Master Protocol for Early Treatment and Post-Exposure Prophylaxis of COVID-19 Adaptive Platform Trial PROTECT-APT 1
Phase: PHASE2
Conditions: SARS-CoV-2
Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

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Master Protocol for Early Treatment and Post-Exposure 
Prophylaxis of COVID-19 Adaptive Platform Trial 
PROTECT-APT 1 
 
Protocol Number: PC06 
 
Sponsored by: FHI Clinical 
 
Funded by: Joint Program Executive Office (JPEO) 
 
Implemented by: The Henry M. Jackson Foundation for the 
Advancement of Military Medicine Inc. (HJF) 
 
Industry Supporters: 
Study Chair: Danielle Clark 
Principal Investigator: Kristen Pettrone 
 
Version 5.0 
07 Feb 2024 

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SUMMARY OF CHANGES FROM PREVIOUS VERSION 
Version and 
Date
Affected Section(s)
Summary of Revisions Made
Rationale
V 5.0 
07 Feb 2024 
3.2 Background 
Added rationale for expansion of 
the study population to standard 
and intermediate risk 
Rational to support study 
population expansion 
V 5.0  
07 Feb 2024 
5.2 Shared Groups  
Clarified the ability for PSAs to 
choose to participate or not 
participate in placebo sharing 
 
Clarified participants must meet 
final eligibility criteria for all PSAs 
for which they are eligible and 
contributing to a shared placebo 
pool 
Clarification on placebo 
sharing for PSAs and 
participants 
V 5.0 
07 Feb 2024 
7.4.1 Randomization 
Clarified the ability for PSAs to 
choose to participate or not 
participate in placebo sharing 
 
Clarified participants must meet 
final eligibility criteria for all PSAs 
for which they are eligible and 
contributing to a shared placebo 
pool 
Clarification on placebo 
sharing 
V 5.0 
07 Feb 2024 
7.4. Randomization, 
Figure 3 
 
Updated figure to clarify flow for 
participant eligibility for multiple 
PSAs contributing to shared 
placebo pool 
Clarification on placebo 
sharing 
V 5.0  
07 Feb 2024 
14.1.2 Informed 
Consent Process and 
Informational 
Documents Provided 
to Participants  
Clarified that participants must 
complete PSA informed consent for 
all PSAs for which they may be 
eligible and are contributing to a 
shared placebo pool 
Clarification on participant 
eligibility assessment for 
placebo sharing 
V 5.0 
07 Feb 2024 
9.4.2 Enrollment Visit 
– In Person (Day 0) 
Clarified order of activities to 
reflect Informed Consent and 
MP/PSA screening assessments  
Clarification on order to 
activities for participants to 
complete PSA ICF and 
eligibility assessments 
prior to Step 1 
randomization 

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Version and 
Date
Affected Section(s)
Summary of Revisions Made
Rationale
V 5.0 
07 Feb 2024 
6.2 Exclusion Criteria 
Population A 
Expanded study population to 
include standard and intermediate 
risk participants (revised high risk 
exclusion criteria per FDA Type D 
Meeting Request Written 
Response) 
FDA feedback to Type D 
Meeting Request 
V 5.0 
07 Feb 2024 
9.2.3 Screening 
Assessments 
Clarified screening assessments 
under the Master Protocol 
Clarification of 
requirements for screening 
under Master Protocol  

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TABLE OF CONTENTS 
SUMMARY OF CHANGES FROM PREVIOUS VERSION ......................................................... 2 
STATEMENT OF COMPLIANCE ............................................................................................... 8 
SIGNATURE PAGE .................................................................................................................... 9 
1 
PROTOCOL SUMMARY .................................................................................................. 10 
1.1 
Study Synopsis ........................................................................................................... 10 
1.2 
Schedule of Activities (SoA)........................................................................................ 12 
2 
STUDY MANAGEMENT .................................................................................................. 17 
3 
INTRODUCTION .............................................................................................................. 18 
3.1 
Study Rationale .......................................................................................................... 18 
3.2 
Background ................................................................................................................ 18 
3.3 
Study Hypothesis ........................................................................................................ 20 
3.4 
Risk/Benefit Assessment ............................................................................................ 20 
3.4.1 
Known Potential Risks .......................................................................................... 20 
3.4.2 
Known Potential Benefits ...................................................................................... 21 
3.4.3 
Assessment of Potential Risks and Benefits ......................................................... 21 
4 
OBJECTIVES AND ENDPOINTS .................................................................................... 22 
4.1 
Early Treatment .......................................................................................................... 22 
4.2 
Post-Exposure Prophylaxis ......................................................................................... 23 
5 
STUDY DESIGN .............................................................................................................. 24 
5.1 
Overall Design ............................................................................................................ 24 
5.1.1 
Selection of Investigational Products .................................................................... 24 
5.1.2 
Period of Evaluation .............................................................................................. 25 
5.1.3 
Early Termination .................................................................................................. 25 
5.2 
Shared Groups ........................................................................................................... 25 
5.3 
Scientific Rationale for Study Design .......................................................................... 25 
5.4 
Justification for Dose .................................................................................................. 25 
5.5 
End of Study Definition ............................................................................................... 26 
6 
STUDY POPULATION AND STUDY ENROLLMENT ...................................................... 27 
6.1 
Inclusion Criteria ......................................................................................................... 27 
6.2 
Exclusion Criteria ........................................................................................................ 28 
6.3 
Lifestyle Considerations .............................................................................................. 30 
6.4 
Screen Failures .......................................................................................................... 30 
6.5 
Strategies for Recruitment and Retention ................................................................... 30 
7 
STUDY INTERVENTION .................................................................................................. 32 
7.1 
Study Intervention(s) Administration ........................................................................... 32 
7.1.1 
Study Intervention Description .............................................................................. 32 
7.1.2 
Dosing and Administration .................................................................................... 32 
7.2 
Preparation/Handling/Storage/Accountability .............................................................. 32 
7.2.1 
Acquisition and Accountability ............................................................................... 32 
7.2.2 
Acquisition ............................................................................................................ 32 
7.2.3 
Accountability ....................................................................................................... 32 

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7.2.4 
Formulation, Appearance, Packaging, and Labeling ............................................. 33 
7.2.5 
Product Storage and Stability ................................................................................ 33 
7.2.6 
Preparation ........................................................................................................... 33 
7.3 
Prohibited Medications ............................................................................................... 33 
7.4 
Measures to Minimize Bias: Randomization and Blinding ........................................... 33 
7.4.1 
Randomization ...................................................................................................... 33 
7.4.2 
Blinding and Unblinding ........................................................................................ 36 
7.5 
Study Intervention Compliance ................................................................................... 36 
7.6 
Concomitant Therapy ................................................................................................. 37 
7.7 
Standard of Care ........................................................................................................ 37 
7.7.1 
Rescue Medicine .................................................................................................. 38 
8 
PARTICIPANT DISCONTINUATION OR WITHDRAWAL ............................................... 39 
8.1 
Participant Discontinuation of IP ................................................................................. 39 
8.2 
Withdrawal of Consent ................................................................................................ 39 
8.3 
Lost to Follow-Up ........................................................................................................ 40 
9 
STUDY ASSESSMENTS AND PROCEDURES ............................................................... 41 
9.1 
Efficacy Assessments ................................................................................................. 41 
9.2 
Clinical and Laboratory Assessments ......................................................................... 41 
9.2.1 
Clinical Assessments ............................................................................................ 41 
9.2.2 
Lab Assessments ................................................................................................. 44 
9.2.3 
Screening Assessments ....................................................................................... 45 
9.2.4 
Stored Specimens ................................................................................................ 46 
9.2.5 
Blood Volumes...................................................................................................... 46 
9.2.6 
Pharmacokinetics ................................................................................................. 46 
9.3 
Procedures to Follow in the Event of Abnormal Laboratory Test Values or Clinical 
Findings ...................................................................................................................... 47 
9.4 
Study Visits ................................................................................................................. 47 
9.4.1 
Screening Visit - In Person or Remote (Within 24 hours prior to Enrollment) ........ 47 
9.4.2 
Enrollment Visit – In Person (Day 0) ..................................................................... 48 
9.4.3 
Day 3 – Remote or In Person ................................................................................ 49 
9.4.4 
Day 7 – Remote or In Person ................................................................................ 50 
9.4.5 
Day 10 – Remote .................................................................................................. 51 
9.4.6 
Day 14 – In Person ............................................................................................... 51 
9.4.7 
Day 28 – In Person ............................................................................................... 51 
9.4.8 
Week 12 – In Person or Remote ........................................................................... 52 
9.4.9 
Unscheduled Visits – In Person or Remote ........................................................... 53 
9.4.10 
Worsening/Hospitalization .................................................................................... 54 
10 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS .............................................. 55 
10.1 
Definition of Adverse Events (AE) ............................................................................... 55 
10.1.1 
Definition of Treatment Emergent Adverse Events ................................................ 55 
10.1.2 
Definition of Serious Adverse Events (SAE) .......................................................... 55 
10.1.3 
Classification of Adverse Events ........................................................................... 55 
10.1.4 
Relationship to Investigational Product or Study Participation ............................... 56 
10.1.5 
Serious and Unexpected Suspected Adverse Reactions (SUSAR) ....................... 56 

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10.1.6 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 57 
10.1.7 
Adverse Event Recording ..................................................................................... 57 
10.1.8 
Adverse Events of Special Interest ....................................................................... 57 
10.1.9 
Reporting of Pregnancy and Breastfeeding ........................................................... 57 
10.1.10 Serious Adverse Event Reporting ......................................................................... 57 
10.2 
Unanticipated Problems .............................................................................................. 59 
10.2.1 
Definition of Unanticipated Problems (UP) ............................................................ 59 
10.2.2 
Unanticipated Problem Reporting ......................................................................... 59 
10.3 
Methods for Obtaining Adverse Event and Serious Adverse Event Data .................... 59 
10.4 
Serious Adverse Event Follow-up ............................................................................... 60 
11 
SAFETY AND DATA MONITORING ................................................................................ 61 
11.1 
Medical Monitor .......................................................................................................... 61 
11.2 
Protocol Safety Review Team (PSRT) ........................................................................ 61 
11.3 
Data Safety Monitoring Board (DSMB) ....................................................................... 62 
12 
PAUSE AND STOPPING CRITERIA ............................................................................... 63 
12.1 
Individual Participant Pause and Stopping Criteria ..................................................... 63 
12.2 
Study and/or PSA Pause and Stopping Criteria .......................................................... 63 
12.3 
Resumption of Paused Study ..................................................................................... 64 
12.4 
Corrective Actions and Reporting Events to Participants ............................................ 65 
13 
STATISTICAL CONSIDERATIONS ................................................................................. 66 
13.1 
Hypotheses ................................................................................................................ 66 
13.2 
Populations for Analysis ............................................................................................. 66 
13.3 
Primary Endpoint/Estimand Analysis .......................................................................... 67 
13.3.1 
Early Treatment .................................................................................................... 67 
13.3.2 
Post-Exposure Prophylaxis ................................................................................... 68 
13.4 
Outcome Measures and Statistical Analysis ............................................................... 68 
13.4.1 
Early Treatment .................................................................................................... 68 
13.4.1.1 
Primary Outcome ............................................................................................ 68 
13.4.1.2 
Key Secondary Outcomes............................................................................... 69 
13.4.1.3 
Safety and Tolerability ..................................................................................... 69 
13.4.1.4 
Exploratory ...................................................................................................... 69 
13.4.1.5 
Sub-Group Analyses ....................................................................................... 69 
13.4.2 
Post Exposure Prophylaxis ................................................................................... 69 
13.4.2.1 
Primary Outcome ............................................................................................ 69 
13.4.2.2 
Secondary Outcomes ...................................................................................... 69 
13.4.2.3 
Safety and Tolerability ..................................................................................... 69 
13.4.2.4 
Exploratory ...................................................................................................... 69 
13.4.2.5 
Sub-Group Analyses ....................................................................................... 70 
13.5 
Interim Analysis Plan .................................................................................................. 70 
13.6 
Final Analysis Plan ..................................................................................................... 70 
13.7 
Missing Data ............................................................................................................... 70 
13.8 
Sample Size Determination ........................................................................................ 71 
13.8.1 
Early Treatment .................................................................................................... 71 

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13.8.2 
Post-Exposure Prophylaxis ................................................................................... 71 
14 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............. 72 
14.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................... 72 
14.1.1 
Regulatory Review ................................................................................................ 72 
14.1.2 
Informed Consent Process and Informational Documents Provided to 
Participants ........................................................................................................... 72 
14.1.3 
Consent Procedures and Documentation .............................................................. 72 
14.1.4 
Study Discontinuation and Closure ....................................................................... 74 
14.1.5 
Confidentiality and Privacy .................................................................................... 74 
14.1.6 
Future Use of Stored Specimens and Data ........................................................... 75 
14.1.7 
Key Roles and Study Governance ........................................................................ 75 
14.1.8 
Safety Oversight ................................................................................................... 76 
14.1.9 
Clinical Monitoring ................................................................................................ 76 
14.1.10 Quality Assurance and Quality Control ................................................................. 76 
14.1.11 Data Handling and Record Keeping ...................................................................... 77 
14.1.12 Data Collection and Management Responsibilities ............................................... 77 
14.1.13 Study Records Retention ...................................................................................... 78 
14.1.14 Protocol Deviations ............................................................................................... 78 
14.1.15 Publication and Data Sharing Policy ..................................................................... 78 
14.1.16 Conflict of Interest Policy ...................................................................................... 79 
15 
ADDITIONAL CONSIDERATIONS .................................................................................. 80 
16 
ABBREVIATIONS ............................................................................................................ 81 
17 
STUDY-SPECIFIC DEFINITIONS .................................................................................... 83 
18 
PROTOCOL AMENDMENT HISTORY ............................................................................ 84 
19 
REFERENCES ................................................................................................................. 91 
20 
Supplement 1: Screening Symptom Questionnaire ..................................................... 94 
20.1 
Supplement 2: Daily Follow Up Symptom Questionnaire ............................................ 99 
20.2 
Supplement 3: COVID-19 Symptom Review ............................................................. 103 
List of Tables 
Table 1. 
Adverse Event Notification and Study Pausing Guidelines .................................... 64 
List of Figures 
Figure 1. 
Participant Stratification and Randomization Plan ................................................. 34 
Figure 2. 
Randomization Scheme for Early Treatment and PEP Indications: Participant 
Eligible for One PSA ............................................................................................. 35 
Figure 3. 
Randomization Scheme for Early Treatment and PEP Indications: Participant 
Eligible for Two PSAs ........................................................................................... 35 
Figure 4. 
Second Randomization Step: IPs with SOC Treatment Allocation ........................ 37 
 

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STATEMENT OF COMPLIANCE 
The trial will be carried out in accordance with International Council on Harmonization Good 
Clinical Practice (ICH GCP) and the following: 
 United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 
812). 
USG funded investigators and clinical trial site staff who are responsible for the conduct, 
management, or oversight of USG-funded clinical trials have completed Human Subjects 
Protection and ICH GCP Training. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval. Approval of both 
the protocol and the consent form(s) must be obtained before any participant is consented. Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study. All changes to the consent form(s) will be IRB approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 

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SIGNATURE PAGE 
 
 
The signature below constitutes the approval of this protocol and the attachments and provides 
the necessary assurances that this trial will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable US federal regulations and ICH guidelines. 
 
Site Investigator Name: 
 
Site Investigator Title: 
 
Signature: 
 
Date: 
 
 
 
 

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1 
PROTOCOL SUMMARY 
1.1 
Study Synopsis 
Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Adaptive Platform Trial  
Design 
This study is an adaptive, randomized, double blind, platform trial 
evaluating promising investigational products (IP) for safety and efficacy 
as early outpatient treatment and post-exposure prophylaxis for Severe 
Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This 
multicenter trial will be conducted in both domestic and international sites. 
The study will compare IPs to control in standard and intermediate risk, 
non-hospitalized adult SARS-CoV-2 infected participants and uninfected 
adult contacts of SARS-CoV-2 confirmed cases. The master protocol will 
outline the core elements of the study. Investigational products may be 
included in either or both study indications: early treatment and post-
exposure prophylaxis (PEP). The study includes a phase 2 evaluation for 
all IPs. The platform trial design will allow for multiple IPs to be 
incorporated into the protocol as product specific appendices (PSA) as 
products are identified and become available. Each PSA will detail the 
interventions, the endpoints, target treatment effect, intended statistical 
analysis, the relevant control arms, and the sample size range. The PSA 
may define additional adaptive design elements, such as early declaration 
rules.
Regimen 
IPs for early treatment and/or post-exposure prophylaxis will be selected 
by the study investigators for inclusion based on the review of in vitro data 
demonstrating anti-SARS-CoV-2 therapeutic efficacy in pre-clinical and 
early clinical testing, and adequate safety data for the indication. Products 
included in the study for an alternate indication (such as post-exposure 
prophylaxis) will also be chosen based on similar evaluations of efficacy, 
and safety of the initial indication. Selection will also be based on product 
availability. Dosing regimens will be outlined in PSAs and Informed 
Consent Forms (ICFs). 
Duration 
In person and remote follow up will occur twice a week through Day 14 
then at Day 28 and Week 12. Variations to the master protocol schedule 
will be outlined in product specific appendices and ICFs. 
Stratification 
Participants will be stratified as SARS-CoV-2 positive (cases) or SARS-
CoV-2 negative (contacts) after completion of a screening process. SARS-
CoV-2 positive cases will be placed in the Early Treatment indication and 
the SARS-CoV-2 negative close contacts of symptomatic SARS-CoV-2 
positive cases will be placed in the PEP indication. 

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Randomization 
Two step randomization. After completion of the screening process, 
participants will be stratified into the appropriate indication of the trial 
(Early Treatment for SARS-CoV-2 positive cases and PEP for close 
contacts of SARS-CoV-2 positive cases). The first randomization will be 
to an appropriate PSA for which participants are eligible (meeting product-
specific inclusion and exclusion criteria). Participants must be eligible for 
at least one PSA enrolling in that indication. The first randomization will 
not be blinded. The second randomization will be to the arms within the 
PSA (IP or control). The second randomization will be blinded.
Study 
Population 
Population A: Symptomatic, standard and intermediate risk, non-
hospitalized SARS-CoV-2 infected adults (≥18 years)  
Population B: SARS-CoV-2 uninfected adult contacts
Sample Size 
The sample size for each product will be detailed in each PSA.  
Outcome 
Measures 
The primary efficacy assessment in the early treatment indication will be 
time to sustained alleviation or resolution of COVID-19 symptoms 
The primary efficacy assessment in the post-exposure prophylaxis 
indication will be incidence of COVID-19 infection
 
 

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1.2 
Schedule of Activities (SoA) 
STUDY VISIT LOCATION A 
IN PERSON 
OR REMOTE b 
IN PERSON 
IN PERSON 
OR  
REMOTE 
REMOTE 
IN PERSON 
IN PERSON 
OR 
REMOTE 
STUDY PROCEDURES 
SCREENING c 
ENROLLMENT 
D0 
D3 d 
D7 d 
D10 
D14 
D28 
WEEK 
12 
UNSCHEDULED e 
VISIT WINDOW  
(+/- DAYS OR WEEKS) 
UP TO 24 HOURS 
PRIOR TO 
ENROLLMENT 
0 
1 DAY 
1 DAY 
1 DAY 
2 DAYS 
4 DAYS 
2 WEEKS 
NOT APPLICABLE 
SCREENING & PROCEDURES 
Screening Informed 
Consent 
X 
 
 
 
 
 
 
 
 
Demographics f 
X 
X 
 
 
 
 
 
 
 
Medical History f 
X 
X 
 
 
 
 
 
 
 
Vital Signs f 
X 
X 
 
 
 
 
 
 
 
Physician Exam f, g 
X 
X 
 
 
 
 
 
 
 
Height and Weight f 
X 
X 
 
 
 
 
 
 
 
SARS-CoV-2 
Vaccination History   f,i 
X 
X 
X 
X 
 
X 
X 
X 
X 
Screening Symptom 
Questionnaire f fh,i  
X 
X 
 
 
 
 
 
 
 
Concomitant Medication 
Review f,i 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Venous Blood Sampling 
X 
X 
 
 
 
 
 
 
 
Screening Laboratories j,o 
X 
X 
 
 
 
 
 
 
 
Upper respiratory 
Specimen f, 
X 
X 
 
 
 
 
 
 
 

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STUDY VISIT LOCATION A 
IN PERSON 
OR REMOTE b 
IN PERSON 
IN PERSON 
OR  
REMOTE 
REMOTE 
IN PERSON 
IN PERSON 
OR 
REMOTE 
STUDY PROCEDURES 
SCREENING c 
ENROLLMENT 
D0 
D3 d 
D7 d 
D10 
D14 
D28 
WEEK 
12 
UNSCHEDULED e 
VISIT WINDOW  
(+/- DAYS OR WEEKS) 
UP TO 24 HOURS 
PRIOR TO 
ENROLLMENT 
0 
1 DAY 
1 DAY 
1 DAY 
2 DAYS 
4 DAYS 
2 WEEKS 
NOT APPLICABLE 
Diagnostic Test for 
SARS-CoV-2 f,l,k 
X 
X 
 
 
 
 
 
 
 
Pregnancy Test f,m,i 
X 
X 
When pregnancy is suspected 
 
PSA (IP) Informed 
Consent n 
 
X 
 
 
 
 
 
 
 
PSA Screening and 
Eligibility o  
 
X 
 
 
 
 
 
 
 
Randomization (Step 1) 
 
X 
 
 
 
 
 
 
 
Randomization (Step 2) 
 
X 
 
 
 
 
 
 
 
Dispense Study Kit p 
 
X 
 
 
 
 
 
 
 
Collect and Update 
Contacts 
 
X 
X 
X 
 
 
 
 
 
TREATMENT or PROPHYLAXIS 
Administer IP or Control 
 
X 
Refer to PSA 
EFFICACY 
Daily Follow Up 
Symptom Questionnaire q 
 
 
Daily 
X 
X 
Upper Respiratory 
Specimen r 
 
X u 
X 
X 
X 
X 
X 
X 
X 
Clinical Outcome 
Assessment 
 
 
X 
X 
X 
X 
X 
X 
X 

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STUDY VISIT LOCATION A 
IN PERSON 
OR REMOTE b 
IN PERSON 
IN PERSON 
OR  
REMOTE 
REMOTE 
IN PERSON 
IN PERSON 
OR 
REMOTE 
STUDY PROCEDURES 
SCREENING c 
ENROLLMENT 
D0 
D3 d 
D7 d 
D10 
D14 
D28 
WEEK 
12 
UNSCHEDULED e 
VISIT WINDOW  
(+/- DAYS OR WEEKS) 
UP TO 24 HOURS 
PRIOR TO 
ENROLLMENT 
0 
1 DAY 
1 DAY 
1 DAY 
2 DAYS 
4 DAYS 
2 WEEKS 
NOT APPLICABLE 
SAFETY 
Vital Signs 
 
X 
X 
X 
 
X 
X 
X 
X 
Physical Exam g 
 
X 
X 
X 
 
X 
X 
X 
X 
Venous Blood Sampling  
Hematology  
 
X u 
X 
X 
 
X 
X 
X 
X 
Blood Chemistry  
 
X u 
X 
X 
 
X 
X 
X 
X 
Adverse Events 
 
X 
Continuous 
X 
RESEARCH LABS AND PHARMACOKINETICS 
Storage for Future 
Research s,t 
 
 
Refer to PSA 
 
Pharmacokinetics 
 
 
Refer to PSA 
 

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a. In person visits may include those that take place at the research site, home visits or visits to participants admitted to hospital for social, quarantine or 
isolation purposes. Remote visits may take place over the phone or by video conferencing. 
b. If remote visit not feasible or is not permitted under local regulation, the visit may be conducted in person. 
c. If screening visit conducted remotely, screening activities not completed at the Screening visit will be completed at Enrollment. Screening and Enrollment 
activities may take place on the same day. 
d. Day 3 and Day 7 Visits may be Remote or In Person. In person visits may include those that take place at the research site, home visits or visits to 
participants admitted to hospital for social, quarantine or isolation purposes.  Remote visits may take place over the phone or by video conferencing.  
Activities completed during these visits will be dependent on visit type (remote or in person). Refer to PSAs for the location of the visit and the procedures to 
be conducted during the visit. 
e. For Unscheduled Visits - These procedures may be done according to clinical judgement. 
f. These activities may take place at screening or enrollment.  Activities completed at screening do not need to be repeated at enrollment 
g. Physical exam will be performed by a healthcare professional qualified in the clinical practice of medicine. This may include physicians, nurses, or other 
allied health professionals who are registered/licensed in the local jurisdiction and the performance of a physical exam is within the current scope of practice.  
Physical exam may be conducted in person or via a research staff-assisted telehealth physical exam as specified in the PSAs. 
h. The Screening Symptom Questionnaire may be completed at Screening if performed on same day as Enrollment. If Enrollment does not take place on the 
same day as Screening, then Screening Symptom Questionnaire will be repeated at Enrollment. Results of the questionnaire will be used to determine final 
eligibility for enrollment. 
i. Final eligibility will be determined upon completion of these activities. For activities completed at Screening, results will be reviewed and verified at 
enrollment to determine eligibility. 
j. Screening laboratory requirements (if any) will be detailed in the PSA. 
k. Omit at screening if documentation of SARS-CoV-2 test results are available. 
l. Diagnostic testing must be an approved molecular or antigen diagnostic test for SARS-CoV-2 from any upper respiratory specimen performed at screening or 
enrollment or within 5 days of enrollment. The test used must be authorized for use by the relevant national authority for the detection of SARS-CoV-2 in the 
country where the test is administered. Test kits can be obtained from a locally acquired source.  Historical testing results will be acceptable if testing 
performed within the required window. The local testing result, specimen type, assay type, and date of test will be recorded in the CRF. The test result must 
be available and reviewed by site PI or study staff to confirm eligibility. 
m. Pregnancy testing will be completed in all females of childbearing potential defined as premenopausal females capable of becoming pregnant. This includes 
women on oral, injectable, or mechanical contraception and women whose male sexual partners have been vasectomized or are using contraceptive devices. 
If screening and enrollment are not conducted on the same day, then pregnancy testing will not be repeated for enrollment. Pregnancy testing may be 
performed with serum or urine and must be authorized for use by the relevant national authority for the detection of pregnancy in the country where the test is 
administered. 
n. Participants will complete informed consent for all PSAs enrolling in their strata for which they may be eligible.  
o. Participants will complete all PSA specific screening assessments for which they have consented to determine final eligibility. PSAs for which the participant 
meets the eligibility criteria will be included in the Step one randomization 
p. Study Kit will include the following:  
 
Copy of informed consent  
 
Study information 

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 
Contact information for study staff and IND Sponsor  
 
Daily Follow Up Symptom Questionnaire – paper version or smart device form as preferred by participant (See Supplement 2) 
 
Supplies and instructions for specimen self-collection 
q. The Daily Follow Up Symptom Questionnaire will be completed by the participants on designated days (Supplement 2). The Daily Follow Up Symptom 
Questionnaire may be delivered and completed electronically via push reminder to participants at the same time each day.  Paper forms may also be 
dispensed to study participants unable to complete the form electronically.  Study staff will input the data from the paper forms into the CRF and may also 
contact the participant and remind them to complete the survey. 
r. For in person visits upper respiratory specimens may be collected by research staff or self-collected by participant with research staff assistance (if needed). 
For remote visits specimens will be self-collected by participants. 
s. Not all blood collected will be used for testing in this study but will be stored to be used in testing for future studies. Section 9.2.4 Stored Specimens outlines 
the potential future testing for each blood type collected. 
t. With participant consent. 
u. Prior to administration of IP or control 

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2 
STUDY MANAGEMENT 
FHI Clinical (FHIC) will serve as the study sponsor (hereinafter referred to as the Investigational 
New Drug (IND) sponsor). FHIC will be responsible for activities related to the regulatory 
approval, study implementation, study execution, data collection and study monitoring. 
The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. (HJF) will 
serve as the study implementer. HJF will be responsible for protocol design and development, 
medical writing, study oversight and serve as a study specimen repository.  
 

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3 
INTRODUCTION 
3.1 
Study Rationale 
SARS-CoV-2, a member of the beta coronavirus family, was first identified in China in 
December 2019 and is responsible for coronavirus disease 2019 (COVID-19) [Zhu 2019]. The 
World Health Organization declared the novel coronavirus outbreak a pandemic in March of 
2020 [Cucinotta 2020]. The high transmissibility, varying degrees of symptom manifestation, 
high case fatality rate, and emergence of viral variants make disease control and prevention 
challenging.  
Early outpatient treatment and post exposure prophylaxis can reduce disease severity and prevent 
disease transmission. While several classes of therapeutics and vaccines are currently available 
as treatment and prophylaxis against COVID-19, the rise of viral variants has led to reduced 
efficacy of these measures and immune escape by the virus [Yamasoba 2022, Cao 2022, Willett 
2022]. Further, many of the approved therapies target hospitalized cases. A limited number of 
options are available for early outpatient treatment and post-exposure prophylaxis of COVID-19. 
Continuing research is needed to address this gap in the face of ongoing surges of COVID-19 
infections and continuing emergence of viral variants.   
3.2 
Background 
In December 2019, a cluster of atypical pneumonia attributed to a novel coronavirus, SARS-
CoV-2, was reported in the city of Wuhan in the Hubei Provence of China [Zhu 2019]. As of Jan 
1st, 2023, there have been over 600 million cases and 6 million deaths globally due to COVID 
19 [Johns Hopkins University 2023]. Symptoms associated with SARS-CoV-2 infection are 
varied and can range from asymptomatic infection to acute respiratory failure [Mudatsir 2020]. 
The most commonly reported symptoms of COVID-19 infection include cough, fever, and 
fatigue [Akaishi 2022, Zhang 2022]. The incubation period ranges from 2 to 17 days with a mean 
of 6 days, although shorter incubation periods have been reported with recent variants of concern 
(VOC) [Elias 2021, Jansen 2021]. Risk factors for progression to severe disease and death from 
COVID-19 include age and presence of comorbidities such as chronic lung disease, diabetes, 
chronic kidney disease and obesity [CDC 2022]. 
Significant focus has been placed on efforts to limit the spread of SARS-CoV-2. Attack rates 
range from 0.8% with asymptomatic index cases to 18% in symptomatic index cases [Toth 
2021]. Recent Variants of Concern (VOC) have secondary attack rates as high as 30%, even 
among fully vaccinated individuals [Lim 2022, López-Muñoz 2022]. One major challenge in 
limiting disease transmission is infected individuals are more likely to transmit the virus in the 
early or pre-symptomatic stages of illness. It is estimated that SARS-CoV-2 infectiousness peaks 
two days before to one day after onset of symptoms and declines within 6 days of symptom onset 
[Cheng 2020].  
Several nonpharmaceutical interventions have demonstrated effectiveness for limiting 
SARS-CoV-2 infection and various levels of these interventions have been adopted by countries 
throughout the globe. These include travel restrictions, quarantine of travelers arriving from 

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affected countries, restrictions of mass gathering, isolation and quarantine of confirmed cases 
and close contacts, social distancing measures, compulsory mask wearing, contact tracing and 
testing, school closures and use of personal protective equipment among health workers [Ayouni 
2021]. These measures, however, have high social, healthcare, and economic costs [Askitas 
2021]. 
Introduction of vaccines against SARS-CoV-2 have had a significant impact on disease 
incidence and disease spread [Britton 2021, Lopez 2021]. While vaccination remains an effective 
way to prevent SARS-CoV-2 infection, many countries, populations, and individuals do not have 
access to or decline vaccination [Brown 2021]. In addition, multiple studies have demonstrated 
waning immunity to SARS-CoV-2 several months following vaccination, among certain 
populations at high risk for development of severe disease, and against viral variants [Willett 
2022, Hewins 2022, Martinuzzi 2022]. 
With the evolution of the pandemic has come the emergence of SARS-CoV-2 variants that have 
exhibited increased transmissibility and virulence [SARS-CoV-2 Variant Classifications and 
Definitions]. Several monoclonal antibodies and antivirals have been approved for the early 
treatment and prophylaxis of SARS-CoV-2 infection. However, continued mutation of the virus 
has led to increasing resistance to immune responses and varying efficacy of these therapies 
[Yamasoba 2022, Cao 2022, Weisblum 2020, Starr 2021, Chen 2021]. This has resulted in 
removal of therapies for approved use or placing of limitations on their indication [Cavazzoni 
2022]. Current treatment guidelines recommend symptomatic care for low or standard risk 
patients who do not require hospitalization or supplemental oxygen. The guidelines also 
recommend against the use of dexamethasone or other systemic steroids in this population. For 
those who are at high risk to progress to severe disease the guidelines recommend therapies 
including antivirals (Ritonavir-boosted nirmatrelvir (Paxlovid), remdesivir, and molnupiravir) 
[COVID-19 Treatment Guidelines 2022]. However, increase use, coupled with continued 
mutation of the virus, has led to concerns of development of resistance to these therapies 
[Service 2022, Sedova 2022, Jochmans 2022].   
There remains an unmet medical need in prevention and treatment of outpatients with 
COVID-19. Significant research has been directed at the prevention of hospitalization and death 
in patients at high risk for progression to severe disease. However, 50-60% of infections occur in 
standard risk outpatients with SARS-CoV-2 infection [Koma 2023].  Currently, there are no 
approved therapies for these patients at standard risk for progression to severe disease 
[COVID-19 Treatment Guidelines 2022]. In 2022 alone, 316 million working days were lost due 
to the COVID pandemic, the majority (191 million) were due to acute mild or moderate illness 
[Berdan 2023]. Similarly, for intermediate risk patients, in many regions globally, currently 
approved therapies are not accessible or available. In addition, numerous drug-drug interactions 
and contraindications, limit the use of these medications in infected patients. The ongoing 
evolution of SARS-CoV-2 and the continued emergence of resistance to vaccines and therapies 
by viral variants has highlighted the need for ongoing research and new therapies to treat 
COVID-19 and prevent its continued spread. Additionally, there is a gap in available outpatient 
treatment options that shorten disease duration for standard and intermediate risk patients. This 
study will investigate the safety and efficacy of promising investigational products for both early 
outpatient treatment and post-exposure prophylaxis for SARS-CoV-2. The study will focus on 

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inclusion of products with broad neutralizing and antiviral activity, ease of administration, and 
potential to avoid SARS-CoV-2 variant escape. 
3.3 
Study Hypothesis 
Early Treatment:  The primary hypothesis is that early treatment with IP among standard and 
intermediate risk outpatients infected with SARS-CoV-2 can shorten time to sustained symptom 
alleviation or resolution compared to standard care. 
Post-exposure Prophylaxis: The primary hypothesis is that post-exposure prophylaxis with IP 
can prevent COVID-19 infection among close contacts of symptomatic SARS-CoV-2 positive 
cases compared to standard care.  
3.4 
Risk/Benefit Assessment 
3.4.1 
Known Potential Risks 
The risks of study participation may include:  
 
Phlebotomy can infrequently cause temporary bruising, erythema, pain, infection, or 
bleeding.  
 
Upper respiratory specimen collection – upper respiratory swabs may cause the 
participant to gag, cough, or vomit. The swab may cause some discomfort or mild 
bleeding. 
 
Loss of confidentiality.  
 
Product specific risks are defined in the product specific appendices. 
Steps taken to minimize risks:  
 
To diminish the risks of phlebotomy, only adequately trained study personnel will draw 
venous blood.  
 
Blood volumes taken from the study participants will fall within the Human Research 
Protection Office (HRPO) guidelines. 
 
Only adequately trained study personnel will collect upper respiratory specimens, 
collection may be self-administered after appropriate instruction. 
 
See Section 14.1.5 Confidentiality and Privacy.  

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3.4.2 
Known Potential Benefits 
Direct Benefits:  
Study participants are not guaranteed benefit. Investigational products may decrease the severity 
of COVID-19 disease in exposed or infected individuals and may prevent infection with SARS-
CoV-2 altogether. Information gained from this study will inform product development 
decisions. 
Participants in the study will be enrolled early in illness onset or soon after a SARS-CoV-2 case 
is identified, and they will be closely monitored. Early medical evaluation and regular 
monitoring of COVID-19 could offset the severe consequences of the disease. Diagnostic test 
results may be provided to study participants faster than results obtained through routine clinical 
care. 
Indirect Benefits:  
Participation in the study will help provide information about the benefits of early treatment and 
post-exposure prophylaxis therapy for COVID-19. 
3.4.3 
Assessment of Potential Risks and Benefits 
Known potential risks and benefits of each IP (also referred to as study drug or intervention) will 
be described in the product specific appendices. They will include the rationale for the necessity 
of exposing participants to risks, summary of the plan to minimize risk to participants and risk 
benefit justification. 

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4 
OBJECTIVES AND ENDPOINTS 
This section is a summary of the of the primary endpoints for the early treatment and post-
exposure prophylaxis indications. Each PSA will include a more detailed discussion of the 
primary endpoints in addition to presentation of secondary, safety and any exploratory endpoints. 
4.1 
Early Treatment 
Objective 
Endpoint 
Primary 
To determine if early treatment 
with IP can shorten time to 
sustained symptom alleviation 
or resolution in participants 
infected with SARS-CoV-2 
x Time to sustained alleviation or resolution 
of COVID-19 symptoms  
o Defined as the number of days from 
randomization in a PSA to the first day 
the participant reports all symptoms as 
mild or none (or returning to pre-illness 
levels) for at least 3 consecutive days 
(the first day being considered the Event 
Day). 
[Timeframe: Day 0 to Day 28]
Key 
Secondary
To evaluate the clinical 
efficacy of IP compared to 
control  
x Number and proportion of all cause 
hospitalizations 
x Number and proportion of all cause deaths 
[Timeframe: Day 0 to Day 28]
Safety 
To evaluate the safety and 
tolerability of IP compared to 
control 
x Incidence of Serious Adverse Events (SAE) 
x Comparison between active and placebo 
treatment groups in proportion of all and 
≥Grade 3 AEs as assessed by the National 
Institutes of Health, Division of AIDS 
Table for Grading the Severity of Adult and 
Pediatric Adverse Events (NIH, DAIDS AE 
Grading Table), corrected Version 2.1, July 
2017. 
x Incidence of AEs causing IP 
discontinuation 
x Incidence of all-cause IP discontinuation or 
interruption 
x Incidence of Adverse Events of Special 
Interest (AESI) (if applicable to PSA) 
x Number of participants hospitalized due to 
adverse events regardless of cause
Refer to PSA for additional IP specific objectives and endpoints 
£x

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4.2 
Post-Exposure Prophylaxis 
Objective 
Endpoint 
Primary 
To determine if post-exposure 
prophylaxis with IP can reduce 
incidence of symptomatic 
COVID 19 infection 
 Proportion of participants who develop 
COVID-19 infection by Day 14 
o Defined as positive RT-PCR test and 
presence of at least one COVID-19 
symptom
Safety 
To evaluate the safety and 
tolerability of IP compared to 
placebo 
 Incidence of Serious Adverse Events 
(SAEs) 
 Comparison between active and placebo 
treatment groups in proportion of all and 
≥grade 3 adverse events as assessed by the 
National Institutes of Health, Division of 
AIDS Table for Grading the Severity of 
Adult and Pediatric Adverse Events 
(DAIDS AE Grading Table), corrected 
Version 2.1, July 2017. 
 Incidence of AEs causing IP 
discontinuation 
 Incidence of all-cause IP discontinuation or 
interruption 
 Incidence of Adverse Events of Special 
Interest (AESI) (if applicable to PSA) 
 Number of participants hospitalized due to 
adverse events regardless of cause
Refer to PSA for additional IP specific objectives and endpoints. 

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5 
STUDY DESIGN 
5.1 
Overall Design 
This study is an adaptive, randomized, double blind, platform trial evaluating promising 
investigational products (IP) for safety and efficacy as early outpatient treatment and post-
exposure prophylaxis for SARS-CoV-2. This multicenter trial will be conducted in both 
domestic and international sites. The study will compare IPs to standard of care in non-
hospitalized SARS-CoV-2 infected participants and uninfected adult contacts of SARS-CoV-2 
confirmed cases. The master protocol is described here and outlines the core elements of the 
study. The study includes a phase 2 evaluation for all IPs. Phase 2/3 or phase 3 evaluations may 
be included as amendments to the MP and detailed in the PSA. 
Investigational products may be evaluated for either or both study indications: early treatment 
and/or post-exposure prophylaxis (PEP). The platform trial design will allow for multiple IPs to 
be incorporated into the protocol as product specific appendices (PSA) as products are identified 
and become available. An independent Data and Safety Monitoring Board (DSMB) will monitor 
the study both for futility and early efficacy to manage participant risk appropriately. 
Each PSA will detail the interventions, intended study phase, the endpoints, target treatment 
effect, intended statistical analysis, the relevant control arms, and the sample size range. The 
PSA may define additional adaptive design elements, such as early declaration rules. The DSMB 
will monitor interim data and the adaptive designs to make recommendations about early study 
closure or adaptive elements to the PSA. 
Safety will be evaluated based on clinical laboratory studies, vital signs, assessment of adverse 
events (AEs), symptom monitoring and physical exams. Efficacy will be evaluated based on 
viral testing, symptom scoring and outcome ascertainment. 
5.1.1 
Selection of Investigational Products 
Investigational products for inclusion will be selected based on review of the preclinical and 
early clinical data. Review will evaluate safety, tolerability, and efficacy of the IP. Two 
physicians will determine eligibility based on review of available data. Review will include 
evaluation of the following: 
 
In vitro assays and in vivo studies demonstrating anti-SARSCoV2 activity 
 
Treatment emergent adverse events (TEAE) 
 
Infusion related reactions (for intravenous products), hypersensitivity reactions 
 
Completion of optimum dose selection and tolerability studies 
 
PK studies of bioavailability, neutralizing-level serum concentrations appropriate for 
early treatment or PEP, and time to maximum serum concentration 
 
In vitro and/or in vivo studies demonstrating efficacy against currently circulating VOC 
 
Development of anti-drug antibodies/ neutralizing ab to IP 

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Selection will also be based on route of administration and product availability. Products with 
oral, subcutaneous, and intramuscular delivery modes may be prioritized due to acceptability, 
and feasibility of administration. If after the review, the two physicians cannot agree on a 
decision to include or exclude the IP in the trial, adjudication will be performed by a third 
physician. 
5.1.2 
Period of Evaluation 
Participants will be followed for a period of up to 12 weeks. Safety evaluations will include 
monitoring of symptoms and adverse events throughout the study period. Efficacy evaluations 
will include prevention of SARS-CoV-2 infection and symptom duration in exposed contacts, 
and reduction in viral load and COVID-19 symptom severity in SARS-CoV-2 positive cases. 
5.1.3 
Early Termination 
An external Data Safety Monitoring board (DSMB) will review adverse events and safety 
information and may recommend early termination based on this review. Additionally, the 
interim analyses detailed in the PSAs will detail early study declaration for superior efficacy, 
futility or if there is a safety signal. 
5.2 
Shared Groups 
One of the primary advantages of the platform design is the ability to share control groups 
among different PSAs. For example, if two PSAs are enrolling PEP participants, each with a 
placebo control group, the analysis of each may include the placebo participants from the other 
PSA. To be eligible to contribute to a shared placebo pool, participants must meet the eligibility 
criteria for all PSA’s contributing to that shared pool. PSAs may choose not to participate in 
placebo sharing. PSA contribution to a shared placebo pool will be determined prior to 
commencement of enrollment for that PSA.   
Each PSA will define the intervention, primary analysis, and the relevant control group. For 
analysis, the control group will include all participants randomized to the placebo control arm 
from all PSAs contributing to the shared placebo pool and meeting the eligibility criteria for the 
PSA being analyzed. If participants are eligible for only a subset of PSAs enrolling in that 
stratum, the statistical analyses for that PSA will be based on comparisons against only those 
control arm participants who were eligible for that PSA. 
5.3 
Scientific Rationale for Study Design 
The purpose of this investigation is to evaluate the safety and efficacy of promising 
investigational products for early outpatient treatment and post-exposure prophylaxis for SARS-
CoV-2.  
5.4 
Justification for Dose 
Refer to appendix/appendices for details of investigational products. 

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5.5 
End of Study Definition 
A participant is considered to have completed the study if they have completed all phases of the 
study including the last visit or the last scheduled procedure shown in Section 1.2 Schedule of 
Activities (SoA). 
This platform trial will be conducted until all PSAs have concluded and all participants within all 
PSAs have completed follow up.  

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6 
STUDY POPULATION AND STUDY ENROLLMENT 
The target populations for the study are:  
A. Non-hospitalized SARS-CoV-2 infected adults  
B. Uninfected adult SARS-CoV-2 contacts 
6.1 
Inclusion Criteria 
Individuals who meet the following criteria may be included in the study: 
Population A: Symptomatic adults seeking care or testing for COVID-19. 
1) Age ≥ 18 years  
2) Positive molecular or antigen diagnostic test for SARS-CoV-2 at study enrollment or within 
≤ 5 days prior to enrollment  
3) Presence of two or more Screening Symptoms listed in Supplement 3 with at least two 
symptoms classified as moderate to severe (and/or ≥ 2 on the frequency questions or loss of 
taste/smell questions) at the time of enrollment 
a) For participants who have preexisting conditions causing mild or moderate symptoms 
listed on the Screening Symptom Questionnaire, there must be an increase of at least one 
severity level for that symptom at enrollment (For example, prior to illness participant 
routinely experienced headaches rated as moderate severity, now rating headache as 
severe at enrollment) 
4) Symptom onset ≤ 5 days prior to enrollment 
Population B: Uninfected adult contacts of symptomatic SARS-CoV-2 infected individuals 
1) Age ≥ 18 years  
2) Asymptomatic contact of an individual with laboratory confirmed SARS-CoV-2 infection 
defined as:  
a) Indoor exposure to the symptomatic case or cases within 6 feet (2 meters) for 
≥ 15 minutes over a 24-hour period without the use of personal protective equipment 
3) Negative screening SARS-CoV-2 molecular or antigen diagnostic test performed at screening 
or within less than or equal to 24 hours of enrollment 
4) Exposure and enrollment within 6 days or less from when the symptomatic, confirmed 
SARS-CoV-2 positive case first had symptoms 
For Both Populations 
1) Must also meet the intervention specific inclusion/exclusion criteria for at least one PSA that 
is enrolling participants. 

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6.2 
Exclusion Criteria 
This study will exclude individuals who meet any of the following criteria: 
Population A: Symptomatic adults seeking care or testing for COVID-19 
1) Hospital admission at the time of enrollment 
2) Hospitalization will be defined as requiring medical care not available in an outpatient setting 
for greater than 24 hours.  
3) Hospitalization for isolation or quarantine requirements or for social reasons will NOT 
constitute an exclusion criterion  
4) Laboratory confirmed SARS-CoV-2 infection 6 to 90 days prior to enrollment 
5) Oxygen saturation < 92% on room air 
6) Baseline use of supplemental oxygen at the time of enrollment 
7) Presence of any of the following comorbidities that per the PI puts the patient at high risk of 
developing severe COVID-19 illness:  
a) Age ≥ 75 years 
b) Active treatment for solid tumor and hematologic malignancies 
c) Hematologic malignancy, myeloma, or related disorder (e.g., myelodysplastic syndrome, 
myelofibrosis) 
d) Receipt of solid-organ transplant or an islet transplant and taking immunosuppressive 
therapy 
e) Chemotherapy or radiotherapy for solid organ cancer in last 12 months 
f) Receipt of chimeric antigen receptor (CAR)-T-cell therapy or hematopoietic stem cell 
transplant (within 2 years of transplantation or taking immunosuppressive therapy) 
g) Moderate 
or 
severe 
primary 
immunodeficiency 
(e.g., 
common 
variable 
immunodeficiency disease, severe combined immunodeficiency, DiGeorge syndrome, 
Wiskott-Aldrich syndrome) 
h) Advanced or untreated HIV infection (people with HIV and CD4 cell counts less than 
200/mm3, history of an AIDS-defining illness without immune reconstitution, or clinical 
manifestations of symptomatic HIV) 
i) Active treatment with high-dose corticosteroids (i.e., 20 or more mg of prednisone or 
equivalent per day when administered for 2 or more weeks), alkylating agents, 
antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic 
agents classified as severely immunosuppressive, tumor necrosis factor (TNF) blockers, 
and other biologic agents that are immunosuppressive or immunomodulatory 
j) Sickle cell disease 
k) Chronic liver disease (e.g., Child-Pugh Class A, B or C cirrhosis) 
l) Down syndrome 

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m) Dementia or neurocognitive disability (e.g., Parkinson’s disease) 
n) Participants with 3 or more of the following conditions:  
i) No prior COVID-19 infection OR has not completed a COVID-19 vaccine series 
within the last 6 months OR has not received a vaccine booster within the last 6 
months 
ii) Age 65-74 years 
iii) BMI ≥35 (or >95th percentile in adolescents) 
iv) Type 1 or type 2 diabetes mellitus 
v) Cardiovascular disease (including HTN if age >55) 
vi) Chronic lung disease (including bronchiectasis, CF, COPD, ILD, PHTN, PE, 
moderate-to-severe asthma) 
vii) Chronic kidney disease (eGFR <30) 
8) Participants who are receiving or plan to receive anti-SARS-CoV-2 antivirals for treatment of 
their COVID-19 
Population B: Post-exposure adult contacts of SARS-CoV-2 infected Individuals 
1) Symptoms attributed to COVID-19 as assessed by the investigator 
2) Positive molecular or antigen diagnostic test for SARS-CoV-2 from any upper respiratory 
specimen within 90 days prior to enrollment 
3) SARS-CoV-2 vaccination within 90 days prior to enrollment EXCEPT if severely 
immunocompromised or a known vaccine non-responder 
4) Severely immunocompromised or a known vaccine non-responder defined as: solid organ or 
stem cell transplant recipient, B cell leukemia, receiving B cell depletion therapy (e.g., 
rituximab), agammaglobulinemia, or negative serology ≥2 weeks after vaccination with two 
doses of a vaccine 
5) Hospital admission at the time of enrollment 
a) Hospitalization will be defined as requiring medical care not available in an outpatient 
setting for greater than 24 hours.  
6) Hospitalization for isolation or quarantine requirements or for social reasons will NOT 
constitute an exclusion criterion 
For Both populations: 
1) Absence of informed consent 
2) Pregnancy 
3) Breastfeeding 
4) Individuals who the study investigators believe are unable to comply with the requirements 
of the study 

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5) Participation in another intervention trial for the treatment or prophylaxis of SARS-CoV-2 
infection or COVID-19 disease at the time of enrollment  
Any product-specific exclusion criteria will be added in the product specific appendices. 
6.3 
Lifestyle Considerations 
During this study, participants are asked: 
1) Not to participate in another clinical trial with an IP for the duration of their enrollment in the 
trial 
Refer to appendix/appendices for investigational product specific considerations 
Refer to appendix/appendices for investigational product specific co-enrollment guidelines 
6.4 
Screen Failures 
Screen failures are defined as participants who consent to participate in this study but do not 
meet entry criteria for the study. Individuals who do not meet the criteria for participation in this 
study (screen failure) because of not meeting one or more of the entry criteria that are likely to 
change over time may be rescreened. Rescreened participants will be assigned a new participant 
number. 
6.5 
Strategies for Recruitment and Retention 
Study participants will be recruited from collaborating healthcare systems and shared or 
congregate living arrangements. Recruitment may be conducted at healthcare facilities, 
community health clinics, or drive through testing centers affiliated with the healthcare system, 
and/or health system registries.  
The study team will use multiple means of communicating study awareness to enhance 
recruitment efforts, including periodic briefings delivered by the site Principal Investigator (PI)s 
or their study teams to the clinical trial site staff. If permitted, information notices with points of 
contacts will be posted or distributed at recruitment locations.  
Clinical trial sites may also use existing SARS-CoV-2 testing registries at the sites to conduct 
additional outreach. Contact information (email and telephone numbers) provided by SARS-
CoV-2 positive individuals at the time of testing may be used to recruit eligible participants 
through IRB approved scripted outreach communications such as phone call or emails. Clinical 
trial sites may use IRB approved recruitment and retention services for potential SARS-CoV-2-
positive individuals and contacts. 
SARS-CoV-2 positive individuals will be recruited and screened for enrollment in the early 
treatment indication (if currently enrolling at the site). The study team will work with the 
individual to help them recall everyone with whom they have had contact during the timeframe 
while they may have been infectious. The study team will then reach out to those individuals 
identified as contacts, either via phone, email or in person, to recruit for study enrollment. To 
protect participant privacy, contacts are only informed that they may have been exposed to an 

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individual with the infection. They are not told the identity of the individual who may have 
exposed them. SARS-CoV-2 positive cases do not need to be enrolled in the early treatment 
indication of the study to serve as source of contacts for PEP indication (such as children or 
those who decline enrollment). 
Recruitment of household contacts will represent an important source of contact enrollment. 
Household enrollment will facilitate coordination of testing and follow up for multiple study 
participants. Adult contacts of positive cases meeting entry criteria will be eligible for 
enrollment. Recruitment of adult SARS-CoV-2 confirmed study participants residing in 
institutional care facilities will rely heavily on direct interface of the study team with facility 
staff. Once an infected resident or facility staff has been confirmed, other adult residents or staff 
may be recruited.  
 Clinical trial sites may receive referrals of SARS-CoV-2-positive individuals and their contacts 
from other local medical facilities. Site team members will engage with relevant facility staff to 
identify presumptively eligible participants. The study will be described to the individual, and if 
they are interested, the informed consent will be reviewed with the participant. After 
signing/acknowledging the screening informed consent, their eligibility to participate will be 
assessed. For those with confirmed infection in shared or congregate living arrangements, room 
access may be limited, and consent may be performed by study staff members with participant 
access. 
Compensation for study participation will be provided. The amount and mechanism of 
compensation will be determined locally and in accordance with local IRB requirements and 
subject to local IRB approval.  
 

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7 
STUDY INTERVENTION 
Information about the study product(s) can be found in the product specific appendix. Product 
specific appendices for each investigation product will outline toxicity, side effects, 
administration procedures, monitoring, and pregnancy/breastfeeding restrictions. 
7.1 
Study Intervention(s) Administration 
Refer to appendix/appendices for details of investigational products. 
7.1.1 
Study Intervention Description 
Refer to appendix/appendices for details of investigational products. 
7.1.2 
Dosing and Administration 
Refer to appendix/appendices for details of investigational products.  
7.2 
Preparation/Handling/Storage/Accountability 
Refer to appendix/appendices for details of investigational products. 
7.2.1 
Acquisition and Accountability 
Refer to appendix/appendices for details of investigational products. 
7.2.2 
Acquisition 
Refer to appendix/appendices for details of investigational products. 
7.2.3 
Accountability 
The site PI is responsible for study product distribution and disposition and has ultimate 
responsibility for study product accountability. The site PI may delegate to the participating 
site’s research pharmacist responsibility for study product accountability. The participating site’s 
research pharmacist will be responsible for maintaining complete records and documentation of 
study product receipt, accountability, dispensation, storage conditions, and final disposition of 
the study product(s). Time of study drug administration to the participant will be recorded on the 
appropriate Case Report Form (CRF). All study product(s), whether administered or not, must be 
documented on the appropriate study product accountability record or dispensing log. The IND 
Sponsor’s monitoring staff will verify the participating site’s study product accountability 
records and dispensing logs per the site monitoring plan. 
After the study is completed or terminated return, export, or destruction of unused IP shall occur 
at the Industry Supporter's written directive. 

PROTECT-APT 1 Version 5.0 
Master Protocol/PC06 
07 Feb 2024 
 
33 | 103 
7.2.4 
Formulation, Appearance, Packaging, and Labeling 
Refer to appendix/appendices for details of investigational products. 
7.2.5 
 Product Storage and Stability 
Refer to appendix/appendices for details of investigational products. 
7.2.6 
Preparation 
Refer to appendix/appendices for details of investigational products. 
7.3 
Prohibited Medications 
Refer to appendix/appendices for details of investigational products. 
7.4 
Measures to Minimize Bias: Randomization and Blinding 
7.4.1 
Randomization 
Following completion of the screening informed consent and determination of eligibility under 
that Master Protocol, participants will be stratified as either an eligible SARS-CoV-2 positive 
case or SARS-CoV-2 negative contact. Once identified as a case or contact, participants will then 
undergo product specific informed consenting.  If eligible to contribute to a shared placebo pool 
(i.e., participant potentially meets eligibility criteria for more than one PSA), the participant will 
complete informed consent for all PSAs for which they may be eligible.  Following PSA 
informed consenting, the participant will complete all product specific screening requirements to 
determine final eligibility for all PSAs for which they may be eligible. 
Once PSA eligibility has been determined, the participant will undergo the first randomization to  
a PSA enrolling in their strata for which they are eligible.  Participants must be eligible for at 
least one PSA enrolling in their strata. Probability of randomization to a PSA for which a 
participant is eligible will be equally likely to each PSA. For example, if a participant has 
consented and meets the eligibility criteria for three products enrolling in the PEP indication at 
the same time, probability of randomization of a contact to one of these PSAs is 1:1:1. The first 
randomization is unblinded. 
Following the first randomization, a second randomization, within each PSA, will be to the arms 
within the respective PSA. The default is an investigational product or the investigational 
product’s control arm. Probability of randomization will be dependent on the number of PSAs 
enrolling in the indication at that time which are contributing to a shared placebo pool and for 
which the participant is eligible. In order to be considered for placebo sharing, the participant 
must meet product specific eligibility criteria for all PSAs contributing to the shared placebo 
pool. The ratio of assignment to IP or control would be r:1 where r is the number of PSAs 
contributing to a shared placebo pool that a given participant is determined to be eligible to 
receive. For example, if two products are enrolling in the PEP indication simultaneously for 
which the participant meets the eligibility criteria and are contributing to a shared placebo pool, 

PROTECT-APT 1 Version 5.0 
Master Protocol/PC06 
07 Feb 2024 
34 | 103 
the probability of randomization of the participant to IP or placebo would be 2:1.  The second 
randomization is blinded.  
Following randomization and double blinded administration of intervention, participants will be 
monitored with regular physical exams and laboratory tests to assess safety and efficacy. The 
visit schedule and data collection will be the same within a stratum across the different 
appendices. Figure 1 outlines the randomization schema.  
Figure 1. 
Participant Stratification and Randomization Plan 
 
The randomization plan for both the Early Treatment and PEP indications are presented in 
Figure 2 and Figure 3.  Figure 2 outlines the randomization scheme if a participant only meets 
the eligibility criteria for one PSA enrolling in their strata. Figure 3 outlines the randomization 
scheme if a participant meets the eligibility criteria for two PSAs enrolling in their strata 
contributing to a shared placebo pool.  
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PROTECT-APT 1 Version 5.0 
Master Protocol/PC06 
07 Feb 2024 
35 | 103 
Figure 2. 
Randomization Scheme for Early Treatment and PEP Indications: 
Participant Eligible for One PSA 
 
 
Figure 3. 
Randomization Scheme for Early Treatment and PEP Indications: 
Participant Eligible for Two PSAs 
 
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PROTECT-APT 1 Version 5.0 
Master Protocol/PC06 
07 Feb 2024 
 
36 | 103 
7.4.2 
Blinding and Unblinding 
There will be a two-step randomization process (described above in Section 7.4.1 
Randomization). Participants, study staff, and study investigators will not be blinded to the first 
step, randomization to the PSA. Participants will be randomized to a PSA for which they meet 
the eligibility criteria, and which are enrolling in their strata. Participants will then be 
randomized to an arm within their respective PSA. Both participants and study investigators will 
be blinded to the second randomization. IP delivery methods and packaging will be similar for 
each arm within a PSA (for example, an intravenously administered IP will have a similar 
appearing, intravenously administered control).  
Randomization to the arm within the respective PSA will be implemented through an Interactive 
Voice/Web Response System (IxRS) managed by IND Sponsor.  
Unblinding will be permitted during the trial in the following events: 
 Emergency Unblinding: where knowledge of the treatment randomization is necessary to 
provide acute medical care or where there is a safety concern by the treating clinician. 
Details of the unblinding will be captured in the CRF including: 
o Date/timing 
o Reasons for unblinding 
o Name and roles of staff and participants involved in unblinding 
o Required clinical care 
o Event outcome 
 To the DSMB for safety monitoring 
 Statistical Analysis: unblinded results will be used in the interim and final analyses 
 Participant notification: All participants will have the option to learn their randomization 
assignment after their PSA has been completed 
In the event unblinding is required every effort will be made to limit this information to those 
individuals directly involved in the statistical analysis or care decisions and not with study staff.  
7.5 
Study Intervention Compliance 
To enhance validity of the study data, several methods will be used to assess compliance with the 
intervention. These will include pill counts, self-reported medication compliance, adherence 
reminders with each study visit, and feedback investigating reasons for noncompliance. 
Adherence reminders will take place at each applicable study visit and with the Daily Follow Up 
Symptom Questionnaire (depending on the dosing schedule of the study drug). Study staff will 
also review dosing instructions, as well as allow the participant to provide feedback on 
challenges with study drug compliance.  

PROTECT-APT 1 Version 5.0 
Master Protocol/PC06 
07 Feb 2024 
37 | 103 
7.6 
Concomitant Therapy 
Patient-reported medication history during the 30 days prior to ICF signing will be recorded at 
Screening. Thereafter, any changes in concomitant medications or new medications added will 
be recorded in the data collection forms. While most systemic medications taken by the subject, 
other than study drug, are considered concomitant medications and should be recorded, the 
following specific exceptions do not need to be recorded: topical medications (eye drops, ear 
drops, intranasal drops or sprays, dermatologic treatments, topical lidocaine). In contrast, the 
following should be recorded: vitamins and supplements (e.g., vitamins, minerals, herbal 
supplements, dietary supplements, iron/ferrous sulfate, magnesium, calcium, electrolyte 
replacements) and nicotine replacement products (e.g., patches, lozenges, gums, nasal sprays). 
7.7 
Standard of Care 
Treatment that experts agree is appropriate, accepted, and widely used and that follows 
established and approved local treatment algorithms will be allowed in the study. Both placebo 
control and IP intervention arms will be eligible for receipt of Standard of Care (SOC) treatments 
and decisions will be based on judgement by the treating clinician. Figure 4 presents the second 
randomization step outlining the use of IPs in conjunction with SOC. 
Figure 4. 
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are 

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07 Feb 2024 
 
38 | 103 
7.7.1 
Rescue Medicine 
For this protocol, rescue medication is defined as a medication (prescribed or over the counter) 
for the treatment of SARS-CoV-2 infection, anticipated adverse reactions, and anticipated 
emergency situations. Use of these medications will be allowed with participation in the 
protocol. Drug, timing, dose, and frequency of rescue medications will be reported in the CRF. 
 

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39 | 103 
8 
PARTICIPANT DISCONTINUATION OR WITHDRAWAL 
Participants will be informed that participation is voluntary and that they may withdraw from the 
study or discontinue the IP at any time, without prejudice upon request. Discontinuation of the 
investigational product does not mean discontinuation from the study. When a participant’s 
withdrawal request is limited to discontinuation of the IP, other activities outlined in the schedule 
of activities for which the participant previously gave consent may continue. The study staff will 
clarify whether the participant wishes to withdraw from all components of the trial or only from 
the IP.  
8.1 
Participant Discontinuation of IP  
A participant may discontinue IP at their request for any reason. Every effort should be made to 
encourage subjects to remain in the study for the duration of their planned outcome assessments. 
Unless the subject withdraws the consent, those who discontinue study drug early will remain in 
the study. The reason for subject IP discontinuation will be documented in the case report form. 
If a participant discontinues the IP, data collection, both clinical and lab, for which the 
participant consents will continue as per the schedule of activities.  
An investigator, in consultation with the medical monitor, may discontinue IP administration for 
a participant in the study for the following reasons: 
 If any clinical AE, laboratory abnormality, or other medical condition or situation occurs 
such that continued participation in the study would not be in the best interest of the 
participant 
8.2 
Withdrawal of Consent 
Participants who request to discontinue receipt of the IP will remain in the study and will 
continue to be followed for protocol specified follow up procedures. The only exception to this is 
when a participant specifically withdraws consent for participation in any further study activities 
and further contact from study staff. Participants should notify the investigator in writing of the 
decision to withdraw consent from future follow up, whenever possible.  Participants may also 
continue or revoke consent for access to health information for the purpose of the research study. 
Revoking access to health information will require a written notification from the participant.  
If a participant withdraws fully from the study and does not consent to continued follow-up of 
associated clinical and laboratory data, then the active collection of participant study data ends 
when consent is withdrawn. The IND Sponsor may retain and continue to use any data collected 
before withdrawal of consent. 
Although a participant is not obligated to give reason(s) for withdrawal from a trial, the site 
investigator will make a reasonable effort to ascertain the reason(s), while fully respecting the 
participant's rights. Reasons for withdrawal, if obtained, will be entered into the CRF.  

PROTECT-APT 1 Version 5.0 
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40 | 103 
8.3 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she is unable to be contacted by the 
clinical trial site staff. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
 The site will attempt to contact the participant and reschedule the missed visit within the 
visit window and counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain if the participant wishes to and/or should continue in the 
study. 
 Periodic attempts will be made to contact subjects who are noncompliant with study 
visits and study activities 
 Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant's last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant's 
research record or study file. 
 Should the participant continue to be unreachable, he or she will be considered lost to 
follow up  
 Should a participant be hospitalized during their time on-study, efforts will be made to 
collect study data and clinical specimens in accordance with the study Schedule of 
Activities where possible. 
Participants who withdraw from the study or are lost to follow up after signing the ICF and 
administration of the IP will not be replaced. 
 

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41 | 103 
9 
STUDY ASSESSMENTS AND PROCEDURES 
The study assessments are outlined in Section 1.2 Schedule of Activities (SoA).  
Every effort will be made to ensure that the protocol required tests and procedures are completed 
as described. However, it is anticipated that, from time to time, there may be circumstances, 
outside of the control of the investigator, that make it not feasible to perform the activity. In 
these cases, the investigator will take all steps necessary to ensure the safety and wellbeing of the 
participant. If the participant is not able to complete the activities during this timeframe, the visit 
and associated activities may still take place; the visit will be identified as a protocol deviation 
and captured in the appropriate CRF. If the visit is not completed, the participant may continue to 
be enrolled in the study and proceed with the subsequent schedule of activities; incomplete visits 
will be captured in the appropriate CRF. When a protocol required assessment cannot be 
performed, the investigator will document the reason for this and any corrective and preventive 
actions which he/she has taken/will take to ensure that normal processes are adhered to as soon 
as possible. The study team will be informed of these incidents in a timely manner. 
9.1 
Efficacy Assessments 
The key efficacy assessment in the early treatment indication is time to sustained alleviation or 
resolution of symptoms among SARS-CoV-2 positive cases. Time to sustained alleviation or 
resolution of targeted COVID-19 symptoms (listed in Supplement 3) will be defined as the 
number of days from randomization in a PSA (Step 2 of randomization) to the first day the 
participant reports all symptoms as mild or none (≤ 1 on the Daily Follow Up Symptom 
Questionnaire) for at least 3 consecutive days (the first day being considered the Event Day).  
The key efficacy assessment in post-exposure prophylaxis is incidence of COVID-19 infection 
defined as positive RT-PCR test and presence of at least one COVID-19 symptom. 
9.2 
Clinical and Laboratory Assessments 
Study procedures are specified in Section 1.2 Schedule of Activities (SoA).  
9.2.1 
Clinical Assessments 
Clinical assessments include: 
Vital Signs  
Temperature, pulse, blood pressure, respiratory rate, and pulse oximetry. 
Physical Exam 
Performance and documentation of an exam that evaluates the following systems: General, Head 
Eyes Ear Nose and Throat, Pulmonary, Cardiac, Abdomen, Neurologic, Extremities, and Skin. 

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42 | 103 
Symptom Review: Screening Symptoms Questionnaire and Daily Follow Up Symptom 
Questionnaire 
Participants will complete two symptom questionnaires during their time in the study: the 
Screening Symptoms Questionnaire and the Daily Follow Up Symptom Questionnaire 
(Supplements 1&2) adapted from the US Food and Drug Administration (FDA) guidance 
[Guidance for Industry]. Prior to use in the study, the symptom questionnaires will be certified 
translated and back translated with comparisons of the original language version and the back 
translated version.  Pilot testing of the questionnaires will be conducted among individuals 
whose language is the translated language of the instrument to evaluate the instructions, response 
format and the items in the instrument for clarity. 
The Screening Symptom Questionnaire (Supplement 1) will be completed at Screening and 
Enrollment (Day 0). If Screening and Enrollment visits are completed on the same day, 
Screening Questionnaire will be completed once. If Screening and Enrollment visits are 
completed on separate days, Screening Questionnaire will be completed on both days. The 
Screening Questionnaire will be used to establish baseline symptoms and study eligibility.  The 
questionnaire will also ascertain pre-COVID-19 illness screening symptom levels. 
Participants will complete Daily Symptom Follow Up Questionnaire (Supplement 2) on Days 1 
through 28 and then at follow up visits. Participants will have the option to complete the 
questionnaire on their personal computer or personal smart device, or on paper.  For participants 
completing the questionnaire electronically, paper forms will be provided as back up. Paper 
forms will be entered into the clinical database by research staff. Participants will be encouraged 
to use the same method (email, personal smart device, or paper) throughout their study 
participation.  
Several methods will be used to assess compliance with the intervention. These will include pill 
counts, self-reported medication compliance, adherence reminders with each study visit, and 
feedback investigating reasons for noncompliance. Daily reminders will be sent via text, email, 
or phone call on Days 1 through 28. Adherence reminders will also take place at each applicable 
study visit and with the Daily Follow Up Symptom Questionnaire (depending on the dosing 
schedule of the study drug). Study staff will also review dosing instructions, as well as allow the 
participant to provide feedback on challenges with study drug compliance.  
Study staff may also provide the questionnaire in an interview format (in person or remotely) to 
the participant and input verbal responses from the participant into the clinical database or on 
paper for participants who are unable to complete the questionnaire (ex. illiterate participants or 
other inability to complete an electronic or paper format). The format in which the questionnaire 
was completed (self-evaluation vs interview format) will be recorded. 
Symptoms elicited in the Daily Symptom Follow Up Questionnaire are outlined in Supplement 2 
and include nasal congestion, sore throat, hoarse voice, shortness of breath, cough, fatigue, 
myalgias, headache, chills, fever, nausea or vomiting, change in taste and change in smell. 
Symptoms will be reported on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe). 
Additional questions will assess overall symptom severity (on the 4-point scale), return to health, 

PROTECT-APT 1 Version 5.0 
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07 Feb 2024 
 
43 | 103 
and return to usual activities. The questionnaire will also ascertain the presence of any new 
symptoms not elicited in the questionnaire.  
Medication Review 
Self-reported medication use including prescription, traditional medicines, and nonprescription 
medications. Reporting will inquire about indication, symptom(s) being addressed, frequency, 
dosing, and duration of use. 
Medical History 
Reviewed by research staff with participant. Documentation of comorbidities (identifying current 
diagnoses or history of condition) and other lifestyle factors including:  
 Cardiac arrhythmia 
 Ischemic health disease 
 Peripheral vascular disease 
 Venous thromboembolism 
 Diabetes (insulin dependent or non-insulin dependent) 
 Human Immunodeficiency Virus (HIV) 
 Asthma 
 Chronic obstructive pulmonary disease (COPD)  
 Chronic Kidney Disease (dialysis dependent or not on dialysis) 
 Liver Disease 
 Hypertension 
 Cancer (solid tumor) 
 Cancer (hematologic) 
 Immunosuppressive conditions or Chronic immunosuppressant use 
 Obesity (defined as body mass index [BMI] >30; may be based on self-report or 
calculation from height and weight) 
 Dementia or other chronic neurologic condition 
 Smoking/Vaping 
 Severe genetic or developmental disabilities 
 Sickle cell disease or thalassemia 
 Solid or hematologic organ transplant 
 Tuberculosis 

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44 | 103 
Clinical Outcome 
Medical chart abstraction will be performed if participant seeks additional care, is hospitalized, 
or for unanticipated visits.  
Clinical data collection from the healthcare encounter will capture: 
 Date and timing of clinical care 
 Clinical presentation  
 Clinical care delivered 
 Results of diagnostic testing 
 Medication administration 
 Response to treatment 
 Clinical outcome 
Vaccination status 
Vaccine manufacturer and date of each dose if recalled by the participant.  
Adverse Events 
Participants will be assessed at every visit for any new symptoms or additional care sought and 
their relationship to the study intervention. Participants will also be provided contact information 
to report any of these new symptoms or healthcare visits to research staff between visits. See 
Section 10.3 Methods for Obtaining Adverse Event and Serious Adverse Event Data. 
9.2.2 
Lab Assessments 
The following laboratory evaluations are for all investigational products:  
Hematology 
Complete blood count: white blood cell count with differential, hemoglobin, hematocrit, platelet 
count measured using Abbot CellDyn® Hematology Analyzer or similar equipment. 
Refer to PSA for additional testing requirements.  
Chemistry 
Serum: sodium, potassium, chloride, CO2, glucose, BUN, creatinine, calculated eGFR, alanine 
aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total 
bilirubin, direct bilirubin, and total protein using Piccolo® General Chemistry 13 or similar 
equipment. 
Refer to PSA for additional testing requirements. 
Pregnancy Testing 
Pregnancy testing will be completed at screening and any time pregnancy is suspected. 
Pregnancy testing will be completed in all females of childbearing potential defined as 

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premenopausal females capable of becoming pregnant. This includes women on oral, injectable, 
or mechanical contraception and women whose male sexual partners have been vasectomized or 
are using contraceptive devices. For females of childbearing potential, negative serum or urine 
pregnancy test will be completed at or within 24 hours prior to study enrollment by any clinic or 
laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its 
equivalent, or by a point of care (POC)/CLIA-waived test. 
In the event of pregnancy occurring during the study, pregnancy and pregnancy outcome will be 
reported. See Section 10.1.9 Reporting of Pregnancy and Breastfeeding.   
Refer to PSA for additional pregnancy testing requirements. 
SARS-CoV-2 Testing 
Diagnostic testing must be an approved molecular or antigen diagnostic test for SARS-CoV-2 
from any upper respiratory specimen. The test used must be authorized for use by the relevant 
national authority for the detection of SARS-CoV-2 in the country where the test is administered.  
Historical testing results will be acceptable if testing performed within the required window 
(within 24 hours of enrollment for post-exposure prophylaxis and within 5 days of enrollment for 
early treatment) and the verified result can be presented to the research staff at screening. The 
local testing result, specimen type, assay type, and date of test will be recorded in the CRF. 
For efficacy assessments, nasal swabs will be collected for SARS- CoV-2 ribonucleic acid 
(RNA). A core laboratory will be used for the performance of all study testing. Qualitative and 
quantitative PCR will use the Abbott RealTime SARS-CoV-2 RT-PCR assay on the M200 
platform and ThermoFisher assays which have been authorized for emergency use by FDA under 
an EUA for use by authorized laboratories. Viral sequencing will be performed using the Ion 
Ampliseq™ SARS-CoV-2 research panel on the Genexus instrument, for research use only. 
Remote sampling will utilize the Zymo Research Corporation Swab Collection Kit or similar for 
extracting and purifying RNA.  The kit contains a sonication medium to maintain the integrity of 
the RNA, while disrupting cells and dissolving cell components. RNA can remain stable in a 
specimen for up to 30 days at room temperature. 
For self-collected specimens, participants will first be instructed on proper self-collection 
technique and be provided a pictorial instruction guide.  
9.2.3 
Screening Assessments 
For the MP, screening assessment include: 
 SARS-CoV-2 diagnostic testing 
 SARS-CoV-2 vaccination status 
 Concomitant medications 
 Pregnancy testing 
 Screening symptom questionnaire 
PSAs will detail any additional product specific screening assessment requirements. Final 
eligibility will be determined by the site PI after review of all screening assessments.  

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9.2.4 
Stored Specimens 
With participant consent, collected upper respiratory specimens, plasma, sera, or nucleic acid 
stabilized whole blood (or whole blood) will be collected and may be used to assess SARS-
CoV-2 virologic and immune responses. All Entry/Day 0 specimens should be collected prior to 
the first dose of IP or placebo. Specimens will be stored indefinitely, or until none is left for use. 
Stored Whole Blood 
Stored whole blood and nucleic acid stabilized whole blood will be collected and stored for 
future testing which may include: 
 Immunologic host-response studies 
 Host transcriptomics analysis 
Stored Plasma 
Blood plasma will be collected and stored for future testing which may include: 
 Immunologic host-response studies 
 SARS-CoV-2 seroconversion and antibody titers (among seroconverters) 
 Quantitative SARS-CoV-2 RNA 
Stored Serum 
Blood sera will be collected and stored for future testing which may include: 
 Total and neutralizing antibody assays 
 Immunologic host-response studies 
Stored Upper Respiratory Specimens 
Upper respiratory specimens will be collected and stored for future testing which may include: 
 Quantitative and qualitative SARS-CoV-2 RNA 
 Quantitative and qualitative influenza-like illness respiratory pathogen RNA 
 SARS-CoV-2 variant identification 
Additional specimens will be collected for product-specific evaluations per the PSAs. 
9.2.5 
Blood Volumes 
Product specific study assessments, specimen collection schedules and specimen volumes will be 
outlined in the product specific appendices.  
9.2.6 
Pharmacokinetics  
Refer to PSA 

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9.3 
Procedures to Follow in the Event of Abnormal Laboratory Test Values or 
Clinical Findings 
Abnormal findings from clinical or laboratory assessments will be evaluated for clinical 
significance throughout the trial. If a test is deemed to be clinically significant, it may be 
repeated, for verification. If a test remains clinically significant, the participant will be informed 
of the results and the appropriate medical care or follow up will be arranged with the permission 
of the participant. Decisions to exclude the participant from enrolling in the trial or withdraw the 
participant from the trial will be at the discretion of the site principal investigator (PI) in 
coordination with the medical monitor. Laboratory adverse events will be recorded in the 
appropriate CRF. 
9.4 
Study Visits 
9.4.1 
Screening Visit - In Person or Remote (Within 24 hours prior to 
Enrollment) 
Potential participants will be screened for presumptive eligibility for the study according to the 
procedures described below. All procedures may be completed in a stepwise manner, as 
suggested below, for potential participants who meet the study eligibility criteria. For 
participants who do not meet the eligibility criteria, screening will be discontinued when 
ineligibility is determined. For potential participants who participate in the screening visit 
remotely and are found to be presumptively eligible, final eligibility will be confirmed upon 
completion of screening procedures at the Enrollment Visit scheduled to take place within 24 
hours of screening. Screening and enrollment may take place on the same day (Day 0). 
 
Screening Informed Consent (in person or verbal (See Section  14.1.2 Informed Consent 
Process) 
 
Screening Symptom Questionnaire 
 
Demographics 
 
Medical History 
 
Physical Exam 
 
Vital Signs 
 
Height and Weight 
 
SARS-CoV-2 Vaccination Status 
 
Diagnostic Test for SARS-CoV-2 (for eligibility assessment) 
 
Pregnancy test for women of childbearing potential 
 
Concomitant medication review 

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9.4.2 
Enrollment Visit – In Person (Day 0) 
Participants who are found to be presumptively eligible at their Screening Visit will complete the 
Enrollment visit within 24 hours of the Screening Visit. Participants who completed the 
screening visit remotely will complete all remaining screening procedures as well as enrollment 
procedures during the in-person Enrollment Visit. Participants who do not complete an 
Enrollment Visit within 24 hours of screening must repeat the entire Screening Visit. All 
participants must complete the screening evaluation prior to study enrollment. For those who 
meet the study eligibility criteria from the screening procedures, the enrollment procedures 
below may be undertaken in a stepwise manner, as suggested below, to confirm eligibility. As 
done with the Screening Visit, procedures will be discontinued if ineligibility is determined at 
this visit. The site investigator will review all screening assessments (physical exam, medical 
history, laboratories etc.) prior to product administration to determine final eligibility for the 
PSA to which the participant has been randomized 
 
Screening Symptom Questionnaire (repeat if visit not performed on same day as 
Screening) 
 
PSA (IP) Informed Consent (in person) (for all PSAs for which the participant may be 
eligible and are contributing to a shared placebo pool) 
 
PSA screening assessments (for all PSAs for which the participant may be eligible, 
completed informed consent, and are contributing to a shared placebo pool) 
 
Randomization (Step 1) (upon completion and review of all MP and PSA screening 
assessments by the site PI) 
 
Randomization (Step 2) 
 
Vital Signs 
 
Upper Respiratory Specimen Collection (prior to administration of IP or control) 
 
Venous Blood Sampling (prior to administration of IP or control) 
 
Administer IP or Control (Refer to PSA) 
 
Dispense Study Kit 
 
Collect and Update Contacts 
 
Adverse Event Recording and Reporting 

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9.4.3 
Day 3 – Remote or In Person  
This visit is scheduled to take remotely or in person on Day 3. Every effort should be made to 
complete the Day 3 visit requirements on Day 3; however, the visit may take place - if necessary 
+/- 1 days. Remote visits may include visits by the study staff to the participant or via 
phone/video conference. If remote visit not feasible or is not permissible under local rules or 
standards, the visit may be conducted in person 
If conducted remotely the following procedures will be performed: 
 SARS-CoV-2 Vaccination Status 
 Concomitant Medication Review 
 Collect and Update Contacts 
 Daily Follow Up Symptom Questionnaire (Day 1 until Day 28 then at Week 12) 
 Upper Respiratory Specimen Collection (self-collection) 
 Clinical Outcome Assessment 
 Adverse Event Recording and Reporting 
If conducted in person following procedures will be performed: 
 SARS-CoV-2 Vaccination Status 
 Concomitant Medication Review 
 Collect and Update Contacts 
 Daily Follow Up Symptom Questionnaire (Day 1 until Day 28 then at Week 12) 
 Upper Respiratory Specimen Collection 
 Clinical Outcome Assessment 
 Vital Signs 
 Physical Exam 
 Venous Blood Sampling  
 Adverse Event Recording and Reporting 

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9.4.4 
Day 7 – Remote or In Person 
This visit is scheduled to take place in person or remotely on Day 7. Every effort should be made 
to complete the Day 7 visit requirements on Day 7; however, the visit may take place — if 
necessary +/- 1 days. Remote visits may include visits by the study staff to the participant or via 
phone/video conference. If remote visit not feasible or is not permissible under local rules or 
standards, the visit may be conducted in person 
If conducted remotely the following procedures will be performed: 
 SARS-CoV-2 Vaccination Status 
 Concomitant Medication Review 
 Collect and Update Contacts 
 Daily Follow Up Symptom Questionnaire (Day 1 until Day 28 then at Week 12) 
 Upper Respiratory Specimen Collection (self-collection) 
 Clinical Outcome Assessment 
 Adverse Event Recording and Reporting 
If conducted in person following procedures will be performed: 
 SARS-CoV-2 Vaccination Status 
 Concomitant Medication Review 
 Collect and Update Contacts 
 Daily Follow Up Symptom Questionnaire (Day 1 until Day 28 then at Week 12) 
 Upper Respiratory Specimen Collection 
 Clinical Outcome Assessment 
 Vital Signs 
 Physical Exam 
 Venous Blood Sampling  
 Adverse Event Recording and Reporting 

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9.4.5 
Day 10 – Remote 
This visit is scheduled to take place remotely on Day 10. Every effort should be made to 
complete the Day 10 visit requirements on Day 10; however, the visit may take place — if 
necessary +/- 1 days. Remote visits may include visits by the study staff to the participant or via 
phone/video conference. If remote visit not feasible or is not permissible under local rules or 
standards, the visit may be conducted in person 
 Daily Follow Up Symptom Questionnaire (Day 1 until Day 28 then at Week 12) 
 Concomitant medication review 
 Clinical outcome assessment  
 Upper Respiratory Specimen Collection (self-collection) 
 Adverse Event Recording and Reporting 
9.4.6 
Day 14 – In Person 
This visit is scheduled to take place on Day 14. Every effort should be made to complete the Day 
14 visit requirements on Day 14; however, the visit may take place — if necessary +/- 2 days.  
 SARS-CoV-2 Vaccination Status 
 Concomitant Medication Review 
 Daily Follow Up Symptom Questionnaire (Day 1 until Day 28 then at Week 12) 
 Upper Respiratory Specimen Collection 
 Clinical Outcome Assessment 
 Vital Signs 
 Physical Exam 
 Venous Blood Sampling  
 Adverse Event Recording and Reporting 
9.4.7 
Day 28 – In Person 
This visit is scheduled to take place on Day 28. Every effort should be made to complete the Day 
28 visit requirements on Day 28; however, the visit may take place — if necessary +/- 4 days.  
 SARS-CoV-2 Vaccination Status 
 Concomitant Medication Review 
 Daily Follow Up Symptom Questionnaire (Day 1 until Day 28 then at Week 12) 
 Upper Respiratory Specimen Collection 
 Clinical Outcome Assessment 

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 Vital Signs 
 Physical Exam 
 Venous Blood Sampling  
 Adverse Event Recording and Reporting 
9.4.8 
Week 12 – In Person or Remote 
This visit is scheduled to take place at Week 12. The visit may be conducted in person or 
remotely. Every effort should be made to complete the Week 12 visit requirements at Week 12; 
however, the visit may take place - if necessary +/- 2 weeks. Remote visits may include visits by 
the study staff to the participant or via phone/video conference. If remote visit not feasible or is 
not permissible under local rules or standards, the visit may be conducted in person 
If conducted remotely the following procedures will be performed: 
 SARS-CoV-2 Vaccination Status 
 Concomitant Medication Review 
 Daily Follow Up Symptom Questionnaire (Day 1 until Day 28 then at Week 12) 
 Upper Respiratory Specimen Collection (self-collection) 
 Clinical Outcome Assessment 
 Adverse Event Recording and Reporting 
If conducted in person following procedures will be performed: 
 SARS-CoV-2 Vaccination Status 
 Concomitant Medication Review 
 Daily Follow Up Symptom Questionnaire (Day 1 until Day 28 then at Week 12) 
 Upper Respiratory Specimen Collection 
 Clinical Outcome Assessment 
 Vital Signs 
 Physical Exam 
 Venous Blood Sampling  
 Adverse Event Recording and Reporting 

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9.4.9 
Unscheduled Visits – In Person or Remote 
An unscheduled visit is defined as any visit to the clinical trial site outside of the protocol 
evaluation time points, where the participant is seen by a member of the clinical research staff. 
Participants will be encouraged to report any medical problems or discomfort to the study staff 
and may be instructed to return to the clinical trial site if they experience new or worsening 
COVID-19 symptoms or become infected with SARS-CoV-2 any time after enrollment. Remote 
visits may include visits by the study staff to the participant or via phone/video conference. If 
remote visit not feasible or is not permissible under local rules or standards, the visit may be 
conducted in person. 
In the event of an unscheduled visit these procedures may be done according to clinical 
judgement: 
If conducted remotely the following procedures may be performed: 
 SARS-CoV-2 Vaccination Status 
 Concomitant Medication Review 
 Daily Follow Up Symptom Questionnaire  
 Upper Respiratory Specimen Collection (self-collection) 
 Clinical Outcome Assessment 
 Adverse Event Recording and Reporting 
If conducted in person following procedures may be performed: 
 SARS-CoV-2 Vaccination Status 
 Concomitant Medication Review 
 Daily Follow Up Symptom Questionnaire 
 Upper Respiratory Specimen Collection 
 Clinical Outcome Assessment 
 Vital Signs 
 Physical Exam 
 Venous Blood Sampling  
 Adverse Event Recording and Reporting 
Depending on the reason for the visit, the participant may have additional assessments or 
laboratory tests, as clinically indicated, or may be referred to the appropriate service for follow 
up.  

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9.4.10 
Worsening/Hospitalization 
In the event a participant is worsened and requires other SOC treatment or hospitalization during 
the course of the study, IP administration will be discontinued.  Participant will continue to be 
followed and will not be withdrawn from the study.  If possible, schedule of activities will 
continue during hospitalization. If unable to complete study activities during hospitalization, 
study procedures may resume after discharge. Consent may be obtained from the participant to 
access hospital or autopsy records. 
Clinical data collection from the healthcare encounter will capture the following (when possible): 
 Date and timing of clinical care 
 Clinical presentation  
 Clinical care delivered 
 Results of diagnostic testing 
 Medication administration 
 Response to treatment 
 Clinical outcome 
 Clinical specimen remnants (if available) 

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10 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
10.1 Definition of Adverse Events (AE) 
An adverse event is any untoward medical occurrence associated with the use of an intervention 
in humans, regardless if considered intervention-related or not. All adverse events that occur 
from the first dose of study medication through Week 12 after enrollment must be recorded. All 
changes in health statuses documented by participants must be reviewed by sites to determine if 
it qualifies as an AE. To formally document the AE, the site must complete an Adverse Event 
report.  
10.1.1 
Definition of Treatment Emergent Adverse Events 
A treatment-emergent adverse event is defined as any event not present prior to the initiation of 
the IP or any event already present that worsens in either intensity or frequency following 
exposure to the IP. 
10.1.2 
Definition of Serious Adverse Events (SAE) 
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of 
either the investigator, medical monitor, or sponsor, it results in any of the following outcomes:  
 Death 
 A life-threatening adverse event 
 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. 
 Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the participant and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
10.1.3 
Classification of Adverse Events 
Adverse events can be classified as/by: 
 DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS 
AE Grading Table) corrected Version 2.1, July 2017 [DAIDS] 
 Investigational Product or Study Participation related or not Investigational Product or 
Study Participation related 

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 Severity of Event 
To maintain accuracy and consistency in the evaluation of AEs, study staff will be trained on and 
utilize the National Institutes of Health, Division of AIDS Table for Grading the Severity of 
Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 
2017 for reporting of adverse events.  
For adverse events (AEs) not included in the protocol defined grading system, the following 
guidelines will be used to describe severity. 
 Grade 1 (Mild) – Mild symptoms causing no or minimal interference with usual social & 
functional activities with intervention not indicated. 
 Grade 2 (Moderate) – Moderate symptoms causing greater than minimal interference 
with usual social & functional activities with intervention indicated 
 Grade 3 (Severe) – Severe symptoms causing inability to perform usual social & 
functional activities with intervention or hospitalization indicated. 
 Grade 4 (Life-threatening) – Potentially life-threatening symptoms causing inability to 
perform basic self-care functions with intervention indicated to prevent permanent 
impairment, persistent disability 
 Grade 5 (Death) 
10.1.4 
Relationship to Investigational Product or Study Participation 
All adverse events (AEs) must have their relationship to IP or study procedure assessed by the 
site PI who examines and evaluates the participant based on temporal relationship and his/her 
clinical judgment. The degree of certainty about causality will be graded using the categories 
below. In a clinical trial, the study product must always be suspect.  
 Related – The AE is known to occur with the study procedure, there is a reasonable 
possibility that the IP or study participation caused the AE, or there is a temporal 
relationship between the IP administration or study participation and event. Reasonable 
possibility means that there is evidence to suggest a causal relationship between the IP 
administration or study participation and the AE. 
 Not Related – There is not a reasonable possibility that the IP or study participation 
caused the event, there is no temporal relationship between IP administration or study 
participation and event onset, or an alternate etiology has been established. 
10.1.5 
Serious and Unexpected Suspected Adverse Reactions (SUSAR) 
In addition to meeting the Serious definition in Section 10.1.2, a Serious and Unexpected 
Suspected Adverse Reaction (SUSAR) is considered “unexpected” if it is not listed in the 
investigator brochure or is not listed at the specificity or severity that has been observed.  
Following notification from the site PI or appropriate sub-investigator, the sponsor will report 
any SUSAR in an IND safety report to the FDA and will notify the sites as soon as possible.  

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10.1.6 
Time Period and Frequency for Event Assessment and Follow-Up  
The occurrence of an adverse event (AE) may come to the attention of study personnel during 
study visits and interviews of a study participant presenting for medical care, or upon review by 
a study monitor. At each study visit, the investigator will inquire about the occurrence of AEs 
since the last visit. All AEs occurring while participating in study must be documented 
appropriately regardless of relationship. All AEs will be followed until resolution or 
stabilization. 
10.1.7 
Adverse Event Recording 
Adverse events will be recorded using the appropriate CRF. Information to be collected includes 
the following: 
 Event description 
 IP (treatment/control) – including administration route and dose 
 Time of onset 
 Clinician's assessment of severity and relationship to IP or study participation (assessed 
only by those with the training and authority to make a diagnosis) 
 Time of resolution/stabilization of the event - all AEs occurring while participating in 
study must be documented appropriately regardless of relationship. All AEs will be 
followed to adequate resolution. 
 Additional treatment or stabilization details 
 Outcome 
10.1.8 
Adverse Events of Special Interest 
Refer to PSAs for AEs of special interest for specific investigational agents. 
10.1.9 
Reporting of Pregnancy and Breastfeeding 
The use of IPs in pregnancy and breastfeeding will vary depending upon IP. The ability to 
continue or need to discontinue IP in the event of pregnancy or breastfeeding is outlined in the 
relevant appendix/appendices. 
If a participant becomes pregnant during the study (post enrollment), study follow up will 
continue for the duration of the study. At the end of the pregnancy, outcome and adverse events 
for participant and infant will be recorded on the outcome CRF. 
10.1.10 
Serious Adverse Event Reporting 
All SAEs will be reported to the sponsor and country regulatory agencies independent of its 
relatedness to the use of Investigational Product (IP). US sites and Country sites will be 
responsible to report SAEs to the IND Sponsor up to 24 hours of awareness of the event and, to 

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follow up on those events up to resolution and/or once an outcome is reached. Initial and Follow 
up SAE reports are mandatory.  
Any event that requires expedited reporting to Regulatory Authorities (i.e., Serious Unexpected 
Suspected Adverse Reactions [SUSARs]) based on applicable national regulations will be 
forwarded to the IND sponsor in time to meet reporting requirements (e.g., 7 days for fatal and 
life-threatening initial reports, with follow up reports within another 8 days, 15 days for all other 
SUSARs). The IND sponsor or its in-country representative will submit safety reports (e.g., IND 
safety reports) to the regulatory agencies as necessary and will inform the investigators of such 
regulatory reports. Site investigators must submit safety reports as required by their IRB. 
Documentation of the submission and receipt by the IRB must be retained for each expedited 
safety report.  
Other supporting documentation of the event may be requested by the Henry M. Jackson 
Foundation for the Advancement of Military Medicine Inc. (HJF) or the IND sponsor and should 
be provided as soon as possible. The Medical Monitor will review and assess the SAE for 
regulatory reporting and potential impact on study participant safety and protocol conduct. 
The IND sponsor will be responsible for notifying the Food and Drug Administration (FDA) of 
any unexpected fatal or life-threatening suspected adverse reaction as soon as possible, but in no 
case later than 7 calendar days after the IND sponsor’s initial receipt of the information. In 
addition, the IND sponsor must notify FDA and all participating investigators in an 
Investigational New Drug (IND) safety report of potential serious risks, from clinical trials or 
any other source, as soon as possible, but in no case later than 15 calendar days after the sponsor 
determines that the information qualifies for reporting. 
At any time after completion of the study, if the site PI or appropriate sub-investigator becomes 
aware of an SAE that occurred during the participant’s participation in the trial, the site PI or 
appropriate sub investigator will report the event to the IND sponsor. The IND Sponsor will 
report SAEs that are not SUSARs to the FDA at least annually in a summary format which 
includes all SAEs. 
AEs, SAEs and SUSARs will be reported to the Central IRB (Advarra) or the local IRB of record 
in accordance with the IRB’s (Advarra or local) defined requirements and timelines. Sites may 
have additional local reporting requirements (to national regulatory authority). 

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10.2 Unanticipated Problems 
10.2.1 
Definition of Unanticipated Problems (UP) 
Unanticipated problems involving risks to participants or others to include, in general, any 
incident, experience, or outcome that meets all the following criteria: 
 Unexpected in terms of nature, severity, or frequency given 
o the research procedures that are described in the protocol-related documents, such as 
the IRB approved research protocol and informed consent document; and  
o the characteristics of the participant population being studied. 
 Related to the IP or study participation; and 
 Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
10.2.2 
Unanticipated Problem Reporting 
AEs that are not serious but that are notable and could involve risks to participants will be 
summarized in narrative or other format and submitted to the IRB at the time of continuing 
review. 
The UP report will include the following information: 
 Study identifying information: protocol title and number. 
 A detailed description of the event, incident, experience, or outcome. 
 An explanation of the basis for determining that the event, incident, experience, or 
outcome represents an UP. 
10.3 Methods for Obtaining Adverse Event and Serious Adverse Event Data 
Adverse events will be assessed starting at Day 0 through study completion or discontinuation. 
At every study visit, participants will be asked open ended questions to elicit any changes in their 
well-being. They will also be asked if they have had to seek additional medical care or testing, 
been hospitalized, had any accidents, used any new medications, or changed concomitant 
medication regimens (both prescription and OTC medications). Results will be recorded in the 
appropriate AE CRF  
If the investigator learns of any SAE, including a death, at any time after a participant has been 
discharged from the study, and he/she considers the event to be reasonably related to the 
investigational agent or study participation, the investigator must promptly notify the sponsor. 
Serious AEs that occur after study completion or discontinuation need not be reported unless the 
investigator considers them related to the investigational product. 

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In addition to participant observations, AEs identified from any study data (e.g., laboratory 
values, physical examination findings, or identified from review of other documents that are 
relevant to participant safety will be documented in the AE CRF. 
The investigator (and/or any designees) and medical monitor are responsible for detecting, 
documenting, and reporting events that meet the definition of an adverse event or serious adverse 
event and remain responsible for following up AEs that are serious, considered related to the 
study treatment or the study, or that caused the participant to discontinue the study treatment or 
the study. 
When an adverse event or serious adverse event occurs, it is the responsibility of the investigator 
in conjunction with the medical monitor to review all documentation (e.g., hospital progress 
notes, laboratory, and diagnostics reports) related to the event. 
10.4 Serious Adverse Event Follow-up 
After the initial/serious adverse event report, the investigator in consultation with the medical 
monitor will proactively follow each participant at subsequent visits or contacts via phone or in 
person. All serious adverse events, and events of special interest, if applicable, will be followed 
until resolution, even if this extends beyond the prescribed reporting period. Resolution is the 
return to baseline status or stabilization of the condition with the probability that it will become 
chronic. The serious adverse event outcomes will be reported to the IND Sponsor using the 
appropriate CRF. The investigator and/or medical monitor will submit any updated serious 
adverse event data to the IND Sponsor within 24 hours of receipt of the information. 
If a participant dies during participation in the study the investigator will need to provide a copy 
of any post-mortem findings, including histopathology, if available. 
Investigators are not obligated to actively seek serious adverse events in former participants; 
however, if a serious adverse event that is considered to be related to the IP occurs in a former 
participant and is brought to the attention of the investigator at any time following completion of 
the study, the event will be reported to the Sponsor’s representative. 

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11 
SAFETY AND DATA MONITORING 
11.1 Medical Monitor 
A medical monitor, representing the IND Sponsor, will be responsible for overseeing the safety 
and protection of the participants in the trial. The medical monitor will be available at all times 
and designate a backup if unavailable.  Medical monitor will work closely with the Principal 
Investigator and site PIs and may assist with any of the following: 
 Clarification of Inclusion/Exclusion criteria 
 Participant concerns 
 Adverse events (AEs), Serious adverse events (SAEs), Suspected Unexpected Serious 
Adverse Reactions (SUSARs) 
 Medication errors 
 Concomitant medications 
 Abnormal laboratory values 
 Protocol deviations and waivers 
 Unblinding 
 Early termination or withdraw of a subject 
 Protocol-stopping rules 
The medical monitor will document and store all relevant communications in a secure database.  
11.2 Protocol Safety Review Team (PSRT) 
The PSRT will meet on a regular basis and on an ad hoc basis, as needed.  The PSRT will review 
screening and enrollment summaries, product administration summaries, adverse events, and 
protocol deviations. The PSRT will also review study operations including regulatory, data 
management, and pharmacy. On an expedited bases, the PSRT will review all safety events that 
potentially meet study pause criteria and will decide whether study IP administration should be 
paused for participant safety purposes. The PSRT may pause IP administration at any time but 
will use the study pause criteria listed in Section 12.2 Study and/or PSA Pause and Stopping 
Criteria as a guide. The PSRT may prompt the DSMB to convene to review the events that led to 
a study pause and make the decision to resume, amend or close the study. IP administration will 
resume only if PSRT and DSMB reviews of the events that led to the pause result in a 
recommendation to permit further study IP administration. The IRBs will be notified of the 
decisions taken by the PSRT and DSMB if they involve suspensions, clinical holds (voluntary or 
involuntary), or terminations of this research. The PSRT will include the following: 
 Medical Monitor 
 Study Chair or designee 
 Study PI or designees 

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 IND Sponsor Representative or designee 
 Industry supporter representative or designee 
Additional PSRT participants may also include the following, as needed: 
 Site PIs 
 Sub Investigators 
 Clinical research nursing staff 
 Laboratory staff 
 Data management staff 
 Regulatory staff 
PSRT review via teleconference calls, in-person meetings, or e-mail communications will 
require, at minimum, the participation of the Medical Monitor, the Study Chair or designee, and 
the Study PI or designee. 
11.3 Data Safety Monitoring Board (DSMB) 
An independent Data Safety Monitoring Board (DSMB) will be appointed by the IND Sponsor 
and will consist of a panel of experts who will review the safety and efficacy data for the trial. 
The DSMB charter will define the responsibilities of the DSMB, detail membership 
requirements, describe the data to be reviewed, delineate the meeting process, and outline the 
considerations and policies of the DSMB. Additional details on the DSMB will be provided in 
the DSMB Charter. 
The DSMB may be consulted by the PSRT to review blinded and unblinded data to provide a 
recommendation on continuing enrollment if there are any questions regarding safety. The 
DSMB will convene at least every 6 months and/or at the interim triggers (whichever occurs 
first) to help ensure the safety of the participants in the study. The DSMB will provide 
recommendations to the study including termination or modification for safety reasons or if there 
is persuasive evidence of superiority or inferiority of the IP versus the control in its effect on the 
primary and secondary outcomes.  The DSMB may also recommend termination or modification 
of the MP or PSA if it appears futile on statistical or operational grounds to continue as designed. 
The DSMB will review the completeness of the study data collected, the adherence to the 
protocol, safety, and efficacy data. Unless a study pause has been implemented, study activities 
will continue while awaiting DSMB review.  
If there are no safety concerns, the DSMB may recommend continued enrollment of participants 
pending any interim analyses detailed in the PSA. The DSMB will provide the Study Chair, the 
Study PI, the site PIs, and the IND Sponsor with any recommendations stemming from the 
reviews. The IND Sponsor will inform the reviewing IRBs and the FDA of the DSMB 
recommendations, as needed. 

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12 
PAUSE AND STOPPING CRITERIA 
12.1 Individual Participant Pause and Stopping Criteria 
The administration of IP to any participant may be stopped or paused for any SAE, clinically 
significant AE, severe lab abnormality or any medical condition that may indicate to the 
Investigator or medical monitor that IP continuation is not in the best interest of the participant.  
In addition, IP administration will be stopped or paused for the following: 
 The subject worsens and requires treatment for worsening COVID-19 as recommended 
by the NIH [COVID-19 Treatment Guidelines].  All other study activities will continue, 
participant will not be withdrawn from the study.  
 The subject worsens and requires hospitalization for worsening COVID-19. All other 
study activities will continue, participant will not be withdrawn from the study. Refer to 
Section 9.4.10 Worsening/Hospitalization 
Refer to PSA for additional individual participant pause and stopping criteria 
12.2 Study and/or PSA Pause and Stopping Criteria 
If one of the PSAs is placed on safety pause, all enrollment and IP administration will be 
suspended in that PSA until further notice. Study visits will continue. Enrollment and IP 
administration will resume if and when safety is ensured as determined by the PSRT and medical 
monitor.  
Table 1 summarizes the AEs, which when experienced by at least one participant will lead to a 
safety pause or prompt PSRT (and DSMB, as applicable) AE review.  
 Any Grade 5 event, Grade 4 event, or any Grade 3 hypersensitivity reaction should be 
reported immediately (within hours of the site learning of the event). These events require 
prompt review by the PSRT (and/or DSMB as applicable). These events require an 
immediate study pause. 
 Other Grade 3 events that are judged related to IP administration should be reported 
promptly (within 24 hours of the site learning of the event). These events require prompt 
review by the PSRT (and DSMB as applicable) for a decision if a study pause is 
necessary.  
 Grade 3 events in two or more participants that are judged related to IP administration 
from the same system organ class should be reported promptly (within 24 hours of the 
site learning of the event). These events require prompt review by the PSRT (and DSMB 
as applicable) for a decision if a study pause is necessary. 

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Table 1. 
Adverse Event Notification and Study Pausing Guidelines 
Adverse Event 
Action a 
Grade 5/Grade 4 
(Or Grade 3 Hypersensitivity) b 
Automatic pause  
Immediate reporting 
(Concurrent with observation or report) 
Grade 3 (Other) 
Related b 
Consider pause 
Prompt reporting (within 24 hours of observation or report) 
a: Follow-Up and Resolution: All promptly or immediately reportable AEs are followed until resolution or 
condition is medically stable 
b: Laboratory abnormalities must be verified. Verified definition: If no evidence of disease is present other than 
the abnormal laboratory value, the test must be repeated at least one time in order to be considered “verified”. 
The verification period will be a maximum of 48 hours after initial awareness of the abnormal laboratory value. 
When signs and symptoms are present, repeat test WILL NOT be needed 
For events in the table above, the site PI notifies the PSRT within the time outlined in Table 1 
after the site observes or is notified of the AE. The PSRT will convene within one business day 
to review these adverse events and determine disposition (including whether the DSMB needs to 
review the event). Refer to PSA for additional study and/or PSA pause and stopping criteria. 
12.3 Resumption of Paused Study 
If a decision to resume study enrollment and study treatment administration is made, the PSRT 
(and DSMB, if applicable) will record its judgment in a memorandum to the study file held by 
the IND Sponsor. The IND Sponsor will instruct the clinical site to resume activities upon receipt 
of written notification from the PSRT. As needed, the appropriate regulatory authorities and 
IRBs will be informed by the IND Sponsor, in writing, of the decision to resume or discontinue 
study activities. The IND Sponsor is also responsible for notifying the FDA.  

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12.4 Corrective Actions and Reporting Events to Participants 
The PSRT (in conjunction with the DSMB) will determine whether the incident constitutes an 
AE or UP involving risks to participants or others and may specify any corrective actions.  
Corrective actions may include, but are not limited to the following:  
 Acknowledgement/acceptance without further recommendation 
 A request for further clarification or a corrective action plan from the IND Sponsor or 
study PI 
 Changes in the protocol (e.g., additional tests or visits to detect similar events in a timely 
manner, changes to the confidentiality measures employed in the study, changes to 
inclusion/exclusion criteria) 
 Changes to the ICFs 
 Notification to enrolled participants and/or re-consenting when appropriate 
 A change in frequency of continuing review 
 Additional training for site PIs and/or research staff 
 PSA suspension or termination 

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13 
STATISTICAL CONSIDERATIONS 
The platform trial design allows for more efficient evaluation of multiple IPs through shared 
controls of similarly eligible, concurrently randomized participants.  
The Statistical Analysis Plan (SAP) for any IP will be finalized prior to the first planned analysis. 
This section is a summary of the planned statistical analyses of the primary endpoints for the 
early treatment and post-exposure prophylaxis indications. Each PSA will include a more 
detailed description of the statistical analyses outlined in this section. The PSA will also detail 
secondary endpoints and any additional simulations used to inform the sample size estimates.  
In general, for comparative analyses (IP to control), the control group will be limited to those 
participants who were eligible to receive the IP being evaluated and were concurrently 
randomized to a relevant control arm. 
13.1 Hypotheses 
Early Treatment:  The primary hypothesis is that early treatment with IP among low-risk 
outpatients infected with SARS-CoV-2 can shorten time to sustained symptom alleviation or 
resolution compared to standard care. 
Post-exposure Prophylaxis: The primary hypothesis is that post-exposure prophylaxis with IP 
can prevent COVID-19 infection among close contacts of symptomatic SARS-CoV-2 positive 
cases compared to standard care.  
13.2 Populations for Analysis 
For purposes of analysis, the following analysis sets are defined: 
Full Analysis Population: 
All participants completing the second randomization step (randomization to a PSA) 
Modified Intention to Treat (mITT) Population: 
All participants randomized who receive at least one dose of the IP/control. 
For the primary analysis, the mITT population will be used for the primary efficacy assessment. 
The mITT set will be used for all other secondary efficacy analyses 
Safety Population: 
All participants who receive at least one dose of the IP/control. In the unlikely case a participant 
receives the incorrect study drug, participants will be grouped according to the treatments that 
they received. 
The Safety population will be used in the analyses of the safety data. 

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Per Protocol: 
All participants in the mITT set who completed treatment with IP/control and without major 
protocol deviations that impact the primary efficacy evaluation. Prior to study unblinding, 
protocol deviations will be reviewed and a determination of the population for per protocol 
analysis will be made. 
The PP analysis population may be used for secondary and exploratory endpoints. General 
Considerations 
Baseline demographic and clinical variables will be summarized by treatment group using the 
Full Analysis population. Descriptive summaries of the distribution of continuous variables will 
be presented using percentiles (e.g., median, 25th and 75th percentiles), means and standard 
deviations. Categorical variables will be summarized using frequencies and percentages.  
For binary endpoints, proportion of participants with the event will be summarized by treatment 
group. Comparison between groups will be presented as the difference of proportions with its 
95% confidence interval. For categorical endpoints, proportion of participants in each category 
will be summarized by treatment group. 
13.3 Primary Endpoint/Estimand Analysis 
13.3.1 
Early Treatment  
The primary efficacy assessment is the relative time to sustained alleviation or resolution of 
symptomatic COVID-19 infection for a participant that receives the IP compared to a participant 
that does not receive the IP.  Targeted symptoms will be used for analysis (Supplement 3). 
Sustained alleviation or resolution will be defined as the number of days from randomization 
within a PSA (randomization Step 2) to the first day the participant reports all symptoms as mild 
or none (≤ 1 or returning to pre-illness levels) for at least 3 consecutive days (the first day being 
considered the Event Day). The estimand of interest is the hazard ratio of a participant that has 
symptomatic COVID-19 with standard of care background therapy when starting treatment with 
IP compared to control. The primary analysis population is the mITT population.  
The primary analysis model is a Cox proportional hazards model for the time to sustained 
alleviation or resolution of COVID-19 symptoms, with treatment arm (IP vs control) as a 
covariate.  The model estimated hazard ratio will be used as the estimator for the estimand of 
interest.  The estimate and 95% confidence interval for the hazard ratio will be presented.   
The primary hypothesis test is that IP increases the hazard (decreases time to alleviation or 
resolution of COVID-19 symptoms).  A hypothesis test will be conducted for testing whether the 
IP hazard ratio is less than 1 at a one-sided 2.5% level.   

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13.3.2 
Post-Exposure Prophylaxis 
The estimand of interest is the odds ratio of a participant that has potentially been exposed to 
COVID-19 suffering a symptomatic COVID-19 infection with IP compared to no control. The 
primary analysis population is the modified intent-to-treat population.  
The primary analysis model is a logistic regression model for the likelihood of a symptomatic 
COVID-19 infection, with treatment arm (IP vs control) as a covariate. The model estimated 
odds ratio will be used as the estimator for the estimand of interest. The estimate and 95% 
confidence interval for the odds-ratio will be presented.  
The primary hypothesis test is IP reduces the risk (odds) of symptomatic COVID-19 infections 
among contacts of symptomatic SARS-CoV-2 positive cases compared to placebo. A hypothesis 
test will be conducted for testing whether IP reduces the risk at a one-sided 2.5% level.  
13.4 Outcome Measures and Statistical Analysis 
Refer to PSA for detailed descriptions of outcome measures and planned statistical analysis 
13.4.1 
Early Treatment 
13.4.1.1 Primary Outcome 
 
Time to sustained alleviation or resolution of COVID-19 symptoms evaluated from 
Day 0 through Day 28 assessed via completion of a Daily Follow Up Symptom 
Questionnaire. 
Sustained alleviation or resolution will be defined as the number of days from randomization 
within a PSA to the first day the participant reports all symptoms as mild or none (≤ 1 or 
returning to pre-illness levels) for at least 3 consecutive days (the first day being considered the 
Event Day). Targeted symptoms will be used for analysis (Supplement 3).  
Symptoms will be collected at Enrollment using this Screening Symptom Questionnaire.  
Symptom eligibility requirements for enrollment will be determined using the Symptom 
Questionnaire and to establish baseline symptom status.  Enrollment, randomization within a 
PSA (randomization Step 2), and IP administration/initiation will occur on the same day.  
The primary analysis is a Cox proportional hazards model with treatment assignment as a fixed 
covariate with a proportional effect.  A one-sided p-value for the test of a hazards ratio of 1 
compared to the alternative of a hazard ratio greater than 1 (IP reduces time to resolution of 
symptoms) will be presented and used for testing superiority.   
The hazard ratio for the time to sustained alleviation or resolution of COVID-19 will be 
presented with 95% confidence intervals.  Additional sensitivity analyses for the primary 
analysis will utilize additional covariate adjustments in the Cox proportional hazards model.   

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13.4.1.2 Key Secondary Outcomes 
Key secondary outcome for the Early Treatment indication include: 
 
Number and proportion of all cause hospitalizations 
 
Number and proportion of all cause deaths 
The mITT population will be used for secondary endpoint analyses 
Refer to PSA 
13.4.1.3 Safety and Tolerability 
Refer to PSA 
13.4.1.4 Exploratory 
Refer to PSA 
13.4.1.5 Sub-Group Analyses 
Refer to PSA 
13.4.2 
Post Exposure Prophylaxis 
13.4.2.1 Primary Outcome 
 
Incidence of symptomatic COVID-19 by Day 14 
Symptomatic COVID-19 will be defined as a positive SARS-CoV-2 RT-PCR test and the 
presence of at least one COVID-19 symptom. COVID-19 symptoms will be ascertained using 
the Daily Follow Up Symptom Questionnaire. 
The primary analysis is a logistic regression model with treatment assignment as a fixed 
covariate. A one-sided p-value for the test of an odds-ratio of 1 compared to the alternative of an 
odds-ratio less than 1 (IP reduces incidence) will be presented and used for testing superiority.  
The odds ratio for the incidence of symptomatic COVID-19 will be presented with 95% 
confidence intervals. Additional sensitivity analyses for the primary analysis will utilize 
additional covariate adjustments in the logistic regression model.  
13.4.2.2 Secondary Outcomes 
Refer to PSA 
13.4.2.3 Safety and Tolerability 
Refer to PSA 
13.4.2.4 Exploratory  
Refer to PSA 

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13.4.2.5 Sub-Group Analyses 
Refer to PSA 
13.5 Interim Analysis Plan 
The adaptive elements, including the interim analysis schedule and plan will be detailed in each 
PSA.  
13.6 Final Analysis Plan 
The adaptive elements, including the interim analysis schedule and plan will be detailed in each 
PSA. 
13.7 Missing Data 
The primary analyses for each population will be based on an intent-to-treat approach. Therefore, 
every patient in the intent-to-treat group will be analyzed. A single imputation approach for each 
patient with missing data will be utilized with a range of sensitivity analyses exploring the 
sensitivity of the results to the missing data.  
For the Early Treatment population, the primary analysis is a time to sustained alleviation or 
resolution of symptoms analysis. For a patient that becomes lost-to-follow-up and hence is 
missing the full primary outcome, a last-status imputation will be assumed. If the patient’s last 
day was symptom free, then the patient will be assumed symptom free, and their time of 
resolution will be the first symptom free day. If the patient’s last day was symptoms alleviated, 
then the patient will be assumed symptom alleviated and their time of alleviation the first day of 
alleviated symptoms. If the patient’s last day was non-alleviated or resolved symptoms, they will 
be assumed censored without alleviation or resolution at the last observed day.  
For the PEP population, a single imputation approach will be conducted for the primary analysis 
for each patient with missing daily observations. The following single imputation will be 
utilized: 
 
A patient that tests negative and has missing daily outcomes will have their negative 
status carried forward and be considered negative for the primary analysis.  
 
If a participant tests positive for COVID-19 and has missing symptom scores through 
Day 14 will be considered a positive symptomatic case.  
The details of the missing data imputations and the sensitivity analyses will be detailed in the 
individual appendices Statistical Analysis Plans. 

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13.8 Sample Size Determination 
13.8.1 
Early Treatment 
The maximum sample size for the early treatment indication primary analysis is 300 participants 
with 1:1 allocation to the IP and its control arm. The maximum sample size of 300 participants 
(150 active and 150 controls) and the adaptive design provides 90% power to detect a hazard 
ratio of 1.50 risk (33% reduction in median time to symptom alleviation or resolution) and 
approximately 80% power for a hazard ratio of 1.42, a 30% reduction in the median time to 
symptom alleviation or resolution, assuming a median time to symptom resolution of 9 days for 
the control arm.  This assumption is based on review of relevant literature [Menni 2022, Akavian 
2022]. 
13.8.2 
Post-Exposure Prophylaxis 
The maximum sample size for the primary analysis is 700 participants with 1:1 allocation to the 
IP arm and its control arm. The maximum sample size of 700 participants (350 active and 
350 controls) provides 95% power to detect a reduction in the odds of a symptomatic COVID-19 
infection assuming a control participant is at a 20% risk of symptomatic infection and the IP 
reduces the risk of infection by 50%. The sample size provides approximately 80% power to 
detect a 40% reduction in the risk of symptomatic infection. 

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14 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
14.1 Regulatory, Ethical, and Study Oversight Considerations 
14.1.1 
Regulatory Review 
The United States Food and Drug Administration (FDA), Central IRB (Advarra), US Department 
of Defense Human Subjects Protection Office – USAMRMC HRPO, clinical trial site IRBs, and 
relevant local health authorities will be asked to review and give written approval of the protocol 
and the informed consent forms, and all other written information provided to the participant. 
14.1.2 
Informed Consent Process and Informational Documents Provided to 
Participants  
Similar to the study randomization process, the informed consent process will occur in 2 steps.  
The initial step will be the screening informed consent. This will consist of an overview of the 
study master protocol, study objectives, the randomization process, and the study duration. The 
eligibility criteria and screening procedures will be covered in detail in the Screening ICF. This 
information will be provided to the participant and written documentation of informed consent 
will be required prior to starting any screening procedures.  
The second step will be the PSA Informed Consent. Participants meeting the eligibility criteria 
after completion of the screening process will be randomized to an appropriate PSA for which 
they are eligible and receive the PSA ICF. The PSA ICF will be specific to the IP and will 
describe in detail the study intervention, the second step of the randomization process, blinding, 
study procedures, and potential benefits and risks. This information will be provided to the 
participant and written documentation of informed consent will be required prior to starting 
intervention/administering study intervention.  
If eligible to contribute to a shared placebo pool (i.e., participant potentially meets eligibility 
criteria for more than one PSA participating in placebo sharing), the participant will complete 
informed consent for all PSA ICFs for which they may be eligible and that are contributing to a 
shared placebo pool.   
14.1.3 
Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to the individual's agreeing to participate in 
the study and continues throughout the individual's study participation. Consent forms will be 
IRB approved and the participant will be asked to read and review the document. The 
investigator will explain the research study to the participant and answer any questions that may 
arise. A verbal explanation will be provided in terms suited to the participant's comprehension of 
the purposes, procedures, and potential risks of the study and of their rights as research 
participants. Participants will have the opportunity to carefully review the written consent form 
and ask questions prior to signing. The participants should have the opportunity to discuss the 
study with their family or surrogates or think about it prior to agreeing to participate.  

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The study will use a two-step informed consent process. The first will be the screening informed 
consent and the second will be a product-specific informed consent. Due to the contagious nature 
of the emergent infectious diseases being studied under this protocol and understanding 
recruitment of contacts may not always take place in person, it may not always be feasible for 
study staff to come in direct contact with the potential and/or active study participants or handle 
any items that they may have come in contact with per local site infection control policies. 
Therefore, obtaining signed Informed Consent Forms (ICF) and authorization for use and 
disclosure of protected health information (if applicable) for participants enrolled in this study 
may not always be feasible for study staff. In these instances, for the screening informed 
consent only, the study team may request a waiver of documentation of signed screening 
informed consent. When possible, the participant will provide signed screening ICF. If the 
participant is unable to provide signed screening consent, the waiver of documentation of signed 
screening informed consent will be utilized, allowing the participant to provide verbal, rather 
than written screening consent. If study personnel are unable to work near the potential and/or 
active participant for safety reasons, the study personnel will contact the participant according to 
the requirements of the site. Options may include but are not limited to speaking with the 
participant from a safe distance in person, contacting the patient by phone, in person with a 
barrier in between the potential and/or active participant and the study personnel, contacting the 
patient by phone from a separate location, video conferencing, or having a study physician 
trained in infectious disease safety procedures meet with the potential and/or active participant in 
close proximity (if allowed by the site). An observer (witness) will be present for all verbal 
screening consents. The observer’s name and signature documenting the review of the verbal 
screening consent will be documented on the Screening Consent Form Checklist. The observer 
may be an individual on the site study staff who is not part of the participant’s screening consent 
process. 
In contrast to the screening informed consent, the product-specific informed consent will 
require the consent process to take place in person with a signed ICF and authorization for use 
and disclosure of protected health information (if applicable). Consent will be performed in as 
private a manner as possible. The potential and/or active participant will be thoroughly briefed 
on the study’s Informed Consent and authorization for use and disclosure of protected health 
information. They will also be provided with an opportunity to ask any questions and an 
unsigned copy of the informed consent if permissible by the site. In turn, study staff will 
thoroughly document the informed consent process in the study chart. The study personnel 
designated to conduct consent will sign and file the ICF.  
The informed consent process will be conducted and documented in the source document 
(including the date), and the form signed, before the participant undergoes any study-specific 
procedures. Participants must be informed that participation is voluntary and that they may 
withdraw from the study at any time, without prejudice. A copy of the informed consent 
document will be offered to the participants for their records. The rights and welfare of the 
participants will be protected by emphasizing to them that the quality of their medical care will 
not be adversely affected if they decline to participate in this study.  
For site locations enrolling non-English speaking participants, the consent documents (and other 
participant facing documents) will be translated into the relevant language to ensure proper 

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participant understanding. A study staff member who speaks the relevant language and is 
designated to will conduct the informed consent using the appropriate translated documents.  
For participants enrolled who are illiterate and cannot read the consent form, an impartial witness 
must be present during the consenting process (for both English and non-English speaking 
participants). The impartial witness’ name and signature documenting the review of the consent 
will be documented on the consent reviewed (either Screening ICF or product specific ICF). The 
impartial witness may be an individual on the site study staff who is not part of the participant’s 
consent process.  
14.1.4 
Study Discontinuation and Closure  
This study or PSA may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Determination of study or PSA suspension or termination may be made by the 
IND Sponsor, the Study PI, PSRT or DSMB. PSA suspension or termination may be made by 
Industry Supporter. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending, or terminating party to study participants, 
investigators, Study funder, IND Sponsor, industry supporters, and regulatory authorities. If the 
study or PSA is prematurely terminated or suspended, the IND Sponsor will promptly inform 
study participants, Study PI, site PIs, the IRB and industry supporters and will provide the 
reason(s) for the termination or suspension. Study participants will be contacted, as applicable, 
and be informed of changes to study visit schedule. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
 
Determination of unexpected, significant, or unacceptable risk to participants 
 
Demonstration of efficacy that would warrant early declaration (Section 5.1.3 Early 
Termination) 
 
Insufficient compliance to protocol requirements 
 
Data that are not sufficiently complete and/or evaluable 
 
Determination of futility (Section 5.1.3 Early Termination) 
14.1.5 
Confidentiality and Privacy 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, the IND sponsor(s), the study funder, and the industry supporter(s). This 
confidentiality is extended to cover testing of biological specimens in addition to the clinical 
information relating to participants. Therefore, the study protocol, documentation, data, and all 
other information generated will be held in strict confidence. No information concerning the 
study, or the data will be released to any unauthorized third party without prior written approval 
of the industry supporter(s). 
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the IND sponsor, representatives of the 
IRBs, regulatory agencies, the study funder, or the industry supporter supplying study product 

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may inspect all documents and records required to be maintained by the investigator, including 
but not limited to, medical records (office, clinic, or hospital) and pharmacy records for the 
participants in this study. The clinical study site will permit access to such records. 
The study participant's contact information will be securely stored at each clinical site for 
internal use during the study. At the end of the study, all records will continue to be kept in a 
secure location for as long a period as dictated in clinical trial agreement as prescribed by the 
reviewing IRB, Institutional policies, the study funder, the IND sponsor, local regulatory 
authorities, the US Food and Drug Administration or industry supporter(s) requirements. 
Study participant research electronic data, which is for purposes of statistical analysis and 
scientific reporting, will be transmitted to and stored within IND Sponsor’s secure, HIPAA 
compliant electronic data capture systems and clinical data repository using the Clinical One 
application, a 21 CFR Part 11-compliant data capture system provided by IND Sponsor. This 
data will not include the participant's contact or identifying information. Rather, individual 
participants and their research data will be identified by a unique study identification number. 
The study data entry and study management systems used by clinical trial sites and by IND 
Sponsor research staff will be secured, and password protected.  
14.1.6 
Future Use of Stored Specimens and Data  
With the participant's approval, and as approved by local IRBs, de-identified biological 
specimens will be stored at the study implementer site, Henry M. Jackson Foundation for the 
Advancement of Military Medicine Inc. (HJF), and at associated partners’ sites with the same 
goal as the sharing of data with HJF. These specimens could be used for research to understand 
the natural history of COVID-19 including its clinical course, disease biology and pathology and 
will be shared with clinical trial site member upon request under an appropriate agreement such 
as a Materials Transfer Agreement (MTA). Protocols that will utilize specimens and data 
collected from this study for future use will also be provided with a code-link that will allow 
linking the biological specimens with the phenotypic data from each participant, maintaining the 
blinding of the identity of the participant. 
During the conduct of the study, an individual participant can choose to withdraw consent to 
have biological specimens stored for future research. However, withdrawal of consent regarding 
biospecimen storage may not be possible after the study is completed. 
When product-specific endpoints are completed and the results unblinded, access to study data 
and/or specimens will be provided through HJF which will derive data from the HJF-managed, 
HIPAA-compliant, specimen and data management system. 
14.1.7 
Key Roles and Study Governance  
Key Role 
Name 
Institution  
Principal Investigator
Kristen Pettrone
HJF
CRO Project Manager
Nancy Cameron
FHI Clinical

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14.1.8 
Safety Oversight 
Safety oversight will be under the direction of a Data and Safety Monitoring Board (DSMB) 
composed of individuals with the appropriate expertise, including experts in the clinical aspects 
of COVID-19, biostatisticians, investigators (not directly involved in his study) with expertise in 
current clinical trials conduct and methodology. Members of the DSMB should be independent 
from the study conduct and free of conflict of interest, or measures should be in place to 
minimize perceived conflict of interest. The DSMB will operate under the rules of an approved 
charter that will be written and reviewed at the organizational meeting of the DSMB. At this 
time, each data element that the DSMB needs to assess will be clearly defined. The DSMB will 
provide its input to the IND sponsor and the core investigative team at HJF. 
14.1.9 
Clinical Monitoring 
Clinical trial site monitoring is conducted to ensure that the rights and well-being of trial 
participants are protected, that the reported trial data are accurate, complete, and verifiable, and 
that the conduct of the trial is in compliance with the currently approved protocol/amendment(s), 
with International Conference on Harmonization Good Clinical Practice (ICH GCP), and with 
applicable regulatory requirement(s). 
Monitoring for this study will be performed by IND Sponsor in conjunction with the medical 
monitor. 
 
Details of clinical trial site monitoring are documented in a Clinical Monitoring Plan 
(CMP). The CMP describes in detail who will conduct the monitoring, at what 
frequency monitoring will be done, at what level of detail monitoring will be 
performed, and the distribution of monitoring reports. 
 
HJF and/or IND Sponsor will conduct site initiation visits (in person or remote) at each 
site before the study begins enrollment. 
 
Clinical monitoring will be a combination of on-site and remote monitoring. 
14.1.10 
Quality Assurance and Quality Control  
Each clinical trial site will perform internal quality management of study conduct, data and 
biological specimen collection, documentation, and completion. An individualized quality 
management plan will be developed to describe a site's quality management. 
Quality control (QC) procedures will be implemented beginning with the data entry system and 
data QC checks that will be run on the database will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution. 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the 
clinical trial is conducted, and data are generated, and biological specimens are collected, 
documented (recorded), and reported in compliance with the protocol, International Conference 
on Harmonization Good Clinical Practice (ICH GCP), and applicable regulatory requirements 
(e.g., Good Laboratory Practices (GLP), Good Manufacturing Practices [GMP]). 

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The clinical trial site will provide direct access to all trial related sites, source data/documents, 
and reports for the purpose of monitoring and auditing by the IND Sponsor, and inspection by 
local and regulatory authorities 
14.1.11 
Data Handling and Record Keeping 
The principal investigator and delegated research personnel will manage all study data, including 
paper and electronic files. 
Study documents will be stored at each facility in a locked space or file with access limited to 
study personnel. Participant identities will be protected by a unique study I.D. number and 
linking identification (i.e., the informed consent document and enrollment log) will be kept 
separately from test results, in locked files, with limited access. Electronic data will be handled 
in a confidential, controlled-access fashion in accordance with HJF’s “Use Restricted” 
classification of data security and privacy policies (Policy Number: HJF-0501, “Information 
Classification and Data Protection Policy”, Revision Effective Date: 2019-10-24). The study 
enrollment log will contain a unique study ID (specific to the participant), their name, phone 
numbers, email address, and mailing address. 
The informed consent documents will contain the same unique study ID number and the 
participant’s name. The case report form may include the participant’s unique identifier number, 
sex, age, email address, ethnicity, medical history, vaccinations history, living and working 
conditions, and behaviors.  
The participant will have the right to revoke the authorization for use of his/her Protected Health 
Information (PHI) and this will be made clear, along with procedures for doing so, in the 
informed consent and assent documents. 
14.1.12 
Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. Data recorded in the clinical database derived from source documents 
should be consistent with the data recorded on the source documents. Sites may use either paper 
CRF or direct data entry into the clinical database for their method of data collection. The site 
must document which CRF, if any, will be used as source documents in an SOP for source 
documentation.  
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and 
clinical laboratory data will be entered into the Clinical One application. The data system 
includes password protection and internal quality checks, such as automatic range checks, to 
identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered 
directly from the source documents. All data transmitted to and from the application is done 
using a secure, encrypted transmission (SSL/HTTPS). Clinical One has an audit trail function in 
which all changes are tracked and attributable to individual users. Case report forms will be 

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checked for completeness and consistency in accordance with the Data Management Plan and 
source document verified as part of study monitoring.  
14.1.13 
Study Records Retention 
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an International Conference on Harmonization (ICH) region and until 
there are no pending or contemplated marketing applications in an ICH region or until at least 2 
years have elapsed since the formal discontinuation of clinical development of the study 
intervention. These documents should be retained for a longer period, however, if required by 
local regulations. No records will be destroyed without the written consent of the IND Sponsor, 
if applicable. It is the responsibility of the IND Sponsor to inform the investigator when these 
documents no longer need to be retained. Informed Consent forms will be stored in accordance 
with HIPAA Regulations.  
14.1.14 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, International 
Conference on Harmonization Good Clinical Practice (ICH GCP), or Study Specific Manual of 
Procedures (MOP) requirements. The noncompliance may be either on the part of the participant, 
the investigator, or the clinical trial site staff. As a result of deviations, corrective actions are to 
be developed by the site and implemented promptly. 
These practices are consistent with ICH GCP: 
 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
 
5.1 Quality Assurance and Quality Control, section 5.1.1 
 
5.20 Noncompliance, sections 5.20.1, and 5.20.2. 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 5 working days of identification of the protocol deviation, or within 5 working 
days of the scheduled protocol-required activity. All deviations must be addressed in study 
source documents, reported to the IND Sponsor, the HJF Clinical Research Associate, and the 
HJF Data Manager. Protocol deviations must be sent to the reviewing IRB per their policies. The 
site investigator is responsible for knowing and adhering to the reviewing IRB requirements. 
14.1.15 
Publication and Data Sharing Policy  
Sharing of the data generated by this study is considered a moral obligation for improved 
knowledge (including negative outcomes) of an unregistered product considered potentially 
lifesaving in COVID-19 disease. Published data will adhere to the principles as outlined in the 
World Health Organization’s 2020 Ethical standards for research during public health 
emergencies: Distilling existing guidance to support COVID-19 R&D [WHO reference number: 
WHO/RFH/20.1]. 

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As such, this trial will be registered at ClinicalTrials.gov, and results information from this trial 
will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results 
in peer-reviewed journals.  
MTAs for data and clinical specimen sharing will be established with all collaborating partners 
in the U.S. and internationally. 
14.1.16 
Conflict of Interest Policy  
The independence of this clinical trial from any actual or perceived influence, such as by the 
biopharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who 
have a role in the design, conduct, analysis, publication, or any aspect of this trial will be 
disclosed and managed. Furthermore, persons who have a perceived conflict of interest will be 
required to have such conflicts managed in a way that is appropriate to their participation in the 
design and conduct of this trial. The study leadership in conjunction with IND Sponsor and HJF 
has established policies and procedures for all study group members to disclose all conflicts of 
interest and will establish a mechanism for the management of all reported dualities of interest. 
 

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15 
 ADDITIONAL CONSIDERATIONS 
Refer to PSAs if applicable. 
This section should include a description of any additional considerations not currently covered 
in this protocol template, such as particular institutional or IRB-related requirements. 
 

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16 
ABBREVIATIONS 
AE
Adverse Event
ALP
Alkaline Phosphatase
ALT
Alanine Transferase
AST
Aspartate Aminotransferase
CFR
Code of Federal Regulations
CLIA
Clinical Laboratory Improvement Amendments
CMP
Clinical Monitoring Plan
COVID-19
Coronavirus Disease 2019
CRF
Case Report Form
DAIDS
Division of AIDS
DSMB
Data Safety Monitoring Board
FDA
Food and Drug Administration
FHIC
FHI Clinical
GCP
Good Clinical Practice
GLP
Good Laboratory Practices
GMP
Good Manufacturing Practices
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
HJF
Henry M. Jackson Foundation for the Advancement of Military Medicine Inc.
HRPO
Human Research Protections Office
ICF
Informed Consent Form
ICH
International Conference on Harmonization
IND
Investigational New Drug
IP
Investigational Product
IRB
Institutional Review Board
IxRS
Interactive Voice/Web Response System
JPEO
Joint Program Executive Office
mITT
Modified Intention to Treat
MOP
Manual of Procedures

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MTA
Materials Transfer Agreement
NP
Nasopharyngeal
PEP
Post-Exposure Prophylaxis
PHI
Protected Health Information
PI
Principal Investigator
POC
Point of Care
PSA
Product Specific Appendix
PSRT
Protocol Safety Review Team
RNA
Ribonucleic acid
RT-PCR
Reverse transcription polymerase chain reaction
QC
Quality Control
SAP
Statistical Analysis Plan
SARS-CoV-2
Severe Acute Respiratory Syndrome Coronavirus 2
SOA
Schedule of Activities
SOP
Standard Operating Procedure
SUSAR
Serious Unexpected Suspected Adverse Reactions
TEAE
Treatment Emergent Adverse Events 
UP
Unanticipated Problem
US
United States
VOC
Variant of Concern
VOI
Variant of Interest
WHO
World Health Organization
 
 

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17 
STUDY-SPECIFIC DEFINITIONS 
Arms within PSA 
Once randomized to a specific IP (PSA), second randomization to arms 
within the PSA. The default is two arms: investigational product and 
control. Arms within the PSA will be detailed in the product specific 
appendix.
Hospitalization 
Admission to an acute care facility for longer than 24 hours where 
medical care is delivered to treat and stabilize an emergent condition. 
Hospitalization does not include admission for isolation or quarantine 
purposes or for social admissions such as breakdown of home support
Indication  
Indication is the valid reason to use the investigational product. For this 
protocol the indication refers to either early treatment of COVID-19 or 
post-exposure prophylaxis
Product Specific 
Appendix (PSA) 
Appendix to the master protocol detailing product specific information. 
Also refers to the product-specific arm of the study a participant is 
randomized to after completion of the screening and enrollment process 
and all the study procedures contained within it.
Strata 
Categorization of therapeutic indications within the trial: Early 
Treatment or Post-Exposure Prophylaxis 
Stratification 
From the results of the screening process, categorization of participants 
as: 
1) Symptomatic SARS-CoV-2 positive cases  
OR 
2) Asymptomatic contacts of symptomatic SARS-CoV-2 positive cases
 
 

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18 
PROTOCOL AMENDMENT HISTORY 
 
Version
Date
Description of Change
Brief Rationale
V 1.0 
18 Mar 
2022
NA 
 Initial Protocol 
V 2.0 
26 April 
2023
Updated formatting and sections. 
Consistency. 
 
26 April 
2023
Updated section and figure 
numbering.
Consistency. 
 
26 April 
2023
Added boxes for Site Investigator 
Name, Title, Signature, and Date
Improve formatting. 
 
26 April 
2023 
Updated study design to clarify that 
the study is low risk, Phase 2, and 
each PSA will provide details for the 
investigational products (IP).
Clarified for clear 
expectations. 
 
26 April 
2023
Removed Week 24 visit. 
Shorten study follow-up 
period.
 
26 April 
2023
Updated Study Population A. 
Simplify the population 
definition.
 
26 April 
2023 
Updated Outcome Measures with the 
primary efficacy assessment for both 
the early treatment and post-exposure 
prophylaxis indications.
Clarified for clear 
expectations. 
 
26 April 
2023
Updated study visits to clarify 
activities and procedures.
Clarified for clear 
expectations.
 
26 April 
2023
Added reference information. 
Correct formatting. 
 
26 April 
2023 
Added additional references to 
include most up to date information 
on SARS-CoV-2 since previous 
version.
New information. 
 
26 April 
2023
Added Early Treatment and Post-
exposure Prophylaxis hypotheses.
Include study hypothesis for 
the Master protocol.
 
26 April 
2023 
Added objectives and endpoints for 
the Early Treatment and Post-
Exposure Prophylaxis indications.
Include objectives and 
endpoints for the Master 
protocol.

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Version
Date
Description of Change
Brief Rationale
 
26 April 
2023 
Added selection criteria for IP and 
clarified that two physicians will 
evaluate the criteria in order to 
determine IP eligibility. 
Clarify selection process. 
 
26 April 
2023 
Population A updated to add list of 
Screening Symptoms to Supplement 3 
and explain the symptom rating for 
preexisting conditions. Population B 
updated to clarify that contacts must 
have indoor exposure to the 
symptomatic case.
Updated the list of SARS-
CoV-2 symptoms and 
exposure definition to be in 
line with current guidance. 
 
26 April 
2023 
Population A updated to include 
oxygen saturation or use of 
supplemental oxygen at enrollment 
and added a list of comorbidities. 
Added information about women of 
childbearing potential for both 
Population A and B.
Clarified for clear 
expectations. 
 
26 April 
2023 
Added that participants are asked not 
to participate in another clinical trial 
with an IP during their enrollment in 
this trial.
Clarified for clear 
expectations. 
 
26 April 
2023
Added new section. 
Consistency. 
 
26 April 
2023 
Added that adherence reminders will 
take place with the Daily Follow Up 
Symptom Questionnaire and study 
staff will review dosing instructions.
Updated to improve patient 
adherence. 
 
26 April 
2023 
Updated the definition of concomitant 
therapy and listed specific exceptions 
that do not need to be recorded.
Clarified for clear 
expectations. 
 
26 April 
2023 
Added Figure 4. Second 
Randomization Step: IPs with SOC 
treatment allocation.
Provide a figure for 
clarification. 
 
26 April 
2023 
Updated language to clarify the 
differences between participant 
discontinuation of IP, withdrawal of 
consent, and lost to follow-up.
Clarified for clear 
expectations. 

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Version
Date
Description of Change
Brief Rationale
 
26 April 
2023 
Updated the key efficacy assessment 
for the early treatment indication as 
time to sustained alleviation or 
resolution of targeted symptoms as 
determined by subject responses on 
the Daily Follow Up Symptom 
Questionnaire.
Clarify how efficacy 
assessments will be 
determined. 
 
26 April 
2023 
Added details about the Screening 
Symptoms Questionnaire and Daily 
Follow Up Symptom Questionnaire 
and how these will be completed by 
subjects.
Clarify how symptoms will 
be reviewed. 
 
26 April 
2023 
Updated the SARS-CoV-2 Testing 
section to add that a core laboratory 
will be used for all study testing and 
identified which assays and platforms 
will be used.
Added additional testing 
details. 
 
26 April 
2023 
Added new section to clarify PSAs 
will detail the screening assessment 
requirements and final eligibility will 
be determined by site PIs after 
review.
Consistency. 
 
26 April 
2023
Added new section. 
Consistency. 
 
26 April 
2023 
Added new section to provide 
definition for a treatment emergent 
adverse event.
Consistency. 
 
26 April 
2023 
Added new section to define SUSAR 
and outline reporting requirements to 
Sponsor and FDA.
Added per FDA 
recommendation. 
 
26 April 
2023 
Added new section to outline how AE 
and SAE data will be identified by 
study staff throughout the study.
Added per FDA 
recommendation. 
 
26 April 
2023
Added new section to provide 
guidance on SAE follow-up.
Added per FDA 
recommendation.
 
26 April 
2023 
Added information about a medical 
monitor and their responsibilities 
throughout the study.
Added per FDA 
recommendation. 

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Version
Date
Description of Change
Brief Rationale
 
26 April 
2023
Updated details about DSMB meeting 
frequency and responsibilities.
Clarified for clear 
expectations.
 
26 April 
2023 
Added and updated sections to outline 
pause and stopping criteria at the 
individual participant or Study/PSA 
level.
Added per FDA 
recommendation. 
 
26 April 
2023 
Added details about the Statistical 
Analysis Plan (SAP) to include the 
primary hypotheses, primary 
endpoint/estimand analysis, outcome 
measures and statistical analysis, and 
sample size determination for the 
early treatment and post-exposure 
prophylaxis indications
Update the SAP with 
additional information. 
 
26 April 
2023
Updated CRO Project Manager 
Personnel change 
 
26 April 
2023 
Added new questionnaires to record 
participant symptoms at screening 
and then during follow up.
Updated to support study 
hypotheses. 
 
26 April 
2023 
Added list of COVID-19 symptoms 
to be used for Screening, Daily 
Follow Up, and Analysis.
Updated to most current list 
of symptoms. 
V 3.0 
02 June 
2023 
Updated exclusion criteria related to 
contraceptive use to specify time 
period for use.
Clarified for clear 
expectations. 
V4.0 
01 
November 
2023 
Removed contraceptive requirement 
for women of childbearing potential 
Moved to PSA as will be 
product specific. 
Changed from exclusion to 
inclusion criteria in the PSA
 
01 
November 
2023
Updated SUSAR definition to be 
consistent with current standards of 
“serious” and “unexpected”
Clarification 

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Version
Date
Description of Change
Brief Rationale
 
01 
November 
2023 
Added description of symptom 
severity: 
None- You did not experience the 
symptom at all, 
Mild- You experienced the symptom, 
but it did not affect your ability to 
function, 
Moderate- You experienced the 
symptom, and it reduced your ability 
to function, 
Severe- You experienced the 
symptom, and it greatly limited your 
ability to function.
Added detail to assist 
participants with completion 
of symptom questionnaires 
 
01 
November 
2023
Updated treatment guidelines and 
data to support study rationale 
Updated data 
 
01 
November 
2023 
Clarified testing window for HIV 
CD4 count and Viral load (30 days 
from enrollment) and reported 
compliance with ART (if applicable)
Clarification of eligibility 
criteria 
 
01 
November 
2023
Clarified relatedness to IP or study 
procedure 
DSMB feedback 
 
01 
November 
2023
Changed bullets to numbering 
Data monitoring request 
 
01 
November 
2023
Added requirement to record nicotine 
replacement therapy and herbal 
supplements
FDA recommendation 
 
01 
November 
2023
Increased BMI restriction from 25 to 
30 kg/m2 
Expand eligibility criteria 
 
01 
November 
2023
Clarified mITT population will be 
used for secondary endpoint analyses 
FDA request 
 
01 
November 
2023
Updated personnel: 
Removed Dr. Blair 
Updated PM for CRO (FHI)
Updated study roles 

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Version
Date
Description of Change
Brief Rationale
V5.0 
07 February 
2024 
Clarified the ability for PSAs to 
choose to participate or not 
participate in placebo sharing 
 
Clarified participants must meet final 
eligibility criteria for all PSAs for 
which they are eligible and 
contributing to a shared placebo pool
Clarification on placebo 
sharing for PSAs and 
participants 
 
07 February 
2024 
Clarified the ability for PSAs to 
choose to participate or not 
participate in placebo sharing 
 
Clarified participants must meet final 
eligibility criteria for all PSAs for 
which they are eligible and 
contributing to a shared placebo pool
Clarification on placebo 
sharing 
 
07 February 
2024 
Updated figure to clarify flow for 
participant eligibility for multiple 
PSAs contributing to shared placebo 
pool
Clarification on placebo 
sharing 
 
07 February 
2024 
Clarified that participants must 
complete PSA informed consent for 
all PSAs for which they may be 
eligible and are contributing to a 
shared placebo pool
Clarification on participant 
eligibility assessment for 
placebo sharing 
 
07 February 
2024 
Clarified order of activities to reflect 
Informed Consent and MP/PSA 
screening assessments  
Clarification on order to 
activities for participants to 
complete PSA ICF and 
eligibility assessments prior 
to Step 1 randomization
 
07 February 
2024 
Expanded study population to include 
standard and intermediate risk 
participants (revised high risk 
exclusion criteria per FDA Type D 
Meeting Request Written Response)
FDA feedback to Type D 
Meeting Request 
 
07 February 
2024 
Clarified screening assessments under 
Master Protocol 
Clarification of 
requirements for screening 
under Master Protocol 

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Version
Date
Description of Change
Brief Rationale
 
07 February 
2024 
Added rationale for expansion of the 
study population to standard and 
intermediate risk
Rational to support study 
population expansion 
 

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19 
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Symptoms in Outpatient Adult and Adolescent Subjects in Clinical Trials of Drugs and 
Biological Products for COVID-19 Prevention or Treatment. https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/assessing-covid-19-related-symptoms-outpatient-
adult-and-adolescent-subjects-clinical-trials-drugs. Published Sept 2020. Accessed Apr 2022. 
Hewins B, Richardson C, Rubino S, Kelvin A, Toloue Ostadgavahi A, Kelvin DJ. Molecular 
mechanisms responsible for SARS-CoV-2 antibody waning and vaccine escape in Omicron 
sublineages BA.4 and BA.5. J Infect Dev Ctries. 2022;16(7):1122-1125. 
Jansen L, Tegomoh B, Lange K, et al. Investigation of a SARS-CoV-2 B.1.1.529 (Omicron) 
Variant Cluster - Nebraska, November-December 2021. MMWR Morb Mortal Wkly Rep. 
2021;70(5152):1782-1784. 
Jochmans D, Liu C, Donckers K, et al. The substitutions L50F, E166A and L167F in SARS-
CoV-2 3CLpro are selected by a protease inhibitor <em>in vitro</em> and confer resistance to 
nirmatrelvir. bioRxiv. 2022:2022.2006.2007.495116. 
Johns Hopkins University. COVID Data Tracker: Global Cases and Deaths. 
https://coronavirus.jhu.edu/map.html. . Published 2021. Accessed Oct 21, 2021. 
Koma W, Neuman T, Claxton G et al. How Many Adults Are at Risk of Serious Illness If 
Infected with Coronavirus? Updated Data. Kaiser Foundation Data Note. 
https://www.kff.org/coronavirus-covid-19/issue-brief/how-many-adults-are-at-risk-of-serious-
illness-if-infected-with-coronavirus/. Published Apr 2023.Accessed Oct 23, 2023 
Lim DS, Choe YJ, Man Kim Y, et al. Household Secondary Attack Rates of SARS-CoV-2 
Omicron Variant, South Korea, February 2022. Emerg Infect Dis. 2022;28(8):1731-1734. 
Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of the Pfizer-BioNTech and Oxford-
AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older 
adults in England: test negative case-control study. Bmj. 2021;373:n1088. 
López-Muñoz I, Torrella A, López-Quílez O, et al. SARS-CoV-2 Secondary Attack Rates in 
Vaccinated and Unvaccinated Household Contacts during Replacement of Delta with Omicron 
Variant, Spain. Emerg Infect Dis. 2022;28(10). 
Martinuzzi E, Boutros J, Glaichenhaus N, Marquette CH, Hofman P, Benzaquen J. Escape of 
SARS-CoV-2 Variant Omicron to Mucosal Immunity in Vaccinated Subjects. Open Forum 
Infect Dis. 2022;9(8):ofac362. 
Menni C, Valdes AM, Polidori L, et al. Symptom prevalence, duration, and risk of hospital 
admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant 
dominance: a prospective observational study from the ZOE COVID Study. Lancet. 
2022;399(10335):1618-1624. 
Mudatsir M, Fajar JK, Wulandari L, et al. Predictors of COVID-19 severity: a systematic review 
and meta-analysis. F1000Res. 2020;9:1107. 

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People with Certain Medical Conditions. Centers for Disease Control (CDC) and Prevention 
Web site. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-
medical-conditions.html#print. Published 2022. Accessed Sept 1 2022. 
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trial-standard-risk-population-2022-06-14/. Published June 14 2022. Accessed Sept 2 2022. 
SARS-CoV-2 Variant Classifications and Definitions. https://www.cdc.gov/coronavirus/2019-
ncov/variants/variant-classifications.html. Published 2022. Accessed Sept 1 2022. 
Sedova M, Jaroszewski L, Iyer M, Godzik A. Monitoring for SARS-CoV-2 drug resistance 
mutations in broad viral populations. bioRxiv. 2022:2022.2005.2027.493798. 
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Starr TN, Greaney AJ, Addetia A, et al. Prospective mapping of viral mutations that escape 
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Toth DJA, Beams AB, Keegan LT, et al. High variability in transmission of SARS-CoV-2 within 
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Weisblum Y, Schmidt F, Zhang F, et al. Escape from neutralizing antibodies by SARS-CoV-2 
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Willett BJ, Grove J, MacLean OA, et al. The hyper-transmissible SARS-CoV-2 Omicron variant 
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Yamasoba D, Kosugi Y, Kimura I, et al. Neutralisation sensitivity of SARS-CoV-2 omicron 
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20 
SUPPLEMENT 1: SCREENING SYMPTOM QUESTIONNAIRE 
Screening Symptom Questionnaire Source Document 
SSQ
PROTECT-APT 1 
Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Adaptive Platform Trial 
Subject ID
Visit Date
 
(MM/DD/YYYY)
 Not Done
Symptom Questions  
For items 1-11, what was the severity of each 
symptom below at its worst over the last 24 hours? 
None  
(You did not 
experience the 
symptom at all) 
Mild 
(You experienced 
the symptom, but it 
did not affect your 
ability to function)
Moderate 
(You experienced 
the symptom, and 
it reduced your 
ability to function)
Severe 
(You experienced 
the symptom at a 
level which greatly 
limited your ability 
to function)
1. Stuffy or runny nose
 
 
 
 
1a. Do you usually have a stuffy or runny nose?           Yes     No     
1b. What is the usual severity?




2. Sore throat (painful, scratchy, or irritated)
 
 
 
 
2a. Do you usually have a sore throat?                        Yes     No     
2b. What is the usual severity?





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Screening Symptom Questionnaire Source Document 
SSQ
PROTECT-APT 1 
Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Adaptive Platform Trial 
Subject ID
Visit Date
 
(MM/DD/YYYY)
3. Hoarse voice (raspy, strained, or abnormal 
voice)




3a. Do you usually have a hoarse voice?                      Yes     No     
3b. What is the usual severity?




4. Shortness of breath (difficulty breathing)
 
 
 
 
4a. Do you usually have shortness of breath                 Yes     No     
4b. What is the usual severity?




5. Cough
 
 
 
 
5a. Do you usually have a cough?                                Yes     No     
5b. What is the usual severity?




6. Low energy or tiredness
 
 
 
 
6a. Do you usually have low energy or tiredness?        Yes     No     
6b. What is the usual severity?





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Screening Symptom Questionnaire Source Document 
SSQ
PROTECT-APT 1 
Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Adaptive Platform Trial 
Subject ID
Visit Date
 
(MM/DD/YYYY)
7. Muscle or body aches
 
 
 
 
7a. Do you usually have muscle or body aches?          Yes     No     
7b. What is the usual severity?




None
Mild
Moderate
Severe
8. Headache
 
 
 
 
8a. Do you usually have a headache?                          Yes     No     
8b. What is the usual severity?




9. Chills or shivering (feeling of coldness or 
shaking when not in a cold environment)
 
 
 
 
9a. Do you usually have chills or shivering?             Yes     No     
9b. What is the usual severity?




10. Feeling hot or feverish
 
 
 
 
10a. Do you usually feel hot or feverish?                    Yes     No     
10b. What is the usual severity?





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Screening Symptom Questionnaire Source Document 
SSQ
PROTECT-APT 1 
Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Adaptive Platform Trial 
Subject ID
Visit Date
 
(MM/DD/YYYY)
11. Nausea (feeling like you wanted to throw 
up)
 
 
 
 
11a. Do you usually have nausea?                                Yes     No     
11b. What is the usual severity?




12. How many times did you vomit (throw up) in 
the last 24 hours? 
 I did not vomit at all                     3 or 4 times 
1 or 2 times                                  5 or more times
13. How many times did you have diarrhea (loose 
or watery or more frequent bowel movements) in 
the last 24 hours? 
 I did not have diarrhea at all         3 or 4 times 
 1 or 2 times                                   5 or more times 
14. Rate your sense of smell in the last 24 hours: 
 My sense of smell is THE SAME AS usual 
 My sense of smell is LESS THAN usual 
I have NO sense of smell
15. Rate your sense of taste in the last 24 hours: 
 My sense of taste is THE SAME AS usual 
 My sense of taste is LESS THAN usual 
I have NO sense of taste

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Screening Symptom Questionnaire Source Document 
SSQ
PROTECT-APT 1 
Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Adaptive Platform Trial 
Subject ID
Visit Date
 
(MM/DD/YYYY)
Overall Symptom Severity 
16. In the past 24 hours, what was the severity of 
your overall COVID-19 related symptoms at their 
worst?
None
Mild
Moderate
Severe




CONFIDENTIAL: This material will not be disclosed or used except as authorized by the investigator

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20.1 Supplement 2: Daily Follow Up Symptom Questionnaire 
 
Daily Follow Up Symptom Self Report Questionnaire Source Document                                                    DSQ 
PROTECT-APT 1 
Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Adaptive Platform Trial 
Subject ID
Visit Date
 
(MM/DD/YYYY)
 Not Done
Symptom Questions  
For items 1-11, what was the severity of each 
symptom below at its worst over the last 24 hours? 
None  
(You did not 
experience the 
symptom at all) 
Mild 
(You experienced 
the symptom, but it 
did not affect your 
ability to function) 
Moderate 
(You experienced 
the symptom, and 
it reduced your 
ability to function)
Severe 
(You experienced 
the symptom at a 
level which greatly 
limited your ability 
to function)
1. Stuffy or runny nose
 
 
 
 
2. Sore throat (painful, scratchy, or irritated)
 
 
 
 
3. Hoarse voice (raspy, strained, or abnormal 
voice)




4. Shortness of breath (difficulty breathing)
 
 
 
 
5. Cough
 
 
 
 

PROTECT-APT 1 Version 5.0 
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Daily Follow Up Symptom Self Report Questionnaire Source Document                                                    DSQ 
PROTECT-APT 1 
Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Adaptive Platform Trial 
Subject ID
Visit Date
 
(MM/DD/YYYY)
6. Low energy or tiredness
 
 
 
 
7. Muscle or body aches
 
 
 
 
8. Headache
 
 
 
 
9. Chills or shivering (feeling of coldness or shaking 
when not in a cold environment)
 
 
 
 
10. Feeling hot or feverish
 
 
 
 
11. Nausea (feeling like you wanted to throw up)
 
 
 
 
12. How many times did you vomit (throw up) in 
the last 24 hours? 
 I did not vomit at all                     3 or 4 times 
1 or 2 times                                  5 or more times
13. How many times did you have diarrhea (loose 
or watery or more frequent bowel movements) in 
the last 24 hours? 
 I did not have diarrhea at all         3 or 4 times 
 1 or 2 times                                   5 or more times 
14. Rate your sense of smell in the last 24 hours: 
 My sense of smell is THE SAME AS usual 
 My sense of smell is LESS THAN usual 
I have NO sense of smell

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Daily Follow Up Symptom Self Report Questionnaire Source Document                                                    DSQ 
PROTECT-APT 1 
Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Adaptive Platform Trial 
Subject ID
Visit Date
 
(MM/DD/YYYY)
15. Rate your sense of taste in the last 24 hours: 
 My sense of taste is THE SAME AS usual 
 My sense of taste is LESS THAN usual 
I have NO sense of taste
Overall Symptom Severity 
16. In the past 24 hours, what was the severity of your 
overall COVID-19 related symptoms at their worst? 
None
Mild
Moderate
Severe




Global Impression Items 
17. In the past 24 hours, have you returned to your usual health (before your COVID-19 illness)? 
Yes     No      
18. In the past 24 hours, have you returned to your usual activities (before your COVID-19 illness)? 
Yes     No      
19. In the past 24 hours, have you experienced any new symptoms that are NOT listed in this questionnaire (or that you 
have not reported before today)?
 Yes      No     
If YES, please list all new symptoms NOT listed on this 
questionnaire:
___________________________________________________ 

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Daily Follow Up Symptom Self Report Questionnaire Source Document                                                    DSQ 
PROTECT-APT 1 
Early Treatment and Post-Exposure Prophylaxis of COVID-19 - Adaptive Platform Trial 
Subject ID
Visit Date
 
(MM/DD/YYYY)
General Questions 
20. Have you taken your study medication today? 
 Yes      No      
CONFIDENTIAL: This material will not be disclosed or used except as authorized by the investigator

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07 Feb 2024 
 
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20.2 Supplement 3: COVID-19 Symptom Review  
 
Daily Sign and Symptom Collection
Screening 
Symptoms 
Daily Follow 
Up Symptoms 
Targeted 
Symptoms for 
Analysis 
Stuffy or runny nose 
X 
X 
X 
Hoarse voice 
X 
X 
X 
Sore throat 
X 
X 
X 
Difficulty breathing 
X 
X 
X 
Cough 
X 
X 
X 
Fatigue (Low energy or tiredness) 
X 
X 
X 
Muscle or body aches 
X 
X 
X 
Headache 
X 
X 
X 
Fever (documented temperature >38 °C 
[100.4 °F]) or subjective fever 
X 
 
 
Chills or shivering 
X 
X 
X 
Feeling hot or feverish 
 
X 
X 
Nausea  
X 
X 
X 
Vomiting 
X 
X 
X 
Diarrhea 
X 
X 
X 
Loss of Smell 
X 
X 
X 
Loss of taste 
X 
X 
X 
New symptoms in the last 24 hours 
 
X