a need to reach participants 
quickly to avoid imminent harm, or to report study findings that may otherwise 
concern their health or welfare and their willingness to remain on study. 
When such communication is needed, the CRS will request that its IRB/EC and 
any applicable RE expedite review of the message. If this review cannot be 
completed in a timeframe consistent with the urgency of the required 
communication, the site can contact the participant without IRB/EC approval if 
such communication is necessary to avoid imminent harm to the study participant. 
The CRS must notify the IRB/EC and any applicable RE of the matter as soon as 
possible. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 78 of 166 
13 
Version history 
The Protocol Team may modify the original version of the protocol. 
Modifications are made to CoVPN protocols via clarification memos, letters of 
amendment, or full protocol amendments. 
The version history of, and modifications to, Protocol CoVPN 3006 are described 
below. 
Protocol history and modifications 
Date: May 20, 2021 
Protocol version: Version 4.0 
Protocol modification: Full Protocol Amendment 3 
Item 1 
Revised in Title page, Section 1, Overview, Section 2, Background, Section 
6, Statistical considerations, Section 7.1, Inclusion criteria for main cohort, 
Appendices A, C, and D, Sample informed consent forms, and Appendices 
E-H, Procedures: definition of Main cohort participant expanded to include 
non-student adults aged 18 through 29 
Item 2 
Revised throughout the protocol: delayed vaccination group renamed 
standard of care group 
Item 3 
Added in Section 1, Overview, Section 2, Background, Section 6, 
Statistical considerations, Section 7.1 and 7.2, Inclusion and Exclusion 
criteria for Main Cohort, Immediate Vaccination and Standard of Care 
groups, Section 7.3, Inclusion criteria for Main cohort, Vaccine Declined 
group, Section 7.4, Exclusion criteria for Main cohort, Vaccine Declined 
Group, Section 9, Clinical procedures, Appendix B, Sample informed 
consent form for Main cohort, Vaccine Declined Group, Appendices A, C 
and D, Sample informed consent forms, and Appendix I, Visit windows: 
new observational group, “Vaccine Declined” group, of up to 6000 
participants 
Item 4 
Added in Section 7.2, Exclusion criteria for Main Cohort, Immediate 
Vaccination Group and Standard of Care Group: exclusion for volunteers 
who prefer to be vaccinated immediately 
Item 5 
Revised in Section 1, Overview and Appendices A, C, and D, Sample 
informed consent forms: number of potential participants in close contact 
cohorts increased 
Item 6 
Updated in Section 1, Overview: increased estimated total study duration 
from 7 months to 9 months 
Item 7 
Clarified in Section 2.10, Moderna COVID-19 Vaccine, and Section 8.3, 
Acquisition of Moderna COVID-19 Vaccine: participants may also access 
Moderna COVID-19 EUA vaccine via other sources 
Item 8 
Revised in Section 3, Objectives and endpoints and Section 6, Statistical 
considerations: inclusion of all SARS-CoV-2 infection events in analysis 
for primary endpoints and secondary endpoints 1-5 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 79 of 166 
Item 9 
Revised in Section 3, Objectives and endpoints, exploratory objective 1: 
expanded to main study cohort 
Item 10 Revised in Section 7.1, Inclusion criteria for Main Cohort, Immediate 
Vaccination Group and Standard of Care Group: timing of completion of 
assessment of understanding 
Item 11 Revised in Sections 7.1, 7.3, 7.5, and 7.6, Inclusion criteria for all groups: 
access to device and internet is needed for completion of study procedures 
Item 12 Added in Section 8, Study product: definitions of on-study and outside of 
study vaccination 
Item 13 Clarified in Section 8, Study product: study allocated vaccine can only be 
administered to study participants 
Item 14 Added in Section 8.3, Acquisition of Moderna COVID-19 Vaccine: 
participants can access Moderna COVID-19 EUA vaccine via other sources 
for on-study vaccinations if the administration fee is either paid for by the 
study or is not billed to any party 
Item 15 Deleted from Section 9.3, Enrollment and vaccination visits for Main 
Cohort, Immediate Vaccination Group and Section 9.6, Month 4 (visit 5) 
and Month 5 (visit 6) Visits for Main Cohort, Standard of Care Group and 
Vaccine Declined Group: parenthetical reference to temperature in COVID-
19 symptom check 
Item 16 Added in Section 9, Clinical Procedures, and Appendix F, Procedures for 
Main Cohort, Standard of Care and Vaccine Declined Groups: end of study 
questionnaires as procedures 
Item 17 Added in Section 9.1.2, Protocol-specific consent forms: consent forms for 
close contact cohorts may be managed centrally by the CoVPN 
Item 18 Clarified in Section 9.15, COVID-19 symptom surveillance for Main 
Cohort: symptom overlap between COVID-19 and vaccination is only 
applicable to Immediate Vaccination Group 
Item 19 Corrected in Appendix A, Sample informed consent form for the Main 
cohort, Immediate Vaccination and Standard of Care Groups, Appendix C, 
Sample informed consent form for Prospective Close Contact (PCC) cohort 
and Appendix D, Sample informed consent form for Case-Ascertained 
Close Contact (CACC) cohort: frequency of eDiary entries. 
Item 20 Added in Appendix A, Sample informed consent form for the Main cohort, 
Immediate Vaccination and Standard of Care Groups: we may ask Main 
cohort participants to provide contact information for potential close 
contact cohort volunteers 
Item 21 Clarified in Appendix A, Sample informed consent form for the Main 
cohort, Immediate Vaccination and Standard of Care Groups: Month 4 will 
be the last study visit for Standard of Care participants who receive 
COVID-19 vaccine outside the study prior to Month 4 
Item 22 Added in Appendix A, Sample informed consent form for the Main cohort, 
Immediate Vaccination and Standard of Care Groups: the risk of delaying 
COVID-19 vaccination 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 80 of 166 
Item 23 Added in Appendix C, Sample informed consent form for Prospective 
Close Contact (PCC) cohort and Appendix D, Sample informed consent 
form for Case-Ascertained Close Contact (CACC) cohort: new section 
“Risks of COVID-19” 
Item 24 Deleted from Appendices A, C and D, Sample informed consent forms: 
sentence that states we will not share your name or identifying information 
with the CoVPN 
Item 25 Clarified in Appendix A, Sample informed consent form for the Main 
cohort, Immediate Vaccination and Standard of Care Groups: benefits of 
COVID-19 vaccination 
Item 26 Added in Appendices A, C, and D, Sample informed consent forms: 
participants will be prompted to scan the barcode on nasal swabs 
Item 27 Updated in Appendices A, C, and D, Sample informed consent forms: 
recommendation to follow federal, state, and local guidelines for SARS-
CoV-2 prevention 
Item 28 Updated in Appendices A, C, and D, Sample informed consent forms: 
contact information for Advarra IRB 
Item 29 Updated in Appendix A, Sample informed consent form for the Main 
cohort, Immediate Vaccination and Standard of Care Groups: Moderna 
COVID-19 Vaccine, risks and number of vaccinated people 
Item 30 Updated Title page and Section 13, Version history: contents of this 
amendment 
Item 31 Throughout the protocol: minor editorial changes, clarifications, and 
corrections 
Date: April 12, 2021 
Protocol version: 3.0 
Protocol modification: Full protocol amendment 2 
Item 1 
Added in Section 1, Overview and Section 6, Statistical considerations: 
Clinical Research Sites (CRSs) that can participate in the study expanded to 
include non-university affiliated CoVPN Clinical Research Sites (CRSs) 
Item 2 
Revised in Section 1, Overview, Section 2, Background, Section 6, 
Statistical considerations, Section 7.1, Inclusion criteria for main cohort, 
Section 9, Clinical procedures, and Appendix A, Sample informed consent 
form for the Main cohort: definition of participant expanded to include 
students enrolled in any post-secondary educational institution 
Item 3 
Revised in Section 1, Overview, Section 2, Background, Section 6, 
Statistical considerations, Section 7.3, Inclusion criteria for Prospective 
Close Contact (PCC) cohort, Section 9, Clinical procedures, and 
Appendices A, B, D, E, F: University SARS-CoV-2 testing is not required 
Item 4 
Revised in Section 9.3, Enrollment and vaccination visits for Main Cohort, 
Immediate Vaccination Group, Section 9.5, Enrollment (visit 2) and visit 4 
(Month 2) for Main Cohort, Delayed Vaccination Group and Appendix H, 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 81 of 166 
Visit windows: maximum recommended time between randomization and 
completion of Visit 2 activities increased from 4 days to 7 days 
Item 5 
Clarified in Section 2, Background, Section 6, Statistical considerations, 
and Section 9.7, Procedures for Main Cohort participant diagnosed with a 
SARS-CoV-2 infection during the study: any SARS-CoV-2 test result 
indicative of acute infection (on or off study) obtained from a Main cohort 
participant will trigger “index-case” activities 
Item 6 
Clarified in Section 2, Background, Section 6.4.3, Vaccine efficacy (VE) 
analyses against SARS-CoV-2 infection, Section 7.1, Inclusion criteria for 
main cohort, Section 9, Clinical procedures, Appendix A, Sample informed 
consent form for Main cohort, and Appendix B, Sample informed consent 
form for Prospective Close Contact (PCC) cohort: participants can choose 
to obtain an EUA or licensed COVID-19 vaccine outside the study 
Item 7 
Added to Section 3, Objectives and endpoints: 2 endpoints for the duration 
of viral shedding specified in corresponding secondary objective 4 
Item 8 
Clarified in Section 6, Statistical considerations, 7th paragraph: primary 
analysis occurs when participants complete 4 months of follow-up 
Item 9 
Clarified in Table 6-1, Study analysis sets and definitions: Day 29 is visit 3 
for immediate vaccination arm and will be define in Statistical analysis plan 
(SAP) for delayed vaccination arm 
Item 10 Revised in Section 6.3, Randomization: randomization evaluated within 
levels defined by study site and type of residence 
Item 11 Clarified in Section 6.4.3.1, Primary VE Analysis: rationale for choice of 
analysis 
Item 12 Revised in Section 6.4.5.2, Analyses of the vaccine effect on secondary 
transmission: details of the derivation 
Item 13 Revised in Section 7.2, Exclusion criterion #1 for Main Cohort: removed 
febrile assessment 
Item 14 Clarified in Section 2.10, Moderna COVID-19 Vaccine, and Section 8.3, 
Acquisition of Moderna COVID-19 Vaccine: Moderna COVID-19 Vaccine 
provided under EUA and allocated for this trial 
Item 15 Corrected in Section 9, Clinical procedures: CRS staff will obtain informed 
consent of participants according to the COVPN 3006 SSP 
Item 16 Corrected in Appendix A, Sample informed consent form for Main cohort: 
blood will be collected 3 times for delayed vaccination arm 
Item 17 Added to Appendix B, Sample informed consent form for Prospective 
Close Contact (PCC) cohort: COVID-19 care is not paid for by the study 
Item 18 Added to Appendices A, B, C, Sample informed consent forms: information 
regarding employee/family member participation 
Item 19 Added to Appendices A, B, C, Sample informed consent forms: terms of 
use for data collection via web-based app 
Item 20 Deleted in Appendix B, Sample informed consent form for Prospective 
Close Contact (PCC) cohort, and Appendix C, Sample informed consent 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 82 of 166 
form for Case-Ascertained Close Contact (CACC) cohort, item 8: text 
referring to vaccine receipt 
Item 21 Added to Appendix H, Visit windows for CACC: upper allowable window 
for blood specimen collection 
Item 22 Added changes per Protocol v 2.0, Letter of Amendment 1 
Item 23 Updated Title page and Section 13, Version history: contents of this 
amendment 
Item 24 Updated Section 1.1, Protocol team: deletion of Site Principal Investigator 
representative 
Item 25 
Throughout the protocol: minor editorial changes, clarifications, and 
corrections 
Date: March 10, 2021 
Protocol version: Version 2.0 
Protocol modification: Letter of Amendment 1 
Item 1 
Added in Section 10.1, CRS laboratory procedures, Appendices A, B, and 
C, Sample informed consent forms: return of SARS-CoV-2 nasal swab 
testing results to participants 
Item 2 
Added to Section 1.1, Protocol team: Jasmine Marcelin, co-chair and 
Jeffrey L Carson, Site Principal Investigator representative 
Date: February 26, 2021 
Protocol version: 2.0 
Protocol modification: Full protocol amendment 1 
Item 1 
Revised in Section 3, Objective and Endpoints, Section 6, Statistical 
considerations, Section 9, Clinical procedures, Appendix A, Sample 
informed consent form for the main cohort, and Appendices D and E, 
Procedures for the main cohort: Month 3 visit removed for both Main 
cohort groups, M1 visit removed for delayed vaccination group of Main 
cohort, and Month 1 blood collection removed for immediate vaccination 
group of Main cohort 
Item 2 
Added in Section 1, Overview: 2 new endpoint laboratories 
Item 3 
Updated in Section 1.1, Protocol team: team members 
Item 4 
Deleted Section 6.1, Accrual restrictions: no accrual restrictions for this 
study 
Item 5 
Revised in Section 6.4, Statistical analyses: minor clarifying text revisions 
Item 6 
Corrected in Section 6.4.4.7, VL analyses, 3rd paragraph: reference to 
secondary endpoint number 
Item 7 
Deleted in Section 9.3, Enrollment and vaccination visits for Main Cohort, 
Immediate Vaccination Group and Section 9.5, Enrollment (visit 2) and 
visit 4 (Month 2) for Main Cohort, Delayed Vaccination Group: sentence 
regarding clinical lab results 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 83 of 166 
Item 8 
Added in Section 9.15, Use of electronic Diary (eDiary) for Clinical 
Outcomes Assessments, and Appendices F through G, Procedures: end of 
study questionnaire regarding COVID vaccines received outside the study 
Item 9 
Added in Appendices A, B, and C, Sample informed consent forms, section 
“Being in the study”: participants will take an end of study questionnaire 
Item 10 Added in Appendix B, Sample informed consent form for Prospective 
Close Contact (PCC) cohort, and Appendix C, Sample informed consent 
form for Case-Ascertained Close Contact (CACC) cohort, section “Being 
in the study”: applicable participants will receive SARS-CoV-2 screening 
at the University about two times per week. 
Item 11 Deleted in Appendices A, B, and C, Sample informed consents, second 
sentence: reference to alternate study name of “vPROTECT” 
Item 12 Added in Appendix A, Sample informed consent form for the main cohort: 
additional information for participant regarding text or email reminders for 
nasal swabs 
Item 13 Deleted in Appendices A, B and C, Sample informed consents: reference to 
“electronically” for signature 
Item 14 Deleted in Appendices A, B and C, Sample informed consents, signature 
table: column for denoting time of signature 
Item 15 Deleted in Appendix A, Sample informed consent form for the main cohort, 
section 8: redundant information 
Item 16 Corrected in in Appendix A, Sample informed consent form for the main 
cohort, section10: VAERS reporting requirements 
Item 17 Revised in Appendices F and G: table text and associated footnotes 
Item 18 Revised Appendix H, Visit windows, Case-Ascertained Close Contact 
(CACC) cohort, to include applicable Prospective Close Contact  (PCC) 
participants who test positive for SARS-CoV-2 or whose Main Cohort 
study contact tests positive for SARS-CoV-2 
Item 19 Revised throughout protocol: minor grammatical, editorial, and formatting 
corrections. 
Item 20 Updated Title page, Table of Contents, Section 13, Version history, and 
Appendix I, Protocol signature page: dates, version number, and contents 
of this amendment 
Date: February 17, 2021 
Protocol version:1.0 
Protocol modification: Not applicable 
Original protocol 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 84 of 166 
14 
Document references (other than literature 
citations) 
Other documents referred to in this protocol, and containing information relevant 
to the conduct of this study, include: 
• Assessment of Understanding. Accessible through the CoVPN protocol-
specific website. 
• CDC COVID-19 Vaccination Program Provider Requirements and Support. 
Available at https://www.cdc.gov/vaccines/covid-19/vaccination-provider-
support.html 
• CoVPN Certificate of Confidentiality. Accessible through the CoVPN 
website. 
• CoVPN 3006 Study Specific Procedures. Accessible through the CoVPN 
protocol-specific website. 
• Dangerous Goods Regulations (updated annually), International Air Transport 
Association. Available for purchase at 
https://www.iata.org/publications/dgr/Pages/index.aspx 
• International Council on Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) E6 (R2), Guideline for Good Clinical 
Practice: Section 4.8, Informed consent of trial subjects. Available at 
http://www.ich.org/page/efficacy-guidelines 
• Laboratory Center assay portfolio 
• Moderna COVID-19 Vaccine EUA Fact Sheet and Full PI for Vaccination 
Providers. Available at https://www.modernatx.com/covid19vaccine-eua/. 
• Participants’ Bill of Rights and Responsibilities. Accessible through the 
CoVPN protocol-specific website. 
• NIH Policy on Reporting Race and Ethnicity Data: Subjects in Clinical 
Research. Available at https://grants.nih.gov/grants/guide/notice-files/NOT-
OD-01-053.html 
• Title 21, Code of Federal Regulations, Part 50. Available at 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFR
Part=50 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 85 of 166 
• Title 45, Code of Federal Regulations, Part 46 (2018 requirements). Current 
requirements available at https://www.hhs.gov/ohrp/regulations-and-
policy/regulations/45-cfr-46/index.html 
• VAERS, Vaccine Adverse Event Reporting System. Available at 
https://vaers.hhs.gov/reportevent.html 
• VAERS, Vaccine Adverse Event Reporting System FAQ. Available at 
https://vaers.hhs.gov/faq.html 
• V-safe After Vaccination Health Checker. Available at 
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/vsafe.html 
See Section 16 for literature cited in the background and statistics sections of this 
protocol. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 86 of 166 
15 
Acronyms and abbreviations 
Ab 
 
antibody 
ACIP 
 
Advisory Committee on Immunization Practices 
AE 
 
adverse event 
AUC 
 
area under the curve 
BAMA 
 
binding antibody multiplex assay 
CAB 
 
Community Advisory Board 
CDC 
 
US Centers for Disease Control and Prevention 
CFR 
 
Code of Federal Regulations 
CI 
 
confidence intervals 
COVID-19 
Coronavirus disease 2019 
CoVPN 
 
COVID-19 Prevention Network 
CRF 
 
case report form 
CRPMC 
 
NIAID Clinical Research Products Management Center 
CRS 
 
clinical research site 
DAIDS 
 
Division of AIDS (US NIH) 
DHHS 
 
US Department of Health and Human Services 
EAE 
 
adverse events requiring expedited reporting  
EC 
 
Ethics Committee 
eDiary 
 
Electronic diary 
ELISA 
 
enzyme-linked immunosorbent assay 
EUA 
 
emergency use authorization 
FAS 
 
Full analysis set 
FDA 
 
US Food and Drug Administration 
Fred Hutch 
Fred Hutchinson Cancer Research Center 
GCP 
 
Good Clinical Practice 
GMT 
 
geometric mean titer 
HIPAA 
 
Health Insurance Portability and Accountability Act 
HIV 
 
human immunodeficiency virus 
IB 
 
Investigator’s Brochure 
IBC 
 
Institutional Biosafety Committee 
ICH 
 
International Council on Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
IQR 
 
Interquartile range 
IDMC 
 
Independent Data Monitoring Committee 
IM 
 
Intramuscular 
IRB 
 
Institutional Review Board 
LC 
 
Laboratory Center 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 87 of 166 
LNP 
 
Lipid nanoparticle 
LOC 
 
Leadership and Operations Center 
mRNA 
 
Messenger ribonucleic acid 
nAb 
 
neutralizing antibody 
NHP 
 
nonhuman primate 
NIAID 
 
National Institute of Allergy and Infectious Diseases (US NIH) 
NIH 
 
US National Institutes of Health 
OHRP 
 
US Office for Human Research Protections 
PCR 
 
polymerase chain reaction 
PI 
 
Principal Investigator 
RE 
 
regulatory entity 
SAP 
 
Statistical Analysis Plan 
SCHARP  
Statistical Center for HIV/AIDS Research and Prevention 
SDMC 
 
statistical and data management center 
SSP 
 
Study specific procedures 
SOP 
 
Standard operating procedure 
UW-VL 
 
University of Washington Virology Laboratory 
UW-VSL  
University of Washington Virology Specialty Laboratory 
VAERS 
 
Vaccine Adverse Event Reporting System 
VE 
 
Vaccine efficacy 
VEI 
 
Vaccine efficacy against infectiousness 
VEs 
 
Vaccine efficacy against susceptibility 
VL 
 
Viral load 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 88 of 166 
16 
Literature cited 
1. Johns Hopkins Coronavirus Resource Center. 2020 [Available from: 
https://coronavirus.jhu.edu/map.html. 
2. Lipsitch M, Dean NE. Understanding COVID-19 vaccine efficacy. Science. 
2020. 
3. Mehrotra DV, Janes HE, Fleming TR, Annunziato PW, Neuzil KM, Carpp 
LN, et al. Clinical Endpoints for Evaluating Efficacy in COVID-19 Vaccine 
Trials. Ann Intern Med. 2020. 
4. Long QX, Tang XJ, Shi QL, Li Q, Deng HJ, Yuan J, et al. Clinical and 
immunological assessment of asymptomatic SARS-CoV-2 infections. Nat 
Med. 2020;26(8):1200-4. 
5. Salvatore PP, Sula E, Coyle JP, Caruso E, Smith AR, Levine RS, et al. 
Recent Increase in COVID-19 Cases Reported Among Adults Aged 18-22 
Years - United States, May 31-September 5, 2020. MMWR Morb Mortal 
Wkly Rep. 2020;69(39):1419-24. 
6. Boehmer TK, DeVies J, Caruso E, van Santen KL, Tang S, Black CL, et al. 
Changing Age Distribution of the COVID-19 Pandemic - United States, 
May-August 2020. MMWR Morb Mortal Wkly Rep. 2020;69(39):1404-9. 
7. CDC: Centers for Disease Control and Prevention. COVID-19 
Hospitalization and Death by Age 2020 [Available from: 
https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-
discovery/hospitalization-death-by-age.html. 
8. Halloran ME, Longini IM, Jr., Struchiner CJ. Design and interpretation of 
vaccine field studies. Epidemiol Rev. 1999;21(1):73-88. 
9. Swan DA, Goyal A, Bracis C, Moore M, Krantz E, Brown E, et al. Vaccines 
that prevent SARS-CoV-2 transmission may prevent or dampen a spring 
wave of COVID-19 cases and deaths in 2021. medRxiv. 2020. 
10. Swan DA, Bracis C, Janes H, Moore M, Matrajt L, Reeves DB, et al. 
COVID-19 vaccines that reduce symptoms but do not block infection need 
higher coverage and faster rollout to achieve population impact. medRxiv. 
2020. 
11. Datta S, Halloran ME, Longini IM, Jr. Efficiency of estimating vaccine 
efficacy for susceptibility and infectiousness: randomization by individual 
versus household. Biometrics. 1999;55(3):792-8. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 89 of 166 
12. Milani GP, Dioni L, Favero C, Cantone L, Macchi C, Delbue S, et al. 
Serological follow-up of SARS-CoV-2 asymptomatic subjects. Sci Rep. 
2020;10(1):20048. 
13. Piccoli L, Park YJ, Tortorici MA, Czudnochowski N, Walls AC, Beltramello 
M, et al. Mapping Neutralizing and Immunodominant Sites on the SARS-
CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-
Resolution Serology. Cell. 2020;183(4):1024-42 e21. 
14. Vaccines and Related Biological Products Advisory Committee Meeting. 
Sponsor Briefing Document, Moderna COVID-19 Vaccine 2020 [Available 
from: https://www.fda.gov/media/144452/download. 
15. Vaccines and Related Biological Products Advisory Committee Meeting. 
Sponsor Briefing Document Addendum,Moderna COVID-19 Vaccine 2020 
[Available from: https://www.fda.gov/media/144453/download. 
16. Flood S, King M, Rodgers R, Ruggles S, Warren J. Integrated Public Use 
Microdata Series, Current Population Survey: version 7.0 [dataset]. 2020. 
17. The New York Times. Tracking the Coronavirus at U.S. Colleges and 
Universities 2020 [Available from: 
https://www.nytimes.com/interactive/2020/us/covid-college-cases-
tracker.html. 
18. Business Insider. The 10 biggest coronavirus outbreaks on college campuses 
across the US since the fall semester began 2020 [Available from: 
https://www.businessinsider.com/10-colleges-with-fall-coronavirus-
outbreaks-1200-cases-or-more-2020-9. 
19. Wilson E, Donovan CV, Campbell M, Chai T, Pittman K, Sena AC, et al. 
Multiple COVID-19 Clusters on a University Campus - North Carolina, 
August 2020. MMWR Morb Mortal Wkly Rep. 2020;69(39):1416-8. 
20. Buitrago-Garcia D, Egli-Gany D, Counotte MJ, Hossmann S, Imeri H, Ipekci 
AM, et al. Occurrence and transmission potential of asymptomatic and 
presymptomatic SARS-CoV-2 infections: A living systematic review and 
meta-analysis. PLoS Med. 2020;17(9):e1003346. 
21. Goyal A, Reeves DB, Cardozo-Ojeda EF, Schiffer JT, Mayer BT. Wrong 
person, place and time: viral load and contact network structure predict 
SARS-CoV-2 transmission and super-spreading events. medRxiv. 2020. 
22. He X, Lau EHY, Wu P, Deng X, Wang J, Hao X, et al. Temporal dynamics 
in viral shedding and transmissibility of COVID-19. Nat Med. 
2020;26(5):672-5. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 90 of 166 
23. Tindale LC, Stockdale JE, Coombe M, Garlock ES, Lau WYV, Saraswat M, 
et al. Evidence for transmission of COVID-19 prior to symptom onset. Elife. 
2020;9. 
24. Kissler SM, Fauver JR, Mack C, Tai C, Shiue KY, Kalinich CC, et al. Viral 
dynamics of SARS-CoV-2 infection and the predictive value of repeat 
testing. medRxiv. 2020. 
25. CDC: Centers for Disease Control and Prevention. Scientific Brief: 
Community Use of Cloth Masks to Control the Spread of SARS-CoV-2 2020 
[Available from: https://www.cdc.gov/coronavirus/2019-ncov/more/masking-
science-sars-cov2.html. 
26. Jung CY, Park H, Kim DW, Choi YJ, Kim SW, Chang TI. Clinical 
Characteristics of Asymptomatic Patients with COVID-19: A Nationwide 
Cohort Study in South Korea. Int J Infect Dis. 2020;99:266-8. 
27. Poteat T, Millett GA, Nelson LE, Beyrer C. Understanding COVID-19 risks 
and vulnerabilities among black communities in America: the lethal force of 
syndemics. Ann Epidemiol. 2020;47:1-3. 
28. Davies NG, Klepac P, Liu Y, Prem K, Jit M, group CC-w, et al. Age-
dependent effects in the transmission and control of COVID-19 epidemics. 
Nat Med. 2020;26(8):1205-11. 
29. Richmond CS, Sabin AP, Jobe DA, Lovrich SD, Kenny PA. SARS-CoV-2 
sequencing reveals rapid transmission from college student clusters resulting 
in morbidity and deaths in vulnerable populations. medRxiv. 2020. 
30. Regeneron Pharmaceuticals. Regeneron's REGN-CoV2 antibody cocktail 
reduced viral levels and improved symptoms in non-hospitalized COVID-19 
patients 2020 [Available from: https://newsroom.regeneron.com/news-
releases/news-release-details/regenerons-regn-cov2-antibody-cocktail-
reduced-viral-levels-and. 
31. Chen P, Nirula A, Heller B, Gottlieb RL, Boscia J, Morris J, et al. SARS-
CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. N 
Engl J Med. 2020. 
32. Heneghan C, Brassey J, Jefferson T. SARS-CoV-2 viral load and the severity 
of COVID-19. The Centre for Evidence-Based Medicine. 2020. 
33. Pujadas E, Chaudhry F, McBride R, Richter F, Zhao S, Wajnberg A, et al. 
SARS-CoV-2 viral load predicts COVID-19 mortality. Lancet Respir Med. 
2020;8(9):e70. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 91 of 166 
34. Westblade LF, Brar G, Pinheiro LC, Paidoussis D, Rajan M, Martin P, et al. 
SARS-CoV-2 Viral Load Predicts Mortality in Patients with and without 
Cancer Who Are Hospitalized with COVID-19. Cancer Cell. 2020;38(5):661-
71 e2. 
35. Letizia AG, Ramos I, Obla A, Goforth C, Weir DL, Ge Y, et al. SARS-CoV-
2 Transmission among Marine Recruits during Quarantine. N Engl J Med. 
2020. 
36. Datta S, Halloran ME, Longini IM, Jr. Augmented HIV vaccine trial design 
for estimating reduction in infectiousness and protective efficacy. Stat Med. 
1998;17(2):185-200. 
37. Halloran ME, Struchiner CJ. Causal inference in infectious diseases. 
Epidemiology. 1995;6(2):142-51. 
38. Yang Y, Longini IM, Jr., Halloran ME. Design and Evaluation of 
Prophylactic Interventions Using Infectious Disease Incidence Data from 
Close Contact Groups. J R Stat Soc Ser C Appl Stat. 2006;55(3):317-30. 
39. Klick B, Leung GM, Cowling BJ. Optimal design of studies of influenza 
transmission in households. I: case-ascertained studies. Epidemiol Infect. 
2012;140(1):106-14. 
40. Barnabas RV, Brown ER, Bershteyn A, Stankiewicz Karita HC, Johnston C, 
Thorpe LE, et al. Hydroxychloroquine as Postexposure Prophylaxis to 
Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A 
Randomized Trial. Ann Intern Med. 2020. 
41. Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler 
RN, et al. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N 
Engl J Med. 2020. 
42. Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene 
M, et al. Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine 
in Older Adults. N Engl J Med. 2020;383(25):2427-38. 
43. Vaccines and Related Biological Products Advisory Committee Meeting. 
FDA Briefing Document, Moderna COVID-19 Vaccine 2020 [Available 
from: https://www.fda.gov/media/144434/download. 
44. UNAIDS. Ethical considerations in biomedical HIV prevention trials. 2007 
7/2007. 
45. The National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research. The Belmont Report: Ethical Principles 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 92 of 166 
and Guidelines for the Protection of Human Subjects of Research. 1979 
4/18/1979. 
46. Council for International Organizations of Medical Sciences (CIOMS). 
International ethical guidelines for biomedical research involving human 
subjects. Bull Med Ethics. 2002(182):17-23. 
47. Sun K, Wang W, Gao L, Wang Y, Luo K, Ren L, et al. Transmission 
heterogeneities, kinetics, and controllability of SARS-CoV-2. Science. 
2021;371(6526). 
48. Li F, Li YY, Liu MJ, Fang LQ, Dean NE, Wong GWK, et al. Household 
transmission of SARS-CoV-2 and risk factors for susceptibility and 
infectivity in Wuhan: a retrospective observational study. Lancet Infect Dis. 
2021. 
49. Madewell ZJ, Yang Y, Longini IM, Jr, Halloran ME, Dean NE. Household 
Transmission of SARS-CoV-2: A Systematic Review and Meta-analysis. 
JAMA Network Open. 2020;3(12):e2031756-e. 
50. Kissler SM, Fauver JR, Mack C, Olesen SW, Tai C, Shiue KY, et al. SARS-
CoV-2 viral dynamics in acute infections. medRxiv. 2020. 
51. Grambsch PM, Therneau TM. Proportional Hazards Tests and Diagnostics 
Based on Weighted Residuals. Biometrika. 1994;81(3):515-26. 
52. Hernan MA. The hazards of hazard ratios. Epidemiology. 2010;21(1):13-5. 
53. Follmann D, Huang CY. Incorporating founder virus information in vaccine 
field trials. Biometrics. 2015;71(2):386-96. 
54. Lin DY. Proportional means regression for censored medical costs. 
Biometrics. 2000;56(3):775-8. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 93 of 166 
Appendix A 
Sample informed consent form for Main 
cohort, Immediate Vaccination and Standard of 
Care Groups 
 
Sponsor / Study Title: 
  
National Institutes of Health, “A randomized controlled study to 
assess SARS CoV-2 infection, viral shedding, and subsequent 
potential transmission in individuals immunized with Moderna 
COVID-19 Vaccine” 
Protocol Number: 
 
CoVPN 3006 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
Thank you for your interest in our research study. It is called CoVPN 3006. This 
informed consent form will tell you more about the study. Please read it carefully 
as you decide if you want to join. If you have questions, please ask us. At the end, 
we will ask you to answer a few questions to make sure you understand the study.  
If you decide to join this study, we will ask you to sign this form. We will offer 
you a copy of this form to keep.  
CoVPN 3006 is a research study. Research is not the same as medical care. The 
purpose of a research study is to answer scientific questions. We hope that what 
we learn will help people in the future. 
Key information 
• Joining this research study is voluntary. It is your choice. 
• Our scientific questions are: Does the vaccine protect people from getting 
infected with a coronavirus called SARS-CoV-2? Does the vaccine prevent 
people from transmitting SARS-CoV-2 to others? 
• If you join, your participation in this study will last for about 5 months. 
• If you join, we will ask you to answer questionnaires, get injections, give 
blood, and take daily swabs of your nose.  
Here are the risks of taking part: 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 94 of 166 
• The most common risk is symptoms such as muscle aches or headaches after 
getting the injection. 
• There is a risk of loss of your personal information.   
• There are other, less serious risks. We will tell you more about them later in 
this consent form. 
About the study 
The COVID-19 Prevention Network (CoVPN) is doing a study to test a vaccine 
against SARS-CoV-2. SARS-CoV-2 is the virus that causes the disease called 
COVID-19. We want to know if the vaccine is able to protect people from getting 
infected and if getting the vaccine will affect the amount of virus that is in your 
nose. We also want to know if getting the vaccine will prevent transmitting 
SARS-CoV-2 to others.  
Many young adults will take part in this study around the US. This study has 5 
groups. The first 3 groups, called the Immediate Vaccination, Standard of Care, 
and Vaccine Declined groups, will be in the Main Study.  
• The Immediate Vaccination and Standard of Care groups will have about 
12,000 people that will get vaccine injections either immediately or 4 
months later. In this study, “standard of care” refers to all federal, state, 
and local recommendations regarding COVID-19 prevention, including 
COVID-19 vaccination, masking, social distancing, isolation and 
quarantine. 
• The Vaccine Declined group will have about 6,000 people who prefer not 
to be vaccinated and will be followed for 4 months.  
• The last two groups are close contacts of the Main Study: the Prospective 
Close Contact (PCC) group will have up to 36,000 people, and the Case-
ascertained Close Contact (CACC) group will have up to 2250 people. 
These close contact groups will help researchers determine if the vaccine 
prevents transmission of the SARS-CoV-2 virus to others. We will explain 
more about this later in this form.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 95 of 166 
You have indicated that you are agreeable to getting vaccinated for COVID-19 as 
recommended by the Centers for Disease Control and Prevention (CDC) and have 
no preference as to the timing of vaccination. 
The researcher in charge of this study at this clinic is [Insert name of site PI]. The 
US National Institutes of Health is paying for this study.  
1. This study’s vaccine has an Emergency Use Authorization (EUA) for 
individuals 18 and older. 
The vaccine we will use in this study is called the Moderna COVID-19 Vaccine. 
The vaccine has been given to over 15,000 people in other research studies and 
over 100 million people under EUA. We will give you the most up-to-date “Fact 
Sheet for Recipients and Caregivers” with more information about the Moderna 
COVID-19 Vaccine. The person giving you the vaccine can answer any questions 
you might have about what is in this fact sheet.  
We already know that the vaccine can prevent serious COVID-19 disease, but we 
do not know if the vaccine will work to prevent SARS-CoV-2 infection in others. 
That is what we are testing in this study.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 96 of 166 
The Moderna COVID-19 Vaccine is not approved for sale in the United States by 
the US Food and Drug Administration (FDA).  
Although the vaccine is not approved, it has an Emergency Use Authorization 
(EUA) from the FDA based on its success at preventing disease symptoms from 
SARS-CoV-2 in other studies to date. During a public health emergency, like the 
COVID-19 pandemic, the FDA can issue an EUA to get vaccines to people faster. 
When the FDA issues an EUA, they continue to monitor safety.  
The vaccine was developed by ModernaTX, Inc. Typical vaccines for viruses are 
made from a weakened or killed virus, but the Moderna COVID-19 Vaccine is not 
made from the SARS-CoV-2 virus. The vaccine includes a short segment of 
messenger ribonucleic acid (mRNA). The mRNA is a genetic code that tells cells 
how to make a protein. This mRNA is made in a laboratory. When injected into 
the body, the mRNA vaccine causes some cells to make that viral protein, which 
can trigger the immune system. Your immune system protects you from disease. 
If a person is later infected, their immune system remembers the protein from the 
vaccine which may help it to fight the virus. It is impossible for the vaccine to 
give you SARS-CoV-2 or COVID-19 infection.  
Risks of the Moderna COVID-19 Vaccine: 
To date, more than 100 million people have already received the Moderna 
COVID-19 Vaccine. In clinical trials, most people who got the vaccine had some 
reaction after their injections, especially after the second injection. The reaction to 
the vaccine didn’t affect their daily lives and it went away after two or three days. 
Most of these people said they had pain in the arm where they got the injection. 
These people also felt tired, had headaches, muscle and joint pain, and chills. A 
much smaller number of these people said they had redness or swelling where the 
needle went in their arm. Some people had swelling of the lymph nodes in the 
same arm of the injection. 
The risks of the study vaccine seen so far are the same as what have been seen 
with most vaccines. Generally, vaccines can cause fever, chills, rash, aches and 
pains, nausea, headache, dizziness, and feeling tired. Vaccines can also cause 
pain, redness, swelling, or itching where you got the injection. Most people can 
still do their planned activities after getting a vaccine. Rarely, people have side 
effects that limit their normal activities or make them go to the doctor. 
Rarely, a vaccine can cause you to have an allergic reaction. You might have a 
rash, hives, swelling of your face and throat, a fast heartbeat, dizziness and 
weakness, or trouble breathing. Allergic reactions can be life-threatening. Tell us 
if you have ever had a bad reaction to any injection or vaccine. 
There may be other risks that we don’t yet know about, even serious ones. We 
will tell you if we learn about any new risks. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 97 of 166 
Joining the study 
2. You will receive the vaccine immediately or later. 
Some people will get the study vaccine immediately. Other people will get the 
study vaccine 4 months later.  
We will compare the results from people who got the vaccine immediately with 
results from people who got the vaccine later. In this way, we will be able to tell if 
the vaccine can prevent SARS-CoV-2 infection.  
You have a 50/50 chance of getting the vaccine immediately or later. Whether 
you get the vaccine immediately or a little later is completely random, like 
flipping a coin. 
We have no say in whether you get the vaccine immediately or later.  
3. It is completely up to you whether or not to join this study. 
Take your time in deciding. If it helps, talk to people you trust, such as your 
doctor, friends, or family. If you decide not to join this study, or if you leave it 
after you have joined, it will not change your healthcare. If you do join, you do 
not give up your legal rights.  
You cannot be in this study while you are in another study where you get a study 
product.  
If you choose not to join this study, you may be able to join another study.  
If you have a preference to be vaccinated immediately, you have the option to not 
join the study and instead receive vaccination outside of the study right away.  
If you have a preference to not be vaccinated at all, you have the option to join the 
“Vaccine Declined” observational group. 
If you are an employee or relative of an employee of the study site, you are under 
no obligation to participate in this study. You may withdraw from the study at any 
time and for any reason, and your decision will not have any effect on your/your 
family member’s performance appraisal or employment at the study site. You 
may refuse to participate or you may withdraw from the study at any time without 
penalty or anyone blaming you. 
If you are a student, your participation will not place you in good favor with the 
study doctor or other faculty (for example, receiving better grades, 
recommendations, employment). Also, not participating in this study will not 
adversely affect your relationship with the study doctor or other faculty. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 98 of 166 
4. If you want to join this study, after you sign this consent, you will download 
an electronic diary (eDiary) app and take questionnaires in it. 
We will send you information about how to download the eDiary app onto your 
phone or tablet. We can help you download the app and show you how to use it.  
To find out if you are eligible to join the study, you will answer questionnaires in 
the eDiary. Some of the questions will ask about your health history, what 
medications you take, your age, race, and ethnicity, and where you live. Your 
answers will tell us about some aspects of your health and if you may be eligible 
to join the study. It should only take about 10 minutes to complete the 
questionnaires. 
Your answers to the questions may show you are not eligible to join the study, 
even if you want to. We might contact you to ask some more questions to further 
evaluate whether you can join the study.  
In order to use the app you will be asked to agree to the Terms of Use and Privacy 
Policy which will appear on your mobile device’s screen when you first start 
using the app. If you decide that you do not want to agree, then you should not 
participate in the research. While using the app, data about you including personal 
health information, other communication data, and internet usage will be collected 
and transmitted to the researchers and to the app developer. A complete 
description of this data collection and sharing is found in the Privacy Policy. 
Transmission of information via the internet is not completely secure, so there is a 
small risk of unintentional release of your information and safeguards are in place 
to protect your personal information. While the Terms of Use may include 
statements limiting your rights if you are harmed in this study, you do not release 
the investigator, sponsor, institution, or agents from responsibility for mistakes, 
and these statements do not apply to the use of the app in this research study. 
Being in the study 
If you want to join and you are eligible, here is what will happen: 
You will be in the study about 5 months. 
Visits can be done in-person or remotely depending on the type of procedures that 
need to be done. Visits where you get injections must be done in person. Remote 
visits will be done whenever possible to reduce potential SARS-CoV-2 exposure.   
You may have to come to the clinic if you have a lab or health issue. 
Site: Insert visit lengths.  
Visits can last from [#] to [#] hours. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 99 of 166 
At your first visit, we will give you nasal swab kits and instructions so that you 
can take daily swabs of your nose. Once you receive your first kit, and for four 
months of the study, you will swab your nose every day, and you will be 
prompted by text or email to scan the barcode on the swab. You can ask us 
questions if you need help. You will return your swabs using drop-off location(s) 
specified by the clinic or by mail. 
If you are in the immediate vaccination group, we will take blood samples in the 
clinic at your first injection visit and 2 more times, two months and four months 
later. When we take blood, the amount will depend on the lab tests we need to do. 
Each time we take your blood, the total amount we will take will not be more than 
two tablespoons. If for some reason you cannot come to the clinic, you may be 
asked to self-collect blood using a small device called the Tasso-SST OnDemand. 
Each time you collect your own blood, the amount will be less than one teaspoon. 
We will give you everything you need to take the blood and return it to us. We 
will be looking at how your body responds to the vaccine and if you been exposed 
to the SARS-CoV-2 virus.  
If you are in the Standard of Care group (the later vaccination group), we will take 
blood samples in the clinic at the first visit, and 2 more times, two months and 
four months later. Each time we take your blood, the total amount we will take 
will not be more than one teaspoon. If for some reason you cannot come to the 
clinic, you may be asked to self-collect blood using a small device called the 
Tasso-SST OnDemand. Each time you collect your own blood, the amount will be 
less than one teaspoon. We will give you everything you need to take the blood 
and return it to us. We will be looking to see if you been exposed to the SARS-
CoV-2 virus.  
The self-collection device called the Tasso-SST OnDemand sticks to the skin with 
a light adhesive. When the button is pressed, a vacuum forms and the device will 
prick the surface of the skin. The vacuum draws blood out of the capillaries and 
into a sample pod attached to the bottom of the device. 
You will also take questionnaires in the eDiary that ask about the results of any 
SARS-CoV-2 tests you may have had. The questionnaires will take about 5 
minutes to complete. You will also take an End of Study questionnaire in the 
eDiary. The eDiary will send your phone or tablet a push notification or you will 
receive a reminder email. 
5. We will give you the vaccine on a schedule. 
You will be in one of 2 groups: The Immediate Vaccination group or the Standard 
of Care group. In the Standard of Care group, you will be offered vaccine at 
Month 4 and 5 if you have not received a vaccine already by then. Regardless of 
which group you are in, you will get 1 injection into your upper arm at 2 separate 
visits during the study. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 100 of 166 
We will ask you to sign up for v-safe to report any reactions to the study vaccine. 
V-safe is a smartphone-based tool from the Center for Disease Control (CDC) that 
uses text messaging and web surveys to check in with you after your COVID-19 
vaccination. 
 
 
Procedures for 
Immediate 
Vaccination 
group 
Screening 
visit(s) 
First 
injection 
visit 
1st 
month 
2nd 
month 
4th 
month 
Injection 
 
√ 
√ 
 
 
Medical history 
questionnaire 
√ 
√ 
 
 
 
SARS CoV-2 
testing 
questionnaire  
 
About 2x per week  
eDiary app 
√ 
About 2x per week through month 4 
Blood drawn 
 
√ 
 
√ 
√ 
Nasal swab 
 
Daily through month 4 
 
 
 
Procedures for  
Standard of 
Care group 
Screening 
visit(s) 
1st 
Day 
2nd 
month 
First 
injection 
visit (4th 
month) 
5th 
month 
Injection 
 
 
 
√ 
√ 
Medical history 
questionnaire 
√ 
√ 
 
 
 
SARS CoV-2 
testing 
questionnaire 
 
About 2x per week 
 
eDiary app 
√ 
About 2x per week through 
month 4 
√ 
Blood drawn 
 
√ 
√ 
√ 
 
Nasal swab 
 
Daily through month 4 
 
 
6. We will compensate you for your participation. 
Site: Insert your compensation plan here, e.g. money for number of swabs returned. 
Remember to include any costs to participants. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 101 of 166 
7. In addition to giving you the vaccine: 
We will ask you to give a referral code to people with whom you expect to be in 
frequent close physical proximity during the study, like a roommate or co-worker. 
We want to ask these people to enroll in another part of this study that will help us 
find out if the vaccine prevents transmission of the SARS-CoV-2 virus. We may 
also ask you to provide us with their contact information so that we can reach out 
to them directly. We are calling this group the Prospective Close Contact group or 
PCC.  
As part of their study participation, they will be asked to complete questionnaires 
like the ones you completed in the eDiary. If you become infected with SARS-
CoV-2, we will ask you to share your status with your PCCs. Then your PCC 
participants will be asked to fill out additional questionnaires for 2 weeks as well 
as take nasal swabs and self-collect blood samples. 
When considering who to ask to be your PCC, you should think about whether 
you feel comfortable or safe sharing your infection status with them if you get 
SARS-CoV-2. If you don’t feel comfortable sharing this information with them, 
you should not ask them to participate as a PCC.  
It is possible that someone you know may also be participating in the Main part of 
the study and might identify you as a close contact. They will not know you are 
also participating in the study unless you choose to tell them. If someone else 
identifies you as a close contact, they will give you their referral code. It is okay 
to be enrolled in both the Main part of the study and the PCC group.  
We may also ask you for the name of someone who can tell us how you are doing 
if we can’t reach you or if you are unable to talk. We may contact you after the 
main study ends (for example, to tell you about the study results). 
We will ask you to continue to follow any school or employer program for SARS-
CoV-2 testing and contact tracing, if applicable. If you test positive for SARS-
CoV-2, based on any SARS-CoV-2 testing you receive, please tell us as soon as 
possible. 
8. The CoVPN will test your samples to see how your body, including your 
immune system, responds to the Moderna COVID-19 vaccine. 
We will send your samples to labs approved by the CoVPN. Your samples will 
not be labeled with your name or other identifying information.  
Researchers may also do genetic testing related to this study on your samples. 
Your genes are passed to you from your birth parents. Differences in people’s 
genes can help explain why some people get a disease while others do not. The 
genetic testing will only involve some of your genes, not all of your genes (your 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 102 of 166 
genome). The researchers will study only the genes related to the immune system 
and coronavirus, and genes that may affect how people get coronavirus. 
If you get SARS-CoV-2, the researchers may look at all of the virus’ genes that 
are in your samples. The researchers will use this information to learn more about 
SARS-CoV-2 and how the virus is impacted by the study vaccine. 
The tests the researchers do on your samples are for research purposes, not to 
check your health. However, the nasal swab testing you do as part of this study 
may tell us if you are SARS-CoV-2 positive. Nasal swab test results from the 
study will be provided to the sites and be made available to you. You may be 
asked to get a confirmatory test. For all other lab tests, we will not provide the 
results to you or the site. 
When your samples are no longer needed for this study, the CoVPN will continue 
to store them. 
9. We will do our best to protect your private information. 
US sites: Check Health Insurance Portability and Accountability Act (HIPAA) 
authorization for conflicts with this section. 
We will keep your study records and samples in a secure location. We will label 
all of your samples and most of your records with a code number, not your name 
or other personal information. We will not share your name with anyone who 
does not need to know it. 
Your records may also be reviewed by groups who watch over this study. These 
groups include: 
▪ Study monitors 
• The CoVPN, people who work for it, and companies that help it with this 
study 
• Some government agencies: 
o The US National Institutes of Health 
o The US Office for Human Research Protections 
o Any regulatory agency that reviews research studies 
• Some committees that make sure we protect your rights and keep you safe: 
o The Independent Data Monitoring Committee 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 103 of 166 
o Advarra Institutional Review Board (IRB) 
o Sites may, but are not required to include: [Insert name of local IRB/EC]  
o Sites include: [Insert name of local IBC] 
All reviewers will take steps to keep your records private. 
We cannot guarantee absolute privacy. If you are found to have a medical 
condition that we are required to report by law, then some of your information 
may be shared.  
At this clinic, we have to report the following information:  
Site: Include any public health or legal reporting requirements. Bulleted examples 
should include all appropriate cases (reportable communicable disease, risk of harm 
to self or others, etc.)  
• SARS-CoV-2 
• Pneumonia 
• After receiving the vaccine, we are required to report any of the following that 
may occur to the FDA/CDC Vaccine Adverse Event Reporting System 
(VAERS): 
▪ Vaccine administration errors 
▪ Serious reaction after receiving the vaccine (for example that results in 
death, hospitalization, a life-threatening reaction, a birth defect, or other 
important medical event) 
▪ A condition called “Multisystem Inflammatory Syndrome” 
▪ Cases of COVID-19 that result in hospitalization 
US sites: Include the following boxed text. You can remove the box around the text. 
We have a Certificate of Confidentiality from the US government to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US National Institutes of Health 
funds this research, we cannot withhold information from it.  
The CoVPN may share information from this study with other researchers. 
Researchers may publish the results of this study.  
Site: The text below may not be deleted or changed per FDA requirement. You can 
remove the box. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 104 of 166 
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 website at any time. 
10. We may take you out of the study at any time.  
We may take you out of the study if: 
• you do not follow instructions, 
• we think that staying in the study might harm you, 
• the study is stopped for any reason. 
11. If you get COVID-19, we will ask you to do several things.  
If you find out that you have COVID-19, please let us know right away. We will 
ask you to quarantine per local guidelines. By agreeing to join this study, you also 
agree to share any SARS-CoV-2 test results with us.  
We will ask you to tell anyone with whom you have recently had close physical 
contact that they may have been exposed to COVID-19. We will give you a 
referral code to give to these contacts so that they can decide if they would like to 
join the Case Ascertained Close Contact group (CACC). We may also ask you to 
provide us with their contact information so that we can reach out to them 
directly. You may remember at the beginning of this form that we told you that 
about 2,250 people will be enrolled in the CACC group. The CACC group will 
help us learn if people who got the study vaccine are less likely to give SARS-
CoV-2 to someone else. When considering who to ask to be your CACC, you 
should think about whether you feel comfortable or safe sharing your infection 
status with them if you get SARS-CoV-2. If you don’t feel comfortable sharing 
this information with them, you should not ask them to participate as a CACC. 
It is possible that someone you know may also be participating in the Main part of 
the study and might identify you as a close contact. They will not know you are 
also participating in the study unless you choose to tell them. If someone else 
identifies you as a close contact, they will give you their referral code. It is okay 
to be enrolled in both the Main part of the study and the CACC group.  
If you find out that you have COVID-19, you will be directed to contact the 
clinic, and we will ask you to either come to the clinic to have your blood drawn 
or we will ask you to self-collect less than one teaspoon of blood and complete 
one additional eDiary questionnaire. It is important that you give the blood 
sample as soon as possible after finding out the you have COVID-19. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 105 of 166 
We will ask you to track your COVID-19 symptoms using the eDiary daily for 2 
weeks or until the symptoms go away. 
After you get better, we will ask you to continue your study participation so that 
we can monitor your health and safety for the rest of the study.  
If you are hospitalized, we will pause your participation. We will ask for your 
medical records and results from tests you might have received at the hospital. It 
is unlikely that you will be hospitalized, but to prepare for this, we will ask you to 
sign and date a medical release of information so we can get records from your 
doctor or view your hospital records. When you are released from the hospital, 
please let us know. We will ask you to resume your study participation so that we 
can continue to monitor your health and safety for the rest of the study. 
Site: Modify the following sentence as appropriate. We will not pay for any of 
your COVID-19 care directly.  
12. If you receive an EUA or licensed COVID-19 vaccine outside the study, we 
will stop your on-study vaccinations but you may continue in the study. 
If you receive an EUA or licensed COVID-19 vaccine outside the study, please let 
us know. We will ask you to tell us what vaccine you received and when you 
received it. You may continue to participate in follow-up visits and procedures 
like swabbing your nose and completing eDiary entries. Your continued 
participation is valuable to help us meet our study goals. 
If you are in the Standard of Care group and receive COVID-19 vaccination 
outside the study prior to your Month 4 visit, that Month 4 visit will be your last 
visit and can happen remotely. At this visit, we will ask you for a final blood 
sample (the sample can be self-collected using Tasso-SST OnDemand) and to 
complete an End of Study questionnaire. 
Other Risks 
13. There are other risks to being in this study.  
This section describes the other risks and restrictions we know about. There may 
also be unknown risks, even serious ones. We will tell you if we learn anything 
new that may affect your willingness to stay in the study. 
Risks of routine medical procedures: 
In this study, we will do some routine medical procedures. These are taking blood 
and giving injections. These procedures can cause bruising, pain, fainting, 
soreness, redness, swelling, itching, a sore, bleeding, and (rarely) muscle damage 
or infection where you got the injection. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 106 of 166 
Risks of swabbing your nose: 
The feeling of having a small, soft-tipped swab inserted into your nostril and 
twirled around may be a little uncomfortable, but it should not be painful. There is 
a small chance there could be some bleeding, but this is unlikely.  
Risks to your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could have stress or 
anxiety.  
Risks of genetic testing: 
It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems.  
Risk of anxiety/emotional stress: 
You may feel anxiety or emotional stress if you experience any of the risks 
described here. You may feel worried if tests show that you have SARS-CoV-2. 
Some of the questions we will ask you may make you feel uncomfortable.  
Risk of delaying COVID-19 vaccine: 
COVID-19 vaccines are highly effective at preventing COVID-19 illness. The 
Centers for Disease Control and Prevention (CDC) recommend that you receive a 
COVID-19 vaccine if it is made available to you. By agreeing to potentially delay 
getting the vaccine you may be at risk for serious illness if you get SARS-CoV-2 
infection. 
Unknown risks: 
The vaccine has been shown to prevent adults from getting COVID-19 for at least 
6 months after their injection, but we do not know if it will protect them for any 
longer. If you get COVID-19, we do not know how the vaccine might affect your 
illness. It is also unknown if the vaccine will prevent you from giving the virus to 
someone else. If you get COVID-19, we do not know how the vaccine might 
affect your illness. 
We do not know if getting this vaccine will affect how you respond to any future 
SARS-CoV-2 vaccines. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 107 of 166 
We do not know if getting the vaccine will affect pregnancy or breastfeeding. If 
you have concerns, we recommend that you discuss this with a health care 
provider.  
While you are in this study, you should still follow federal, state, and local 
guidelines for SARS-CoV-2 prevention, which may include wearing a mask and 
keeping physical distance from others. If you get sick, you should follow COVID-
19 precautions and isolate or self-quarantine.   
Benefits 
14. This study may not benefit you. 
COVID-19 vaccination helps protect people from getting sick or severely ill with 
COVID-19. This study may help researchers find out if the vaccine is able to prevent 
infection with SARS-CoV-2. COVID-19 vaccination is an important tool to help stop the 
COVID-19 pandemic. The CDC recommends you get a COVID-19 vaccine as soon as 
one is available to you. 
If the vaccine later becomes approved and sold, there are no plans to share any money 
with you. 
If you decide not to join this study, you could get the Moderna COVID-19 vaccine or 
another COVID-19 vaccine in your community. You can also continue to follow federal, 
state, and local guidelines for SARS-CoV-2 prevention. You do not have to join this 
research study if you don’t want to.  
Your rights and responsibilities 
15. If you join the study, you have rights and responsibilities. 
You have many rights that we will respect. You also have responsibilities. We list 
these in the Bill of Rights and Responsibilities for Research. We will give you a 
copy of it. 
Leaving the study 
16. Tell us if you decide to leave the study. 
You are free to leave the study at any time and for any reason. If you want to 
leave, you will need to tell us. Your care at this clinic, your standing at your 
school, and your legal rights will not be affected. 
Previously collected information about you will remain in the study records and 
will be included in the analysis of results. Your information can not be removed 
from the study records. 
We may ask you to give a final blood sample or nasal swab.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 108 of 166 
We believe these steps are important to protecting your health, but it is up to you 
whether to complete them. 
Injuries 
Sites: Approval from CoVPN Regulatory Affairs (at CoVPN.core.reg@fredhutch.org) is 
needed for any change (other than those that the instructions specifically request or those 
previously approved by CoVPN Regulatory Affairs) to the boxed text. You can remove the box 
around the text. 
17. If you get sick or injured during the study, contact us immediately. 
Paragraph below for all sites.  
Your health is important to us. (Sites: adjust the following 2 sentences if 
applicable to the care available at your site) We will tell you about the care that 
we can give here. For the care that we cannot provide, we will explain how we 
will help you get care elsewhere.  
2 paragraphs below for all sites.  
This research study is covered by a US government program that may provide 
compensation for a serious injury or death. We will give you a handout with more 
information about this program. The National Institutes of Health (NIH) does not 
have a mechanism to provide direct compensation for research related injury. 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in this study. Or you might lose wages because you cannot go to work. 
However, there are no funds to pay for these kinds of injuries, even if they are 
study related.  
You always have the right to use the court system if you are not satisfied.  
18. When samples are no longer needed for this study, the CoVPN wants to use 
them in other studies and share them with other researchers.  
The CoVPN calls these samples “extra samples”. The CoVPN will only allow 
your extra samples to be used in other studies if you agree to this. You will mark 
your decision at the end of this form.  
Do I have to agree? No. You are free to say yes or no, or to change your mind 
after you sign this form. At your request, the CoVPN will destroy all extra 
samples that it has. Your decision will not affect your being in this study. 
Where are the samples stored? Extra samples are stored in a secure central place 
called a repository. Your samples will be stored in the CoVPN repository in the 
United States. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 109 of 166 
How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: Revise the previous sentence to insert limits if your 
regulatory authority imposes them.] 
Will I be paid for the use of my samples? No. Researchers may make scientific 
discoveries or products using your samples. If this happens, there is no plan to 
share any money with you.  
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They may help other people in the future.  
Will the CoVPN sell my samples and information? No, but the CoVPN may share 
your samples with other researchers. Once the CoVPN shares your samples and 
information, it may not be able to get them back. 
What information is shared with researchers? The samples and information will 
be labeled with a code number which will not be removed. The key to the code 
will stay at this clinic. However, some information that the CoVPN shares may be 
personal, such as your race, ethnicity, sex, and health information from the study.  
What kind of studies might be done with my extra samples and information? The 
studies will be related to vaccines, the immune system, coronavirus, and other 
diseases. Researchers may also do genetic testing on your samples. 
If you agree, researchers may compare all of your genes (your genome) to the 
genomes of many other people. Researchers look for common patterns of genes to 
help them understand diseases. The researchers may put the information into a 
protected database so that other researchers can access it. Your name and other 
personal information will not be included.  
Usually, no one could connect your genome to you as a person. There are rules 
against this. It’s also really difficult to do. But there is a risk that someone could 
combine information from your genome and other public information about you 
and identify you. If others found out, it could lead to discrimination or other 
problems. The risk of this happening is very small.  
Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
• Researchers who use your extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and information 
• The researcher’s Institutional Review Board or Ethics Committee 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 110 of 166 
• Any regulatory agency that reviews research studies 
• The people who work with the researcher 
All of these people will do their best to protect your information. If they publish 
their research, they will not use your name or identify you personally. 
Questions  
19. Whom to contact 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 study doctor at the telephone number listed on the first page of this 
consent document. If you seek emergency care, or hospitalization is required, alert 
the treating physician that you are participating in this research study.  
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: 
Study Subject Adviser 
Advarra IRB 
6100 Merriweather Dr., Suite 600Columbia, MD 21044 
or call toll free:    877-992-4724 
or by email:          adviser@advarra.com 
Please reference the following number when contacting the Study Subject 
Adviser: Pro00049375 
US sites may include, but are not required to: You may also contact the [name of 
local IRB/EC] at [insert contact information]. 
Your permissions and signature  
20. In Section 18, we told you above about possible other uses of your extra 
samples and information outside this study. Please choose only one of the options 
below and write your initials in the box next to it. Whatever you choose, the 
CoVPN keeps track of your decision about how your samples and information can 
be used. You can change your mind after signing this form. 
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 111 of 166 
 
I allow my extra samples and information to be used for other studies related to 
vaccines, the immune system, coronavirus, and other diseases. This may include 
genetic testing.  
OR 
 
 
I agree to the option above and also to allow my extra samples and information 
to be used in studies that look at my whole genome. 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes 
not allowing genetic testing, or studies that look at my whole genome.  
 
21. If you agree to join this study, you will need to sign below. Before you sign, 
make sure of the following: 
• You have read this consent form. 
• You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
• You have had your questions answered and know that you can ask more. 
• You agree to join this study. 
• You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s Name (Print) 
 
Participant’s Signature 
 
Date 
 
 
 
 
 
 
 
Clinic Staff Conducting 
Consent 
Discussion (Print) 
 
Clinic Staff Signature 
 
Date 
 
 
 
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 112 of 166 
Appendix B 
Sample informed consent form for Main 
cohort, Vaccine Declined Group 
 
Sponsor / Study Title: 
  
National Institutes of Health, “A randomized controlled study to 
assess SARS CoV-2 infection, viral shedding, and subsequent 
potential transmission in individuals immunized with Moderna 
COVID-19 Vaccine” 
Protocol Number: 
 
CoVPN 3006 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
Thank you for your interest in our research study. It is called CoVPN 3006. This 
informed consent form will tell you more about the study. Please read it carefully 
as you decide if you want to join. If you have questions, please ask us. At the end, 
we will ask you to answer a few questions to make sure you understand the study.  
If you decide to join this study, we will ask you to sign this form. We will offer 
you a copy of this form to keep.  
CoVPN 3006 is a research study. Research is not the same as medical care. The 
purpose of a research study is to answer scientific questions. We hope that what 
we learn will help people in the future. 
Key information 
• Joining this research study is voluntary. It is your choice. 
• Our scientific questions are: Does the vaccine protect people from getting 
infected with a coronavirus called SARS-CoV-2? Does the vaccine prevent 
people from transmitting SARS-CoV-2 to others? 
•  If you join, your participation in this study will last for about 4-5 months. 
• If you join, we will ask you to answer questionnaires, give blood, and take 
daily swabs of your nose.  
Here are the risks of taking part: 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 113 of 166 
• There is a risk of loss of your personal information.   
• There are other, less serious risks. We will tell you more about them later in 
this consent form. 
About the study 
The COVID-19 Prevention Network (CoVPN) is doing a study to test a vaccine 
against SARS-CoV-2. SARS-CoV-2 is the virus that causes the disease called 
COVID-19. We want to know if the vaccine is able to protect people from getting 
infected and if getting the vaccine will affect the amount of virus that is in your 
nose. We also want to know if getting the vaccine will prevent transmitting 
SARS-CoV-2 to others.  
Many young adults will take part in this study around the US. This study has 5 
groups. The first 3 groups, called the Immediate Vaccination, Standard of Care, 
and Vaccine Declined groups, will be in the Main Study.  
• The Immediate Vaccination and Standard of Care groups will have about 
12,000 people that will get vaccine injections either immediately or 4 
months later. In this study, “standard of care” refers to all federal, state, 
and local recommendations regarding COVID-19 prevention, including 
COVID-19 vaccination, masking, social distancing, isolation and 
quarantine. 
• The Vaccine Declined group will have about 6,000 people who prefer not 
to be vaccinated and will be followed for 4 months.  
• The last two groups are close contacts of the Main Study: the Prospective 
Close Contact (PCC) group will have up to 36,000 people, and the Case-
ascertained Close Contact (CACC) group will have up to 2250 people. 
These close contact groups will help researchers determine if the vaccine 
prevents transmission of the SARS-CoV-2 virus to others. We will explain 
more about this later in this form.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 114 of 166 
 
Because you have indicated that you prefer not to receive a COVID-19 vaccine, 
we are asking you to join the Main part of the study in which people are followed 
for 4 months but do not receive vaccine injections (Vaccine Declined group). If at 
the end of the 4 months you indicate that you prefer to be vaccinated, the 
Moderna COVID-19 vaccine will be offered to you. If you choose to take up the 
offer of vaccine, you will continue in the study another month to receive both 
recommended vaccine doses. The researcher in charge of this study at this clinic 
is [Insert name of site PI]. The US National Institutes of Health is paying for this 
study.  
Joining the study 
1. It is completely up to you whether or not to join this study. 
Take your time in deciding. If it helps, talk to people you trust, such as your 
doctor, friends, or family. If you decide not to join this study, or if you leave it 
after you have joined, it will not change your healthcare. If you do join, you do 
not give up your legal rights.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 115 of 166 
You cannot be in this study while you are in another study where you get a study 
product.  
If you choose not to join this study, you may be able to join another study. If at 
any time you decide you want to get vaccinated, you are free to do so. This may 
be in this study (beginning at Month 4) or may be elsewhere at any time. You can 
also get SARS-CoV-2 tested in your community. 
If you are an employee or relative of an employee of a participating site, you are 
under no obligation to participate in this study. You may withdraw from the study 
at any time and for any reason, and your decision will not have any effect on 
your/your family member’s performance appraisal or employment at the study 
site. You may refuse to participate or you may withdraw from the study at any 
time without penalty or anyone blaming you. 
If you are a student, your participation will not place you in good favor with the 
study doctor or other faculty (for example, receiving better grades, 
recommendations, employment). Also, not participating in this study will not 
adversely affect your relationship with the study doctor or other faculty. 
2. If you want to join this study, after you sign this consent, you will download 
an electronic diary (eDiary) app and take questionnaires in it. 
We will send you information about how to download the eDiary app onto your 
phone or tablet. We can help you download the app and show you how to use it.  
To find out if you are eligible to join the study, you will answer questionnaires in 
the eDiary. Some of the questions will ask about your health history, what 
medications you take, your age, race, and ethnicity, and where you live. Your 
answers will tell us about some aspects of your health and if you may be eligible 
to join the study. It should only take about 10 minutes to complete the 
questionnaires. 
Your answers to the questions may show you are not eligible to join the study, 
even if you want to. We might contact you to ask some more questions to further 
evaluate whether you can join the study.  
In order to use the app you will be asked to agree to the Terms of Use and Privacy 
Policy which will appear on your mobile device’s screen when you first start 
using the app. If you decide that you do not want to agree, then you should not 
participate in the research. While using the app, data about you including personal 
health information, other communication data, and internet usage will be collected 
and transmitted to the researchers and to the app developer. A complete 
description of this data collection and sharing is found in the Privacy Policy. 
Transmission of information via the internet is not completely secure, so there is a 
small risk of unintentional release of your information and safeguards are in place 
to protect your personal information. While the Terms of Use may include 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 116 of 166 
statements limiting your rights if you are harmed in this study, you do not release 
the investigator, sponsor, institution, or agents from responsibility for mistakes, 
and these statements do not apply to the use of the app in this research study. 
Being in the study 
If you want to join and you are eligible, here is what will happen: 
3. You will be in the study about 4-5 months. 
Visits can be done in-person or remotely depending on the type of procedures that 
need to be done. If you decide to get vaccine from the study site, visits where you 
get injections must be done in person. Remote visits will be done whenever 
possible to reduce potential SARS-CoV-2 exposure.   
You may have to come to the clinic if you have a lab or health issue. 
Site: Insert visit lengths.  
Visits can last from [#] to [#] hours. 
At your first visit, we will give you nasal swab kits and instructions so that you 
can take daily swabs of your nose. Once you receive your first kit, and for four 
months of the study, you will swab your nose every day, and you will be 
prompted by text or email to scan the barcode on the swab. The questionnaires 
will take about 5 minutes to complete. You can ask us questions if you need help. 
You will return your swabs using drop-off location(s) specified by the clinic or by 
mail. 
We will take blood samples in the clinic at the first visit, and 2 more times, two 
months and four months later. Each time we take your blood, the total amount we 
will take will not be more than one teaspoon. If for some reason you cannot come 
to the clinic, you may be asked to self-collect blood using a small device called 
the Tasso-SST OnDemand. Each time you collect your own blood, the amount 
will be less than one teaspoon. We will give you everything you need to take the 
blood and return it to us. We will be looking to see if you been exposed to the 
SARS-CoV-2 virus. The self-collection device called the Tasso-SST OnDemand 
sticks to the skin with a light adhesive. When the button is pressed, a vacuum 
forms and the device will prick the surface of the skin. The vacuum draws blood 
out of the capillaries and into a sample pod attached to the bottom of the device. 
You will also take questionnaires in the eDiary that ask about the results of any 
SARS-CoV-2 tests you may have had. The questionnaires will take about 5 
minutes to complete. You will also take an End of Study questionnaire in the 
eDiary. The eDiary will send your phone or tablet a push notification or you will 
receive a reminder email. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 117 of 166 
 
Procedures for  
Vaccine Declined 
Group 
Screening 
visit(s) 
1st 
Day 
2nd 
month 
4th  
month 
Medical history 
questionnaire 
√ 
√ 
 
 
SARS-CoV-2 
testing 
questionnaire 
 
About 2x per week 
eDiary app 
√ 
About 2x per week 
through month 4 
Blood drawn 
 
√ 
√ 
√ 
Nasal swab 
 
Daily through month 4 
4. At the end of 4 months the study staff will ask you if want to receive the 
Moderna COVID-19 vaccine. 
If you still prefer not to be vaccinated, your study participation will end at Month 
4, which will be the 5th visit.  
If you prefer to be vaccinated, you will be consented with another different 
consent form, and your study participation will last an additional month.  
5. We will compensate you for your participation. 
Site: Insert your compensation plan here, e.g. money for number of swabs returned. 
Remember to include any costs to participants. 
6. We will ask you to refer your close contacts. 
We will ask you to give a referral code to people with whom you expect to be in 
frequent close physical proximity during the study, like a roommate or co-worker. 
We want to ask these people to enroll in another part of this study that will help us 
find out if the vaccine prevents transmission of the SARS-CoV-2 virus. We may 
also ask you to provide us with their contact information so that we can reach out 
to them directly. We are calling this group the Prospective Close Contact group or 
PCC.  
As part of their study participation, they will be asked to complete a weekly 
eDiary that includes questionnaires like the ones you completed. If you become 
infected with SARS-CoV-2, we will ask you to share your status with your PCCs. 
Then your PCC participants will be asked to fill out additional questionnaires for 
2 weeks as well as take nasal swabs and self-collect blood samples. 
When considering who to ask to be your PCC, you should think about whether 
you feel comfortable or safe sharing your infection status with them if you get 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 118 of 166 
SARS-CoV-2. If you don’t feel comfortable sharing this information with them, 
you should not ask them to participate as a PCC.  
It is possible that someone you know may also be participating in the Main part of 
the study and might identify you as a close contact. They will not know you are 
also participating in the study unless you choose to tell them. If someone else 
identifies you as a close contact, they will give you their referral code. It is okay 
to be enrolled in both the Main part of the study and the PCC group.  
We may also ask you for the name of someone who can tell us how you are doing 
if we can’t reach you or if you are unable to talk. We may contact you after the 
main study ends (for example, to tell you about the study results). 
We will ask you to continue to follow any school or employer program for SARS-
CoV-2 testing and contact tracing, if applicable. If you test positive for SARS-
CoV-2, based on any SARS-CoV-2 testing you receive, please tell us as soon as 
possible. 
7. The CoVPN will test your samples to see how your body, including your 
immune system, responds to a potential infection. 
We will send your samples to labs approved by the CoVPN. Your samples will 
not be labeled with your name or other identifying information.  
Researchers may also do genetic testing related to this study on your samples. 
Your genes are passed to you from your birth parents. Differences in people’s 
genes can help explain why some people get a disease while others do not. The 
genetic testing will only involve some of your genes, not all of your genes (your 
genome). The researchers will study only the genes related to the immune system 
and coronavirus, and genes that may affect how people get coronavirus. 
If you get SARS-CoV-2, the researchers may look at all of the virus’ genes that 
are in your samples. The researchers will use this information to learn more about 
SARS-CoV-2 and how the virus is impacted by the study vaccine. 
The tests the researchers do on your samples are for research purposes, not to 
check your health. However, the nasal swab testing you do as part of this study 
may tell us if you are SARS-CoV-2 positive. Nasal swab test results from the 
study will be provided to the sites and be made available to you. You may be 
asked to get a confirmatory test. For all other lab tests, we will not provide the 
results to you or the site. 
When your samples are no longer needed for this study, the CoVPN will continue 
to store them. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 119 of 166 
8. We will do our best to protect your private information. 
US sites: Check Health Insurance Portability and Accountability Act (HIPAA) 
authorization for conflicts with this section. 
We will keep your study records and samples in a secure location. We will label 
all of your samples and most of your records with a code number, not your name 
or other personal information. We will not share your name with anyone who 
does not need to know it. 
Your records may also be reviewed by groups who watch over this study. These 
groups include: 
▪ Study monitors 
• The CoVPN, people who work for it, and companies that help it with this 
study 
• Some government agencies: 
o The US National Institutes of Health 
o The US Office for Human Research Protections 
o Any regulatory agency that reviews research studies 
• Some committees that make sure we protect your rights and keep you safe: 
o The Independent Data Monitoring Committee 
o Advarra Institutional Review Board (IRB) 
o Sites may, but are not required to include: [Insert name of local IRB/EC]  
o Sites include: [Insert name of local IBC] 
All reviewers will take steps to keep your records private. 
We cannot guarantee absolute privacy. If you are found to have a medical 
condition that we are required to report by law, then some of your information 
may be shared.  
At this clinic, we have to report the following information:  
Site: Include any public health or legal reporting requirements. Bulleted examples 
should include all appropriate cases (reportable communicable disease, risk of harm 
to self or others, etc.)  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 120 of 166 
• SARS-CoV-2 
• Pneumonia 
US sites: Include the following boxed text. You can remove the box around the text. 
We have a Certificate of Confidentiality from the US government to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US National Institutes of Health 
funds this research, we cannot withhold information from it.  
The CoVPN may share information from this study with other researchers. 
Researchers may publish the results of this study.  
Site: The text below may not be deleted or changed per FDA requirement. You can 
remove the box. 
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 website at any time. 
9. We may take you out of the study at any time.  
We may take you out of the study if: 
• you do not follow instructions, 
• we think that staying in the study might harm you, 
• the study is stopped for any reason. 
10. If you get COVID-19, we will ask you to do several things.  
If you find out that you have COVID-19, please let us know right away. We will 
ask you to quarantine per local guidelines. By agreeing to join this study, you also 
agree to share any SARS-CoV-2 test results with us.  
We will ask you to tell anyone with whom you have recently had close physical 
contact that they may have been exposed to COVID-19. We will give you a 
referral code to give to these contacts so that they can decide if they would like to 
join the Case Ascertained Close Contact group (CACC). We may also ask you to 
provide us with their contact information so that we can reach out to them 
directly. You may remember at the beginning of this form that we told you that 
about 2250 people will be enrolled in the CACC group. The CACC group will 
help us learn if people who got the study vaccine are less likely to give SARS-

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 121 of 166 
CoV-2 to someone else. When considering who to ask to be your CACC, you 
should think about whether you feel comfortable or safe sharing your infection 
status with them if you get SARS-CoV-2. If you don’t feel comfortable sharing 
this information with them, you should not ask them to participate as a CACC. 
It is possible that someone you know may also be participating in the Main part of 
the study and might identify you as a close contact. They will not know you are 
also participating in the study unless you choose to tell them. If someone else 
identifies you as a close contact, they will give you their referral code. It is okay 
to be enrolled in both the Main part of the study and the CACC group.  
If you find out that you have COVID-19, you will be directed to contact the 
clinic, and we will ask you to either come to the clinic to have your blood drawn 
or we will ask you to self-collect less than one teaspoon of blood and complete 
one additional eDiary questionnaire. It is important that you give the blood 
sample as soon as possible after finding out the you have COVID-19. 
We will ask you to track your COVID-19 symptoms using the eDiary daily for 2 
weeks or until the symptoms go away. 
After you get better, we will ask you to continue your study participation so that 
we can monitor your health and safety for the rest of the study.  
If you are hospitalized, we will pause your participation. We will ask for your 
medical records and results from tests you might have received at the hospital. It 
is unlikely that you will be hospitalized, but to prepare for this, we will ask you to 
sign and date a medical release of information so we can get records from your 
doctor or view your hospital records. When you are released from the hospital, 
please let us know. We will ask you to resume your study participation so that we 
can continue to monitor your health and safety for the rest of the study. 
Site: Modify the following sentence as appropriate. We will not pay for any of 
your COVID-19 care directly.  
11. If you receive an EUA or licensed COVID-19 vaccine outside the study, 
please tell us. 
If you receive an EUA or licensed COVID-19 vaccine outside the study, please let 
us know. We will ask you to tell us what vaccine you received and when you 
received it. You may continue to participate in follow-up visits and procedures 
like swabbing your nose and completing eDiary entries. Your continued 
participation is valuable to help us meet our study goals. 
If you have received COVID-19 vaccination outside the study prior to your 
Month 4 visit, that Month 4 visit will be your last visit and can happen remotely. 
At this visit, we will ask you for a final blood sample (the sample can be self-

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 122 of 166 
collected using Tasso-SST OnDemand) and to complete an End of Study 
questionnaire. 
Other Risks 
12. There are other risks to being in this study.  
This section describes the other risks and restrictions we know about. There may 
also be unknown risks, even serious ones. We will tell you if we learn anything 
new that may affect your willingness to stay in the study. 
Risks of routine medical procedures: 
In this study, we will do some routine medical procedures. These are taking blood 
and giving injections. These procedures can cause bruising, pain, fainting, 
soreness, redness, swelling, itching, a sore, bleeding, and (rarely) muscle damage 
or infection where you got the injection. 
Risks of swabbing your nose: 
The feeling of having a small, soft-tipped swab inserted into your nostril and 
twirled around may be a little uncomfortable, but it should not be painful. There is 
a small chance there could be some bleeding, but this is unlikely.  
Risks to your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could have stress or 
anxiety.  
Risks of genetic testing: 
It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems.  
Risk of anxiety/emotional stress: 
You may feel anxiety or emotional stress if you experience any of the risks 
described here. You may feel worried if tests show that you have SARS-CoV-2. 
Some of the questions we will ask you may make you feel uncomfortable.  
Risk of declining COVID-19 vaccine: 
The Centers for Disease Control and Prevention (CDC) recommends that you 
receive a COVID-19 vaccine if it is made available to you. COVID-19 vaccines 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 123 of 166 
are highly effective at preventing serious illness. By not getting the vaccine, you 
may be at risk for serious illness if you get SARS-CoV-2 infection. 
While you are in this study, you should still follow federal, state, and local 
guidelines for SARS-CoV-2 prevention, which may include wearing a mask and 
keeping physical distance from others. If you get sick, you should follow COVID-
19 precautions and isolate or self-quarantine.  
Benefits 
13. This study may not benefit you. 
This study may help researchers find out if the vaccine is able to prevent infection 
with SARS-CoV-2. If the vaccine later becomes approved and sold, there are no 
plans to share any money with you. 
The nasal swab testing you do as part of this study may tell us if you are SARS-
CoV-2 positive. Nasal swab test results from the study will be provided to the 
sites and be made available to you. You can still get nasal swab testing for SARS-
CoV-2 at any time outside the study.  
Whether or not you join this study, you could get a COVID-19 vaccine in your 
community. You can also continue to follow local guidelines for SARS-CoV-2 
infection. You do not have to join this research study if you don’t want to.  
Your rights and responsibilities 
14. If you join the study, you have rights and responsibilities. 
You have many rights that we will respect. You also have responsibilities. We list 
these in the Bill of Rights and Responsibilities for Research. We will give you a 
copy of it. 
Leaving the study 
15. Tell us if you decide to leave the study. 
You are free to leave the study at any time and for any reason. If you want to 
leave, you will need to tell us. Your care at this clinic, your standing at your 
school, and your legal rights will not be affected. 
Previously collected information about you will remain in the study records and 
will be included in the analysis of results. Your information can not be removed 
from the study records. 
We may ask you to give a final blood sample or nasal swab.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 124 of 166 
We believe these steps are important to protecting your health, but it is up to you 
whether to complete them. 
 
Injuries 
Sites: Approval from CoVPN Regulatory Affairs (at CoVPN.core.reg@fredhutch.org) 
is needed for any change (other than those that the instructions specifically request or 
those previously approved by CoVPN Regulatory Affairs) to the boxed text. You can 
remove the box around the text. 
16. If you get sick or injured during the study, contact us immediately. 
Paragraph below for all sites.  
Your health is important to us. (Sites: adjust the following 2 sentences if 
applicable to the care available at your site) We will tell you about the care that 
we can give here. For the care that we cannot provide, we will explain how we 
will help you get care elsewhere.  
The National Institutes of Health (NIH) does not have a mechanism to provide 
direct compensation for research related injury. 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in this study. Or you might lose wages because you cannot go to work. 
However, there are no funds to pay for these kinds of injuries, even if they are 
study related.  
You always have the right to use the court system if you are not satisfied.  
17. When samples are no longer needed for this study, the CoVPN wants to use 
them in other studies and share them with other researchers.  
The CoVPN calls these samples “extra samples”. The CoVPN will only allow 
your extra samples to be used in other studies if you agree to this. You will mark 
your decision at the end of this form.  
Do I have to agree? No. You are free to say yes or no, or to change your mind 
after you sign this form. At your request, the CoVPN will destroy all extra 
samples that it has. Your decision will not affect your being in this study. 
Where are the samples stored? Extra samples are stored in a secure central place 
called a repository. Your samples will be stored in the CoVPN repository in the 
United States. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 125 of 166 
How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: Revise the previous sentence to insert limits if your 
regulatory authority imposes them.] 
Will I be paid for the use of my samples? No. Researchers may make scientific 
discoveries or products using your samples. If this happens, there is no plan to 
share any money with you.  
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They may help other people in the future.  
Will the CoVPN sell my samples and information? No, but the CoVPN may share 
your samples with other researchers. Once the CoVPN shares your samples and 
information, it may not be able to get them back. 
What information is shared with researchers? The samples and information will 
be labeled with a code number which will not be removed. The key to the code 
will stay at this clinic. However, some information that the CoVPN shares may be 
personal, such as your race, ethnicity, sex, and health information from the study.  
What kind of studies might be done with my extra samples and information? The 
studies will be related to vaccines, the immune system, coronavirus, and other 
diseases. Researchers may also do genetic testing on your samples. 
If you agree, researchers may compare all of your genes (your genome) to the 
genomes of many other people. Researchers look for common patterns of genes to 
help them understand diseases. The researchers may put the information into a 
protected database so that other researchers can access it. Your name and other 
personal information will not be included.  
Usually, no one could connect your genome to you as a person. There are rules 
against this. It’s also really difficult to do. But there is a risk that someone could 
combine information from your genome and other public information about you 
and identify you. If others found out, it could lead to discrimination or other 
problems. The risk of this happening is very small.  
Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
• Researchers who use your extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and information 
• The researcher’s Institutional Review Board or Ethics Committee 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 126 of 166 
• Any regulatory agency that reviews research studies 
• The people who work with the researcher 
All of these people will do their best to protect your information. If they publish 
their research, they will not use your name or identify you personally. 
Questions  
18. Whom to contact 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 study doctor at the telephone number listed on the first page of this 
consent document. If you seek emergency care, or hospitalization is required, alert 
the treating physician that you are participating in this research study.  
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: 
Study Subject Adviser 
Advarra IRB 
6100 Merriweather Dr., Suite 600 
Columbia, MD 21044 
or call toll free:    877-992-4724 
or by email:          adviser@advarra.com 
Please reference the following number when contacting the Study Subject 
Adviser: Pro00049375 
US sites may include, but are not required to: You may also contact the [name of 
local IRB/EC] at [insert contact information]. 
Your permissions and signature  
19. In Section 18, we told you above about possible other uses of your extra 
samples and information outside this study. Please choose only one of the options 
below and write your initials in the box next to it. Whatever you choose, the 
CoVPN keeps track of your decision about how your samples and information can 
be used. You can change your mind after signing this form. 
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 127 of 166 
 
I allow my extra samples and information to be used for other studies related to 
vaccines, the immune system, coronavirus, and other diseases. This may include 
genetic testing.  
OR 
 
 
I agree to the option above and also to allow my extra samples and information 
to be used in studies that look at my whole genome. 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes 
not allowing genetic testing, or studies that look at my whole genome.  
 
20. If you agree to join this study, you will need to sign below. Before you sign, 
make sure of the following: 
• You have read this consent form. 
• You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
• You have had your questions answered and know that you can ask more. 
• You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s Name (Print) 
 
Participant’s Signature 
 
Date 
 
 
 
 
 
 
 
Clinic Staff Conducting 
Consent 
Discussion (Print) 
 
Clinic Staff Signature 
 
Date 
 
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 128 of 166 
Addendum  Sample informed consent form for Vaccine 
Declined Group participants who decide to take up 
Moderna COVID-19 Vaccine on study 
 
Sponsor / Study Title: 
  
National Institutes of Health, “A randomized controlled study to 
assess SARS CoV-2 infection, viral shedding, and subsequent 
potential transmission in individuals immunized with Moderna 
COVID-19 Vaccine” 
Protocol Number: 
 
CoVPN 3006 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
Thank you for your interest in getting the Moderna COVID-19 Vaccine through 
the research study, CoVPN 3006. Previously you agreed to join this study because 
you did not want to get the vaccine. This informed consent addendum will give 
you more information about getting the Moderna COVID-19 Vaccine. The 
information in the informed consent you previously signed still applies. If you 
have questions, please ask us.  
After reviewing this informed consent addendum, if you decide to get the 
Moderna COVID-19 vaccine in this study, we will ask you to sign this form. We 
will offer you a copy of this form to keep.  
1. This study’s vaccine has an Emergency Use Authorization (EUA) for 
individuals 18 and older. 
The vaccine we use in this study is called the Moderna COVID-19 Vaccine. The 
vaccine has been given to over 15,000 people in other research studies and over 
100 million people under EUA. We will give you the most up-to-date “Fact Sheet 
for Recipients and Caregivers” with more information about the Moderna 
COVID-19 Vaccine. The person giving you the vaccine can answer any questions 
you might have about what is in this fact sheet.  
We already know that the vaccine can prevent serious COVID-19 disease, but we 
do not know if the vaccine will work to prevent SARS-CoV-2 infection in others. 
That is what we are testing in this study.  
The Moderna COVID-19 Vaccine is not approved for sale in the United States by 
the US Food and Drug Administration (FDA).  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 129 of 166 
Although the vaccine is not approved, it has an Emergency Use Authorization 
(EUA) from the FDA based on its success at preventing disease symptoms from 
SARS-CoV-2 in other studies to date. During a public health emergency, like the 
COVID-19 pandemic, the FDA can issue an EUA to get vaccines to people faster. 
When the FDA issues an EUA, they continue to monitor safety.  
The vaccine was developed by ModernaTX, Inc. Typical vaccines for viruses are 
made from a weakened or killed virus, but the Moderna COVID-19 Vaccine is not 
made from the SARS-CoV-2 virus. The vaccine includes a short segment of 
messenger ribonucleic acid (mRNA). The mRNA is a genetic code that tells cells 
how to make a protein. This mRNA is made in a laboratory. When injected into 
the body, the mRNA vaccine causes some cells to make that viral protein, which 
can trigger the immune system. Your immune system protects you from disease. 
If a person is later infected, their immune system remembers the protein from the 
vaccine which may help it to fight the virus. It is impossible for the vaccine to 
give you SARS-CoV-2 or COVID-19 infection.  
Risks of the Moderna COVID-19 Vaccine: 
To date, more than 100 million people have already received the Moderna 
COVID-19 Vaccine. In clinical trials, most people who got the vaccine had some 
reaction after their injections, especially after the second injection. The reaction to 
the vaccine didn’t affect their daily lives and it went away after two or three days. 
Most of these people said they had pain in the arm where they got the injection. 
These people also felt tired, had headaches, muscle and joint pain, and chills. A 
much smaller number of these people said they had redness or swelling where the 
needle went in their arm. Some people had swelling of the lymph nodes in the 
same arm of the injection. 
The risks of the study vaccine seen so far are the same as what have been seen 
with most vaccines. Generally, vaccines can cause fever, chills, rash, aches and 
pains, nausea, headache, dizziness, and feeling tired. Vaccines can also cause 
pain, redness, swelling, or itching where you got the injection. Most people can 
still do their planned activities after getting a vaccine. Rarely, people have side 
effects that limit their normal activities or make them go to the doctor. 
Rarely, a vaccine can cause you to have an allergic reaction. You might have a 
rash, hives, swelling of your face and throat, a fast heartbeat, dizziness and 
weakness, or trouble breathing. Allergic reactions can be life-threatening. Tell us 
if you have ever had a bad reaction to any injection or vaccine. 
There may be other risks that we don’t yet know about, even serious ones. We 
will tell you if we learn about any new risks. 
Unknown risks: 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 130 of 166 
The vaccine has been shown to prevent adults from getting COVID-19 for at least 
6 months after their injection, but we do not know if it will protect them for any 
longer. If you get COVID-19, we do not know how the vaccine might affect your 
illness. It is also unknown if the vaccine will prevent you from giving the virus to 
someone else. If you get COVID-19, we do not know how the vaccine might 
affect your illness. 
We do not know if getting this vaccine will affect how you respond to any future 
SARS-CoV-2 vaccines. 
We do not know if getting the vaccine will affect pregnancy or breastfeeding. If 
you have concerns, we recommend that you discuss this with a health care 
provider.  
While you are in this study, you should still follow federal, state, and local 
guidelines for SARS-CoV-2 prevention, which may include wearing a mask and 
keeping physical distance from others. If you get sick, you should follow COVID-
19 precautions and isolate or self-quarantine.   
Agreeing to get the vaccine 
2. You will receive the vaccine on a schedule. 
If you choose, and if you have not received a vaccine by your Month 4 study visit 
and choose to be vaccinated, you will get the 1st injection of the vaccine at your 
Month 4 study visit. Study staff will schedule you to get your 2nd injection about 4 
weeks later. In total, you will get 1 injection in your upper arm at 2 separate visits 
during the study. 
We will ask you to sign up for v-safe to report any reactions to the study vaccine. 
V-safe is a smartphone-based tool from the Center for Disease Control (CDC) that 
uses text messaging and web surveys to check in with you after your COVID-19 
vaccination. 
3. We will do our best to protect your private information. 
US sites: Check Health Insurance Portability and Accountability Act (HIPAA) 
authorization for conflicts with this section. 
We will keep your study records and samples in a secure location. We will label 
all of your samples and most of your records with a code number, not your name 
or other personal information. We will not share your name with anyone who 
does not need to know it. 
Your records may also be reviewed by groups who watch over this study. These 
groups include: 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 131 of 166 
• Study monitors 
• The CoVPN, people who work for it, and companies that help it with this 
study 
• Some government agencies: 
▪ The US National Institutes of Health 
▪ The US Office for Human Research Protections 
▪ Any regulatory agency that reviews research studies 
• Some committees that make sure we protect your rights and keep you safe: 
▪ The Independent Data Monitoring Committee 
▪ Advarra Institutional Review Board (IRB) 
▪ Sites may, but are not required to include: [Insert name of local IRB/EC]  
All reviewers will take steps to keep your records private. 
We cannot guarantee absolute privacy. If you are found to have a medical 
condition that we are required to report by law, then some of your information 
may be shared.  
At this clinic, we have to report the following information:  
Site: Include any public health or legal reporting requirements. Bulleted examples 
should include all appropriate cases (reportable communicable disease, risk of harm 
to self or others, etc.)  
• SARS-CoV-2 
• Pneumonia 
• After you receive the vaccine, we are required to report any of the following 
to the FDA/CDC Vaccine Adverse Event Reporting System (VAERS): 
▪ Vaccine administration errors 
▪ Serious reaction after receiving the vaccine (for example that results in 
death, hospitalization, a life-threatening reaction, a birth defect, or other 
important medical event) 
▪ A condition called “Multisystem Inflammatory Syndrome” 
▪ Cases of COVID-19 that result in hospitalization 
US sites: Include the following boxed text. You can remove the box around the text. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 132 of 166 
We have a Certificate of Confidentiality from the US government to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US National Institutes of Health 
funds this research, we cannot withhold information from it.  
The CoVPN may share information from this study with other researchers. 
Researchers may publish the results of this study.  
4. It is completely up to you whether or not to get the vaccine in this study. 
Take your time in deciding. If it helps, talk to people you trust, such as your 
doctor, friends, or family. If you decide not to get vaccine in this study, or if you 
decide to get it outside of this study, it will not change your healthcare.  
If you decide not to get vaccine in this study, you could get the Moderna COVID-
19 vaccine or another COVID-19 vaccine in your community. You can also 
continue to follow local guidelines for SARS-CoV-2 infection. You do not have 
to get vaccine in this study if you don’t want to.  
If you are an employee or relative of an employee of the study site, you are under 
no obligation to get vaccine in this study. You may decline to get vaccine from 
the study at any time and for any reason, and your decision will not have any 
effect on your/your family member’s performance appraisal or employment at the 
study site. If you change your mind at any time, there will be no penalty, and no 
one will get mad at you. 
If you are a student, your decision to get vaccine in this study will not place you 
in good favor with the study doctor or other faculty (for example, receiving better 
grades, recommendations, employment). Also, not getting vaccine in this study 
will not adversely affect your relationship with the study doctor or other faculty. 
5. We will compensate you for getting the vaccine. 
Site: Insert your compensation plan here, e.g. money for number of study visits completed. 
Remember to include any costs to participants. 
Benefits 
6. This study may not benefit you. 
COVID-19 vaccination helps protect people from getting sick or severely ill with 
COVID-19. This study may help researchers find out if the vaccine is able to 
prevent infection with SARS-CoV-2. COVID-19 vaccination is an important tool 
to help stop the COVID-19 pandemic. The CDC recommends you get a COVID-
19 vaccine as soon as one is available to you. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 133 of 166 
If the vaccine later becomes approved and sold, there are no plans to share any 
money with you. 
Injuries 
Sites: Approval from CoVPN Regulatory Affairs (at CoVPN.core.reg@fredhutch.org) 
is needed for any change (other than those that the instructions specifically request or 
those previously approved by CoVPN Regulatory Affairs) to the boxed text. You can 
remove the box around the text. 
7. If you get sick or injured during the study, contact us immediately. 
Paragraph below for all sites.  
Your health is important to us. (Sites: adjust the following 2 sentences if 
applicable to the care available at your site) We will tell you about the care that 
we can give here. For the care that we cannot provide, we will explain how we 
will help you get care elsewhere.  
2 paragraphs below for all sites.  
This research study is covered by a US government program that may provide 
compensation for a serious injury or death. We will give you a handout with more 
information about this program. The National Institutes of Health (NIH) does not 
have a mechanism to provide direct compensation for research related injury. 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in this study. Or you might lose wages because you cannot go to work. 
However, there are no funds to pay for these kinds of injuries, even if they are 
study related.  
You always have the right to use the court system if you are not satisfied.  
 
Questions  
8. Whom to contact 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 study doctor at the telephone number listed on the first page of this 
consent document. If you seek emergency care, or hospitalization is required, alert 
the treating physician that you are participating in this research study.  
An institutional review board (IRB) is an independent committee established to 
help protect the rights of research subjects. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 134 of 166 
If you have any questions about your rights as a research subject, and/or concerns 
or complaints regarding this research study, contact: 
by mail: 
Study Subject Adviser 
Advarra IRB 
6100 Merriweather Dr., Suite 600Columbia, MD 21044 
or call toll free:    877-992-4724 
or by email:          adviser@advarra.com 
Please reference the following number when contacting the Study Subject 
Adviser: Pro00049375 
US sites may include, but are not required to: You may also contact the [name of 
local IRB/EC] at [insert contact information]. 
Your permissions and signature  
9. If you agree to join this study, you will need to sign below. Before you sign, 
make sure of the following: 
• You have read this consent form. 
• You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
• You have had your questions answered and know that you can ask more. 
• You agree to join this study. 
• You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s Name (Print) 
 
Participant’s Signature 
 
Date 
 
 
 
 
 
 
 
Clinic Staff Conducting 
Consent 
Discussion (Print) 
 
Clinic Staff Signature 
 
Date 
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 135 of 166 
Appendix C 
Sample informed consent form for 
Prospective Close Contact (PCC) cohort 
 
Sponsor / Study Title: 
  
National Institutes of Health, “A randomized controlled study to 
assess SARS CoV-2 infection, viral shedding, and subsequent 
potential transmission in individuals immunized with Moderna 
COVID-19 Vaccine” 
Protocol Number: 
 
CoVPN 3006 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
Thank you for your interest in our research study. It is called CoVPN 3006. This 
informed consent form will tell you more about the study. Please read it carefully to help 
you decide if you want to join. If you have questions, please ask us.  
If you decide to join this study, we will ask you to sign this form. We will offer you a 
copy of this form to keep.  
CoVPN 3006 is a research study. Research is not the same as medical care. The purpose 
of a research study is to answer scientific questions. We hope that what we learn will help 
people in the future. 
Key information 
• Joining this research study is voluntary. It is your choice. 
• Our scientific questions are: Does the study vaccine protect people from 
getting infected with a coronavirus called SARS-CoV-2? Does the study 
vaccine prevent people from transmitting SARS-CoV-2 to others? 
• If you join, your participation in this study will last for about 5 months. 
• If you join, we will ask you to answer eDiary questionnaires. If you or your 
contact in the main study group becomes SARS-CoV-2 infected, then we will 
ask you to take daily swabs of your nose, answer daily eDiary questionnaire 
for 2 weeks, and give 2 blood samples.  
Here are the risks of taking part: 
• There is a risk of loss of your personal information.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 136 of 166 
• There are other, less serious risks. We will tell you more about them later in 
this consent form. 
About the study 
The COVID-19 Prevention Network (CoVPN) is doing a study to test a vaccine 
against SARS-CoV-2. SARS-CoV-2 is the virus that causes the disease called 
COVID-19. We want to know if the vaccine is able to protect people from getting 
infected and if getting the vaccine will affect the amount of virus that is in your 
nose. We also want to know if getting the vaccine will prevent transmitting 
SARS-CoV-2 to others.  
We are asking you to join this study because you have been referred as a close 
contact with someone who is in the Main study.  
Many young adults will take part in this study around the US. This study has 5 
groups. The first 3 groups, called the Immediate Vaccination, Standard of Care, 
and Vaccine Declined groups, will be in the Main Study.  
• The Immediate Vaccination and Standard of Care groups will have about 
12,000 people that will get vaccine injections either immediately or 4 
months later. In this study, “standard of care” refers to all federal, state, 
and local recommendations regarding COVID-19 prevention, including 
COVID-19 vaccination, masking, social distancing, isolation and 
quarantine. 
• The Vaccine Declined group will have about 6,000 people who prefer not 
to be vaccinated and will be followed for 4 months.  
• The last two groups are close contacts of the Main Study: the Prospective 
Close Contact (PCC) group will have up to 36,000 people, and the Case-
ascertained Close Contact (CACC) group will have up to 2250 people. 
These close contact groups will help researchers determine if the vaccine 
prevents transmission of the SARS-CoV-2 virus to others. We will explain 
more about this later in this form.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 137 of 166 
You are being asked to participate in the PCC group. The researcher in charge of 
this study at this clinic is [Insert name of site PI]. The US National Institutes of 
Health is paying for this study.  
Joining the study 
1. It is completely up to you whether or not to join this study. 
Take your time in deciding. If it helps, talk to people you trust, such as your 
friends or family. If you decide not to join this study, or if you leave it after you 
have joined, it will not change your healthcare. If you do join, you do not give up 
your legal rights.  
If you are an employee or relative of an employee of the study site, you are under 
no obligation to participate in this study. You may withdraw from the study at any 
time and for any reason, and your decision will not have any effect on your/your 
family member’s performance appraisal or employment at the study site. You 
may refuse to participate or you may withdraw from the study at any time without 
penalty or anyone blaming you. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 138 of 166 
If you are a student, your participation will not place you in good favor with the 
study doctor or other faculty (for example, receiving better grades, 
recommendations, employment). Also, not participating in this study will not 
adversely affect your relationship with the study doctor or other faculty. 
Being in the study 
If you want to join, here is what will happen: 
We will send you information about how to download an electronic diary (eDiary) 
app onto your phone or tablet. We can help you download the app and show you 
how to use it. In order to use the app you will be asked to agree to the Terms of 
Use and Privacy Policy which will appear on your mobile device’s screen when 
you first start using the app. If you decide that you do not want to agree, then you 
should not participate in the research. While using the app, data about you 
including personal health information, other communication data, and internet 
usage will be collected and transmitted to the researchers and to the app 
developer. A complete description of this data collection and sharing is found in 
the Privacy Policy. Transmission of information via the internet is not completely 
secure, so there is a small risk of unintentional release of your information and 
safeguards are in place to protect your personal information. While the Terms of 
Use may include statements limiting your rights if you are harmed in this study, 
you do not release the investigator, sponsor, institution, or agents from 
responsibility for mistakes, and these statements do not apply to the use of the app 
in this research study. 
Initially, you will answer a 5-minute questionnaire in the eDiary. It will ask you 
about things such as your sex, age, race, and ethnicity. During the study, you will 
also answer questionnaires about whether you are sick or if you have tested 
positive for SARS-CoV-2. You will take an End of Study questionnaire in the 
eDiary at your last study visit. If you are a student, you may get SARS-CoV-2 
testing at your school about twice a week. If you have tested positive, you will 
enter the results of your SARS-CoV-2 tests taken at school or another location 
into the eDiary. 
If you or your contact in the main study group becomes SARS-CoV-2 infected, 
then we will ask you to take swabs of your nose and answer eDiary questionnaires 
every day for 2 weeks. You will be prompted by text or email to scan the barcode 
on the swab. You will return your nasal swabs using drop-off location(s) specified 
by the clinic or by mail. 
We will ask you to self-collect a small amount of your blood twice using a small 
device called the Tasso-SST OnDemand. You will take the first blood sample as 
soon as possible once you begin the daily swabs, and then you will take another 
sample about a month later. This will be less than one teaspoon of blood taken 
from one of your upper arms using a small device. We will give you everything 
you need to take the blood and return it to us.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 139 of 166 
The self-collection device sticks to the skin with a light adhesive. When the 
button is pressed, a vacuum forms, and the device will prick the surface of the 
skin. The vacuum draws blood out of the capillaries and into a sample pod 
attached to the bottom of the device. 
It is important that you continue to follow the federal, state, and local guidelines 
for SARS-CoV-2 prevention, which may include wearing a mask and keeping 
physical distance from others. If you get COVID-19 and are hospitalized, we will 
pause your participation. We will ask for your medical records and results from 
tests you might have received at the hospital. It is unlikely that you will be 
hospitalized, but to prepare for this, we will ask you to sign and date a medical 
release of information so we can get records from your doctor or view your 
hospital records. When you are released from the hospital, please let us know. We 
will ask you to resume your study participation so that we can continue to monitor 
your health and safety for the rest of the study. 
We will not pay for any of your COVID-19 care directly. 
2. The CoVPN will test your samples to see how your body, including your 
immune system, responds to the potential infection. 
We will send your samples to labs approved by the CoVPN. Your samples will 
not be labeled with your name or other identifying information.  
Researchers may also do genetic testing related to this study on your samples. 
Your genes are passed to you from your birth parents. Differences in people’s 
genes can help explain why some people get a disease while others do not. The 
genetic testing will only involve some of your genes, not all of your genes (your 
genome). The researchers will study only the genes related to the immune system 
and coronavirus, and genes that may affect how people get coronavirus. 
If you get SARS-CoV-2, the researchers may look at all of the virus’ genes that 
are in your samples. The researchers will use this information to learn more about 
SARS-CoV-2 and how the virus is impacted by the study vaccine. 
The tests the researchers do on your samples are for research purposes, not to 
check your health. However, the nasal swab testing you may do as part of this 
study may tell us if you are SARS-CoV-2 positive. Nasal swab test results from 
the study will be provided to the sites and be made available to you. You may be 
asked to get a confirmatory test. For all other lab tests, we will not provide the 
results to you or the site. 
When your samples are no longer needed for this study, the CoVPN will continue 
to store them. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 140 of 166 
3.  When samples are no longer needed for this study, the CoVPN wants to use 
them in other studies and share them with other researchers.  
The CoVPN calls these samples “extra samples”. The CoVPN will only allow 
your extra samples to be used in other studies if you agree to this. You will mark 
your decision at the end of this form.  
Do I have to agree? No. You are free to say yes or no, or to change your mind 
after you sign this form. At your request, the CoVPN will destroy all extra 
samples that it has. Your decision will not affect your being in this study. 
Where are the samples stored? Extra samples are stored in a secure central place 
called a repository. Your samples will be stored in the CoVPN repository in the 
United States. 
How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: Revise the previous sentence to insert limits if your 
regulatory authority imposes them.] 
Will I be paid for the use of my samples? No. Researchers may make scientific 
discoveries or products using your samples. If this happens, there is no plan to 
share any money with you.  
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They may help other people in the future.  
Will the CoVPN sell my samples and information? No, but the CoVPN may share 
your samples with other researchers. Once the CoVPN shares your samples and 
information, it may not be able to get them back. 
What information is shared with researchers? The samples and information will 
be labeled with a code number which will not be removed. The key to the code 
will stay at this clinic. However, some information that the CoVPN shares may be 
personal, such as your race, ethnicity, sex, and health information from the study.  
What kind of studies might be done with my extra samples and information? The 
studies will be related to vaccines, the immune system, coronavirus, and other 
diseases. 
Researchers may also do genetic testing on your samples. 
If you agree, researchers may compare all of your genes (your genome) to the 
genomes of many other people. Researchers look for common patterns of genes to 
help them understand diseases. The researchers may put the information into a 
protected database so that other researchers can access it. Your name and other 
personal information will not be included.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 141 of 166 
Usually, no one could connect your genome to you as a person. There are rules 
against this. It’s also really difficult to do. But there is a risk that someone could 
combine information from your genome and other public information about you 
and identify you. If others found out, it could lead to discrimination or other 
problems. The risk of this happening is very small.  
Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
• Researchers who use your extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and information 
• The researcher’s Institutional Review Board or Ethics Committee 
• Any regulatory agency that reviews research studies 
• The people who work with the researcher 
All of these people will do their best to protect your information. If they publish 
their research, they will not use your name or identify you personally. 
4. We will compensate you for your participation. 
Site: Insert your compensation plan here, e.g. money for number of swabs returned. 
Remember to include any costs to participants. 
5. We will do our best to protect your private information. 
Site: Check HIPAA authorization for conflicts with this section. 
Your study records and samples will be kept in a secure location. We will label all 
of your samples and most of your records with a code number, not your name or 
other personal information. We will not share your name with anyone who does 
not need to know it. 
Your records may also be reviewed by groups who watch over this study. These 
groups include: 
• Study monitors 
• The CoVPN, people who work for it, and companies that help it with this 
study 
• Some government agencies: 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 142 of 166 
o The US National Institutes of Health 
o The US Office for Human Research Protections 
o Any regulatory agency that reviews research studies 
• Some committees that make sure we protect your rights and keep you safe: 
o The Independent Data Monitoring Committee 
o Advarra Institutional Review Board (IRB) 
o Sites may but are not required to include: [Insert name of local IRB/EC]  
o Sites include: [Insert name of local IBC] 
All reviewers will take steps to keep your records private. 
Sites: Include the following boxed text. You can remove the box around the text. 
We have a Certificate of Confidentiality from the US government to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US National Institutes of Health 
funds this research, we cannot withhold information from it.  
The CoVPN may share information from this study with other researchers. 
Researchers may publish the results of this study.  
Sites: The text below may not be deleted or changed per FDA requirement. You can 
remove the box. 
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 website at any time. 
6. We may take you out of the study at any time.  
We may take you out of the study if: 
• you do not follow instructions, 
• we think that staying in the study might harm you, 
• the study is stopped for any reason. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 143 of 166 
Risks 
7. There are some risks to being in this study. 
This section describes the risks we know about. There may also be unknown risks, 
even serious ones. We will tell you if we learn anything new that may affect your 
willingness to stay in the study. 
Risks of blood draws: 
In this study, we will either take your blood or ask you to self-collect your blood 
with a small device. Taking blood can cause bruising, pain, fainting, soreness, 
redness, and itching.  
Risks of swabbing your nose: 
The feeling of having a small, soft-tipped swab inserted into your nostril and 
twirled around may be a little uncomfortable, but it should not be painful. There is 
a small chance there could be some bleeding, but this is unlikely.  
Risks to your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could have stress or 
anxiety. 
Risks of COVID-19:  
While you are in this study, you should still follow federal, state, and local 
guidelines for SARS-CoV-2 prevention, which may include wearing a mask and 
keeping physical distance from others. If you get sick, you should follow COVID-
19 precautions and isolate or self-quarantine.   
Benefits 
8. This study may not benefit you. 
This study may help researchers find out if people who got the vaccine are less 
likely to give it to people who they have been in close contact with. If the vaccine 
later becomes approved and sold, there are no plans to share any money with you. 
You do not have to join this research study if you don’t want to.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 144 of 166 
Leaving the study 
9. Tell us if you decide to leave the study. 
You are free to leave the study at any time and for any reason. If you want to 
leave, you will need to tell us. Your legal rights will not be affected. 
Previously collected information about you will remain in the study records and 
will be included in the analysis of results. Your information can not be removed 
from the study records. 
We may ask you to give a final blood sample or nasal swab.  
We believe these steps are important to protecting your health, but it is up to you 
whether to complete them. 
Injuries 
Sites: Approval from CoVPN Regulatory Affairs (at CoVPN.core.reg@fredhutch.org) 
is needed for any change (other than those that the instructions specifically request or 
those previously approved by CoVPN Regulatory Affairs) to the boxed text. You can 
remove the box around the text. 
10. If you have a life-threatening medical emergency, call 911 right away or seek 
help immediately. 
We do not expect you to get sick or injured as a result of being in this study. If 
you get COVID-19 while you are in the study, please let us know. (Sites: adjust 
the following 2 sentences if applicable to the care available at your site) We will 
tell you about the care that we can give here. For the care that we cannot provide, 
we will explain how we will help you get care elsewhere. You or your health 
insurance will have to pay for the care you get elsewhere. 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in this study. Or you might lose wages because you cannot go to work. 
However, there are no funds to pay for these kinds of injuries, even if they are 
study related. 
You always have the right to use the court system if you are not satisfied. 
Questions  
11. Whom to contact 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 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 145 of 166 
contact the study doctor at the telephone number listed on the first page of this 
consent document.  
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: 
Study Subject Adviser 
Advarra IRB 
6100 Merriweather Dr., Suite 600 
Columbia, MD 21044 
or call toll free:    877-992-4724 
or by email:          adviser@advarra.com 
Please reference the following number when contacting the Study Subject 
Adviser: Pro00049375 
US sites may include, but are not required to: You may also contact the [name of 
local IRB/EC] at [insert contact information]. 
Your permissions and signature  
12. In Section 3, we told you above about possible other uses of your extra 
samples and information outside this study. Please choose only one of the options 
below and write your initials in the box next to it. Whatever you choose, the 
CoVPN keeps track of your decision about how your samples and information can 
be used. You can change your mind after signing this form. 
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 146 of 166 
 
I allow my extra samples and information to be used for other studies related to 
vaccines, the immune system, coronavirus, and other diseases. This may include 
genetic testing.  
OR 
 
 
I agree to the option above and also to allow my extra samples and information 
to be used in studies that look at my whole genome. 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes 
not allowing genetic testing, or studies that look at my whole genome.  
 
13. If you agree to join this study, you will need to sign below. Before you sign, make 
sure of the following: 
• You have read this consent form. 
• You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
• You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s Name (Print) 
 
Participant’s Signature 
 
Date 
 
 
 
 
 
 
 
Clinic Staff Conducting 
Consent 
Discussion (Print) 
 
Clinic Staff Signature 
 
Date 
 
 
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 147 of 166 
Appendix D 
Sample informed consent form for Case-
Ascertained Close Contact (CACC) cohort 
 
Sponsor / Study Title: 
  
National Institutes of Health, “A randomized controlled study to 
assess SARS CoV-2 infection, viral shedding, and subsequent 
potential transmission in individuals immunized with Moderna 
COVID-19 Vaccine” 
Protocol Number: 
 
CoVPN 3006 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
Thank you for your interest in our research study. It is called CoVPN 3006. This 
informed consent form will tell you more about the study. Please read it carefully 
to help you decide if you want to join. If you have questions, please ask us.  
If you decide to join this study, we will ask you to sign this form. We will offer 
you a copy of this form to keep.  
CoVPN 3006 is a research study. Research is not the same as medical care. The 
purpose of a research study is to answer scientific questions. We hope that what 
we learn will help people in the future. 
Key information 
• Joining this research study is voluntary. It is your choice. 
• Our scientific questions are: Does the study vaccine protect people from getting 
infected with a coronavirus called SARS-CoV-2? Does the study vaccine prevent 
people from transmitting SARS-CoV-2 to others? 
• If you join, your participation in this study will last for about 1 month. 
• If you join, we will ask you to answer questionnaires, give blood, and take daily 
swabs of your nose for 2 weeks.  
Here are the risks of taking part: 
• There is a risk of loss of your personal information.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 148 of 166 
• There are other, less serious risks. We will tell you more about them later in this 
consent form. 
About the study 
The COVID-19 Prevention Network (CoVPN) are doing a study to test a vaccine 
against SARS-CoV-2. SARS-CoV-2 is the virus that causes the disease called 
COVID-19. We are asking you to join this study because you recently had close 
physical contact with someone who is in the Main study and who got infected 
with SARS-CoV-2. We want to find out if the person you had close physical 
contact might have transmitted SARS-CoV-2 to you.  
Many young adults will take part in this study around the US. This study has 5 
groups. The first 3 groups, called the Immediate Vaccination, Standard of Care, 
and Vaccine Declined groups, will be in the Main Study.  
• The Immediate Vaccination and Standard of Care groups will have about 
12,000 people that will get vaccine injections either immediately or 4 
months later. In this study, “standard of care” refers to all federal, state, 
and local recommendations regarding COVID-19 prevention, including 
COVID-19 vaccination, masking, social distancing, isolation and 
quarantine. 
• The Vaccine Declined group will have about 6,000 people who prefer not 
to be vaccinated and will be followed for 4 months.  
• The last two groups are close contacts of the Main Study: the Prospective 
Close Contact (PCC) group will have up to 36,000 people, and the Case-
ascertained Close Contact (CACC) group will have up to 2250 people. 
These close contact groups will help researchers determine if the vaccine 
prevents transmission of the SARS-CoV-2 virus to others. We will explain 
more about this later in this form.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 149 of 166 
You are being asked to participate in the CACC group. The researcher in charge 
of this study at this clinic is [Insert name of site PI]. The US National Institutes of 
Health is paying for this study.  
Joining the study 
1. It is completely up to you whether or not to join this study. 
Take your time in deciding. If it helps, talk to people you trust, such as your 
friends or family. If you decide not to join this study, or if you leave it after you 
have joined, it will not change your healthcare. If you do join, you do not give up 
your legal rights.  
If you are an employee or relative of an employee of the study site, you are under 
no obligation to participate in this study. You may withdraw from the study at any 
time and for any reason, and your decision will not have any effect on your/your 
family member’s performance appraisal or employment at the study site. You 
may refuse to participate or you may withdraw from the study at any time without 
penalty or anyone blaming you. 
If you are a student, your participation will not place you in good favor with the 
study doctor or other faculty (for example, receiving better grades, 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 150 of 166 
recommendations, employment). Also, not participating in this study will not 
adversely affect your relationship with the study doctor or other faculty. 
Being in the study 
If you want to join, here is what will happen: 
We will send you information about how to download an electronic diary (eDiary) 
app onto your phone or tablet. We can help you download the app and show you 
how to use it. In order to use the app you will be asked to agree to the Terms of 
Use and Privacy Policy which will appear on your mobile device’s screen when 
you first start using the app. If you decide that you do not want to agree, then you 
should not participate in the research. While using the app, data about you 
including personal health information, other communication data, and internet 
usage will be collected and transmitted to the researchers and to the app 
developer. A complete description of this data collection and sharing is found in 
the Privacy Policy. Transmission of information via the internet is not completely 
secure, so there is a small risk of unintentional release of your information and 
safeguards are in place to protect your personal information. While the Terms of 
Use may include statements limiting your rights if you are harmed in this study, 
you do not release the investigator, sponsor, institution, or agents from 
responsibility for mistakes, and these statements do not apply to the use of the app 
in this research study. 
You will take a 5-minute questionnaire in the eDiary. It will ask you about your 
contact with the person who tested positive for SARS-CoV-2, as well as other 
things such as your sex, age, race, and ethnicity. You will also take an End of 
Study questionnaire in the eDiary. If you have tested positive for SARS-CoV-2, 
you will enter the results of your SARS-CoV-2 tests taken at school or another 
location into the eDiary. 
If you are affiliated with a school that provides SARS-CoV-2 testing, you may get 
tested about twice a week. 
We will ask you to take daily swabs of both of your nostrils and track your 
COVID-19 symptoms in the eDiary daily for two weeks. You will be prompted 
by text or email to scan the barcode on the swab. You will return your nasal 
swabs using drop-off location(s) specified by the clinic or by mail. 
We will also ask you to collect a small amount of blood from one of your upper 
arms twice during the study using a small device called the Tasso-SST 
OnDemand. This will be less than one teaspoon of blood taken from one of your 
upper arms using a small device. You will take the first blood sample as soon as 
possible, and then you will take another sample about a month later. We will give 
you everything you need to take these samples and return them to us.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 151 of 166 
The self-collection device sticks to the skin with a light adhesive. When the 
button is pressed, a vacuum forms, and the device will prick the surface of the 
skin. The vacuum draws blood out of the capillaries and into a sample pod 
attached to the bottom of the device. 
It is important that you continue to follow the federal, state, and local guidelines 
for SARS-CoV-2 prevention, which may include wearing a mask and keeping 
physical distance from others.  
If you are hospitalized, we will pause your participation. We will ask for your 
medical records and results from tests you might have received at the hospital. It 
is unlikely that you will be hospitalized, but to prepare for this, we will ask you to 
sign and date a medical release of information so we can get records from your 
doctor or view your hospital records. When you are released from the hospital, 
please let us know. We will ask you to resume your study participation so that we 
can continue to monitor your health and safety for the rest of the study. 
2. The CoVPN will test your samples to see how your body, including your 
immune system, responds to the potential infection. 
We will send your samples to labs approved by the CoVPN. Your samples will 
not be labeled with your name or other identifying information.  
Researchers may also do genetic testing related to this study on your samples. 
Your genes are passed to you from your birth parents. Differences in people’s 
genes can help explain why some people get a disease while others do not. The 
genetic testing will only involve some of your genes, not all of your genes (your 
genome). The researchers will study only the genes related to the immune system 
and coronavirus, and genes that may affect how people get coronavirus. 
If you get SARS-CoV-2, the researchers may look at all of the virus’ genes that 
are in your samples. The researchers will use this information to learn more about 
SARS-CoV-2 and how the virus is impacted by the study vaccine. 
The tests the researchers do on your samples are for research purposes, not to 
check your health. However, the nasal swab testing you do as part of this study 
may tell us if you are SARS-CoV-2 positive. Nasal swab test results from the 
study will be provided to the sites and be made available to you. You may be 
asked to get a confirmatory test. For all other lab tests, we will not provide the 
results to you or the site.  
When your samples are no longer needed for this study, the CoVPN will continue 
to store them. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 152 of 166 
3. When samples are no longer needed for this study, the CoVPN wants to use 
them in other studies and share them with other researchers.  
The CoVPN calls these samples “extra samples”. The CoVPN will only allow 
your extra samples to be used in other studies if you agree to this. You will mark 
your decision at the end of this form.  
Do I have to agree? No. You are free to say yes or no, or to change your mind 
after you sign this form. At your request, the CoVPN will destroy all extra 
samples that it has. Your decision will not affect your being in this study. 
Where are the samples stored? Extra samples are stored in a secure central place 
called a repository. Your samples will be stored in the CoVPN repository in the 
United States. 
How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: Revise the previous sentence to insert limits if your 
regulatory authority imposes them.] 
Will I be paid for the use of my samples? No. Researchers may make scientific 
discoveries or products using your samples. If this happens, there is no plan to 
share any money with you.  
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They may help other people in the future.  
Will the CoVPN sell my samples and information? No, but the CoVPN may share 
your samples with other researchers. Once the CoVPN shares your samples and 
information, it may not be able to get them back. 
What information is shared with researchers? The samples and information will 
be labeled with a code number which will not be removed. The key to the code 
will stay at this clinic. However, some information that the CoVPN shares may be 
personal, such as your race, ethnicity, sex, and health information from the study.  
What kind of studies might be done with my extra samples and information? The 
studies will be related to vaccines, the immune system, coronavirus, and other 
diseases. 
Researchers may also do genetic testing on your samples. 
If you agree, researchers may compare all of your genes (your genome) to the 
genomes of many other people. Researchers look for common patterns of genes to 
help them understand diseases. The researchers may put the information into a 
protected database so that other researchers can access it. Your name and other 
personal information will not be included.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 153 of 166 
Usually, no one could connect your genome to you as a person. There are rules 
against this. It’s also really difficult to do. But there is a risk that someone could 
combine information from your genome and other public information about you 
and identify you. If others found out, it could lead to discrimination or other 
problems. The risk of this happening is very small.  
Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
• Researchers who use your extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and information 
• The researcher’s Institutional Review Board or Ethics Committee 
• Any regulatory agency that reviews research studies 
• The people who work with the researcher 
All of these people will do their best to protect your information. If they publish 
their research, they will not use your name or identify you personally. 
4. We will compensate you for your participation. 
Site: Insert your compensation plan here, e.g. money for number of swabs returned. 
Remember to include any costs to participants. 
5. We will do our best to protect your private information. 
Site: Check HIPAA authorization for conflicts with this section. 
Your study records and samples will be kept in a secure location. We will label all 
of your samples and most of your records with a code number, not your name or 
other personal information. We will not share your name with anyone who does 
not need to know it. 
Your records may also be reviewed by groups who watch over this study. These 
groups include: 
• Study monitors 
• The CoVPN, people who work for it, and companies that help it with this 
study 
• Some government agencies: 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 154 of 166 
o The US National Institutes of Health 
o The US Office for Human Research Protections 
o Any regulatory agency that reviews research studies 
• Some committees that make sure we protect your rights and keep you safe: 
o The Independent Data Monitoring Committee 
o Advarra Institutional Review Board (IRB) 
o Sites may but are not required to include: [Insert name of local IRB/EC]  
o Sites include: [Insert name of local IBC] 
All reviewers will take steps to keep your records private. 
Sites: Include the following boxed text. You can remove the box around the text. 
We have a Certificate of Confidentiality from the US government to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US National Institutes of Health 
funds this research, we cannot withhold information from it.  
The CoVPN may share information from this study with other researchers. 
Researchers may publish the results of this study.  
Sites: The text below may not be deleted or changed per FDA requirement. You can 
remove the box. 
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov, as required by U.S. Law. This website will not 
include information that can identify you. At most, the website will include a 
summary of the results. You can search this website at any time. 
6. We may take you out of the study at any time.  
We may take you out of the study if: 
• you do not follow instructions, 
• we think that staying in the study might harm you, 
• the study is stopped for any reason. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 155 of 166 
Risks 
7. There are some risks to being in this study.  
This section describes the risks we know about. There may also be unknown 
risks, even serious ones. We will tell you if we learn anything new that may affect 
your willingness to stay in the study. 
Risks of blood draws: 
In this study, we will either take your blood or ask you to self-collect your blood 
with a small device. Taking blood can cause bruising, pain, fainting, soreness, 
redness, and itching.  
Risks of swabbing your nose: 
The feeling of having a small, soft-tipped swab inserted into your nostril and 
twirled around may be a little uncomfortable, but it should not be painful. There is 
a small chance there could be some bleeding, but this is unlikely.  
Risks to your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could have stress or 
anxiety.  
Risks of COVID-19:  
While you are in this study, you should still follow federal, state, and local 
guidelines for SARS-CoV-2 prevention, which may include wearing a mask and 
keeping physical distance from others. If you get sick, you should follow COVID-
19 precautions and isolate or self-quarantine.   
Benefits 
8. This study may not benefit you. 
This study may help researchers find out if people who got the vaccine and later 
got infected with SARS-CoV-2 are less likely to give it to people who they have 
been in close contact with. If the vaccine later becomes approved and sold, there 
are no plans to share any money with you. 
You do not have to join this research study if you don’t want to.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 156 of 166 
Leaving the study 
9. Tell us if you decide to leave the study. 
You are free to leave the study at any time and for any reason. If you want to 
leave, you will need to tell us. Your legal rights will not be affected. 
Previously collected information about you will remain in the study records and 
will be included in the analysis of results. Your information can not be removed 
from the study records. 
We may ask you to give a final blood sample or nasal swab.  
We believe these steps are important to protecting your health, but it is up to you 
whether to complete them. 
Injuries 
Sites: Approval from CoVPN Regulatory Affairs (at CoVPN.core.reg@fredhutch.org) 
is needed for any change (other than those that the instructions specifically request or 
those previously approved by CoVPN Regulatory Affairs) to the boxed text. You can 
remove the box around the text. 
10. If you have a life-threatening medical emergency, call 911 right away or seek 
help immediately. 
We do not expect you to get sick or injured as a result of being in this study. If 
you get COVID-19 while you are in the study, please let us know. (Sites: adjust 
the following 2 sentences if applicable to the care available at your site) We will 
tell you about the care that we can give here. For the care that we cannot provide, 
we will explain how we will help you get care elsewhere. You or your health 
insurance will have to pay for the care you get elsewhere. 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in this study. Or you might lose wages because you cannot go to work. 
However, there are no funds to pay for these kinds of injuries, even if they are 
study related. 
You always have the right to use the court system if you are not satisfied. 
Questions  
11. Whom to contact 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 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 157 of 166 
contact the study doctor at the telephone number listed on the first page of this 
consent document.  
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: 
Study Subject Adviser 
Advarra IRB 
6100 Merriweather Dr., Suite 600 
Columbia, MD 21044 
or call toll free:    877-992-4724 
or by email:          adviser@advarra.com 
Please reference the following number when contacting the Study Subject 
Adviser: Pro00049375 
Sites may include, but are not required to: You may also contact the [name of 
local IRB/EC] at [insert contact information]. 
Your permissions and signature  
12. In Section 3, we told you above about possible other uses of your extra 
samples and information outside this study. Please choose only one of the options 
below and write your initials in the box next to it. Whatever you choose, the 
CoVPN keeps track of your decision about how your samples and information can 
be used. You can change your mind after signing this form. 
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 158 of 166 
 
I allow my extra samples and information to be used for other studies related to 
vaccines, the immune system, coronavirus, and other diseases. This may include 
genetic testing.  
OR 
 
 
I agree to the option above and also to allow my extra samples and information 
to be used in studies that look at my whole genome. 
OR 
 
 
I do not allow my extra samples to be used in any other studies. This includes 
not allowing genetic testing, or studies that look at my whole genome.  
 
13. If you agree to join this study, you will need to sign below. Before you sign, 
make sure of the following: 
• You have read this consent form. 
• You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
• You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s Name (Print) 
 
Participant’s Signature 
 
Date 
 
 
 
 
 
 
 
Clinic Staff Conducting 
Consent 
Discussion (Print) 
 
Clinic Staff Signature 
 
Date 
 
 
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 159 of 166 
Appendix E 
Procedures for Main Cohort, Immediate 
Vaccination Group 
 
Visit: 
011 
022 
03 
04 
05 
06 
Day: 
 
D1 
D29 
D57 
D113 
D141 
Week: 
 
W0 
W4 
W8 
W16 
W20 
Month: 
 
M0 
M1 
M2 
M4 
M5 
Procedure 
Scr. 
VAC1 
VAC2 
 
 
 
Study procedures 
 
 
 
 
 
 
Screening consent (if used) 
✓ 
– 
– 
– 
– 
– 
Assessment of understanding 
✓ 
– 
– 
– 
– 
– 
Protocol consent (eConsent) 
✓ 
– 
– 
– 
– 
– 
Medical history questionnaire3 
✓ 
✓ 
– 
– 
– 
– 
SARS-CoV-2 infection risk 
assessment3 
✓ 
Weekly  
 
COVID-19 symptom surveillance3 
– 
Weekly starts at week 2, not during week 5 
 
Confirm eligibility 
✓ 
– 
– 
– 
– 
– 
Obtain demographics3 
✓ 
– 
– 
– 
– 
– 
Randomize  
– 
✓ 
– 
– 
– 
– 
SARS-CoV-2 testing questionnaire3 
– 
approximately 2x per week 
 
End of study questionnaire3 
– 
– 
– 
– 
✓ 
– 
Research Samples4 
 
 
 
 
 
 
Serum for Immunogenicity Assays 
and Storage 
– 
✓ 
– 
✓ 
– 
– 
Serum for SARS-CoV-2 clinical 
serology5 
– 
✓6 
– 
✓6 
✓ 
– 
Nasal swab 
– 
Daily7 
– 
Vaccination procedures 
 
 
 
 
 
 
COVID-19 symptom check8 
– 
✓ 
✓ 
– 
– 
– 
Vaccination 
– 
✓ 
✓ 
– 
– 
– 
 
Greyed out visit column does not apply to this group. 
1 Screening may occur over the course of several contacts/visits up to and including day 
1, prior to vaccination. 
2 Blood draws required at vaccination visits must be performed prior to vaccination. 
3 Results from screening at school, if applicable, or at other locations will be captured via 
eDiary, please see Section 9.16. 
4 From screening to the final study visit, the total blood volume to be collected from each 
participant will be approximately 40 mL (maximum) with a maximum of approximately 
17 mL collected in a single visit.  
5 For blood self-collected by a participant the maximum volume will be less than 1 mL in 
a single collection. 
6 SARS-CoV-2 clinical serology testing may be performed on leftover blood from 
samples collected for immunogenicity assays. No separate blood sample is needed. If a 
Main cohort participant is also in the Prospective Close Contact (PCC) cohort related to 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 160 of 166 
an index case or in the Case-ascertained Close Contact (CACC) cohort, one additional 
blood collection (self-collection) will be performed (see table below ). 
7 Daily swabs will be collected from vaccination through D113. Swabs will be returned 
via drop-off location(s) specified by the clinic or through the mail. 
8 COVID-19 Symptom Check to be performed within 24 hours prior to vaccination. 
 
The following additional procedures will occur for Main cohort, immediate vaccination 
participants, who fall under any of the following categories: 
•  tested positive for SARS-CoV-2 from enrollment through Month 4 (see Section 9.7) 
•  enrolled also in the PCC cohort and are related to an index case (see Section 9.8) 
•  enrolled also in the CACC cohort (see Section 9.9) 
 
Day relative to notification of infection: 
D1-14 
Study procedures 
 
Symptom tracking via eDiary 
daily 
Research Samples 
 
Serum for SARS-CoV-2 clinical serology1  
✓2 
1 For blood self-collected by a participant the maximum volume will be less than 1 mL in a 
single collection. 
2 Sample for serology will be collected as soon as possible following report of positive 
SARS-CoV-2 test. 
 
In addition, we may ask participants to sign a release to allow us to review their COVID-19 
related medical records.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 161 of 166 
Appendix F 
Procedures for Main Cohort, Standard of 
Care and Vaccine Declined Groups 
 
Visit:  
011 
02 
03 
04 
05 
06 
Day: 
 
D1 
D29 
D57 
D113 
D141 
Week: 
 
W0 
W4 
W8 
W16 
W20 
Month: 
 
M0 
M1 
M2 
M4 
M5 
Procedure 
Scr. 
 
 
 
VAC1 
VAC2 
Study procedures 
 
 
 
 
 
 
Screening consent (if used) 
✓ 
– 
 
– 
– 
– 
Assessment of understanding 
✓ 
– 
 
– 
– 
– 
Protocol consent (eConsent) 
✓ 
– 
 
– 
– 
– 
Medical history questionnaire2 
✓ 
✓ 
 
– 
– 
– 
SARS-CoV-2 infection risk 
assessment2 
✓ 
Weekly 
– 
COVID-19 symptom surveillance2 
– 
Weekly 
– 
Confirm eligibility 
✓ 
– 
 
– 
– 
– 
Obtain demographics2 
✓ 
– 
 
– 
– 
– 
Randomize, Standard of Care Group 
only  
– 
✓ 
 
– 
– 
– 
SARS-CoV-2 testing questionnaire2 
– 
approximately 2x per week 
– 
End of study questionnaire2 
– 
– 
 
– 
✓7 
✓ 
Research Samples 
 
 
 
 
 
 
Serum for SARS-CoV-2 clinical 
serology3 
– 
✓ 
 
✓ 
✓ 
– 
Nasal swab 
– 
Daily4 
– 
Vaccination procedures6 
 
 
 
 
 
 
COVID-19 symptom check5 
– 
– 
 
– 
✓ 
✓ 
Vaccination 
– 
– 
 
– 
✓ 
✓ 
Greyed out visit does not apply to this group. 
1 Screening may occur over the course of several contacts/visits up to and 
including day 1, prior to randomization. 
2 Results from screening at school, if applicable, or at other locations will be 
captured via eDiary, please see Section 9.16. 
3 From screening to the final study visit, the total blood volume to be collected 
from each participant will be approximately 15 mL (maximum) with a 
maximum of approximately 5 mL collected in a single visit. For blood self-
collected by a participant the maximum volume will be less than 1 mL in a 
single collection. If a Main cohort participant is also in the Prospective Close 
Contact (PCC) cohort related to an index case or in the Case-ascertained Close 
Contact (CACC) cohort, one additional blood collection (self-collection) will be 
performed (see table below). 
4 Daily swabs will be collected from D1 through D113. Swabs will be returned 
via drop-off location(s) specified by the clinic or through the mail. 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 162 of 166 
5 COVID-19 Symptom Check to be performed within 24 hours prior to 
vaccination. 
6 Vaccination procedures only apply to participants who have not received 
COVID-19 vaccine outside the study and for participants in the Vaccine 
Declined Group who request to be vaccinated. 
7 Only applies to participants who are not receiving vaccination on study, ie, 
who have already received COVID-19 vaccine outside the study or who have 
declined vaccination (Visit 5 will be the last study visit for these participants). 
The following additional procedures will occur for Main cohort, standard of care and 
vaccine declined participants, who fall under any of the following categories: 
• 
tested positive for SARS-CoV-2 from enrollment through Month 4 (see 
Section 9.7) 
• 
enrolled also in the PCC cohort and are related to an index case (see Section 
9.8) 
• 
enrolled also in the CACC cohort (see Section 9.9) 
 
Day relative to notification of infection: 
D1-14 
Study procedures 
 
Symptom tracking via eDiary 
daily 
Research Samples 
 
Serum for SARS-CoV-2 clinical serology1  
✓2 
1For blood self-collected by a participant the maximum volume will be less than 1 mL 
in a single collection. 
2 Sample for serology will be collected as soon as possible following report of 
positive SARS-CoV-2 test 
 
In addition, we may ask participants to sign a release to allow us to review their 
COVID-19 related medical records.  
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 163 of 166 
Appendix G 
Procedures for Prospective Close Contact 
(PCC) cohort 
 
Visit: 
100 
101 
Day: 
D1 
D113 
Month: 
M0 
M4 
 
Enrollment 
Follow-up 
Study procedures 
 
 
Protocol consent (eConsent) 
✓ 
– 
Obtain demographics1  
✓ 
– 
SARS-CoV-2 testing questionnaire1 
approximately 2x per week 
End of study questionnaire1 
– 
✓ 
1 Results from screening at school, if applicable, or at other locations will be captured via 
eDiary, please see Section 9.16. 
 
If a PCC participant (or their Main study contact) tests positive for SARS-CoV-2, the 
following additional procedures will occur: 
Day relative to notification of 
infection: 
D1 
D29 
Study procedures 
 
 
Report of exposure1 
✓ 
 
Symptom tracking1 
Daily for 14 
days 
– 
Research Samples 
 
 
Serum for SARS-CoV-2 clinical 
serology2  
✓ 
✓ 
Nasal swab3 
Daily for 14 
days 
– 
1 Will be captured via eDiary , please see Section 9.16. 
2For blood self-collected by a participant the maximum volume will be less than 1 mL 
in a single collection. Sample for serology will be collected as soon as possible 
following report of positive SARS-CoV-2 test. 
3Swabs will be returned via drop-off location(s) specified by the clinic or through the 
mail. Nasal swabs will be collected as soon as possible following report of positive 
SARS-CoV-2 test. 
 
In addition, we may ask participants to sign a release to allow us to review their 
COVID-19 related medical records.  

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 164 of 166 
Appendix H 
Procedures for Case-Ascertained Close 
Contact Cohort 
 
Visit: 
200 
201 
202 
Day: 
D1 
D1-D3 
D29 
Month: 
M0 
M0 
M1 
 
Enrollment 
Initial specimen 
collection 
Follow-up 
Study procedures 
 
 
 
Protocol consent (eConsent) 
✓ 
– 
– 
Collection of demographic 
information1 
✓ 
– 
– 
Report of exposure1 
✓ 
– 
– 
Symptom tracking1 
 
Daily for 14 days 
– 
SARS-CoV-2 testing questionnaire1 
approximately 2x per week 
End of study questionnaire1 
– 
– 
✓ 
Research Samples 
 
 
 
Serum for SARS-CoV-2 clinical 
serology2  
 
✓ 
✓ 
Nasal swab3  
 
Daily for 14 days 
– 
1Results from screening at school, if applicable, or at other locations will be captured 
via eDiary, please see Section 9.16. 
2 For blood self-collected by a participant the maximum volume will be less than 1 
mL in a single collection. Sample for serology will be collected as soon as possible 
following report of positive SARS-CoV-2 test (ie, as early as Day 1). 
3Swabs will be returned via drop-off location(s) specified by the clinic or through the 
mail. Nasal swabs will be collected as soon as possible following report of positive 
SARS-CoV-2 test (ie, as early as Day 1). 
 
In addition, we may ask participants to sign a release to allow us to review their 
COVID-19 related medical records.  
 

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 165 of 166 
Appendix I 
Visit windows 
Main Cohort, Immediate Vaccination, Visit Windows 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target Day 
Target 
Day1 
Upper 
Target Day 
Upper Allowable 
Window  
01.0 
Screening 
-56 
- 
 
- 
0 
02.0 
Enrollment/Randomization
2 
- 
- 
1 
- 
- 
03.0 
Vaccination 2 
- 
-3 
293 
+7 
+14 
04.0 
Month 2 Follow-up  
- 
-7 
57 
+7 
+14 
05.0 
Month 4 Follow-up  
-13 
-7 
113 
+14 
+56 
1.Target dates are relative to Visit 2.0 (Enrollment/Randomization), except for cases described in footnote 3. 
2. Completion of post enrollment activities may occur up to approximately 7 days post enrollment (see Section 9.3) . 
3. In the event that Vaccination 1 occurs on a different day than Visit 2.0 (Enrollment/Randomization), Visit 3.0 target dates are 
relative to date of Vaccination 1.   
Main Cohort, Standard of Care and Vaccine Declined, Visit Windows 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower Target 
Day 
Target 
Day1 
Upper Target 
Day 
Upper Allowable 
Window  
01.0 
Screening 
-56 
- 
 
- 
0 
02.0 
Enrollment/Randomization2 
- 
- 
1 
- 
- 
04.0 
Month 2 Follow-up  
- 
-7 
57 
+7 
+14 
05.0 
Vaccination 13  
-13 
-7 
113 
+14 
+28 
06.0 
Vaccination 21, 3  
- 
-3 
141 
+7 
+14 
1. Target dates are relative to Visit 2.0 (Enrollment/Randomization), except visit 06.0, which is relative to visit 05.0.   
2. Completion of post enrollment activities may occur up to approximately 7 days post enrollment (see Section 9.5) . 
3. Vaccination visits only apply to participants who have not received COVID-19 vaccine outside the study and for participants in 
the Vaccine Declined Group who request to be vaccinated.  
Case-Ascertained Close Contact (CACC) Cohort and applicable Prospective Close 
Contact (PCC) participants1, Visit Windows 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower Target 
Day 
Target 
Day2 
Upper Target 
Day 
Upper Allowable 
Window  
200.0 
Enrollment 
- 
- 
1 
- 
- 
201.0 
Initial blood specimen 
collection 
 
-2 
3 
+1 
+4 
202.0 
Day 29 Follow-up  
- 
-7 
29 
+14 
+28 
1. Applicable to PCC participants when they (or their Main study contact) tests positive for SARS-CoV-2. 
2. Target dates are relative to Visit 200.0 (Enrollment).   

CoVPN 3006 Version 4.0 / May 20, 2021 
CoVPN 3006_v4.0_Final.docx / Page 166 of 166 
Appendix J 
Protocol Signature Page 
 
A randomized controlled study to assess SARS CoV-2 infection, viral shedding, 
and subsequent potential transmission in individuals immunized with Moderna 
COVID-19 Vaccine 
I will conduct the study in accordance with the provisions of this protocol and all 
applicable protocol-related documents. I agree to conduct this study in 
compliance with United States (U.S.) Health and Human Service regulations (45 
CFR 46); applicable U.S. Food and Drug Administration regulations; standards of 
the International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice (E6) 
(R2); Institutional Review Board/Ethics Committee determinations; all applicable 
in-country, state, and local laws and regulations; and other applicable 
requirements (eg, U.S. National Institutes of Health, Division of AIDS) and 
institutional policies. 
 
 
 
 
 
 
 
 
 
Investigator of Record Name (print) 
 
Investigator of Record Signature 
 
Date 
 
 
Protocol Number: CoVPN 3006 
Protocol Version: Version 4.0 
Protocol Date: May 20, 2021