Clinical trial NCT04501952
Conditions: COVID-19
Sponsor: Gilead Sciences
Start date: 2020-09-18; Completion date: 2021-05-06
Enrollment: 584 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objectives of this study are to evaluate the efficacy of remdesivir (RDV) in reducing the rate of of coronavirus disease 2019 (COVID-19) related hospitalization or all-cause death in non-hospitalized participants with early stage COVID-19 and to evaluate the safety of RDV administered in an outpatient setting.

Detailed description:

Arms: arm 1: Participants will receive a single dose of intravenous (IV) RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3. arm 2: Participants will receive IV placebo to match (PTM) RDV on Days 1 to 3.
Interventions: intervention 1: RDV intervention 2: Placebo to Match RDV
Intervention descriptions: intervention 1: Administered as an intravenous infusion intervention 2: Administered as an intravenous infusion

Protocol documents:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL
Study Title:
A Phase 3 Randomized, Double-Blind Placebo-Controlled Trial to 
Evaluate the Efficacy and Safety of Remdesivir (GS-5734™) 
Treatment of COVID-19 in an Outpatient Setting
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
147753
2020-003510-12
NCT04501952
Indication:
COVID-19
Protocol ID:
GS-US-540-9012
Contact Information:
The medical monitor name and contact information will be 
provided on the Key Study Team Contact List.
Protocol 
Version/Date:
Original:
21 July 2020
Amendment 1:
11 August 2020
Amendment 1.1 (United Kingdom): 07 October 2020
Amendment 1.1 (Germany):
14 October 2020
Amendment 2:
06 November 2020
Amendment 3:
12 November 2020
Amendment 4:
14 January 2021 
This study will be conducted under United States Food and Drug Administration investigational 
new drug (IND) regulations (21 Code of Federal Regulations Part 312); however, sites located in 
the European Economic Area and Switzerland are not included under the IND and are considered 
non-IND sites.
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable 
institutional review board or independent ethics committee. The information is only to be used 
by you in connection with authorized clinical studies of the investigational drug described in 
the protocol. You will not disclose any of the information to others without written 
authorization from Gilead Sciences, Inc., except to the extent necessary to obtain informed 
consent from those persons to whom the drug may be administered.
(rJ GILEAiJ 


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TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................................. 2 
LIST OF IN-TEXTTABLES ........................................................................................................................................ 4 
LIST OF IN-TEXT FIG URES ...................................................................................................................................... 4 
PROTOCOL SYNOPSIS .............................................................................................................................................. 5 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................... I I 
I. 
INTRODUCTION .............................................................................................................................................. 13 
1.1. 
Background ............................................................................................................................................ 13 
1.2. 
Remdesivir (ROY, GS-5734) ................................................................................................................. 13 
1.2.1. 
General Information ............................................................................................................. 13 
1.3. 
Rationale for This Study ........................................................................................................................ 13 
1.4. 
Rationale for Duration of Treatment ...................................................................................................... 14 
1.5. 
Rationale for Dose Selection of Remdesivir .......................................................................................... 14 
1.6. 
Risk/Benefit Assessment for the Study .................................................................................................. 15 
1.7. 
Compliance ............................................................................................................................................ 15 
2. 
OBJECTIYES ..................................................................................................................................................... 16 
3. 
STUDY DESIGN ................................................................................................................................................ 17 
3.1. 
3.2. 
3.3. 
3.4. 
3.5. 
3.6. 
3.7. 
Endpoints ............................................................................................................................................... 17 
Study Design .......................................................................................................................................... 18 
Study Treatments ................................................................................................................................... 18 
Duration of Treatment ............................................................................................................................ 18 
End of Study ........................................................................................................................................... 19 
Poststudy Care ........................................................................................................................................ 19 
Source Data ............................................................................................................................................ 19 
4. 
PARTICIPANT POPULATION ......................................................................................................................... 2 1 
4.1. 
Number of Participants and Participant Selection .................................................................................. 2 1 
4.1.1. 
Participant Replacement... .................................................................................................... 2 1 
4.2. 
Inclusion Criteria .................................................................................................................................... 2 1 
4.3. 
Exclusion Criteria ................................................................................................................................... 22 
5. 
INYESTIGATIONAL MEDICINAL PRODUCTS ........................................................................................... 23 
5.1. 
Randomization, Blinding, and Treatment Codes Access ....................................................................... 23 
5.1.1. 
Randomization ..................................................................................................................... 23 
5.1.2. 
Blinding ................................................................................................................................ 23 
5.1.3. 
Procedures for Breaking Treatment Codes ........................................................................... 23 
5.2. 
Description and Handling of Remdesivir ............................................................................................... 24 
5.2.1. 
Formulation .......................................................................................................................... 24 
5.2.2. 
Packaging and Labeling ....................................................................................................... 24 
5.2.3. 
Storage and Handling ........................................................................................................... 24 
5.3. 
Dosage and Administration of Remdesivir ............................................................................................ 25 
5.3.1. 
Administration Insttuctions .................................................................................................. 25 
5.3 .2. 
Infusion-related Reactions .................................................................................................... 25 
5.4. 
Prior and Concomitant Medications ....................................................................................................... 25 
5.5. 
Accountability for lnvestigational Medicinal Product ........................................................................... 26 
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5.5.1. 
Investigational Medicinal Product Return or Disposal ......................................................... 26 
6. 
STUDY PROCEDURES .................................................................................................................................... 27 
6.1. 
6.2. 
6.3. 
6.4. 
6.5. 
6.6. 
6.7. 
6.8. 
6.9. 
6.10. -
Participant Enrollment and Treatment Assignment ................................................................................ 27 
Pretreatment Assessments ...................................................................................................................... 27 
6.2.1. 
Screening Visit ..................................................................................................................... 27 
Treatment Assessments (Baseline/Day I, Day 2, and Day 3) ................................................................ 28 
Post-treatment Assessments (Day 4 Through Day 14) ........................................................................... 29 
Day 28 Follow-up Assessment(± 5 Days) ............................................................................................. 30 
Assessments for Early Discontinuation from Study ............................................................................... 30 
Procedures and Specifications ................................................................................................................ 31 
6.7.1. 
Complete Physical Examination ........................................................................................... 31 
6.7.2. 
Clinical Laborator Assessments ......................................................................................... 31 
nteria for D1scontmuat1on o Stu y Treatment ................................................................................... . 
End of Study ........................................................................................................................................... 33 
Poststud Care ........................................................................................................................................ 33 
7. 
ADVERSE EVENTS AND TOXICITY MANAGEMENT ............................................................................... 35 
7.1. 
Definitions of Adverse Events and Serious Adverse Events .................................................................. 35 
7.1.1. 
Adverse Events ..................................................................................................................... 35 
7 .1.2. 
Serious Adverse Events ........................................................................................................ 35 
7.2. 
Assessment of Adverse Events and Serious Adverse Events ................................................................. 36 
7 .2.1. 
Assessment of Causality for Study Drugs and Procedures ................................................... 36 
7 .2.2. 
Assessment of Severity ........................................................................................................ 36 
7.3. 
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events ....................................................................................................................................... 37 
7.3.1. 
Requirements for Collection Prior to Study Drug Initiation ................................................. 37 
7.3.2. 
Adverse Events ..................................................................................................................... 37 
7.3.3. 
Serious Adverse Events ........................................................................................................ 37 
7.4. 
Gilead Reporting Requirements ............................................................................................................. 38 
7.5. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or 
Serious Adverse Events .......................................................................................................................... 39 
7.6. 
Toxicity Management ............................................................................................................................ 39 
7.7. 
Special Situations Reports ...................................................................................................................... 39 
7.7.1. 
Definitions of Special Situations .......................................................................................... 39 
7.7.2. 
Instructions for Reporting Special Situations ....................................................................... 40 
8. 
STATISTICAL CONSIDERA TIONS ................................................................................................................ 42 
8.1. 
Analysis Objectives and Endpoints ........................................................................................................ 42 
8.1.1. 
Analysis Objectives .............................................................................................................. 42 
8.1.2. 
Primary Endpoint ................................................................................................................. 42 
8.1.3. 
Secondar End oint ............................................................................................................. 43 
8.2. 
-
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8.2.1. 
Interim Analysis ................................................................................................................... 44 
8.2.2. 
Final Analysis ....................................................................................................................... 44 
8.3. 
Analysis Conventions ............................................................................................................................. 44 
8.3. I. 
Analysis Sets ........................................................................................................................ 44 
8.3.2. 
Data Handling Conventions ................................................................................................. 45 
8.4. 
Demographic and Baseline Characteristics Analysis ............................................................................. 45 
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8.5.
Efficacy Analysis ...................................................................................................................................45
8.5.1.
Primary Analysis..................................................................................................................45
8.5.2.
Secondary Analyses .............................................................................................................46
8.6.
Safety Analysis.......................................................................................................................................46
8.6.1.
Extent of Exposure...............................................................................................................46
8.6.2.
Adverse Events.....................................................................................................................46
8.6.3.
Laboratory Evaluations ........................................................................................................46
8.7.
Adjustments for Multiplicity..................................................................................................................47
8.9.
Sample Size............................................................................................................................................47
8.9.1.
Sample Size Re-estimation...................................................................................................48
8.10.
Independent Data Monitoring Committee..............................................................................................48
9.
RESPONSIBILITIES..........................................................................................................................................49
9.1.
Investigator Responsibilities ..................................................................................................................49
9.1.1.
Good Clinical Practice..........................................................................................................49
9.1.2.
Financial Disclosure.............................................................................................................49
9.1.3.
Institutional Review Board/Independent Ethics Committee Review and 
Approval...............................................................................................................................49
9.1.4.
Informed Consent.................................................................................................................49
9.1.5.
Confidentiality......................................................................................................................50
9.1.6.
Study Files and Retention of Records ..................................................................................50
9.1.7.
Case Report Forms...............................................................................................................52
9.1.8.
Investigator Inspections........................................................................................................52
9.1.9.
Protocol Compliance............................................................................................................52
9.2.
Sponsor Responsibilities ........................................................................................................................52
9.2.1.
Protocol Modifications.........................................................................................................52
9.2.2.
Study Report and Publications .............................................................................................53
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................53
9.3.1.
Payment Reporting...............................................................................................................53
9.3.2.
Access to Information for Monitoring..................................................................................53
9.3.3.
Access to Information for Auditing or Inspections ..............................................................54
9.3.4.
Study Discontinuation..........................................................................................................54
10.
REFERENCES ...................................................................................................................................................55
11.
APPENDICES ....................................................................................................................................................56
Appendix 1.
Investigator Signature Page....................................................................................................57
Appendix 2.
Study Procedures Tablea.........................................................................................................58
Appendix 3.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................60
LIST OF IN-TEXT TABLES
Table 1.
Recommended Rate of Infusion—Diluted RDV for Injection Lyophilized Powder in 
Adults and Pediatric Patients 12 Years of Age and Older and Weighing at Least 
40 kg.......................................................................................................................................25
LIST OF IN-TEXT FIGURES
Figure 1.
Study Schema.........................................................................................................................19
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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3, Randomized Double-Blind Placebo-Controlled Trial to 
Evaluate the Efficacy and Safety of Remdesivir (GS-5734™) 
Treatment of COVID-19 in an Outpatient Setting 
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
147753
2020-003510-12
NCT04501952
Study Centers 
Planned:
Approximately 150 centers globally
Objectives:
The purpose of this trial is to evaluate treatment with intravenous 
(IV) administered remdesivir (RDV, GS-5734) in an outpatient 
setting in participants with confirmed coronavirus disease 2019 
(COVID-19) who are at risk for disease progression.
The primary objectives of this study are as follows:

To evaluate the efficacy of RDV in reducing the rate of 
COVID-19 related hospitalization or all-cause death in
non-hospitalized participants with early stage COVID-19

To evaluate the safety of RDV administered in an outpatient 
setting
The secondary objectives of this study are as follows: 

To evaluate the efficacy of RDV in reducing the rate of 
COVID-19 related medically attended visits (MAVs; medical 
visits attended in person by the participant and a health care 
professional) or all-cause death in non-hospitalized participants
with early stage COVID-19

To determine the antiviral activity of RDV on severe acute 
respiratory syndrome (SARS)-coronavirus (CoV)-2 viral load

To assess the impact of RDV on symptom duration and severity 
 
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Study Design: 
This is a Phase 3, randomized, double-blind, placebo-controlled, 
multicenter study of RDV therapy for outpatients with early stage 
COVID-19 who are at higher risk of disease progression. 
Number of 
Participants 
Pla1med: 
Target Population: 
Duration of 
Treatment: 
Diagnosis and Main 
Eligibility Criteria: 
CONFIDENTIAL 
Participants who meet all eligibility criteria may be randomized in a 
1: 1 ratio to RDV or placebo. Randomization will be stratified by 
participants who reside in a skilled nursing facility, by participant's 
age(< 60 vs~ 60 years), and by region (United States [US] vs 
ex-US): 
Treatment Group A: single dose of IV RDV 200 mg on Day 1 
followed by IV RDV 100 mg on Days 2 and 3 (RDV group) 
Treatment Group B: IV placebo-to-match (PTM) RDV on Days 1 
to 3 (PTM group) 
Approximately 1264 participants 
Non-hospitalized participants with early stage COVID-19 and at 
least one risk factor for disease progression. 
Participants will receive study treatment with RDV or PTM for 
3 days 
Participants with COVID-19 who meet the following inclusion 
criteria may be included: 
• 
Willing and able to provide written infonned consent (age ~18) 
or assent (age ~12 to <18, where locally and nationally 
approved), or with a legal representative who can provide 
infonned consent (where locally and nationally approved) 
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
Either:
At least 1 pre-existing risk factor for progression to 
hospitalization (chronic lung disease, hypertension, 
cardiovascular or cerebrovascular disease, diabetes, obesity
(BMI , immunocompromised, chronic mild or 
moderate kidney disease, chronic liver disease, current 
cancer, or sickle cell disease);
OR age years

SARS-CoV-2 infection confirmed by molecular diagnostics 
(nucleic acid [eg, PCR] or antigen testing) ≤ 4 days prior to 
screening

Presence of ≥1 symptom(s) consistent with COVID-19 for 
≤7 days prior to randomization (such as fever, cough, fatigue, 
shortness of breath, sore throat, headache, myalgia/arthralgia)

Not currently receiving, requiring, or expected to require 
supplemental oxygen 

Not currently requiring hospitalization (hospitalization defined 
as ≥24 hours of acute care)
Exclusion criteria for participation include:

Participation in any other clinical trial of an experimental 
treatment and prevention for COVID-19

Prior hospitalization for COVID-19 (hospitalization defined as 
≥24 hours of acute care)

Treatment with other agents with actual or possible direct 
antiviral activity against SARS-CoV-2 or administration of any 
SARS-CoV-2 (or COVID-19) vaccine

Known hypersensitivity to the study drug, metabolites, or 
formulation excipient
Study Procedures/
Frequency:
At screening, after the participant has provided informed consent, 
demographic and baseline characteristics and medical history will 
be collected. Current clinical history, and concomitant medications 
will be documented. Physical examination findings, vital signs 
including temperature, respiratory rate, and SpO2 on room air will 
be documented. Women of childbearing potential will have a urine 
pregnancy test.


Remdesivir (RDV; GS-5734T") 
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After screening procedures, eligible participants may be randomized 
in a 1: 1 ratio to receive treatment with RDV or PTM. 
Randomization will be stratified by residence in a skilled nursing 
facility, participant's age (<60 vs;::: 60 years), and region (US vs 
ex-US). 
After randomization, all participants randomized to receive RDV or 
PTM should receive their initial dose on Day 1. 
Nasopharyngeal swabs and sputum samples will be collected on 
Days 1, 2, 3, 7, and 14 for SARS-CoV-2 quantitative reverse 
transcriptase polymerase chain reaction viral load testing and 
possible resistance testing. 
On study Days 1 through 3, vital signs including respiratory status 
will be measured, and adverse events (AEs), medically attended 
visit infonnation and concomitant medications will be documented. 
Laboratory tests for safety (hematology, chemistry, and 
coa ulation will be erformed on Da s 1 3 7 and 14.-
On study 
Day 14 physical examination findings, vital signs including 
temperature, respiratory rate, and SpO2, AEs, medically attended 
visit infonnation and concomitant medications will be documented. 
Symptom severity will be assessed daily from Day 1 through 
Day 14 using the COVID-19-adapted FLU-PRO Plus questionnaire 
(if available). 
On study Day 28, there will be an in-person or phone visit. Physical 
examination, vital signs including temperature, respiratory rate, and 
SpO2, AEs, medically attended visit infonnation and concomitant 
medications will be docmnented ( only AEs, medically attended visit 
infonnation and concomitant medications needed if perfonned by 
phone). 
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Test Product, Dose, 
Remdesivir for injection, 100 mg, for IV administration 
and Mode of 
Administration: 
Reference Therapy, 
Dose, and Mode of 
Administration: 
Criteria for 
Evaluation: 
CONFIDENTIAL 
Placebo-to-Match 
The primary endpoints of this study are: 
• 
Composite endpoint of COVID-19 related hospitalization 
( defined as at least 24 hours of acute care) or all-cause death by 
Day28 
• 
Proportion of participants with treatment-emergent AEs 
The secondary endpoints of this study are: 
• 
Composite endpoint of COVID-19 related MA Vs (medical 
visits attended in person by the participant and a health care 
professional) or all-cause death by Day 28 
• 
All-cause mortality at Day 28 
• 
Proportion of participants hospitalized by Day 28 
• 
Composite endpoint of COVID-19 related hospitalization 
( defined as at least 24 hours of acute care) or all-cause death by 
Day 14 
• 
Composite endpoint of COVID-19 related MA Vs (medical 
visits attended in person by the participant and a health care 
professional) or all-cause death by Day 14 
• 
Time-weighted average change in SARS-CoV-2 viral load from 
baseline to Day 7 
• 
Time to alleviation (mild or absent) of baseline COVID-19 
symptoms as reported on the COVID-19-adapted FLU-PRO 
Plus 
• 
Proportion of participants progressing to requiring oxygen 
supplementation by Day 28 
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I I 
I I 
I 
I 
I 
The total sample size of the study will be approximately 
1264 participants. 
FINAL 
Amendment4 
A sample size of approximately 1264 participants (632 in each 
group with 1: 1 randomization) achieves> 90% power to detect a 
ratio of 0.55 (RDV to placebo in proportion of COVID-19 related 
hospitalization or all-cause death rate, which is equal to a hazard 
ratio of 0.534) using a 2-sided significance level of 0.05 assuming 
the overall hospitalization or death rate is 9.3% (12% in the placebo 
group and 6.6% in the RDV group) and a 5% drop out rate. The 
sample size provides approximately 80% power to detect a ratio of 
0.60 (RDV to placebo). This analysis will be stratified by residence 
in skilled nursing facility, age (<60 vs ~60 years), and region (US vs 
ex-US). An m1blinded sample size re-estimation is planned after 
50% participants completed Day 28. 
The primary endpoint will be analyzed using Cox model with 
stratification factors as covariates. The null hypothesis being tested 
is whether the ratio of hospitalization or death is the same for either 
RDV or placebo treatment. The ratio and 95% confidence interval 
will be provided. 
Treatment-emergent AEs and laboratory abnonnalities will be 
summarized using descriptive statistics and listed by participant. 
This study will be conducted in accordance with the guidelines of Good Clinical Practice 
including archiving of essential documents. 
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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
AE
adverse event
ALT
alanine aminotransferase
aPTT
activated partial thromboplastin time
ARDS
acute respiratory distress syndrome
AST
aspartate aminotransferase
ATP
adenosine triphosphate
CI
confidence interval
CLcr
creatinine clearance
CoV
coronavirus
COVID-19
coronavirus disease 2019
CP
conditional power
CRF
case report form
DAIDS
Division of AIDS
DMC
data monitoring committee
eCCGs
eCRF completion guidelines
eCRF
electronic case report form
EDC
electronic data capture
eGFR
estimated glomerular filtration rate
eSAE
electronic serious adverse event
EU
European Union
FDA
Food and Drug Administration
FLU-PRO Plus©
InFLUenza Patient-Reported Outcome Plus
GCP
Good Clinical Practice
Gilead
Gilead Sciences, Inc.
GLPS
Global Patient Safety
HIV
human immunodeficiency virus
IB
investigator’s brochure
ICH
International Council for Harmonisation (of Technical Requirements for Pharmaceuticals 
for Human Use)
IDMC
independent data monitoring committee
IEC
independent ethics committee
IND
investigational new drug
INR
international normalized ratio
IRB
institutional review board
IV
intravenous
IXRS
interactive voice/web response system
LLOQ
lower limit of quantitation
MAV
medically attended visit
O2
oxygen


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PCR
polymerase chain reaction
PI
principal investigator
PK
pharmacokinetic(s)
PT
prothrombin time
PTM
placebo-to-match
qRT-PCR
quantitative reverse transcriptase polymerase chain reaction
RDV
remdesivir (GS-5734™)
RNA
ribonucleic acid
SAE
serious adverse event
SARS
severe acute respiratory syndrome
SBECD
sulfobutylether β-cyclodextrin sodium
SDV
source data verification
SOC
standard of care
SOP
standard operating procedure
SpO2
oxygen saturation
SUSAR
suspected unexpected serious adverse reaction
ULN
upper limit of normal
US
United States


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1.
INTRODUCTION
1.1.
Background
Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2, a single-stranded RNA virus,
is identified as the cause of an outbreak of respiratory illness that was first detected in Wuhan, 
China in December 2019. The virus has now spread globally, resulting in a global pandemic and 
causing severe respiratory illness throughout the world. Severe cases progress to pneumonia and 
multi-organ failure, which can lead to death. Gilead Sciences, Inc. (Gilead) has been working 
with global health authorities to respond to the ongoing pandemic and to evaluate the utility of 
intravenous (IV) remdesivir (RDV; GS-5734™) as a treatment option for coronavirus disease 
2019 (COVID-19) through clinical trials. Remdesivir is approved for the treatment of 
COVID-19 in the United States (US), European Union (EU), Japan, and other countries for 
populations including adults and pediatric patients (12 years and older and weighing at least 
40 kg).
1.2.
Remdesivir (RDV, GS-5734)
Remdesivir is being developed by Gilead and is formulated for IV administration.
1.2.1.
General Information
Remdesivir is an adenosine nucleotide prodrug that distributes into cells where it is metabolized
to form the pharmacologically active nucleoside triphosphate metabolite. Metabolism of
remdesivir to remdesivir triphosphate has been demonstrated in multiple cell types. Remdesivir
triphosphate acts as an analog of adenosine triphosphate (ATP) and competes with the natural
ATP substrate for incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent
RNA polymerase, which results in delayed chain termination during replication of the viral
RNA.
For further information on RDV, refer to the investigator’s brochure (IB) for RDV.
1.3.
Rationale for This Study
Remdesivir is a novel antiviral drug that exhibits potent nanomolar antiviral activity against 
SARS-CoV-2 in primary human airway epithelial cells {Sheahan 2017}. In 
SARS-CoV-2-infected rhesus monkeys, administration of RDV resulted in a significant 
reduction in clinical signs of respiratory disease, lung pathology and gross lung lesions, and viral
RNA levels compared with vehicle-treated animals {Williamson 2020}. The safety and efficacy 
of RDV has been demonstrated in clinical studies of patients hospitalized with COVID-19.


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The risk of adverse outcomes from COVID-19 increases with age and the presence of chronic 
health conditions, such as cardiovascular disease, diabetes, and chronic lung disease{Stokes 
2020, The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team 2020, 
World Health Organization (WHO) 2020a}. In acute viral infection with influenza, a short 
course of antiviral treatment has shown improved clinical outcome {Nicholson 2000}. Treatment
intervention in the earlier phase of COVID-19, such as in an outpatient setting, may prevent
disease progression to moderate disease requiring hospitalization. The resulting reduction in 
hospitalizations would significantly benefit patients and would reduce the burden to health care 
systems.
There is currently no approved treatment for patients with COVID-19 who have not been 
hospitalized. This study will evaluate the potential for a 3-day treatment with IV RDV to change 
the clinical trajectory of early COVID-19. The double blinded design will allow stringent 
evaluation of the safety and efficacy of RDV in this population.
Participants in this study will be treated with RDV for a maximum of 3 days receiving a total of 
400 mg RDV. This dose corresponds to a total administration of 12 g of sulfobutylether 
β-cyclodextrin sodium (SBECD) using the lyophilized powder. Based on the European 
Medicines Agency (EMA) review summarizing the safety of cyclodextrins as excipients 
{Committee for Medicinal Products for Human Use (CHMP) 2014}, which indicates 
approximately 250 mg/kg/day of SBECD (12 g/day based on a 48 kg human) is safe, participants 
will not be required to discontinue RDV if their creatinine clearance is < 30 mL/min during the 
dosing period.
1.4.
Rationale for Duration of Treatment
In patients with severe COVID-19 who do not require mechanical ventilation, 5 days of RDV
showed similar efficacy to a 10 day regimen. Similarly, 5 days treatment of RDV in participants 
with moderate COVID-19 was associated with a significant improvement in clinical status 
compared with standard of care (SOC) and approximately a third of participants were discharged 
prior to completion of 5 days RDV therapy.
In early viral infection, shorter courses of antivirals are often effective in preventing disease 
progression {Nicholson 2000}. As such, a shorter duration of 3 days of RDV treatment is 
proposed in participants with early stage COVID-19 not requiring hospitalization or oxygen 
supplementation with the goal of preventing disease progression.
1.5.
Rationale for Dose Selection of Remdesivir
The dosing of RDV in this study, 200 mg on Day 1 and 100 mg on each of Days 2 and 3 is the 
initial dosing recommended by US Food and Drug Administration (FDA) and approved by EMA
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1.6.
Risk/Benefit Assessment for the Study
In addition to the established risks associated with IV RDV, potential risks associated with the 
study include unknown adverse events (AEs) and laboratory abnormalities. There is the potential 
for resistance to develop with shorter treatment duration.
Intravenous RDV for up to 10 days is approved for the treatment of COVID-19 in the US, Japan,
and the EU.
The shorter duration of treatment may lower the risk of some adverse findings associated with 
RDV, eg, the transient elevations of alanine aminotransferase (ALT) and aspartate 
aminotransferase (AST). However, other risks may not be ameliorated or may not have been 
evident in the studies of participants with more severe disease. 
An independent data monitoring committee (IDMC) will review safety and efficacy data of the 
study when 50% of the participants have been enrolled. In addition, a futility interim analysis is 
planned when approximately 50% of the participants have completed the Day 28 visit to stop a 
non-efficacious treatment. The IDMC will make a recommendation of stopping enrollment to the 
study if the pre-specified futility stopping criteria are met. 
The risk mitigation strategy for this study includes restriction of the study population to those
without a history of significant hepatic or renal disease:

Exclusion of participants with contraindicated known hepatic or renal disease

Exclusion of coadministration of other investigational agents against COVID-19

Serum chemistry assessments, including liver function tests, will be monitored during the 
study period.
There are currently no investigational agents with demonstrated clinical efficacy or approved 
treatments for COVID-19 patients not requiring in-patient care. The timely evaluation of a safe 
and effective antiviral agent with demonstrated safety and efficacy addresses a serious unmet 
medical need. In consideration of the information included in this protocol, the overall risks to 
participants are outweighed by the potential benefits of RDV investigational therapy for the 
treatment of COVID-19. The benefit-risk balance for this study is considered positive.
1.7.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


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2. 
OBJECTIVES 
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The purpose of this trial is to evaluate treatment with IV administered RDV in an outpatient 
setting in participants with confinned COVID-19 who are at higher risk for disease progression. 
The primary objectives of this study are as follows: 
• 
To evaluate the efficacy of RDV in reducing the rate of COVID-19 related hospitalization or 
all-cause death in non-hospitalized participants with early stage COVID-19 
• 
To evaluate the safety of RDV administered in an outpatient setting 
The secondary objectives of this study are as follows: 
• 
To evaluate the efficacy of RDV in reducing the rate of COVID-19 related medically 
attended visits (MA Vs; medical visits attended in person by the participant and a health care 
professional) or all- cause death in non-hospitalized participants with early stage COVID-19 
• 
To detenn ine the antiviral activity of RDV on SARS-CoV-2 viral load 
• 
To assess the impact of RDV on symptom duration and severity 
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3. 
STUDY DESIGN 
3.1. 
Endpoints 
The primary endpoints of this study are as follows: 
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• 
Composite endpoint of COVID-19 related hospitalization ( defined as at least 24 hours of 
acute care) or all-cause death by Day 28 
• 
Proportion of participants with treatment-emergent AEs 
The secondary endpoints of this study are as follows: 
• 
Composite endpoint ofCOVID-19 related MA Vs (medical visits attended in person by the 
participant and a health care professional) or all-cause death by Day 28 
• 
All-cause mortality at Day 28 
• 
Proportion of participants hospitalized by Day 28 
• 
Composite endpoint ofCOVID-19 related hospitalization (defined as at least 24 hours of 
acute care) or all-cause death by Day 14 
• 
Composite endpoint of COVID-19 related MA Vs (medical visits attended in person by the 
participant and a health care professional) or all-cause death by Day 14 
• 
Time-weighted average change in SARS-CoV-2 viral load from baseline to Day 7 
• 
Time to alleviation (mild or absent) of baseline COVID-19 symptoms as reported on the 
COVID-19-adapted FLU-PRO Plus 
• 
Proportion of participants progressing to requiring oxygen supplementation by Day 28 
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Study Design 
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This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study of RDV 
therapy for outpatients with early stage COVID-19 who are at higher risk of disease progression. 
3.3. 
Study Treatments 
Approximately 1264 participants who meet all eligibility criteria may be randomized in a 
1: 1 ratio into either treatment group: 
Treatment Group A: single dose ofIV RDV 200 mg on Day 1 followed by IV RDV 100 mg on 
Days 2 and 3 (RDV group) 
Treatment Group B: IV placebo-to-match (PTM) RDV on Days 1 to 3 (PTM group) 
Randomization will be stratified by participants who reside in a skilled nursing facility, by 
participant's age (<60 vs ~60 years), and by region (US vs ex-US). 
3.4. 
Duration of Treatment 
Participants will receive study treatment with RDV for 3 days (Treatment Group A) or PTM for 
3 days (Treatment Group B). 
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Figure 1. 
Study Schema 
3.5. 
n= 
1264 
Day 
1 
n = 632 
End of Study 
3 
RDVx3days 
PHI x 3days 
28 
• 
Primary end:point 
composite oi 
hospitaliza tion/death 
by day 28 
The end of the study will be the last participant's last observation ( or visit). 
3.6. 
Poststudy Care 
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The long-tenn care of the participant will remain the responsibility of their primary treating 
physician. Remdesivir is being supplied with curative intent. There is no provision for post-study 
availability. 
3.7. 
Source Data 
The source data for this study will be obtained from electronic data ca 
laboratory, local laboratory, specialty laboratory 
interactive voice/web response system (IXRS) data. 
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4.
PARTICIPANT POPULATION
4.1.
Number of Participants and Participant Selection
Approximately 1264 participants who meet the eligibility criteria will be enrolled in one of 
2 treatment groups. Participants will receive study drug in an outpatient, skilled nursing facility
or home health setting. 
4.1.1.
Participant Replacement
Participants who discontinue before the end of study will not be replaced.
4.2.
Inclusion Criteria
Participants must meet all of the following inclusion criteria to be eligible for participation in this 
study:
1) Willing and able to provide written informed consent (participants ≥ 18 years of age) or 
assent (participants ≥ 12 and < 18 years of age) prior to performing study procedures. 
Participants aged ≥18 years may be enrolled with the consent of a legal representative where 
permitted according to local law and approved nationally and by the relevant institutional 
review board (IRB) or independent ethics committee (IEC). For participants ≥ 12 and 
< 18 years of age, a parent or legal guardian must be willing and able to provide written 
informed consent prior to performing study procedures
2) Either:
Age ≥ 18 years (at all sites) or aged ≥ 12 and < 18 years of age weighing ≥ 40 kg (where 
permitted according to local law and approved nationally and by the relevant IRB or IEC)
with at least 1 of the following pre-existing risk factors for progression to hospitalization:
a) Chronic lung disease: chronic obstructive pulmonary disease, moderate-to-severe asthma, 
cystic fibrosis, pulmonary fibrosis
b) Hypertension: systemic or pulmonary
c) Cardiovascular or cerebrovascular disease: coronary artery disease, congenital heart 
disease, heart failure, cardiomyopathy, history of stroke, atrial fibrillation, hyperlipidemia
d) Diabetes mellitus: Type 1, type 2, or gestational
e) Obesity (BMI 
f)
Immunocompromised state; having a solid organ transplant, blood, or bone marrow 
transplant; immune deficiencies; HIV with a low CD4 cell count or not on HIV 
treatment; prolonged use of corticosteroids; or use of other immune weakening medicines
g) Chronic mild or moderate kidney disease
h) Chronic liver disease


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i)
Current cancer
j)
Sickle cell disease
OR age years, regardless of the presence of other pre-existing risk factors for 
progression
3) SARS-CoV-2 infection confirmed by molecular diagnostics (nucleic acid [eg, PCR] or 
antigen testing) ≤4 days prior to screening
4) Presence of ≥ symptom(s) consistent with COVID-19 for ≤ 7 days prior to randomization
(such as fever, cough, fatigue, shortness of breath, sore throat, headache, myalgia/arthralgia)
{Stokes 2020, World Health Organization (WHO) 2020b}
5) Not currently receiving, requiring, or expected to require supplemental oxygen
6) Not currently requiring hospitalization (hospitalization defined as ≥24 hours of acute care)
7) Participants of childbearing potential who engage in heterosexual intercourse must agree to 
use protocol-specified method(s) of contraception as described in Appendix 3
4.3.
Exclusion Criteria
Participants who meet any of the following exclusion criteria are not eligible to be enrolled in 
this study:
1) Participation in any other clinical trial of an experimental treatment and prevention for 
COVID-19
2) Prior hospitalization for COVID-19 (hospitalization defined as ≥24 hours of acute care)
3) Treatment with other agents with actual or possible direct antiviral activity against 
SARS-CoV-2 or administration of any SARS-CoV-2 (or COVID-19) vaccine
4) Criterion removed
5) Requiring oxygen supplementation
6) ALT or AST ≥ 5 × upper limit of normal (ULN) at screening or within 90 days of screening
Note: if per local practice only ALT is routinely measured, exclusion criteria will be evaluated 
on ALT alone
7) Creatinine clearance < 30 mL/min at screening or within 90 days of screening using the 
Cockcroft-Gault formula in participants ≥ 18 years of age or estimated glomerular filtration 
rate (eGFR) < 30 mL/min/1.73m2 at screening or within 90 days of screening using the 
Schwartz formula in participants < 18 years of age (see Section 6.7.2) 
8) Currently breastfeeding (nursing)
9) Known hypersensitivity to the study drug, the metabolites, or formulation excipient
10) Use or planned use of exclusionary medications, refer to Section 5.4


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5. 
5.1. 
5.1.1. 
INVESTIGATIONAL MEDICINAL PRODUCTS 
Randomization, Blinding, and Treatment Codes Access 
Randomization 
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Participants who meet all randomization eligibility criteria will be randomized in a 1: 1 ratio to 
Treatment Group A or Treatment Group B and assigned a participant nmnber. Randomization 
will be stratified by residence in a skilled nursing facility, age (<60 vs~ 60), and region (US vs 
ex-US). 
Randomization may occur approximately one day prior to the Day 1 visit. 
5.1.2. 
Blinding 
During the randomized phase participants and all personnel directly involved in the conduct of 
the study will be blinded to treatment assignment. Specified perso1mel may be unblinded based 
on their study role. Stud dru 
· 
· 
· 
· 
· 
. 
. 
Individuals in clinical virology 
per onnmg samp e se echon or resistance ana ys1s may e unblinded. Individuals in Clinical 
Packaging and Labeling or Clinical Supply Management who have an Unblinded Inventory 
Manager role in the IXRS system for purposes of study drug inventory management will remain 
unblinded. Individuals in Global Patient Safety (GLPS) responsible for safety signal detection, 
investigational new drug (IND) safety reporting, and/or expedited reporting of suspected 
unexpected serious adverse reactions (SUSARs) may be unblinded to individual case data and/or 
group level smmnaries. External (ie, contract research organizations) biostatisticians and 
prograimners will be unblinded for the IDMC, IND safety reporting. Regulatory Quality and 
Compliance perso1mel in Research and Development may also be unblinded for purposes of 
supporting Quality Assurai1ce activities and/or Regulatory Agency inspections. 
5.1.3. 
Procedures for Breaking Treatment Codes 
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the participai1t, the investigator may obtain treatment assigmnent directly from the IXRS 
system for that participant. Gilead recommends but does not require that the investigator contact 
the Gilead medical monitor before breaking the blind. Treatment assigmnent should remain 
blinded unless that knowledge is necessary to detennine participant emergency medical care. 
The rationale for unblinding must be clearly explained in source documentation ai1d on the 
electronic case report fonn ( eCRF), along with the date on which the treatment assigmnent was 
obtained. The investigator is requested to contact the Gilead medical monitor promptly in case of 
any treatment m1blinding. 
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Blinding of study treatment is critical to the integrity of this clinical study. Therefore, if a 
participant’s treatment assignment is disclosed to the investigator, the participant will have study 
treatment discontinued. All participants will be followed until study completion unless consent to 
do so is specifically withdrawn by the participant.
5.2.
Description and Handling of Remdesivir
5.2.1.
Formulation
Remdesivir for injection, 100 mg, is a preservative-free, white to off-white to yellow, lyophilized 
solid containing 100 mg of RDV that is to be reconstituted with sterile water for injection and 
diluted into 0.9% saline prior to administration by IV infusion.
In addition to the active ingredient, RDV for injection, 100 mg, contains the following inactive 
ingredients: SBECD, water for injection, hydrochloric acid, and sodium hydroxide. Hydrochloric 
acid and sodium hydroxide are used to adjust the formulation to a pH of 3.0 to 4.0.
The supplied PTM RDV for injection, 100 mg, is identical in physical appearance to the active 
formulation and contains the same inactive ingredients.
5.2.2.
Packaging and Labeling
Remdesivir for injection and PTM, 100 mg, is supplied as a sterile product in a single-use, 
30-mL Type I clear glass vial. Each vial is sealed with a rubber stopper and an aluminum over
seal with a red, plastic flip-off cap. Following reconstitution, each single-use vial contains 
sufficient volume to allow withdrawal of 20 mL (100 mg RDV or PTM).
Remdesivir for injection and PTM, 100 mg, shall be labeled to meet all applicable requirements 
of the US FDA, EU Guideline to Good Manufacturing Practice Annex 13 (Investigational 
Medicinal Products), the J-GCP (Ministerial Ordinance on Good Clinical Practice for Drugs), as 
applicable, and/or other local regulations.
5.2.3.
Storage and Handling
Remdesivir for injection and PTM, 100 mg, vials should be stored below 30 °C (86 °F) prior to 
use. Storage conditions are specified on the label. Until dispensed for dosing, all vials of study 
drugs should be stored in a securely locked area, accessible only to authorized site personnel.
To ensure the sterility, stability, and proper identification, study drug(s) should not be stored in a 
container other than the container in which they were supplied.
Measures that minimize drug contact with the body should always be considered during 
handling, preparation, and disposal procedures.
The total storage time of reconstituted solution containing RDV or placebo should not exceed 
24 hours at room temperature (20 °C to 25 °C) or 48 hours at refrigerated temperature (2 °C to 
8 °C). Any unused reconstituted solution containing RDV or placebo should be discarded.


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5.3.
Dosage and Administration of Remdesivir
Remdesivir for injection, 100 mg, or PTM will be provided by Gilead.
Participants in Treatment Group A will receive IV RDV 200 mg on Day 1 followed by IV RDV 
100 mg on Days 2 and 3. Participants in the Treatment Group B will receive IV PTM on Days 1
to 3.
5.3.1.
Administration Instructions
The prepared diluted solution should not be administered simultaneously with any other 
medication. The compatibility of RDV injection with IV solutions and medications other than 
0.9% sodium chloride is not known. Administer RDV via IV infusion over 30 minutes. Slower 
infusion rates of up to 120 minutes can be considered to potentially prevent signs and symptoms 
of infusion related reaction. Infusion rates for different infusion volumes and times are described 
in Table 1.
Table 1.
Recommended Rate of Infusion—Diluted RDV for Injection 
Lyophilized Powder in Adults and Pediatric Patients 12 Years of Age 
and Older and Weighing at Least 40 kg
Infusion bag volume
Infusion time
Rate of infusion
250 mL
30 min
8.33 mL/min
60 min
4.17 mL/min
120 min
2.08 mL/min
100 mL
30 min
3.33 mL/min
60 min
1.67 mL/min
120 min
0.83 mL/min
5.3.2.
Infusion-related Reactions
Infusion-related reactions have been observed during and following administration of RDV. 
Signs and symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, 
fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion 
rates, with a maximum infusion time of up to 120 minutes, can be considered to potentially 
prevent these signs and symptoms. If signs and symptoms of a severe infusion-related reaction 
occur, immediately discontinue administration of RDV and initiate appropriate treatment. Please 
refer to Section 7.6.
5.4.
Prior and Concomitant Medications
Concomitant medications taken within 30 days prior to screening and up to and including 
30 days after the last dose of study drug need to be recorded in the source documents and eCRFs.


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Concomitant use of the following is prohibited in participants receiving RDV:

Investigational or approved agents for the SARS-CoV-2 virus including approved HIV 
protease inhibitors such as lopinavir/ritonavir, interferon, etc. Use of these medications for an 
approved indication other than SARS-CoV-2 infection is not prohibited

Use of hydroxychloroquine or chloroquine for any indication

Strong inducers of P-glycoprotein (eg, rifampin or herbal medications)
5.5.
Accountability for Investigational Medicinal Product
The investigator is responsible for ensuring adequate accountability of all used and unused study 
drug vials. This includes acknowledgment of receipt of each shipment of study drug (quantity 
and condition). 
Each study site must keep accountability records that capture:

The date received and quantity of study drug vials.

The date, participant number, and the study drug vial number dispensed.

The date, quantity of used and unused study drug vials returned, along with the initials of the 
person recording the information.
5.5.1.
Investigational Medicinal Product Return or Disposal
Gilead recommends that used and unused study drug supplies be destroyed at the site. If the site 
has an appropriate standard operating procedure (SOP) for drug destruction as determined by 
Gilead, the site may destroy used (empty or partially empty) and unused study drug supplies in 
accordance with that site’s approved SOP. A copy of the site’s approved SOP will be obtained 
for eTMF. If study drug is destroyed on site, the investigator must maintain accurate records for 
all study drugs destroyed. Records must show the identification and quantity of each unit 
destroyed, the method of destruction, and the person who disposed of the study drug. Upon study 
completion, copies of the study drug accountability records must be filed at the site. Another 
copy will be returned to Gilead. 
If the site does not have an appropriate SOP for drug destruction, used and unused study drug
supplies are to be sent to the designated disposal facility for destruction. The study monitor will 
provide instructions for return.
The study monitor will review study drug supplies and associated records at periodic intervals.
For both disposal options listed above, the study monitor must first perform drug accountability 
during an on-site or remote monitoring visit.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each participant enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows. 
The investigator must document any deviation from the protocol procedures and notify Gilead or 
the contract research organization.
6.1.
Participant Enrollment and Treatment Assignment
Entry into screening does not guarantee enrollment into the study. In order to manage the total 
study enrollment, Gilead, at its sole discretion, may suspend screening and/or enrollment at any 
site or study-wide at any time. Study visits may be performed in an outpatient setting, at the 
participant’s home via tele-health, virtually or remotely, as permitted by local and institutional 
regulations.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Participants will be screened within 2 days before randomization to determine eligibility for 
participation in the study. The following will be performed and documented at screening:

Obtain written informed consent

Obtain medical history including the following information: date of first symptoms, overall 
symptoms, exposure source, demographics, baseline characteristics, allergies and all other 
medical history

Review and document prior and concomitant medications

Complete physical examination including, vital signs (heart rate, temperature, blood 
pressure), body weight, and height. 

Respiratory status:
Respiratory rate
Oxygenation: SpO2 on room air

Obtain ALT (and AST where available), serum creatinine, and creatinine clearance/eGFR
(calculated using Cockcroft-Gault or Schwartz formula; see Section 6.7.2) if not available 
within 90 days of screening, using a local laboratory.

Women of childbearing potential will have a urine pregnancy test performed


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
Documentation of SARS-CoV-2 infection confirmed by molecular diagnostics (nucleic acid 
[eg, PCR] or antigen testing) ≤ 4 days prior to screening

Confirmation of presence of COVID-19 symptoms 

Record any SAEs and all AEs related to protocol-mandated procedures occurring after 
signing of the consent form
Participants meeting all of the inclusion criteria and none of the exclusion criteria may be 
enrolled the same day as screening for randomization into the study.
From the time of obtaining informed consent through the first administration of study drug, 
record all SAEs, as well as any AEs related to protocol-mandated procedures on the Adverse 
Events eCRF. All other untoward medical occurrences observed during the screening period, 
including exacerbation or changes in medical history are to be considered medical history. 
See Section 7 Adverse Events and Toxicity Management for additional details.
6.3.
Treatment Assessments (Baseline/Day 1, Day 2, and Day 3)
The following evaluations are to be completed at the Day 1 visit. The investigator must have 
confirmed eligibility before proceeding with randomization and the Day 1 visit. If the screening 
and Day 1 visits occur on the same day, no procedures need to be repeated except for clinical 
laboratory samples that must be collected locally to confirm eligibility. Clinical laboratory 
samples must be collected at Day 1 to be sent to the central laboratory, even if completed locally, 
as described in Section 6.7.2. Participants must complete the following assessments before being 
administered study drug:

Vital signs (heart rate, temperature, blood pressure) pre-infusion, postinfusion, and when 
postinfusion observation is completed

Respiratory status:
Respiratory rate
Oxygenation: SpO2 on room air

Complete physical examination (Day 1)

Clinical symptom-directed physical examination (Day 2, Day 3)

Review of AEs and concomitant medications

Review any interactions with health care professionals, other than study staff or designees,
including hospitalization; in-person emergency, urgent, or primary care visits; or any other 
in-person visit attended by the participant and a health care profession. Identify the nature 
and cause of the visit.


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
Obtain blood samples as described in Section 6.7.2 (Day 1, Day 3)

Nasopharyngeal swab samples for SARS-CoV-2 quantitative reverse transcriptase PCR
(RT-qPCR) testing 

Sputum sample collection from participants with productive cough for SARS-CoV-2 
RT-qPCR testing

Completion of the COVID-19-adapted FLU-PRO Plus questionnaire (if available)

Administration of study drug. Instructions on study drug administration are available in a 
separate manual.
Remdesivir infusions will be administered to participants at the site under close supervision or in 
the participant’s home by a home health service provider. Health care professionals 
administering RDV infusions will have the appropriate medication available for immediate use 
in case of hypersensitivity or infusion-related reactions. The participant should be treated 
according to the SOC for management of hypersensitivity reaction or infusion-related reactions. 
Postinfusion monitoring should be done according to site or home health protocol. All 
information related to home administration of RDV will be provided to the investigator by the 
home health provider, wherever applicable, in a timely manner.
6.4.
Post-treatment Assessments (Day 4 Through Day 14)
The following evaluations are to be completed at the specified study days. The study visits are to 
be completed on the protocol-specified visit date (based on the Day 1 visit). The Day 7 and 
Day 14 visits have a ± 1 day window.

Vital signs (heart rate, temperature, blood pressure), body weight (Day 7, Day 14)

Review of AEs and concomitant medications (Day 7, Day 14)

Review MAV information, including any interactions with health care professionals other 
than study staff or designees including hospitalization; in-person emergency, urgent, or 
primary care visits; or any other in-person visit attended by the participant and a health care 
profession. Identify the nature and cause of the visit.

Complete physical examination (Day 14).

Clinical symptom-directed physical examination (Day 7).

Respiratory status (Day 7, Day 14):
Respiratory rate
Oxygenation: SpO2 on room air
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
Obtain blood samples as described in Section 6.7.2 (Day 7, Day 14)

Nasopharyngeal swab samples for SARS-CoV-2 RT-qPCR testing 
 

Sputum sample collection from participants with productive cough for SARS-CoV-2 
RT-qPCR testing 

Completion of the COVID-19-adapted FLU-PRO Plus questionnaire (if available) (Days 4, 
5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
6.5.
Day 28 Follow-up Assessment (± 5 Days)
The following evaluations are to be completed if the visit is conducted in person. The final 
evaluation can be performed by phone (only AEs, concomitant medications review, and MAV
information needed if done by phone).

Clinical symptom-directed physical examination, vital signs (heart rate, temperature, blood 
pressure), and body weight.

Respiratory status:
Respiratory rate
Oxygenation: SpO2 on room air

Review of AEs and concomitant medications

Review MAV information, including any interactions with health care professionals, other 
than study staff or designees, including hospitalization; in-person emergency, urgent, or 
primary care visits; or any other in-person visit attended by the participant and a health care 
profession. Identify the nature and cause of the visit.
6.6.
Assessments for Early Discontinuation from Study
If a participant discontinues study dosing (for example, as a result of an AE), every attempt 
should be made to keep the participant in the study and continue to perform the required 
study-related follow-up and procedures (see Section 6.8, Criteria for Discontinuation of Study 
Treatment). If this is not possible or acceptable to the participant or investigator, the participant 
may be withdrawn from the study.
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6.7. 
6.7.1. 
Procedures and Specifications 
Complete Physical Examination 
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A complete physical examination must include source documentation of general appearance and 
the following body systems: Head, neck, and thyroid; eyes, ears, nose, throat, mouth, and tongue; 
chest (excluding breasts); respiratory; cardiovascular; lymph nodes, abdomen; skin, hair, nails; 
musculoskeletal; and neurological. Urogenital and reproductive examination should only be 
completed if clinically indicated. 
6.7.2. 
Clinical Laboratory Assessments 
Blood sample collection for the following laboratory analyses will be perfonned at the specified 
time points: 
• 
Chemistry profile: alkaline phosphatase, AST, ALT, total bilirubin, total protein, albumin, 
lactate dehydrogenase, creatine phosphokinase, bicarbonate, blood urea nitrogen, calcium, 
chloride, creatinine, glucose, lipase, magnesium, phosphorus, potassium, sodimn, uric acid 
(Day 1, Day 3, Day 7, Day 14) 
• 
Estimated glomerular filtration rate (screening [ifrequired], Day 1, Day 3, Day 7, Day 14) 
according to: 
Schwartz fonnula for participants < 18 years of age, where Ser is serum creatinine 
(mg/dL) 
Adolescent boys~ 12 years of age: 0.70 x L/ Ser (Lis height in cm) 
Adolescent girls~ 12 years of age: 0.55 x LI Ser (L is height in cm) 
Height at baseline will be used for all calculations using the Schwartz fonnula. 
Cockcroft-Gault fonnula for creatinine clearance (CLcr) for participants 
18 years of 
age. Weight at screening will be used for Days 1-3. 
Men: 
Women: 
040 age in years) x (wt in kg) 
CLcr (mL/min) 
72 x (serum creatinine in mg/dL) 
040 age in years) x (wt in kg) x 0.85 
CLcr (mL/min) 
72 x (sermn creatinine in mg/dL) 
• 
Hematology profile: complete blood count with differential (Day 1, Day 3, Day 7, Day 14) 
• 
Coagulation: international nonnalized ratio (INR), prothrombin time (PT), activated partial 
thromboplastin time (aPTT) (Day 1, Day 3, Day 7, Day 14) 
• 
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Criteria for Discontinuation of Study Treatment 
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Study medication will be discontinued for individual participants in the following instances, 
unless the potential for resmn ing dosing is specifically noted: 
• 
Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the 
participant may resume study dosing at the discretion of the investigator. 
• 
Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the participant's 
best interest 
• 
ALT or AST ~ 5 x ULN; or ALT > 3 x ULN and total bilirubin > 2 x ULN, confinned by 
immediate repeat testing 
• 
Other Grade 3 or Grade 4 abnonnal laboratory results related to RDV 
• 
Lack of efficacy 
• 
Participant request to discontinue for any reason 
• 
Participant noncompliance 
• 
Discontinuation of the study at the request of Gilead, a regulatory agency or an IRB or IEC 
• 
Infusion-related systemic reaction 
Grade 2 or infusion-related localized reaction Grade 3 
6.9. 
End of Study 
The end of the study will be the last participant's last observation ( or visit). 
6.10. 
Poststudy Care 
The long-tenn care of the participant will remain the responsibility of their primary treating 
physician. Remdesivir is being supplied with curative intent. There is no provision for post-study 
availability . 
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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events and Serious Adverse Events
7.1.1.
Adverse Events
An AE is any untoward medical occurrence in a clinical study participant administered an 
investigational product, which does not necessarily have a causal relationship with the treatment. 
An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally 
associated with the use of an investigational product, whether or not the AE is considered related 
to the investigational product. AEs may also include pre- or post-treatment complications that 
occur as a result of protocol-specified procedures or special situations (Section 7.7).
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion.
The condition that led to the procedure may be an AE and must be reported.

Preexisting diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (eg, hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (Section 7.7.1)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be preexisting and should be documented as medical history.

Preexisting events or conditions that increase in severity or change in nature after the consent 
form is signed or as a consequence of participation in the clinical study will be considered 
AEs.
7.1.2.
Serious Adverse Events
A SAE is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the participant was at risk of death at the time of the event; it does not refer to 
an event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization

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
A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participant or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. 
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to study 
drug using clinical judgment and the following considerations:

No: Evidence exists that the AE has an etiology other than the study drug. For SAEs, an 
alternative causality must be provided (eg, preexisting condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the study drug.
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of AE reporting. 
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the AE has an etiology other than the study procedure.

Yes: The AE occurred as a result of protocol procedures (eg, venipuncture).
7.2.2.
Assessment of Severity
The severity of AEs will be graded using the Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017. For each episode, 
the highest grade attained should be reported as defined in the grading scale. The DAIDS scale is 
available at the following location:
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7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events 
7.3.1.
Requirements for Collection Prior to Study Drug Initiation
After informed consent, but prior to initiation of study medication, the following types of events 
must be reported on the applicable eCRFs: all SAEs and AEs related to protocol-mandated 
procedures.
7.3.2.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
throughout the duration of the study, including the protocol-defined follow-up period, must be 
reported on the eCRFs as instructed.
All AEs and clinically significant laboratory abnormalities will be followed until resolution or 
stability of the abnormality has been demonstrated, if possible. Gilead may request that certain
AEs be followed beyond the protocol-defined follow-up period.
7.3.3.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occur after the participant first consents to 
participate in the study (i.e., signing the informed consent) and throughout the duration of the 
study, including the post-treatment follow-up visit, must be reported on the applicable eCRFs
and to GLPS as instructed below in this section. This also includes any SAEs resulting from 
protocol-associated procedures performed after informed consent is signed.
Any SAEs and deaths that occur after the post-treatment follow-up visit but within 30 days of the 
last dose of study drug, regardless of causality, should also be reported. 
Investigators are not obligated to actively seek SAEs after the protocol-defined follow-up period;
however, if the investigator learns of any SAEs that occur after the protocol-defined follow-up 
period has concluded and the event is deemed relevant to the use of study drug, the investigator
should promptly document and report the event to Gilead GLPS.

All SAEs will be recorded in the case report form (CRF)/eCRF database within 24 hours.  
7.3.3.1.
Electronic Serious Adverse Event Reporting Process

Site personnel record all SAE data on the applicable eCRFs and from there transmit the SAE 
information to Gilead GLPS within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines (eCCGs).


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
If it is not possible to record and transmit the SAE information electronically, record the SAE 
on the paper SAE reporting form and submit within 24 hours to:
Gilead GLPS
Email: 
 
or
Fax: 

As soon as it is possible to do so, any SAE reported via paper must be transcribed on the 
applicable eCRFs according to instructions and within the timelines outlined in the eCCGs.

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary.

For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be submitted by email or fax when requested and applicable. 
Transmission of such documents should occur without personal participant identification, 
maintaining the traceability of a document to the participant identifiers.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the participant’s eCRF and the SAE narrative section of the Safety 
Report Form eCRF.
7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and relevant updates, and 
other country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse drug reactions, or SUSARs. In 
accordance with the EU Clinical Trials Directive (2001/20/EC), Gilead or a specified designee 
will notify worldwide regulatory agencies and the relevant IEC in concerned Member States of 
applicable SUSARs as outlined in current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the IB or relevant local label as applicable. 
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study drug. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy. 
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7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and coagulation) that 
require medical or surgical intervention or lead to study drug interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 
laboratory or other abnormal assessments (eg, electrocardiogram, x-rays, vital signs) that are 
associated with signs and/or symptoms must be recorded as an AE or SAE if they meet the 
definition of an AE or SAE as described in Sections 7.1.1 and 7.1.2. If the laboratory 
abnormality is part of a syndrome, record the syndrome or diagnosis (eg, anemia), not the 
laboratory result (i.e., decreased hemoglobin).
Severity should be recorded and graded according to the DAIDS Table for Grading the Severity 
of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017. For AEs associated with 
laboratory abnormalities, the event should be graded on the basis of the clinical severity in the 
context of the underlying conditions; this may or may not be in agreement with the grading of 
the laboratory abnormality.
7.6.
Toxicity Management 
Remdesivir infusions will be administered to participants at the site under close supervision or in 
the participant’s home by a home health service provider. Health care professionals 
administering RDV infusions will have the appropriate medication available for immediate use 
in case of hypersensitivity or infusion-related reactions. The participant should be treated 
according to the SOC for management of hypersensitivity reaction or infusion-related reactions. 
Postinfusion monitoring should be done according to site or home health protocol. All 
information related to home administration of RDV will be provided to the investigator by the 
home health provider, wherever applicable, in a timely manner. 
7.7.
Special Situations Reports
7.7.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, 
occupational exposure, drug interactions, exposure via breastfeeding, unexpected benefit, 
transmission of infectious agents via the product, counterfeit of falsified medicine, and 
pregnancy regardless of an associated AE. 
Medication error is any unintentional error in the prescribing, dispensing, preparation for 
administration or administration of an investigational product while the medication is in the 
control of a health care professional, patient, or consumer. Medication errors may be classified as
a medication error without an AE, which includes situations of missed dose; medication error 
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Abuse is defined as persistent or sporadic intentional excessive use of an investigational product 
by a participant.
Misuse is defined as any intentional and inappropriate use of an investigational product that is 
not in accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of an 
investigational product given per administration or cumulatively which is above the maximum 
recommended dose as per protocol or in the product labeling (as it applies to the daily dose of the
participant in question). In cases of a discrepancy in drug accountability, overdose will be 
established only when it is clear that the participant has taken the excess dose(s). Overdose 
cannot be established when the participant cannot account for the discrepancy except in cases in 
which the investigator has reason to suspect that the participant has taken the additional dose(s).
Occupational exposure is defined as exposure to an investigational product as a result of one’s 
professional or non-professional occupation.
Drug interaction is defined as any drug/drug, drug/food, or drug/device interaction.
Unexpected benefit is defined as an unintended therapeutic effect where the results are judged to 
be desirable and beneficial.
Transmission of infectious agents is defined as any suspected transmission of an infected agent 
through a Gilead investigational product.
Counterfeit or falsified medicine: Any investigational product with a false representation of: 
a) its identity, b) its source, or c) its history.
7.7.2.
Instructions for Reporting Special Situations
7.7.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study participants that are identified after 
initiation of study drug and throughout the study, including the post study drug follow-up period, 
to Gilead GLPS using the pregnancy report form within 24 hours of becoming aware of the 
pregnancy.
Refer to Section 7.3 for GLPS contact information and the eCCGs for full instructions on the 
mechanism of pregnancy reporting.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons.
Any premature termination of pregnancy (eg, a spontaneous abortion, an induced therapeutic 
abortion due to complications or other medical reasons) must be reported within 24 hours as an 
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A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3.2. Furthermore, any SAE occurring as an adverse pregnancy outcome post study
must be reported to Gilead GLPS.
The participant should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead GLPS using the pregnancy outcome report 
form. If the end of the pregnancy occurs after the study has been completed, the outcome should 
be reported directly to Gilead GLPS. Gilead GLPS contact information is as follows: 
email:
 and fax: 
 
Pregnancies of female partners of male study participants exposed to Gilead or other study drugs 
must also be reported and relevant information should be submitted to Gilead GLPS using the 
pregnancy and pregnancy outcome forms within 24 hours. If the end of the pregnancy occurs 
after the study has been completed, the outcome should be reported directly to Gilead GLPS, 
fax number 
 or email 
 
Refer to Appendix 3 Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.7.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead GLPS within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study drug and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead concomitant medications do not need to be reported on 
the special situations report form; however, special situations that result in AEs due to a 
non-Gilead concomitant medication, must be reported as an AE. 
Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.3 for GLPS contact information and the eCCGs for instructions on special 
situation reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.
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8.1. 
8.1.1. 
STATISTICAL CONSIDERATIONS 
Analysis Objectives and Endpoints 
Analysis Objectives 
The primary objectives of this study are as follows: 
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To evaluate the efficacy of RDV in reducing the rate of COVID-19 related hospitalization or 
all-cause death when given over 3 days to non-hospitalized participants with early stage 
COVID-19 
• 
To evaluate the safety of RDV administered in an outpatient setting 
The secondary objectives of this study are as follows: 
• 
To evaluate the efficacy of RDV in reducing the rate of COVID-19 related MA Vs (medical 
visits attended in person by the participant and a health care professional) or all-cause death 
in non-hospitalized participants with early stage COVID-19. An MA V includes in-person 
clinic visit, urgent care visit, emergency room visit, or hospitalization 
• 
To detenn ine the antiviral activity of RDV on SARS-CoV-2 viral load 
• 
To assess the impact of RDV on symptom duration and severity 
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Primary Endpoint 
The primary endpoints of this study are as follows: 
• 
Composite endpoint of COVID-19 related hospitalization ( defined as at least 24 hours of 
acute care) or all-cause death by Day 28 
• 
Proportion of participants with treatment-emergent AEs 
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Secondary Endpoint 
The secondary endpoints of this study are as follows: 
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Composite endpoint of COVID-19 related MA Vs (medical visits attended in person by the 
participant and a health care professional) or all cause death by Day 28 
• 
All-cause mortality at Day 28 
• 
Proportion of participants hospitalized by Day 28 
• 
Composite endpoint of COVID-19 related hospitalization ( defined as at least 24 hours of 
acute care) or all-cause death by Day 14 
• 
Composite endpoint of COVID-19 related (medical visits attended in person by the 
participant and a health care professional) or all cause death by Day 14 
• 
Time-weighted average change in SARS-CoV-2 viral load from baseline to Day 7 
• 
Time to alleviation (mild or absent) of baseline COVID-19 symptoms as reported on the 
COVID-19-adapted FLU-PRO Plus 
• 
Proportion of participants progressing to requiring oxygen supplementation by Day 28 
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8.2.
Planned Analyses
8.2.1.
Interim Analysis 
Prior to the final analysis, interim analyses may be conducted and the analyses may be submitted 
to regulatory agencies to seek guidance for the overall clinical development program m.
8.2.1.1.
Data Monitoring Committee Analysis
An external data monitoring committee (DMC) will review safety data on a regular basis. One 
futility interim analysis is planned after approximately 50% of participants complete Day 28.
Enrollment may pause for the IDMC review if enrollment is faster than projected. The DMC will 
review the interim safety data and summary of primary efficacy data by treatment group and 
make recommendation of stopping enrollment to a treatment due to lack of efficacy and decision 
on sample size re-estimation.  
8.2.2.
Final Analysis
The final analysis will be performed after all participants have completed the study, outstanding 
data queries have been resolved or adjudicated as unresolvable, and the data have been cleaned 
and finalized. The analysis of the primary endpoint of COVID-19 related hospitalization or all-
cause death by Day 28 will be conducted at the time of the final analysis and will be tested at the 
0.05 significance level.
8.3.
Analysis Conventions
8.3.1.
Analysis Sets
8.3.1.1.
Efficacy
The primary analysis set for efficacy analysis is defined as the Full Analysis Set, which will 
include all participants who (1) are randomized into the study and (2) have received at least 
1 dose of study treatment. Participants will be grouped according to the treatment to which they 
were randomized.
8.3.1.2.
Safety
The primary analysis set for safety analyses is defined as the Safety Analysis Set, which will 
include all participants who (1) are randomized into the study and (2) have received at least 
1 dose of study treatment. Participants will be grouped according to the treatment to which they 
received.
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Laboratory data that are continuous in nature but are less than the LLOQ or above the upper limit 
of quantitation, will be imputed to the value of the lower or upper limit plus or minus 1 
significant digit, respectively ( eg, if the result of a continuous laboratory test is < 20, a value of 
19 will be assigned). 
Missing data can have an impact upon the interpretation of the trial data. In general, values for 
missing data will not be imputed. However, a missing pre-treatment laboratory result would be 
treated as nonnal (i.e., no toxicity grade) for the laboratory abnormality smmnary. 
All available data for participants that do not complete the study will be included in data listings 
8.4. 
Demographic and Baseline Characteristics Analysis 
Demographic and baseline measurements will be smmnarized using standard descriptive 
methods. Demographic smmnaries will include sex, race/ethnicity, randomization stratification 
group, and age. For categorical demographic and baseline characteristics, a 
Cochran-Mantel-Haenszel test will be used to compare treatment groups. For continuous 
demographic and baseline characteristics, a Wilcoxon rank smn test will be used to compare 
treatment groups. 
8.5. 
8.5.1. 
Efficacy Analysis 
Primary Analysis 
The primary endpoint of the study is the composite endpoint of COVID-19 related 
hospitalization or all-cause death by Day 28. The null hypothesis being tested is whether the ratio 
of proportion of COVID-19 related hospitalization or all-cause death is the same for the 2 
treatment groups (ie, whether ratio is equal to 1 across all strata). 
The hazard ratio, p-value, and 95% CI for the hazard ratio will be calculated using a Cox model 
with stratification factors as covariates. 
Participants with missing outcomes for the primary endpoint due to prematurely discontinuation 
of the study will be censored at the date of last contact. 
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8.5.2.
Secondary Analyses
The secondary endpoint of COVID-19 related hospitalization or all-cause death by Day 14, 
COVID-19 related MAVs (medical visits attended in person by the participant and a health care 
professional) or death by Day 28, and COVID-19 related MAVs (medical visits attended in 
person by the participant and a health care professional) or death by Day 14 will be analyzed 
similarly as in the primary analysis. The all-cause mortality at Day 28 will be compared between 
the 2 treatment groups using a Fisher exact test. The proportion of participants hospitalized by 
Day 28 and the proportion of participants progressing to requiring oxygen supplementation by 
Day 28 will be estimated using the Kaplan-Meier method and compared between the 2 treatment 
groups using a log-rank test. Other endpoints of interest related to proportion of participants will 
be compared between treatment groups using a chi-square test or Fisher exact test. Endpoints 
that are measured as time to first event will be compared between treatment groups using the 
log-rank test and continuous endpoints will be compared between treatment groups using a 
Wilcoxon rank sum test or analysis of variance model.
8.6.
Safety Analysis
All safety data collected on or after the randomization date through the Day 28 visit will be 
summarized by treatment group (according to the study drug received). Data for the pretreatment 
will be included in data listings. 
8.6.1.
Extent of Exposure
A participant’s extent of exposure to study drug data will be generated from the study drug
administration data. Exposure data will be summarized by treatment group.
8.6.2.
Adverse Events
Clinical and laboratory AEs will be coded using the Medical Dictionary for Regulatory 
Activities. System Organ Class, High-Level Group Term, High-Level Term, Preferred Term, and 
Lower-Level Term will be attached to the clinical database.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
AE will be defined as any AE that begins on or after the randomization date up to the date of last 
dose of study drug plus 30 days.
Summaries (number and percentage of participants) of treatment-emergent AEs (by system 
organ class and preferred term) will be provided by treatment group.
8.6.3.
Laboratory Evaluations
Selected laboratory data will be summarized using only observed data. Data and change from 
baseline at all scheduled time points will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme in DAIDS Table for 
Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.


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Incidence of treatment-emergent laboratory abnonnalities, defined as values that increase at least 
1 toxicity grade from baseline at any time post baseline up to the end date of the study, will be 
smmnarized by treatment group. If baseline data are missing, then any graded abnonnality (ie, at 
least a Grade 1) will be considered treatment-emergent. 
Laboratory abnonnalities that occur before the first dose of study drug or after the participant has 
been discontinued from treatment for more than 30 days will be included in a data listing. 
8.7. 
Adjustments for Multiplicity 
No adjustments for multiple comparisons are needed for the primary analysis of this study. 
8.9. 
Sample Size 
The total sample size of the study will be approximately 1264 participants. 
The sample size computation is based on proportions of COVID-19 related hospitalization or all-
cause death by Day 28 for the RDV and placebo treatment groups. The sample size needed for a 
1: 1 randomization using a 2-tailed test at level a is given by: 
(z1-a;2 + Z1-p ) 2 
P(1 - R2)<J2B2 
Where P is the overall rate of COVID-19 related hospitalization or all-cause death, B is the log 
hazard ratio, cr is the standard deviation of treatment indicator variable, R is the R-Squared that is 
obtained when treatment indicator variable is regressed on the other covariates, and z, a12 and z, 13 
are the 1-a/2 and 1-P quantiles of the standard nonnal distribution. 
A sample size of 1264 participants (632 in each group with 1: 1 randomization) achieves > 90% 
power to detect a ratio of 0.55 (RDV to placebo in proportion of COVID-19 related 
hospitalization or all-cause death, which is equal to a hazard ratio of 0.534) using a 2-sided 
significance level of 0.05 assuming the overall hospitalization or death rate is 9.3% (12% in the 
placebo group and 6.6% in the RDV group) and a 5% drop out rate. The sample size provides 
approximately 80% power to detect smaller treatment effect size with a ratio of 0.60 (RDV to 
placebo), assuming a 2-sided significance level of 0.05 and the overall hospitalization or death 
rate is 9.6% (12% in the placebo group and 7.2% in the RDV group) and a 5% drop out rate. 
The sample size calculation was done using software PASS (Version 14.0, module of Cox 
regression for survival). 
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8.9.1.
Sample Size Re-estimation
A sample size re-estimation is planned at the interim analysis with approximately 50% 
participants having completed Day 28 visit due to the uncertainty in hospitalization or death rate 
in the placebo arm. All possible interim results will be partitioned into 3 zones Favorable, 
Promising, and Unfavorable, depending on the size of observed conditional power (CP) under 
the current trend at the interim. If the CP falls into the Favorable zone, the trial will continue 
with the originally planned sample size of 1264 patients. If the CP falls into the Promising zone, 
the total sample size will be increased (up to 1500) according to the algorithm specified in the 
adaptation plan. If the CP falls into the Unfavorable zone but the interim result has not met the 
futility boundary, the trial will also continue with the originally planned sample size of 1264
patients.
The DMC will review the unblinded data at the interim and communicate the decision on sample 
size to the study team. The overall type I error is controlled at 0.05 using the method proposed by 
{Muller 2004}. Further details will be included in the DMC charter and an adaptation plan.
8.10.
Independent Data Monitoring Committee
An external multidisciplinary IDMC will review the progress of the study, perform interim 
reviews of safety data on a regular basis and provide recommendation(s) to Gilead whether the 
nature, frequency, and severity of AEs associated with study treatment warrant the early 
termination of the study in the best interests of the participants, whether the study should 
continue as planned, or the study should continue with modifications. The IDMC will review the 
interim futility analysis and make a recommendation of stopping enrollment to the study if the 
pre-specified futility stopping criteria are met.
The IDMC may also provide recommendations as needed regarding study design.
The IDMC’s specific activities will be defined by a mutually agreed charter, which will define 
the IDMC’s membership, conduct and meeting schedule
While the IDMC will be asked to advise Gilead regarding future conduct of the study, including 
possible early study termination, Gilead retains final decision-making authority on all aspects of 
the study.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with International Council 
for Harmonisation (of Technical Requirements for Pharmaceuticals for Human Use) (ICH) 
E6(R2) addendum to its guideline for GCP and applicable laws and regulations.
9.1.2.
Financial Disclosure
The investigator and subinvestigators will provide prompt and accurate documentation of their 
financial interest or arrangements with Gilead, or proprietary interests in the investigational drug 
during the course of a clinical study. This documentation must be provided prior to the 
investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last participant completes the protocol-defined activities.
9.1.3.
Institutional Review Board/Independent Ethics Committee Review and 
Approval
The investigator (or Gilead as appropriate according to local regulations) will submit this 
protocol, informed consent form, and any accompanying material to be provided to the 
participant (such as advertisements, participant information sheets, or descriptions of the study 
used to obtain informed consent) to an IRB/IEC. The investigator will not begin any study 
participant activities until approval from the IRB/IEC has been documented and provided as a 
letter to the investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/IEC any modifications made to the protocol or any accompanying material to be 
provided to the participant after initial IRB/IEC approval, with the exception of those necessary 
to reduce immediate risk to study participants.
9.1.4.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study before undertaking any study-related procedures. The investigator 
must use the most current IRB- or IEC-approved consent form for documenting written informed 
consent. Each informed consent (or assent as applicable) will be appropriately signed and dated 
by the participant or the participant’s legally authorized representative and the person conducting 
the consent discussion, and also by an impartial witness if required by IRB or IEC or local 
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9.1.5. 
Confidentiality 
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The investigator must assure that participants' anonymity will be strictly maintained and that 
their identities are protected from unauthorized parties. Only an identification code and any other 
unique identifier(s) as allowed by local law (such as year of birth) will be recorded on any fonn 
or biological sample submitted to Gilead, IRB or IEC, or the laboratory. Laboratory specimens 
must be labeled in such a way as to protect participant identity while allowing the results to be 
recorded to the proper participant. Refer to specific laboratory instructions. NOTE: The 
investigator must keep a screening log with details for all participants screened and enrolled in 
the study, in accordance with the site procedures and regulations. Participant data will be 
processed in accordance with all applicable regulations. 
The investigator agrees that all infonnation received from Gilead, including but not limited to the 
IB, this protocol, CRF/eCRF, the study drug, and any other study infonnation, remain the sole 
and exclusive property of Gilead during the conduct of the study and thereafter. This infonnation 
is not to be disclosed to any third party ( except employees or agents directly involved in the 
conduct of the study or as required by law) without prior written consent from Gilead. The 
investigator further agrees to take all reasonable precautions to prevent the disclosure by any 
employee or agent of the study site to any third party or otherwise into the public domain. 
9.1.6. 
Study Files and Retention of Records 
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully docmnented and the study data to be subsequently verified. These docmnents should 
be classified into at least the following 2 categories: (1) investigator's study file, and 
(2) participant clinical source documents. 
The investigator's study file will contain the protocol/amendments, electronic completed 
participant CRFs, IRB or IEC and govenunental approval with correspondence, infonned 
consent fonn(s), drug records, staff curriculmn vitae and authorization fonns, and other 
appropriate documents and correspondence. 
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The required source data should include sequential notes containing at least the following 
information for each participant:

Participant identification

Documentation that participant meets eligibility criteria, i.e., medical history, physical 
examination, and confirmation of diagnosis (to support inclusion and exclusion criteria)

Documentation of the reason(s) a consented participant is not enrolled

Participation in study (including study number)

Study discussed and date of informed consent

Dates of all visits

Documentation that protocol-specific procedures were performed

Results of efficacy parameters, as required by the protocol

Start and end date (including dose regimen) of study drug, including dates of dispensing and 
return

Record of all AEs and other safety parameters (start and end date, and including causality 
and severity), and documentation that adequate medical care has been provided for any AE

Concomitant medication (including start and end date, dose if relevant; dose changes)

Date of study completion and reason for early discontinuation, if it occurs
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (i.e., US, Europe, or Japan) and until there are no pending or planned marketing 
applications in an ICH region; or, if no application is filed or if the application is not approved 
for such indication, until 2 years after the investigation is discontinued and regulatory authorities 
have been notified. Investigators may be required to retain documents longer if specified by 
regulatory requirements, by local regulations, or by an agreement with Gilead. The investigator 
must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
participant, appropriate copies should be made for storage away from the site.


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9.1.7.
Case Report Forms
For each participant consented, an eCRF casebook will be completed by an authorized study 
staff member whose training for this function is completed in the EDC system. The eCRF 
casebook will only capture the data required per the protocol schedule of events and 
procedures. The Inclusion/Exclusion Criteria and Enrollment eCRFs should be completed only
after all data related to eligibility have been received. Data entry should be performed in 
accordance with the eCCGs provided by the sponsor. Subsequent to data entry, a study monitor 
will perform source data verification (SDV) within the EDC system. System-generated or 
manual queries will be issued in the EDC system as data discrepancies are identified by the 
monitor or Gilead staff, who routinely review the data for completeness, correctness, and 
consistency. The site investigator or site coordinator or other designee is responsible for 
responding to the queries in a timely manner, within the system, either by confirming the data as 
correct or updating the original entry, and providing the reason for the update (eg, data entry 
error). Original entries as well as any changes to data fields will be stored in the audit trail of the 
system. At a minimum, prior to any interim time points or database lock (as instructed by 
Gilead), the investigator will use his/her log in credentials to confirm that the forms have been 
reviewed, and that the entries accurately reflect the information in the source documents. At the 
conclusion of the study, Gilead will provide the site investigator with a read-only archive copy of 
the data entered by that site. This archive must be stored in accordance with the records retention 
requirements outlined in Section 9.1.6.
9.1.8.
Investigator Inspections
The investigator will make available all source documents and other records for this study to 
Gilead’s appointed study monitors, to IRBs/IECs, or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study participants, 
may be made only by Gilead. The investigator must submit all protocol modifications to the
IRB/IEC in accordance with local requirements and receive documented IRB/IEC approval 
before modifications can be implemented.


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9.2.2.
Study Report and Publications
A clinical study report will be prepared and provided to the regulatory agency. Gilead will ensure 
that the report meets the standards set out in the ICH Guideline for Structure and Content of 
Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in certain 
cases.
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly media only after the following conditions have been met:
The results of the study in their entirety have been publicly disclosed by or with the consent of 
Gilead in an abstract, manuscript, or presentation form or the study has been completed at all 
study sites for at least 2 years
The investigator will submit to Gilead any proposed publication or presentation along with the 
respective scientific journal or presentation forum at least 30 days before submission of the 
publication or presentation. 
No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.5).
The investigator will comply with Gilead’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, eg, attendance at Investigator Meetings. If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical study payments, meal, 
travel expenses or reimbursements, consulting fees, and any other transfer of value.
9.3.2.
Access to Information for Monitoring
The monitor is responsible for routine review of the CRF/eCRF at regular intervals throughout 
the study to verify adherence to the protocol and the completeness, consistency, and accuracy of 
the data being entered on them. The monitor should have access to any participant records 
needed to verify the entries in the CRF/eCRF. The investigator agrees to cooperate with the 
monitor to ensure that any problems detected through any type of monitoring (central, on site)
are resolved.


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9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both Gilead and the investigator reserve the right to terminate the study at any time. Should this 
be necessary, both parties will arrange discontinuation procedures and notify the participants, 
appropriate regulatory authority(ies), IRBs, and IECs. In terminating the study, Gilead and the 
investigator will assure that adequate consideration is given to the protection of the participants’ 
interests.


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10.
REFERENCES
Committee for Medicinal Products for Human Use (CHMP). Background review for 
cyclodextrins used as excipients in the context of the revision of the guideline on 
‘Excipients in the label and package leaflet of medicinal products for human use’ 
(CPMP/463/00 Rev. 1). Draft report published in support to the propylene glycol 
Q&A document. For information only. European Medicines Agency (EMA)  20 
November, 2014.
Muller HH, Schafer H. A general statistical principle for changing a design any time during the 
course of a trial. Stat Med 2004;23 (16):2497-508.
Nicholson KG, Aoki FY, Osterhaus AD, Trottier S, Carewicz O, Mercier CH, et al. Efficacy and 
safety of oseltamivir in treatment of acute influenza: a randomised controlled trial. 
Neuraminidase Inhibitor Flu Treatment Investigator Group. Lancet 2000;355 
(9218):1845-50.
Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. Broad-
Spectrum Antiviral GS-5734 Inhibits Both Epidemic and Zoonotic Coronaviruses. 
Science translational medicine 2017;9 (396):eaal3653.
Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S, et al. 
Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 
2020. MMWR. Morbidity and mortality weekly report 2020;69 (24):759-65.
The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The 
Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus 
Diseases (COVID-19) 
China, 2020. Chinese Center for Disease Control and 
Prevention 2020;2 (8):113-22.
Williamson BN, Feldmann F, Schwarz B, Meade-White K, Porter DP, Schulz J, et al. Clinical 
benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature 
2020.
World Health Organization (WHO). Coronavirus Disease (COVID-2019) Situation Reports. 
Available at: https://www.who.int/emergencies/diseases/novel-coronavirus-
2019/situation-reports. Accessed: 18 March.  2020a:
World Health Organization (WHO). Report of the WHO-China Joint Mission on Coronavirus 
Disease 2019 (COVID-19). 16-24 February.  2020b.


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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Tablea
Appendix 3.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements


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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGMENT 
FINAL 
Amendment4 
A Phase 3 Randomized, Double-Blind Placebo-Controlled Trial to Evaluate the Efficacy and 
Safety of Remdesivir (GS-5734™) Treatment of COVID-19 in an Outpatient Setting 
GS-US-540-9012, Amendment 4, 15 January 2021 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
PD 
PD 
Date 
Signature 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
infonnation provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully infonned about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
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Appendix 2.
Study Procedures Tablea
Screening
Baseline/
Day 1
Day 2
Day 3
Day 7
(± 1 day)
Day 14
(± 1 day)
Day 28t
Follow-up 
(± 5 days)
Written Informed Consent
X
Medical Historyb
X
Complete Physical Examinationc
X
X
X
Clinical Symptom Directed Physical Examinationd
X
X
X
X
Height
X
Vital Signse and Weight
X
Xf
Xf
Xf
X
X
X
Respiratory Statusg
X
X
X
X
X
X
X
ALT, AST, Serum Creatinine, and Creatinine 
Clearance/eGFRh
X
Chemistryi, Hematologyj, and Coagulationk Panels
X
X
X
X
Urine Pregnancy Testm
X
SARS CoV 2 RT qPCR Testing and Potential Resistance 
Testingn
X
X
X
X
X
Documentation of SARS CoV 2 Infection
X
Medically Attended Visit Informationr
X
X
X
X
X
X
FLU PRO Plus Questionnaires
X
X
X
X
X
Study Drug Dosing
X
X
X
Adverse Events and Concomitant Medications
X
X
X
X
X
X
X
a
Study visits may be performed in an outpatient setting, at the participant’s home via tele health, virtually or remotely, as permitted by local and institutional regulations. The 
Day 28 visit may be performed via a phone call.
b
Medical history will include the date of first symptoms, overall symptoms, exposure source, demographics, baseline characteristics, allergies and all other medical history.
c
A complete physical examination must include source documentation of general appearance and the following body systems: Head, neck, and thyroid; eyes, ears, nose, throat, 
mouth, and tongue; chest (excluding breasts); respiratory; cardiovascular; lymph nodes, abdomen; skin, hair, nails; musculoskeletal; and neurological. Urogenital and 
reproductive examination should only be completed if clinically indicated.
CCI
CCI
CCI
CCI
---------------------------------------------
---------------------------------------------
------------


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d 
Clinical symptom directed physical examination will include at least cardiac and respiratory evaluation. 
e 
Vital signs include heart rate, temperature, and blood pressure. 
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f 
On Days I, 2 and 3, vital signs to be completed pre infusion, postinfusion, and when postinfusion observation is completed; weight from Screening may be used at Days I 3. 
g 
Respiratory status includes respiratory rate and SpOi on room air. 
h 
Obtain ALT (and AST where available), semm creatinine, and creatinine clearanc.deGFR (calculated using Cockcroft Gault or Schwartz fomrnla; see Section 6.7.2) if not 
available within 90 days of screening, using a local laboratory. 
Chemistry: alkaline phosphatase, AST, ALT, total bilimbin, total protein, albumin, lactate dehydrogenase, creatine phosphokinase, bicarbonate, blood urea nitrogen, calcium, 
chloride, creatinine, glucose, lipase, magnesium, phosphoms, potassium, sodium, uric acid. 
j 
Hematology: Complete blood count with differential. 
k 
Coagulation: INR PT aPTT 
r 
m 
n ne pregnancy test w1 on y e one tor women of c 1 
ean ng potent1a . 
n 
· 
PCR and potential resistance testing. 
I 
I 
r 
luding hospitalization; in person 
emergency, urgent, or primary care visits; or any other in person visit attended by the participant and a health care profession. Identify the nature and cause of the visit. 
s 
FLU PRO Plus questionnaire should be completed daily from Day I through Day 14 (if available). 
t 
Only AEs, medically attended visit infom1ation, and concomitant medications review are needed if the visit is done by phone. 
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Appendix 3.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a. Definition of Childbearing Potential
For the purposes of this study, a female born participant is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure. No documentation of Tanner 
stage will be required for people unless deemed prepubescent.
Women are considered to be in a postmenopausal state when they are ≥54 years of age with 
cessation of previously occurring menses for ≥12 months without an alternative cause.  
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female participant of any age.
b. Definition of Male Fertility
For the purposes of this study, a male born participant is considered fertile after the initiation of 
puberty unless the participant is permanently sterile by bilateral orchidectomy or with medical 
documentation.
2) Contraception Requirements for Female Participants
a. Study Drug Effects on Pregnancy and Hormonal Contraception
Data from nonclinical studies of RDV have demonstrated no adverse effect on fertility or
embryo-fetal development. Remdesivir has not yet been studied in pregnant women. Before
enrolling into studies with RDV, women of childbearing potential must have pregnancy testing
performed at screening.
Available data indicate that RDV potentially causes an interaction with hormonal contraception
that is considered of limited significance. Hormonal methods must be used with a barrier
method.  
b. Contraception Requirements for Female Participants of Childbearing Potential 
The inclusion of non-pregnant female participants of childbearing potential requires the use at 
least an acceptable contraceptive measure. Female participants must agree to 1 of the following 
from screening until 30 days after the last study drug dose:

Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the participant’s preferred and usual 
lifestyle.


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Or

Consistent and correct use of 1 of the following methods of birth control listed below:
Non-hormonal intrauterine device (IUD)
Hormonal IUD (must be used in conjunction with a barrier method)
Bilateral tubal occlusion (upon medical assessment of surgical success)
Vasectomy in the male partner (upon medical assessment of surgical success)
Or

Female participants who wish to use a hormonally-based method must use it in conjunction 
with a barrier method, preferably a male condom. Hormonal methods are restricted to those 
associated with the inhibition of ovulation. Hormonally-based contraceptives and barrier 
methods permitted for use in this protocol are as follows:
Hormonal methods (each method must be used with a barrier method, preferably male 
condom)
■
Oral contraceptives (either combined or progesterone only)
■
Injectable progesterone
■
Subdermal contraceptive implant
■
Transdermal contraceptive patch
■
Contraceptive vaginal ring
Barrier methods
■
Male condom (with or without spermicide)
■
Female condom (with or without spermicide)
■
Diaphragm with spermicide
■
Cervical cap with spermicide
■
Sponge with spermicide


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Inclusion of methods of contraception in this list of permitted methods does not imply that the 
method is approved in any country or region. Methods should only be used if locally approved.
Female participants must also refrain from egg donation and in vitro fertilization during 
treatment and until the end of contraception requirement.
3) Contraception Requirements for Male Participants
During the study male participants with female partners of childbearing potential should use 
condoms when engaging in intercourse of reproductive potential.
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method. A female condom and a male condom should not be used 
together.
5) Procedures to be Followed in the Event of Pregnancy
Participants will be instructed to notify the investigator if they become pregnant at any time 
during the study, or if they become pregnant within 30 days of last study drug dose. Participants
who become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator. Participants whose partner has become pregnant or suspects she 
is pregnant during the study must report the information to the investigator. Instructions for 
reporting pregnancy, partner pregnancy, and pregnancy outcome are outlined in Section 7.7.2.1.

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 3 Randomized, Double-Blind Placebo-Controlled 
Trial to Evaluate the Efficacy and Safety of Remdesivir 
(GS-5734™) Treatment of COVID-19 in an Outpatient 
Setting
Name of Test Drug:
Remdesivir
Study Number:
GS-US-540-9012
Protocol Version (Date):
Amendment 4:
14 January 2021
Analysis Type:
Final Analysis
Analysis Plan Version:
1.0
Analysis Plan Date:
12 August 2021 
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
GILEAU 


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TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN ............................................................................................................................... 1 
TABLE OF CONTENTS ................................................................................................................................................ 2 
LIST OF IN-TEXT TABLES ........................................................................................................................................ .4 
LIST OF IN-TEXT FIGURES ....................................................................................................................................... .4 
LIST OF ABBREVIATIONS ......................................................................................................................................... 5 
................................................................................................................. 7 
1. 
INTRODUCTION .................................................................................................................................................. 8 
1. 1. 
Study Objectives ........................................................................................................................................ 8 
1.2. 
Study Design ............................................................................................................................................. 9 
1.3. 
Sample Size and Power ........................................................................................................................... 12 
2. 
TYPE OF PLANNED ANALYSIS ...................................................................................................................... 13 
2.1. 
Interi1n Analyses ...................................................................................................................................... 13 
2.1. 1. 
DMC Analysis ....................................................................................................................... 13 
2.2. 
Final Analysis .......................................................................................................................................... 13 
2.3. 
Changes from Protocol-Specified Analyses ............................................................................................ 13 
3. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES ............................................................................. 14 
3.1. 
3.2. 
3.3. 
3.4. 
3.5. 
3.6. 
3.7. 
3.8. 
Analysis Sets ........................................................................................................................................... 14 
3 .1. 1. 
All Randomized Analysis Set ................................................................................................ 14 
3.1.2. 
Full Analysis Set. ................................................................................................................... 14 
3.1.3. 
Modified Full Analysis Set .................................................................................................... 14 
3.1.4. 
Safe Anal sis Set ................................................................................................................ 15 
3.1.7. 
VrroogyAnaysisSet ............................................................................................................ 15 
Subject Grouping ..................................................................................................................................... 15 
Strata and Covariates ............................................................................................................................... 15 
Examination of Subject Subgroups ......................................................................................................... 16 
Multiple Co1nparisons ............................................................................................................................. 16 
Missing Data and Outliers ....................................................................................................................... 17 
3.6.1. 
Missing Data .......................................................................................................................... 17 
3.6.2. 
Outliers .................................................................................................................................. 17 
Data Handling Conventions and Transfo1mations .................................................................................. 17 
Analysis Visit Windows .......................................................................................................................... 19 
3.8.1. 
Definition of Study Day ........................................................................................................ 19 
3.8.2. 
Analysis Visit Windows ........................................................................................................ 19 
3.8.3. 
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window ................................................................................................................................. 21 
4. 
SUBJECT DISPOSITION ................................................................................................................................... 24 
4.1. 
Subject Enrollment and Disposition ........................................................................................................ 24 
4.2. 
Extent of Study Thug Exposme and Adherence ...................................................................................... 24 
4.3. 
Protocol Deviations ................................................................................................................................. 24 
5. 
BASELINE CHARACTERISTICS ..................................................................................................................... 26 
5.1. 
Demographics and Baseline Characteristics ........................................................................................... 26 
5.2. 
Other Baseline Characteristics ................................................................................................................ 26 
5.3. 
Medical Histoiy ....................................................................................................................................... 27 
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6. 
EFFICACY ANALYSES ..................................................................................................................................... 28 
6.1. 
Pri1nruy Efficacy Endpoint ...................................................................................................................... 28 
6.1. 1. 
Definition of the Prima1y Efficacy Endpoint ........................................................................ 28 
6.1.2. 
Statistical Hypothesis for the Primruy Efficacy Endpoint ..................................................... 28 
6.1.3. 
Primruy Analysis of the Prima1y Efficacy Endpoint.. ........................................................... 28 
6.1.4. 
Secondruy Analyses of the Prima1y Efficacy Endpoint ........................................................ 28 
6.2. 
Secondruy Endpoints ............................................................................................................................... 29 
6.2.1. 
Anal sis ofSecondru End oints .......................................................................................... 31 
6.4. 
Change from Protocol Specified Efficacy Analyses ............................................................................... 33 
7. 
SAFETY ANALYSES ......................................................................................................................................... 34 
7 .1. 
Adverse Events and Deaths ..................................................................................................................... 34 
7.1. 1. 
Adverse Event Dictiona1y ..................................................................................................... 34 
7.1.2. 
Adverse Event Severity ......................................................................................................... 34 
7.1.3. 
Relationship of Adverse Events to Study Dmg ..................................................................... 34 
7.1.4. 
Relationship of Adverse Events to Study Procedme ............................................................. 34 
7.1.5. 
Serious Adverse Events ......................................................................................................... 35 
7.1.6. 
Treatinent-Emergent Adverse Events .................................................................................... 35 
7.1.6.1. 
Definition of Treatinent-Emergent Adverse Events ........................................ 35 
7 .1.6.2. 
Inco1nplete Dates ............................................................................................. 35 
7. 1. 7. 
SW'lllllaries of Adverse Events and Deaths ............................................................................ 36 
7 .2. 
Laborato1y Evaluations ........................................................................................................................... 37 
7.2.1. 
SW'lllllaries of Numeric Laborat01y Results .......................................................................... 37 
7.2.2. 
Graded Laborato1y Values .................................................................................................... 38 
7.2.2.1. 
Treatinent-Emergent Laborato1y Abnonnalities ............................................. 38 
7 .2.2.2. 
Smnmaries of Laborat01y Abnonnalities ........................................................ 38 
7.3. 
Body Weight, Vital Signs and Respirato1y Status ................................................................................... 39 
7 .4. 
Prior and Concomitant Medications ........................................................................................................ 39 
7. 5. 
Other Safety Measmes ........................................................................................................................... .40 
7 .6. 
Changes from Protocol-Specified Safety Analyses ................................................................................ .40 
I 
9. 
REFERENCES ..................................................................................................................................................... 44 
10. SOFTWARE ........................................................................................................................................................ .45 
11. SAP REVISION .................................................................................................................................................. .46 
12. APPENDICES ..................................................................................................................................................... .47 
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LIST OF IN-TEXT TABLES
Table 3-1.
Analysis Visit Windows for Vital signs ..................................................................................20
Table 3-2.
Analysis Visit Windows for Weight, SpO2 and Respiratory status.........................................20
Table 3-3.
Analysis Visit Windows for PCR............................................................................................20
Table 3-4.
Analysis Visit Windows for Hematology, Coagulation and Chemistry Laboratory 
Tests.........................................................................................................................................21
Table 8-1.
Pharmacokinetic Parameters for Each Analyte .......................................................................42
LIST OF IN-TEXT FIGURES
Figure 1-1.
Study Schema ..........................................................................................................................11


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LIST OF ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BLQ
below the limit of quantitation
BMI
body mass index
CI
confidence interval
CMH
Cochran-Mantel-Haenszel
CoV
coronavirus
COVID-19
coronavirus disease 2019
CRF
case report form
CSR
clinical study report
DAIDS
Division of AIDS
DAVG
Time-weighted average change from baseline
DMC
data monitoring committee
ED
Emergency department
ET
early termination
FAS
Full Analysis Set
FLU-PRO©
InFLUenza Patient-Reported Outcome
Hb
Hemoglobin
HLT
high-level term
HLGT
high-level group term
ICH
International Conference on Harmonization (of Technical Requirements for Registration of 
Pharmaceuticals for Human Use)
IV
Intravenous 
IXRS
interactive voice or web response system
LLT
lower-level term
LOD
Limit of detection
LOQ
limit of quantitation
MedDRA
Medical Dictionary for Regulatory Activities
PCR
polymerase chain reaction
PT
preferred term
PTM
Placebo to match
Q1, Q3
first quartile, third quartile
RDV
remdesivir (GS-5734™)
SAE
serious adverse event
SAP
statistical analysis plan
SARS
severe acute respiratory syndrome
SD
standard deviation
CCI


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SI (units)
international system of units
SOC
system organ class
SpO2
oxygen saturation
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
ULN
upper limit of normal
WHO
World Health Organization


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L 
INTRODUCTION 
Version 1.0 
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This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the clinical study repo1t (CSR) 
for Study GS-US-540-9012. This SAP is based on the study protocol amendment 4 dated 
14 Januaiy 2021 and the electronic case repo1t f01m (eCRF). The SAP will be finalized before 
database finalization. Any changes made after the finalization of the SAP will be documented in 
the CSR. 
1.1. 
Study Objectives 
The primaiy objectives of this study ai·e as follows: 
• 
To evaluate the efficacy of RDV in reducing the rate of COVID-19 related hospitalization or 
all-cause death in non-hospitalized paiticipants with early stage COVID-19 
• 
To evaluate the safety of RDV administered in an outpatient setting 
The secondaiy objectives of this study ai·e as follows: 
• 
To evaluate the efficacy of RDV in reducing the rate of COVID-19 related medically 
attended visits (MA Vs; medical visits attended in person by the paiticipant and a health care 
professional) or all-cause death in non-hospitalized paiticipants with eai·ly stage COVID-19 
• 
To dete1mine the antiviral activity ofRDV on SARS-CoV-2 viral load 
• 
To assess the impact of RDV on symptom duration and severity 
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1.2.
Study Design
This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study of RDV 
therapy for outpatients with early stage COVID-19 who are at higher risk of disease progression.
Participants who meet all eligibility criteria may be randomized in a 1:1 ratio to RDV or placebo. 
Randomization will be stratified by participants who reside in a skilled nursing facility, by 
participant’s age (< 60 vs  years), and by region (United States [US] vs. ex-US):
Treatment Group A: single dose of IV RDV 200 mg on Day 1 followed by IV RDV 100 mg on 
Days 2 and 3 (RDV group)
Treatment Group B: IV placebo-to-match (PTM) RDV on Days 1 to 3 (PTM group)
Participants must meet all of the following inclusion criteria to be eligible for participation in this 
study: 
1) Willing and able to provide written informed consent (participants ≥ 18 years of age) or 
assent (participants ≥ 12 and < 18 years of age) prior to performing study procedures. 
Participants aged ≥ 18 years may be enrolled with the consent of a legal representative where 
permitted according to local law and approved nationally and by the relevant institutional 
review board (IRB) or independent ethics committee (IEC). For participants ≥ 12 and 
< 18 years of age, a parent or legal guardian must be willing and able to provide written 
informed consent prior to performing study procedures 
2) Either:
Age ≥ 18 years (at all sites) or aged ≥ 12 and < 18 years of age weighing ≥ 40 kg (where 
permitted according to local law and approved nationally and by the relevant IRB or IEC) 
with at least 1 of the following pre-existing risk factors for progression to hospitalization:
a) Chronic lung disease: chronic obstructive pulmonary disease, moderate-to-severe 
asthma, cystic fibrosis, pulmonary fibrosis
b) Hypertension: systemic or pulmonary
c) Cardiovascular or cerebrovascular disease: coronary artery disease, congenital heart 
disease, heart failure, cardiomyopathy, history of stroke, atrial fibrillation, 
hyperlipidemia
d) Diabetes mellitus: Type 1, type 2, or gestational
e) Obesity (BMI ≥ 30)


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f)
Immunocompromised state; having a solid organ transplant, blood, or bone marrow 
transplant; immune deficiencies; HIV with a low CD4 cell count or not on HIV 
treatment; prolonged use of corticosteroids; or use of other immune weakening 
medicines
g) Chronic mild or moderate kidney disease
h) Chronic liver disease
i)
Current cancer
j)
Sickle cell disease
OR age ≥ 60 years, regardless of the presence of other pre-existing risk factors for 
progression
3) SARS-CoV-2 infection confirmed by molecular diagnostics (nucleic acid [eg, PCR] or 
antigen testing) ≤ 4 days prior to screening
4) Presence of ≥ 1 symptom(s) consistent with COVID-19 for ≤ 7 days prior to randomization 
(such as fever, cough, fatigue, shortness of breath, sore throat, headache, myalgia/arthralgia)
5) Not currently receiving, requiring, or expected to require supplemental oxygen 
6) Not currently requiring hospitalization (hospitalization defined as ≥ 24 hours of acute care)
7) Participants of childbearing potential who engage in heterosexual intercourse must agree to 
use protocol-specified method(s) of contraception
Exclusion criteria for participation include: 
1) Participation in any other clinical trial of an experimental treatment and prevention for 
COVID-19 
2) Prior hospitalization for COVID-19 (hospitalization defined as ≥ 24 hours of acute care)
3) Treatment with other agents with actual or possible direct antiviral activity against 
SARS-CoV-2 or administration of any SARS-CoV-2 (or COVID-19) vaccine
4) Criterion removed
5) Requiring oxygen supplementation
6) ALT or AST ≥ 5 × upper limit of normal (ULN) at screening or within 90 days of screening 
Note: if per local practice only ALT is routinely measured, exclusion criteria will be 
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7) Creatinine clearance < 30 mL/min at screening or within 90 days of screening using the 
Cockcroft-Gault fonnula in paii icipants 
18 years of age or estimated glomernlar filtration 
rate ( eGFR) < 30 mL/min/1. 73m2 at screening or within 90 days of screening using the 
Schwaiiz fonnula in paii icipants < 18 yeai·s of age (see Section 6.7.2 of protocol) 
8) Cunently breastfeeding (nursing) 
9) Known hypersensitivity to the study diug, metabolites, or fo1mulation excipient 
10) Use or planned use of exclusionaiy medications (refer to Section 5 .4 of protocol) 
Paiiicipants will receive study treatment with RDV for 3 days (Treatment Group A) or PTM for 
3 days (Treatment Group B). 
Figure 1-1. 
Study Schema 
Day 
1 
ROV x 3 days 
PTIII x 3days 
3 
28 
• 
Primary endpoint 
composite of 
hospitalization/ death 
byday28 
On study Days 1 through 3, vital signs including respirato1y status and SpO2 will be measured, 
and adverse events (AEs) and concomitant medications will be documented. Laborato1y tests for 
safety (hematology, coagulation and chemistry) will be peifonned on Days 1, 3, 7, and 14. 
Nasophaiyngeal swabs and sputum sainples will be collected on Days 1, 2, 3, 7, and 14 for 
SARS-CoV-2 quantitative reverse ti·anscriptase polymerase chain reaction viral load testing and 
possible resistance testing. 
On study Day 14 physical examination findings, vital signs including temperature, respirato1y 
rate, and SpO2, AEs and concomitant medications will be documented. 
Symptom severity will be assessed daily from Day 1 through Day 14 using the COVID-19 
adapted FLU-PRO Plus questionnaire (if available). On study Day 28, there will be an in-person 
or phone visit. Physical examination, vital signs including temperature, respirato1y rate, and 
SpO2, AEs, MA V infonnation and concomitant medications will be documented ( only AEs, 
MA V infonnation and concomitant medications needed if perfo1med by phone). 
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1.3.
Sample Size and Power
The total sample size of the study will be approximately 1264 participants.
The sample size computation is based on proportions of COVID-19 related hospitalization or 
all-cause death by Day 28 for the RDV and placebo treatment groups. The sample size needed 
for a 1:1 randomization using a 2-tailed test at level α is given by:
(𝑧1―𝛼/2 + 𝑧1―𝛽)2
𝑃(1 ― 𝑅2)𝜎2𝐵2
Where P is the overall rate of COVID-19 related hospitalization or all-cause death, B is the log 
hazard ratio, σ is the standard deviation of treatment indicator variable, R is the R-Squared that is 
obtained when treatment indicator variable is regressed on the other covariates, and z1-α/2 and z1-β 
are the 1-α/2 and 1-β quantiles of the standard normal distribution.
A sample size of 1264 participants (632 in each group with 1:1 randomization) achieves > 90% 
power to detect a ratio of 0.55 (RDV to placebo) in proportion of COVID-19 related 
hospitalization or all-cause death, which is equal to a hazard ratio of 0.534) using a two-sided 
significance level of 0.05 assuming the overall COVID-19 related hospitalization or all-cause 
death rate is 9.3% (12% in the placebo group and 6.6% in the RDV group) and a 5% drop out 
rate. The sample size provides approximately 80% power to detect a smaller treatment effect size 
with a ratio of 0.60 (RDV to placebo), assuming a 2-sided significance level of 0.05 and the 
overall COVID-19 related hospitalization or all-cause death rate is 9.6% (12% in the placebo 
group and 7.2% in the RDV group) and a 5% drop out rate. The proportion of patients with 
COVID-19-related hospitalizations or emergency department (ED) visits was 13.5% in high risk 
patients (age ≥ 65 or BMI ≥ 35) who received placebo{Gottlieb 2021}, 12% is assumed for the 
study to account for decrease in hospitalization rate in recent months. 
The sample size calculation was done using software PASS (Version 14.0, module of Cox 
regression for survival).


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
Prior to the final analysis, interim analyses may be conducted, and the analyses may be 
submitted to regulatory agencies to seek guidance for the overall clinical development program.
2.1.1.
DMC Analysis
One external multidisciplinary DMC was planned to review the progress of the study and to 
perform interim reviews of the efficacy (futility assessment) and safety data. However, this DMC 
analysis was not performed due to the stop of study enrollment after 584 participants  
randomized and prior to reaching the planned DMC analysis schedule (ie, approximately 50% of 
the total 1264 planned participants have completed Day 28 assessment). 
2.2.
Final Analysis
The final analysis will be performed after all participants have completed or discontinued from 
the study, outstanding data queries have been resolved or adjudicated as unresolvable, and the 
data have been cleaned and finalized. This SAP describes the analysis plan for the final analysis. 
2.3.
Changes from Protocol-Specified Analyses
The DMC analysis was not performed due to the stop of enrollment on 08 April 2021 after less 
than 50% of the participants were randomized. The reasons of stopping enrollment were due to 
significant changes in the epidemiology of COVID-19 from a combination of lower 
hospitalization rates and high vaccine rates in high-risk patients, and a change in the unmet 
patient need for convenient at home options for non-hospitalized patients with COIVD-19. The 
decsion to stop study ernollment was documented on 06-APR-2021 Study Management Team 
meeting minutes. 


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of participants in each category will be presented; for continuous 
variables, the number of participants (n), mean, standard deviation (SD) or standard error (SE), 
median, first quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
All statistical tests will be 2-sided and performed at the 5% significance level unless otherwise 
specified.
By-subject listings will be presented for all participants in the All Randomized Analysis Set and 
sorted by subject ID number, visit date, and time (if applicable). Data collected on log forms, 
such as AEs, will be presented in chronological order within the participant. The treatment group 
to which participants were randomized will be used in the listings. Age, sex at birth, race, and 
ethnicity will be included in the listings, as space permits.
3.1.
Analysis Sets
Analysis sets define the participants to be included in an analysis. Analysis sets and their 
definitions are provided in this section. Participants included in each analysis set will be 
determined before the study blind is broken for analysis. The analysis set will be identified and 
included as a subtitle of each table, figure, and listing.
For each analysis set, the number and percentage of participants eligible for inclusion, will be 
summarized by treatment group.
A listing of reasons for exclusion from analysis sets will be provided by participant.
3.1.1.
All Randomized Analysis Set
All Randomized Analysis Set includes all participants who were randomized in the study.
3.1.2.
Full Analysis Set
The primary analysis set for efficacy analysis is defined as the Full Analysis Set (FAS), which 
will include all participants who (1) are randomized into the study, and (2) have received at least 
1 dose of study treatment. Participants will be grouped according to the treatment to which they 
were randomized.
3.1.3.
Modified Full Analysis Set
A modified full analysis set (mFAS) includes all participants who (1) are randomized into the 
study, and (2) have received at least 1 dose of study treatment, and (3) enrolled under protocol 
amendment 2 or later. Participants will be grouped according to the treatment to which they were 
randomized.


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Safety Analysis Set 
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The prima1y analysis set for safety analyses is defined as the Safety Analysis Set, which will 
include all pa1ticipants who (1) are randomized into the study and (2) have received at least 
1 dose of study treatment. Pait icipants will be grouped according to the treatment which they 
received. -
-
3.1.7. 
Virology Analysis Set 
The Virology Analysis Set will include all pa1ticipants who (1) are randomized into the study, 
(2) have received at least 1 dose of study treatment, and (3) have positive SARS-Co V-2 viral 
load at baseline (result of 'No SARS-Co V-2 detected' is considered as negative, results of 
'Inconclusive', "<2228cp/mL SARSCo V2 detected" and numerical results ai·e considered as 
positive). 
3.2. 
Subject Grouping 
For analyses based on the All Randomized Analysis Set, FAS, mF AS or Virology Analysis Set, 
paiticipants will be grouped according to the ti·eatment to which they were randomized. For the 
safety analysis set, the actual ti·eatment received will differ from the randomized ti·eatment only 
when their actual ti·eatment differs from randomized ti·eatment for the entire ti·eatment duration. 
3.3. 
Strata and Covariates 
Paiticipants will be randomly assigned to h'eatment groups via the interactive voice or web 
response system (IXRS) in a 1: 1 ratio using a sti·atified randomization schedule. Sti·atification 
will be based on the following vai·iables: 
• 
Region: US vs. ex-US 
• 
Paiticipant's age: < 60 vs~ 60 yeai·s 
• 
Resident of skilled nursing facility: Yes vs. No 
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Stratification discrepancies will be reviewed and assessed. The values recorded in the clinical 
database will be used for analyses in case there are discrepancies between the IXRS and the 
clinical database. Based on the assessment of stratification discrepancies, a sensitivity analysis of 
the primary endpoint may be performed.
The primary efficacy endpoint will be evaluated in a stratified analysis based on the same 
3 factors used for randomization, as specified in Section 6.1.3. In addition, observed imbalances 
between treatment groups in other baseline characteristics may be considered as covariates in 
sensitivity analyses of efficacy endpoints.  
3.4.
Examination of Subject Subgroups
The primary endpoint will be examined for the following participant subgroups: 

region (US vs. ex-US)

participant’s age (<18, 18≤ - < 60,   years), 

participants who reside in a skilled nursing facility (Yes, No), 

Sex at birth: (a) male and (b) female

Race: (a) Asian, (b) Black, (c)White, (d) other

Baseline risk factor:  Chronic lung disease (Yes, No), Hypertension (Yes, No), 
Cardiovascular or cerebrovascular disease (Yes, No), Diabetes mellitus (Yes, No), Obesity 
(Yes, No), Immunocompromised state (Yes, No), Chronic mild or moderate kidney disease 
(Yes, No), Chronic liver disease (Yes, No), Current cancer (Yes, No), Sickle cell disease 
(Yes, No)

Common COVID-19 symptoms at baseline:  absence or presence for each of the following 
symptoms: Stuffy or runny nose; Sore throat; Shortness of breath (difficulty breathing); 
Cough; Low energy or tiredness; Muscle or body aches; Headache; Chills or shivering; 
Feeling hot or feverish; Nausea; Vomit; Diarrhea; Loss of Smell; Loss of taste.
In addition, other subgroups may be considered based on imbalances between treatment groups 
observed in other baseline characteristics.
3.5.
Multiple Comparisons
There will be no multiplicity adjustment in the final analysis. Efficacy will be evaluated using 
the primary efficacy endpoint at the significance level of 0.05. All other efficacy endpoints are 
exploratory in nature and will be tested using 2-sided tests at the 5% significance level without 
multiplicity adjustment.


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3.6.
Missing Data and Outliers
3.6.1.
Missing Data
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document.
Participants with missing outcomes for the primary endpoint due to premature discontinuation of 
the study will be censored at last study date.
In this study, a missing pre-treatment laboratory result would be treated as normal (ie, no toxicity 
grade) for the laboratory abnormality summary. The handling of missing or incomplete dates for 
AE onset is described in Section 7.1.6.2, and for prior and concomitant medications in 
Section 7.4.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process. No sensitivity 
analyses to evaluate the impact of outliers on efficacy or safety outcomes are planned. Unless 
specified otherwise, all data will be included in the analyses.
3.7.
Data Handling Conventions and Transformations
In general, age collected at Day 1 (in years) will be used for analyses and presented in listings. If 
age at Day 1 is not available for a participant, then age derived based on date of birth and the 
first dose date will be used instead. If an enrolled participant was not dosed with any study drug, 
the randomization date will be used instead of the Day 1 visit date. For screen failures, the date 
the first informed consent was signed will be used for the age derivation. Age required for 
longitudinal and temporal calculations and analyses (e.g., estimates of creatinine clearance, age 
at date of AE) will be based on age derived from date of birth and the date of the measurement or 
event, unless otherwise specified.
The following conventions will be used for the imputation of date of birth when it is partially 
missing or not collected:

If only year of birth is collected, then “01 July” will be imputed as the day and month of birth

If year of birth is missing, then date of birth will not be imputed.


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Laborato1y data that are continuous in nature but are less than the lower limit of quantitation 
(LOQ) or above the upper LOQ will be imputed as follows: 
• 
A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is repo1t ed in the fo1m of"< x" (where xis considered the LOQ). For example, if the 
values are repo1ted as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate summaiy statistics. An exception to this mle is any value repo1t ed as < 1 or < 0.1, 
etc. For values repo1ted as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used to 
calculate summaiy statistics. 
• 
A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is repo1t ed in the fo1m of"> x" (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above. 
• 
The LOQ will be used to calculate descriptive statistics if the datum is repo1ted in the fonn of 
":'.S x" or"::::: x" (where xis considered the LOQ). 
SARS-COV2 viral load results that are below LOQ but have a positive signal will be repo1ted as 
"<2228cp/mL SARSCo V2 detected" and those that are below lower limit of detection(LOD) and 
negative will be repo1ted as "No SARS-CoV2 detected". The data will be imputed as follows: 
• 
A value of 1114 copies/ml (half of the LOQ 2228 copies/ml) will be used to calculated 
descriptive statistics if the datum is repo1t ed as "<2228cp/mL SARSCoV2 detected". 
• 
A value of 746.5 copies/ml (1/2 of the LOD 1493 copies/ml) will be used to calculated 
descriptive statistics if the datum is repo1t ed as "No SARS-Co V2 detected" 
Any SARS-CoV-2 viral load samples collected on or after the paiticipants ai·e receiving 
additional COVID-19 treatments (see Appendix 2) will be excluded from the viral load analysis. 
Base 10 logai·ithm transfo1mation will be used for analyzing SARS-CoV-2 viral load. 
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3.8. 
3.8.1. 
Analysis Visit Windows 
Definition of Study Day 
Version 1.0 
Final 
Study day will be calculated from the first dosing date of study drng and derived as follows: 
• 
For postdose study days: Assessment Date - First Dosing Date + 1 
• 
For days prior to the first dose: Assessment Date - First Dosing Date 
Therefore, study day 1 is the day of first dose of study drng administration. 
Last Dose Date is defined as the maximum, nonmissing, nonzero dose end date of treatment 
recorded on the Study Drng Administrntion eCRF fo1m with "Study Drng Pennanently 
Withdrawn" box checked for paiiicipants who prematurely discontinued or completed study diug 
according to the Study Drng Completion eCRF. Refer to Appendix 2 for missing date 
imputation, if necessaiy. 
Last Study Date is the latest of the study diug sta1i dates and end dates, the in-person or phone 
visit dates, the vital sign or respirato1y sta.tus collection dates, Flu-PRO Plus questionnaire 
collection date and the laborato1y collection dates, including the 28-day follow-up visit date, and 
the death date (if applicable, only for paii icipants who prematurely discontinued study according 
to the Study Completion eCRF). 
Baseline value is defined as the last value obtained on or prior to the first dose date (and time, 
if available) unless othe1w ise specified (see Section 3.8.3). 
3.8.2. 
Analysis Visit Windows 
Paiiicipant visits might not occm on protocol-specified days. Therefore, for the purpose of 
analysis, observations will be assigned to analysis windows. 
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The analysis windows for Vital signs are provided in Table 3-1.
Table 3-1.
Analysis Visit Windows for Vital signs
Visit Window Study Day
Nominal Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1
(none)
1 (Pre Dose)*
Day 1
1
1 (Post Dose) *
1 (Post Dose)
Day 2#
2
2
2
Day 3#
3
3
4
Day 7
7
5
9
Day 14
14
10
21
Day 28
28
22
(none)
*
For baseline, the upper limit includes values collected at or prior to the first dose date/time. For Day 1, the lower limit 
includes values collected after the first dose date/time on Day 1. 
#
The pre dose and post dose timepoints for Days 2 and 3 will be based on nominal time point. The analysis 
windows for Weight, and Respiratory status are provided in Table 3-2.
Table 3-2.
Analysis Visit Windows for Weight, SpO2 and Respiratory status
Visit Window Study Day
Nominal Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1
(none)
1 (Pre Dose)*
Day 2
2
1 (Post Dose) *
2
Day 3
3
3
4
Day 7
7
5
9
Day 14
14
10
21
Day 28
28
22
(none)
*
For baseline, the upper limit includes values collected at or prior to the first dose date/time. For Day 2, the lower limit 
includes values collected after the first dose date/time on Day 1.
The analysis windows for PCR are provided in Table 3-3.
Table 3-3.
Analysis Visit Windows for PCR
Visit Window Study Day
Nominal Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1
(none)
1 (Pre Dose)
Day 2
2
1 (Post Dose)
2
Day 3
3
3
4
Day 7
7
5
9
Day 14
14
10
21
Post Day 14
22
22
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The analysis windows for Chemistry and Hematology laboratory parameters are provided in 
Table 3-4.
Table 3-4.
Analysis Visit Windows for Hematology, Coagulation and Chemistry 
Laboratory Tests
Visit Window Study Day
Nominal Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1
(none)
1 (Pre Dose)
Day 3
3
1 (Post Dose)
4
Day 7
7
5
9
Day 14
14
10
(none)
FLU-PRO Plus Questionnaire were to be collected daily from Day 1 through Day 14; therefore, 
windows are not assigned and results will be summarized for each Study Day.
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time-to-event analysis would use all data regardless of analysis window.
If multiple valid, nonmissing measurements exist in an analysis window, records will be chosen 
based on the following rules if a single value is needed:

For baseline, the last nonmissing value on or prior to the first dosing date (and time, 
if available) of study drug will be selected, unless specified differently. If there are multiple 
records with the same time or no time recorded on the same day, the baseline value will be 
the average of the measurements for continuous data, or the measurement with the lowest 
severity for categorical data.
For baseline, if both local lab and central lab results are available, central lab results will 
be selected first for baseline, local lab results will be used when central lab results are 
missing.
For FLU-PRO Plus data, if there are multiple records on Day 1, the baseline value will be 
selected as follows:
■
The record closest to the dosing day will be selected. 
■
If there are more than 1 records on the selected day with different times, the least 
severe score will be selected as baseline. If there are multiple records with same 
severity, the measurement with the lowest severity at later time will be selected. 


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
For postbaseline values (other than PCR negative confirmation and PCR for time-weighted
average change from baseline (DAVG)):
The record closest to the nominal day for that visit will be selected.
If there are 2 records that are equidistant from the nominal day, the later record will be
selected.
If there is more than 1 record on the selected day, values will be selected for analysis as 
follows:
■
For PCR, if there is more than 1 record on the selected day, the latest value will be
selected. If there are multiple records with the same time or no time recorded on the
same day, the geometric mean value (copies/mL) will be taken. For laboratory values
(other than PCR) and SpO2, if there is more than 1 record on the selected day, the
average value will be selected.
■
For FLU-PRO Plus data, if there are more than 1 record on the same day, the worst
value will be selected.
■
For RBC Morphology result, if there is more than 1 record on the selected day, all
results will be selected.
■
For vital signs, the pre dose and post dose timepoints for Days 2 and 3 will be
summarized by nominal time point. If there is more than 1 record on a time point, the
average will be taken.
■
For other parameters, if there is more than 1 record on the selected day, the average
will be taken for continuous data and the worst severity will be taken for categorical
data, unless otherwise specified.

For postbaseline values of PCR negative confirmation:
All available data will be used to derive negative confirmation except if there are multiple
records on the same day, the worst value will be used for negative confirmation for that 
day
The record closest to the nominal day for that visit will be selected.
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.

For postbaseline values PCR for DAVG calculation:
All values from different days within an analysis windows will be used for DAVG
calculation.


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If there is more than 1 record on a study day, the latest value will be selected. If there are 
multiple records with the same time or no time recorded on the same day, the geometric 
mean value (copies/mL) will be taken. 


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
The number and percentage of participants randomized at each investigator site will be 
summarized by treatment group and overall using the Safety Analysis Set and All Randomized 
Analysis Set. The number and percentage of participants enrolled by randomized stratum will be 
summarized using stratum assignment captured in the IXRS. Discrepancy between IXRS and 
clinical database will be noted if applicable. The denominator for this calculation will be the 
number of participants in the Safety Analysis Set.
The summary of subject disposition will be provided by treatment group and overall for all 
screened participants. This summary will include the number of participants screened, screen 
failure participants who were not randomized, participants who met all eligibility criteria and 
were not randomized, participants randomized, participants randomized but never treated, 
participants in the Safety Analysis Set, participants in the modified FAS and participants in the 
FAS.
In addition, the number and percentage of the participants in the following categories will be 
summarized: 

Completed randomized treatment on study drug as recorded on the Study Drug Completion 
form

Prematurely discontinuing study drug prior to completion with summary of reasons for 
discontinuing study drug as recorded on the Study Drug Completion form

Completed study

Prematurely discontinuing from study (with summary of reasons for discontinuing study) as 
recorded on the Study Completion form
The denominator for the percentages of participants in each category will be the number of 
participants in the Safety Analysis Set. 
No inferential statistics will be generated. A data listing of reasons for premature study 
drug/study discontinuation will be provided.
4.2.
Extent of Study Drug Exposure and Adherence
Number of doses received will be summarized by treatment group for the Safety Analysis Set.
4.3.
Protocol Deviations 
A listing will be provided for all randomized participants who violated at least 1 inclusion or 
exclusion criterion. The listing will include the criteria not met.


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Protocol deviations occurring after participants entered the study are documented during routine 
monitoring. The number and percentage of participants with important protocol deviations and 
the total number of important protocol deviations by deviation reason (e.g., nonadherence to 
study drug, violation of select inclusion/exclusion criteria) will be summarized by treatment 
group for the FAS. A by-subject listing will be provided for those participants with important 
protocol deviation.


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Participant demographic data (eg, sex, race/ethnicity, age, and age group (<18, ≥18 - < 60, ≥ 60) 
and baseline characteristics (eg, body weight, height, and body mass index [BMI]) will be 
summarized by treatment group and overall using descriptive statistics (n, mean, SD, median, 
Q1, Q3, minimum, and maximum) for continuous data and by the number and percentage of 
participants for categorical data. The summaries of demographic data and baseline participant 
characteristics will be provided for the Safety Analysis Set.
For categorical data, the Cochran-Mantel-Haenszel (CMH) test (ie, general association statistic 
for nominal data and row mean scores for ordinal data) will be used to compare the 2 treatment 
groups. For continuous data, the 2-sided Wilcoxon rank sum test will be used to compare the 2 
treatment groups. 
Similar summaries will be produced for the following subgroups: region (US vs. ex-US), 
participant’s age (< 60 vs   years), and participants who reside in a skilled nursing facility 
(Yes, No).
A by-subject demographic listing will be provided.
5.2.
Other Baseline Characteristics
The following baseline disease characteristics will be summarized by treatment group and 
overall using descriptive statistics:

Baseline risk factor as defined in Section 3.4

Duration of symptoms prior to first dose of study drug

Duration from SARS-CoV-2 nucleic acid/antigen confirmation to first dose of study drug

Alanine aminotransferase (ALT)

Aspartate aminotransferase (AST)

Baseline SARS-CoV-2 viral Load (as a continuous variable, and a categorical variable with 
categories of < median and ≥ median)

Baseline respiration rate
For categorical data, the CMH test (general association statistic for nominal data) will be used to 
compare the 2 treatment groups. For continuous data, the 2-sided Wilcoxon rank sum test will be 
used to compare the 2 treatment groups. Similar summaries will be produced for the following 


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subgroups: region (US vs. ex-US), participant’s age (< 60 vs  years), and participants who 
reside in a skilled nursing facility (Yes, No).
Categorical baseline COVID-19 symptoms from Flu-PRO Plus will be summarized by treatment 
group separately from other baseline characteristics. 
5.3.
Medical History
Any medical condition or clinically significant laboratory abnormality with an onset date before 
the consent form is signed and not related to a protocol-associated procedure is considered to be 
preexisting and should be documented as medical history. General medical history data will be 
collected at screening. It will be coded using the current version of MedDRA. A summary table 
will present the percentages of participants reporting each medical history preferred term, sorted 
first in alphabetical order by system organ class (SOC) and then by preferred term (PT) in 
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6.
EFFICACY ANALYSES
6.1.
Primary Efficacy Endpoint
6.1.1.
Definition of the Primary Efficacy Endpoint
The primary endpoint of the study is the composite endpoint of COVID-19 related 
hospitalization (defined as at least 24 hours of acute care) or all-cause death by Day 28. The 
endpoint will be derived by combining the available all-cause death and COVID-19 related 
hospitalization reported by the site.  The first COVID-19 related hospitalization will be used for 
the proportion of COVID-19 related hospitalization or all-cause death.  
6.1.2.
Statistical Hypothesis for the Primary Efficacy Endpoint
Null hypothesis:  The hazard ratio of COVID-19 related hospitalization or all-cause death by 
Day 28 between the 2 treatment groups equals to 1.
Alternative hypothesis:  The hazard ratio of COVID-19 related hospitalization or all-cause 
death by Day 28 between the 2 treatment groups does not equal to 1.
6.1.3.
Primary Analysis of the Primary Efficacy Endpoint
The hazard ratio of COVID-19 related hospitalization or all-cause death between the two 
treatment groups will be estimated using a Cox model with stratification factors as covariates. 
If a participant prematurely discontinues from the study prior to Day 28 or the hospitalization 
status is missing, the participant is censored at last study date or day 28 whichever is earlier. If a 
participant has a COVID-19 related hospitalization first and then dies, then date of the 
COVID-19 related hospitalization and status will be used for the primary analysis for this 
participant. If a participant has a non COVID-19 related hospitalization first and then dies 
without experiencing a COVID-19 related hospitalization, then date of the death and status will 
be used for the primary analysis for this participant.
The hazard ratio, p-value, 95% CI for the hazard ratio from Cox model, and proportion of 
COVID-19 related hospitalization or all-cause death at Day 28 from Kaplan-Meier estimate will 
be provided.  
The FAS will be the primary analysis set for efficacy endpoint evaluation.  The primary endpoint 
may be analyzed for each of the subgroups defined in Section 3.3. 
6.1.4.
Secondary Analyses of the Primary Efficacy Endpoint
Sensitivity analyses maybe conducted using the following alternative approaches for the primary 
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
A CMH test including baseline stratification factors as strata for the statistical comparison 
between the two treatment groups. If a participant prematurely discontinues from the study 
prior to Day 28 with no event before discontinuation or the hospitalization/death status is 
missing, the participant will be considered as with no hospitalization/death.
The analysis is for the purposes of evaluating the robustness of the estimates of the primary 
analysis.
6.2.
Secondary Endpoints 
The other endpoints of interest include:

Composite endpoint of COVID-19 related MAVs (medical visits attended in person by the 
participant and a health care professional) or all cause death by Day 28

All-cause mortality by Day 28

Proportion of participants hospitalized (COVID-19 related) by Day 28

Composite endpoint of COVID-19 related hospitalization (defined as at least 24 hours of 
acute care) or all-cause death by Day 14

Composite endpoint of COVID-19 related MAVs (medical visits attended in person by the 
participant and a health care professional) or death by Day 14

Time-weighted average change in SARS-CoV-2 viral load from baseline to Day 7
The time-weighted average change from baseline to study Day 7 (DAVG7) in 
SARS-CoV-2 viral load (log10 copies/mL) is defined as the time-weighted average 
between the first postbaseline value through the last available value up to Day 7 minus 
the baseline value in SARS-CoV-2 viral load (log10 copies/mL). DAVG7 is calculated 
using the trapezoidal rule and the area-under-the-curve (AUC) concept as follows:
𝐷𝐴𝑉𝐺7 =
𝐴𝑈𝐶𝑡1―𝑡7
(𝑡7 ― 𝑡1) ― 𝑌0
The AUC between 𝑡1 and 𝑡𝑛 in a time (ie, day) versus SARS-CoV-2 viral load (log10 
copies/mL) plot is calculated as 
𝐴𝑈𝐶𝑡1―𝑡𝑛=
𝑖=1 𝑡𝑜 (𝑛―1)
1
2 (𝑌𝑖+ 𝑌𝑖+1) × (𝑡𝑖+1 ― 𝑡𝑖)
Where 𝑌𝑖 is the SARS-CoV-2 viral load (log10 copies/mL) at time 𝑡𝑖, 𝑡1 is the first 
postbaseline time, and 𝑌0 is the baseline SARS-CoV-2 viral load (log10 copies/mL). 
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For subject with SARS-CoV-2 viral load data only available up to Day 𝑥 (𝑥< 7), 
𝐷𝐴𝑉𝐺7 is defined as 
𝐷𝐴𝑉𝐺7 =
𝐴𝑈𝐶𝑡1―𝑡𝑥
(𝑡𝑥― 𝑡1) ― 𝑌0
If baseline viral load is missing or there is no post-baseline data, then the participant will 
be excluded from the analysis. If there is one post-baseline data value 𝑌𝑖, 𝐷𝐴𝑉𝐺7 = 𝑌𝑖―
𝑌0. If a participant receives additional COVID-19 treatments (see Appendix 2), the viral 
load from the start of additional treatment will be excluded.  

Time to alleviation (mild or absent) of baseline COVID-19 symptoms as reported on the 
COVID-19-adapted FLU-PRO Plus 
The alleviation of baseline COVID-19 symptoms, i.e. overall alleviation of all symptoms 
scored 1 or higher at baseline for each participant, is defined as:
■
Symptoms scored as 2 or higher at baseline are scored as 0 or 1 at postbaseline, AND
■
Symptoms scored as 1 at baseline are scored as 0 at postbaseline, AND
■
for two consecutive days. 
Time to alleviation of baseline COVID-19 symptoms is defined (in days) as: 
First Date of the two consecutive dates achieving alleviation - First dose Date + 1
If a participant has not achieved symptom alleviation at last FLU-PRO Plus assessment 
or early discontinuation of study, the participant will be censored at last FLU-PRO Plus 
assessment date. Last assessment date is the last date when at least one of the baseline 
symptoms is assessed.
Similar endpoints of time to alleviation of all symptoms or selected symptoms as reported on 
the COVID-19-adapted FLU-PRO Plus may be included. 

Worsening after alleviation of baseline COVID-19 symptoms 
The worsening after alleviation of baseline COVID-19 symptoms is defined as: 
■
For a participant who has achieved alleviation of baseline COVID-19 symptoms
■
If any symptom scored as 2 or higher at baseline is scored as 2 or higher postbaseline 
after achieved alleviation, or 
■
Any symptom scored as 1 at baseline are scored as 1 or higher postbaseline after 
achieved alleviation.

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The FAS will be the primaiy analysis set for secondaiy endpoints. The mF AS will be used for 
seconda1y endpoints of composite endpoint of COVID-19 related MA Vs or death. 
All-cause mo1iality by Day 28 will be compai·ed between the 2 treatment groups using the Fisher 
exact test. If a paiticipant prematurely discontinues from the study prior to Day 28 or the Death 
status is missing, the pa1ticipant will not be included in the analysis. 
The secondaiy endpoint of COVID-19 related hospitalization or all-cause death by Day 14, 
COVID-19 related MA Vs or death by Day 28, and COVID-19 related MA Vs or death by Day 14 
will be analyzed using the same method as used for the primaiy endpoint, described in 
Section 6.1.3. 
The propo1tion of pa1ticipants hospitalized (COVID-19 related) by Day 28 will be estimated 
using the Kaplan-Meier method and compared between the 2 ti·eatment groups using a log-rank 
test. Hazard ratio and two-sided 95% CI estimated using the Cox regression with baseline 
sti·atification factors as covai·iates will be provided. 
Number and percentage of paiiicipants progressing to requiring oxygen supplementation by Day 
28 will be summarized and compai·ed between treatment groups using the Fisher Exact test. 
Paiiicipants discontinued from the study before progressing to requiring oxygen supplementation 
will be considered as not requiring oxygen supplementation. 
The Kaplan-Meier product limit method will be used to estimate and log-rank test will be used to 
compai·e u-eatment groups for the time to alleviation of baseline COVID-19 symptoms. Hazai·d 
ratio and two-sided 95% CI estimated using the Cox regression with baseline sti·atification 
factors as covariates will be provided. Number and propo1iion of paiiicipants with worsening 
after alleviation of baseline COVID-19 symptoms will be summai·ized. 
Time-weighted average change in SARS-CoV-2 viral load from baseline to Day 7 will be 
smnmai·ized by ti·eatment groups and compai·ed between ti·eatment groups using an ANCOV A 
model with baseline viral load as covai·iate, the analysis will be based on the Virology Analysis 
Set. 
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Change from Protocol Specified Efficacy Analyses 
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The protocol states that the propo1iion of paiiicipants progressing to requiring oxygen 
supplementation by Day 28 will be estimated using the Kaplan-Meier method and compai·ed 
between the 2 treatment groups using a log-rank test In the SAP, the number and percentage of 
paiiicipants progressing to requiring oxygen supplementation by Day 28 will be summarized and 
compai·ed between treatment groups using the Fisher Exact test due to ve1y small number of 
paiiicipants progressing to requiring oxygen supplementation. 
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7.
SAFETY ANALYSES
7.1.
Adverse Events and Deaths
Safety data will be summarized for the participants in the safety analysis set. All safety data 
collected on or after the date that study drug was first dispensed through 30 days after last dose 
will be summarized by treatment group for the Safety Analysis Set, unless specified otherwise. 
All safety data will be included in data listings.
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the current version of 
MedDRA. System organ class (SOC), high-level group term (HLGT), high-level term (HLT), 
preferred term (PT), and lower-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
The severity of AEs will be graded using the Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017. For each episode, 
the highest grade attained should be reported as defined in the grading scale. The DAIDS scale is 
available at the following location:
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf
Adverse events are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 
(severe), Grade 4 (life threatening) or Grade 5 (fatal) according to toxicity criteria specified in 
the document above. The severity grade of events for which the investigator did not record 
severity will be left as “missing” for data listings.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE CRF to the 
question of “Related to Study Treatment.” Relatedness will always default to the investigator’s 
choice, not that of the medical monitor. Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.1.4.
Relationship of Adverse Events to Study Procedure
Study procedure-related AEs are those for which the investigator selected “Yes” on the AE CRF 
to the question of “Related to Study Procedures.” Events for which the investigator did not 
record relationship to study procedure will be considered as missing. No summary table for 
relationship of AE to study procedure will be presented.


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7.1.5.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if the AEs met the 
definitions of SAEs that were specified in the study protocol. SAEs captured and stored in the 
clinical database will be reconciled with the SAE database from the Gilead Global Patient Safety 
(GLPS) Department before data finalization.
7.1.6.
Treatment-Emergent Adverse Events 
Proportion of participants with treatment-emergent AEs (TEAEs) is the primary safety endpoint 
of the study. No statistical comparison will be provided for proportion of participants with 
TEAE.
7.1.6.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the study drug start date and no later than 30 days 
after permanent discontinuation of study drug

Any AEs leading to premature discontinuation of study drug.
7.1.6.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The AE onset date is the same as or after the month and year (or year) of the first dosing date 
of study drug, and

The AE onset date is the same as or before the month and year (or year) of the date 
corresponding to 30 days after the date of the last dose of study drug 
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of study drug, or with the onset date missing and the AE is 
marked as ongoing, will be considered to be treatment emergent. In addition, an AE with the 
onset date missing and incomplete stop date with the same or later month and year (or year alone 
if month is not recorded) as the first dosing date of study drug will be considered treatment 
emergent.


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7.1.7.
Summaries of Adverse Events and Deaths
Treatment-emergent AEs will be summarized based on the Safety Analysis Set.
The number and percentage of participants who experienced at least 1 TEAE will be provided 
and summarized by SOC, High lever term (HLT), PT, and treatment group.  For other AEs 
described below, summaries will be provided by system organ class, PT, and treatment group: 

Grade 3 or higher treatment-emergent AEs

All treatment-emergent study drug-related AEs

Grade 3 or higher treatment-emergent study drug-related AEs

All treatment-emergent SAEs

All treatment-emergent study drug-related SAEs

All treatment-emergent AEs that caused premature discontinuation from study drug 
TEAE and study drug related TEAE will summarized by system organ class, PT, Severity and 
treatment group.
A brief, high-level summary of the number and percentage of participants who experienced at 
least 1 TEAE in the categories described above, and treatment emergent deaths will be provided 
by treatment group. Treatment-emergent death refers to deaths that occurred between the first 
dose date and the last dose date plus 30 days (inclusive).
Multiple events will be counted only once per participant in each summary. Adverse events will 
be summarized and listed first in alphabetic order of SOC and HLT within each SOC 
(if applicable), and then by PT in descending order of total frequency within each SOC. For 
summaries by severity grade, the most severe grade will be used for those AEs that occurred 
more than once in an individual participant during the study. 
In addition to the above summary tables, all treatment-emergent AEs, treatment-emergent AEs 
with Grade 3 or higher, treatment-emergent study drug-related AEs, and treatment-emergent 
study drug-related AEs with Grade 3 or higher, will be summarized by PT only, in descending 
order of total frequency.
In addition, data listings will be provided for the following:

All AEs

Study-Drug-Related AEs 

AEs with severity of Grade 3 or higher

SAEs


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
Study-Drug-Related SAEs 

Deaths

AEs leading to premature discontinuation of study drug
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected up to the last dose of study drug plus 30 days. 
The analysis will be based on values reported in conventional units. When values are below the 
LOQ, they will be listed as such, and the closest imputed value will be used for the purpose of 
calculating summary statistics as specified in Section 3.7.. SAR-COV-2 PCR result of 
“Inconclusive” will not be included in numeric summary and will be considered as not negative 
result  for PCR negative confirmation. 
A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, coagulation, and serum chemistry separately. Values falling 
outside of the relevant reference range and/or having a severity grade of 1 or higher on the 
DAIDS Grading Scale will be flagged in the data listings, as appropriate.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for each laboratory test specified in the 
study protocol as follows:

Baseline values 

Values at each postbaseline analysis window

Change from baseline at each postbaseline analysis window

Percentage change from baseline to each postbaseline analysis window (if specified)
A baseline laboratory value will be defined as the last nonmissing measurement obtained on or 
prior to the date/time of first dose of study drug. Change from baseline to a postbaseline visit will 
be defined as the visit value minus the baseline value. The mean, median, Q1, Q3, minimum, and 
maximum values will be displayed to the reported number of digits; SD values will be displayed 
to the reported number of digits plus 1.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.


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7.2.2.
Graded Laboratory Values
The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Event, Version 2.1 
(July 2017) will be used for assigning toxicity grades (0 to 4) to laboratory results for analysis. 
Grade 0 includes all values that do not meet the criteria for an abnormality of at least Grade 1. 
For laboratory tests with criteria for both increased and decreased levels, analyses for each 
direction (i.e., increased, decreased) will be presented separately. 
For baseline, if both local lab and central lab results are available, central lab results will be 
selected first for baseline toxicity grade, local lab results will be used when central lab results are 
missing. 
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last 
dose of study drug plus 30 days. If the relevant baseline laboratory value is missing, any 
abnormality of at least Grade 1 observed within the time frame specified above will be 
considered treatment emergent with the exception of Glucose (See Appendix 2 for details.)
7.2.2.2.
Summaries of Laboratory Abnormalities
Laboratory data that are categorical will be summarized using the number and percentage of 
participants in the study with the given response at baseline and each scheduled postbaseline 
visit.
The following summaries (number and percentage of participants) for treatment-emergent 
laboratory abnormalities will be provided by lab test and treatment group; participants will be 
categorized according to the most severe postbaseline abnormality grade for a given lab test:

Treatment-emergent laboratory abnormalities

Treatment-emergent Grade 3 or 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of participants 
with nonmissing postbaseline values up to 30 days after last dosing date.
A by-subject listing of all treatment-emergent laboratory analyses and treatment-emergent 
Grade 3 or 4 laboratory abnormalities will be provided by subject ID number and visit in 
chronological order. 
Abnormalities in coagulation parameters will be graded for international normalized ratio (INR) 
and aPTT.


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For the international normalized ratio (INR) of prothrombin time (PT) and aPTT, protocol 
specified toxicity grading scale depends on the upper limit of normal range (ULN). While the 
ULN of INR and aPTT depends on whether the subject is taking anticoagulant medication or not 
(ie, Not taking oral anticoagulant: 0.8 – 1.2; Taking oral anticoagulant: 2.0 – 3.0), this 
information is not collected by the reference laboratory. As a result, INR and aPTT will be 
graded by assuming subject is not taking an oral anticoagulant, which is a conservative approach 
that may lead to over-reporting of abnormalities for INR and aPTT.
7.3.
Body Weight, Vital Signs and Respiratory Status
Descriptive statistics will be provided by treatment group for body weight and vital signs 
(including heart rate, respiratory rate on room air and blood pressure) as follows:

Baseline value

Values at each postbaseline analysis window for rate respiratory rate on room air or at each 
timepoint for heart rate and blood pressure

Change from baseline at each postbaseline analysis window for rate respiratory rate on room 
air or at each timepoint for heart rate and blood pressure
Similar descriptive statistics will be provided by treatment group for SpO2 on room air.
Two types of baseline will be defined for vital signs. An overall baseline value will be defined as 
the last available value collected on or prior to the date/time of first dose of study drug. Day 1 
pre-dose baseline is defined the same as the overall baseline. A pre-dose baseline per day for 
each of dosing days 2-3 will use the “Pre-infusion” record on that day as baseline. Change from 
overall baseline to a postbaseline visit and change from pre-dose baseline for dosing days will be 
defined as the postbaseline value minus the respective baseline value. 
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3. No formal statistical testing is planned.
A by-subject listing of body weight, BMI, vital signs (including heart rate, temperature, and 
blood pressure), and respiratory status (including respiratory rate and SpO2) will be provided by 
subject ID number and visit in chronological order. 
7.4.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the Gilead-modified World Health Organization (WHO) Drug dictionary.
Concomitant medications are defined as medications taken while a participant took study drug. 
Use of concomitant medications will be summarized by preferred name using the number and 
percentage of participants for each treatment group. A participant reporting the same medication 
more than once will be counted only once when calculating the number and percentage of 
participants who received that medication. The summary will be ordered by preferred term in 


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descending overall frequency. For drugs with the same frequency, sorting will be done 
alphabetically.
For the purposes of analysis, any medications with a start date prior to or on the first dosing date 
of study drug and continued to be taken after the first dosing date, or started after the first dosing 
date but prior to or on the last dosing date of study drug will be considered concomitant 
medications. Medications started and stopped on the same day as the first dosing date or the last 
dosing date of study drug will also be considered concomitant. Medications with a stop date prior 
to the date of first dosing date of study drug or a start date after the last dosing date of study drug 
will be excluded from the concomitant medication summary. If a partial stop date is entered, any 
medication with the month and year (if day is missing) or year (if day and month are missing) 
prior to the date of first study drug administration will be excluded from the concomitant 
medication summary. If a partial start date is entered, any medication with the month and year 
(if day is missing) or year (if day and month are missing) after the study drug stop date will be 
excluded from the concomitant medication summary. Medications with completely missing start 
and stop dates will be included in the concomitant medication summary, unless otherwise 
specified. Summaries will be based on the Safety Analysis Set. No formal statistical testing is 
planned.
7.5.
Other Safety Measures
A data listing will be provided for participants experiencing pregnancy during the study.
7.6.
Changes from Protocol-Specified Safety Analyses
There are no deviations from the protocol-specified safety analyses.


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9.
REFERENCES
Gottlieb RL, Nirula A, Chen P, Boscia J, Heller B, Morris J, et al. Effect of Bamlanivimab as 
Monotherapy or in Combination With Etesevimab on Viral Load in Patients With 
Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA 2021.
Muller HH, Schafer H. A general statistical principle for changing a design any time during the 
course of a trial. Stat Med 2004;23 (16):2497-508.


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10.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.
Phoenix WinNonlin® 8.2. Pharsight Corporation, Princeton, NJ, USA.


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11.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision


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12.
APPENDICES
Appendix 1.
Study Procedures Tablea
Appendix 2.
Programming Specifications


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Appendix 1. 
Study Procedures T able3 
Baseline/ 
Screening 
Day I 
Written Infom1cd Consent 
X 
Medical Historl 
X 
Complete Physical Examination< 
X 
X 
Clinical Symptom-Directed Physical Examinationd 
Height 
X 
Yitai Signs' and Weight 
X 
xr 
Respiratory Statuss 
X 
X 
ALT, AST, Scrum Creatininc, and Creatininc 
X 
Clearnnce/eGFRh 
Chemistryi, Hematologyi, and Coagulationl Panels 
X 
Urine Pregnancy Test"' 
X 
SARS-CoV-2 RT-qPCR Testing and Potential Resistance 
X 
Testing" 
Study Drug Dosing 
X 
Adverse Event and Concomitant Medications 
X 
X 
Day 7 
Day 2 
Day 3 
(± I day) 
X 
X 
X 
xr 
xr 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Day 14 
(± I day) 
X 
X 
X 
X 
X 
X 
Version 1.0 
Final 
Day 28' 
Follow-up 
(± 5 days) 
X 
X 
X 
X 
a 
Study visits may be pe1fo1med in an outpatient setting, at the pa,ticipant's home via tele-health, virtually or remotely, as pennitted by local and institutional regulations. The 
Day 28 visit may be performed via a phone call. 
b 
Medical history will include the date of first symptoms, overall symptoms, exposure sotu·ce, demographics, baseline characteristics, allergies and all other medical histo,y. 
c 
A complete physical exaniination must include sotu·ce documentation of general appearance and the following body systems: Head, neck, and thyroid; eyes, ears, nose, throat, 
mouth, and tongue; chest (excluding breasts); respiratory; cardiovascular; lymph nodes, abdomen; skin, hair, nails; musculoskeletal; and netu·ological. Urogenital and 
reproductive exaniination should only be completed if clinically indicated. 
d 
Clinical symptom-directed physical exaniination will include at least cardiac and respirato,y evaluation. 
e 
Vital signs include heart rate, temperature, and blood pressm·e. 
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m 
n I 
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r 
s 
t 
On Days 1, 2 and 3, vital signs to be completed pre-infusion, postinfusion, and when postinfusion observation is completed; weight from Screening may be used at Days 1-3. 
Respirntory status includes respirntory rate and SpO2 on room air. 
Obtain ALT (and AST where available), senun creatinine, and creatinine clearance (calculated using Cockcroft-Gault or Schwa1tz fonuula; see Protocol Section 6.7.2) if not 
available within 90 days of screening, using a local laboratory. 
Chemistty: alkaline phosphatase, AST, ALT, total bilimbin, total protein, albumin, lactate dehydrogenase, creatine phosphokinase, bicarbonate, blood urea nih'ogen, calcium, 
chloride, creatinine, glucose, lipase, magnesitun, phosphoms, potassitun, soditun, m-ic acid. 
Hematology: Complete blood count with differential. 
Coagulation: 
PT aPTT 
1 resistance testing. 
. 
eluding hospitalization; in-person 
emergency, m·gent, or primary care visits; or any other in-person visit attended by the pa1ticipant and a health care profession. Identify the nattu·e and cause of the visit. 
FLU-PRO Plus questionnaire should be completed daily from Day 1 through Day 14 (if available). 
Only AEs, symptom assessment, medically attended visit info=tion, and concomitant medications review are needed if the visit is done by phone. 
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Appendix 2.
Programming Specifications
1) If the age from the Day 1 eCRF is not available, age will be calculated as follows:
Only year is provided for the date of birth (DOB). Use July 1 for the month and day.
a) AGE (years) is calculated from the number of days between the DOB and Study Day 1,
b) Use the SAS INTCK function to determine the number of “1st-of-month days” 
(eg, January 1st, February 1st, March 1st) between DOB and Day 1 (inclusive),
c) Divide the result in (b) by 12,
AGE = the integer of the result in (c),
Age for laboratory test reference range will be based on the age at the sample collection 
date.
2) All screened participants refer to all participants who are screened (ie, with non-missing 
screening date) and have a screening number. For summaries the same participant is counted 
only once.
3) Screen failure participants are the participants who were screened and answered “No” for any 
inclusion criteria or “Yes” for any exclusion criteria regardless of which version of protocol 
the participant was consented to.
4) Participants in the randomized analysis set are defined as participants randomized into the 
study. IXRSRAND is the source to determine whether the subject is randomized (ie, 
participant with non-missing RGMNDTN in the IXRSRAND dataset), and confirmed by the 
eCRF ENROLL dataset (ie, ENROLLYN = “Yes” in ENROLL dataset).
5) Randomized treatment (ie, TRT01P in ADSL) is derived from IXRSRAND, while actual 
treatment received (ie, TRT01A in ADSL) is assigned as the randomized treatment if 
participant took at least 1 dose of study drug and assigned as blank if the participant was 
never dosed.
6) In the disposition table, the reasons for premature discontinuation are displayed in the order 
as they appear on the eCRF.
7) Body mass index (BMI) 
BMI will be calculated only at baseline as follows:
BMI = (weight [kg]) / (height [meters]2)
Baseline height and weight will be used for this calculation if available.


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8) For demographics tables, “Not Permitted” will be excluded from percentage for detailed race 
categories summary (i.e. race categories collected on eCRF). For combined Race Category 
(e.g. Asian, White, Black, Other), “Not Permitted” is included in “Other” and “Other” will be 
include in the count of percentage. 
9) TEAE
Events with Missing Onset Day and/or Month
An event is considered treatment emergent if all of the following 3 criteria are met:
i.
The month and year (or year) of onset date is the same as or after the month and year 
(or year) of the first dose of study drug, and
ii.
The month and year (or year) of the onset date is the same as or before the month and 
year (or year) of the 30th day after the date of the last dose of study drug, and
iii.
End date is as follows: 
The (complete) end date is on or after the first dose date, or
The month and year (or year) of end date is the same or after the month and year 
(or year) of the first dose of study drug, or
End date is completely missing 
Events with Completely Missing Onset Date
An AE with a completely missing onset date is defined as TEAE if end date meets any of the 
3 criteria specified above.
10) The precision in reporting numerical values should be as follows:
Raw measurements will be reported the same as the data captured electronically or on the 
eCRF for all but hematology and chemistry values.
Standard deviation and standard error will be reported to one more significant decimal place 
than the raw measurement.
Mean, median, minimum, Q1, Q3, and maximum will be reported to the same number of 
decimal places of the raw measurements. 
Exceptions may be considered; for example, if more than 4 significant digits are provided for 
the measurement.


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Precision for derived parameters as follows:
Parameters
Decimal Places
log 10 of SARS-CoV-2 viral load
2
Time-weighted average change in SARS-CoV-2 viral load
2
BMI
2
11) Last dose date is not expected to be missing. However, if last dose date is missing, it will be 
imputed using the maximum of non-missing, non-zero dose, study drug start and stop dates.
12) Incomplete death dates will be imputed as the maximum of the study drug start dates, study 
drug end dates , clinic or phone visit dates (lvis28dt), laboratory visit dates (llab28dt), 
including the 28-day follow-up visit date plus 1.
13) Censoring rules
Time to hospitalization/death: If a participant prematurely discontinues from the study prior 
to Day 28 or the hospitalization status is missing, the participant is censored at last study date 
or day 28 whichever is earlier.
Time to negative SARS-CoV-2 viral load, participants are censored at the last assessment 
day and participants are required to have at least one postbaseline assessment.
Time to alleviation of baseline COVID-19 symptoms: 
■
For overall baseline symptom alleviation, participants are censored at the last 
assessment day that at least one of the baseline symptoms was assessed. For baseline 
symptom alleviation for each domain, participants are censored at the last assessment 
day that at least one of the baseline symptoms within that domain was assessed
14) Graded Laboratory Abnormalities Summary
The following labels will be used for laboratory abnormalities and Grade 3 or 4 laboratory 
abnormalities summary tables and listings:
CCI


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Battery
Lab Test Label Used in 
l-labtox Listing
Toxicity 
Direction
Lab Test Label Used in 
t-labtox Table
Hemoglobin
Decrease
Hemoglobin (Decreased)
Lymphocytes
Decrease
Lymphocytes (Decreased)
Hematology
Neutrophils
Decrease
Neutrophils (Decreased)
Platelets
Decrease
Platelets (Decreased)
WBC
Decrease
WBC (Decreased)
Albumin
Decrease
Albumin (Decreased)
Alkaline Phosphatase
Increase
Alkaline Phosphatase (Increased)
ALT
Increase
ALT (Increased)
AST
Increase
AST (Increased)
Bicarbonate
Decrease
Bicarbonate (Decreased)
Corrected Calcium
Increase
Corrected Calcium (Hypercalcemia)
Corrected Calcium
Decrease
Corrected Calcium (Hypocalcemia)
Creatine Kinase (CK)
Increase
Creatine Kinase (Increased)
Creatinine
Increase
Creatinine (Increased)
Creatinine Clearance 
Decrease
Creatinine Clearance (Decreased)
Lipase
Increase
Lipase (Increased)
Chemistry
Magnesium
Decrease
Magnesium (Hypomagnesemia)
Phosphate
Decrease
Phosphate (Hypophosphatemia)
Serum Glucose (Fasting)
Increase
Serum Glucose (Fasting, Hyperglycemia)
Serum Glucose (Nonfasting)
Increase
Serum Glucose (Nonfasting, Hyperglycemia)
Serum Glucose 
Decrease
Serum Glucose ( Hypoglycemia)
Serum Potassium
Increase
Serum Potassium (Hyperkalemia)
Serum Potassium
Decrease
Serum Potassium (Hypokalemia)
Serum Sodium
Increase
Serum Sodium (Hypernatremia)
Serum Sodium
Decrease
Serum Sodium (Hyponatremia)
Total Bilirubin
Increase
Total Bilirubin (Hyperbilirubinemia)
Uric Acid
Increase
Uric Acid (Hyperuricemia)
Prothrombin Intl. 
Normalized Ratio (INR)
Increase
Prothrombin Intl. Normalized Ratio (Increased)
Coagulation
Activated partial 
thromboplastin time (aPTT)
Increase
Activated partial thromboplastin time 
(Increased)
15) SAS code for ANCOVA:
ods output ParameterEstimates=out1 LSMeans=out2 LSMeanCL=out3 
LSMeanDiffCL=out4; 
proc glm data=dat1 plots=none;
  class trt01pn;
  model DAVG = trt01pn base / solution;
  lsmeans trt01pn / stderr cl pdiff;
  run;


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ods output close; quit;
16) Symptom scores in the FLU-PRO questionnaire raw data start from 1 to n (total number of 
responses in a question), in the FLU-PRO user manual, symptom scores start from 0. In the 
analysis dataset, symptom scores will be re-mapped to match the scoring in the FLU-PRO 
user manual for proper calculation of total score and domain score. 
17) FLU-PRO Total Score and Domain Score:
The presence and severity of influenza signs and symptoms are assessed across 7 body systems: 
Nose (4 items), Throat (3 items), Eyes (3 items), Chest/Respiratory (7 items), 
Gastrointestinal (4 items), Body/Systemic (11 items), and Sense (2 itmes). For 29 of the items, 
the severity scale is as follows: 0 (“Not at all), 1 (“A little bit”), 2 (“Somewhat”), 
3 (“Quite a bit”), and 4 (“Very much”). For 5 items, severity is assessed in terms of frequency, 
i.e., vomiting or diarrhea (0 times, 1 time, 2 times, 3 times, or 4 or more times); with frequency 
coughed up mucus or phlegm evaluated on a scale from 0 (“Never”) to 4 (“Always”). For 
2 items, severity is assessed as 0 (“No”) or 1 (“Yes”).
Domain 
Items 
Scoring 
Minimum Data 
Requirement 
Nose 
Runny or dripping nose 
Congested or stuffy nose 
Sneezing 
Sinus pressure 
Arithmetic mean of 4 items 
within Nose domain 
Daily score for 3 of 4 items 
must be present to 
calculate domain score 
Throat 
Scratchy or itchy throat 
Sore or painful throat 
Difficulty swallowing 
Arithmetic mean of 3 items 
within Throat domain 
Daily score for 2 of 3 items 
must be present to 
calculate domain score 
Eyes 
Teary or watery eyes 
Sore or painful eyes 
Eyes sensitive to light 
Arithmetic mean of 3 items 
within Eyes domain 
Daily score for 2 of 3 items 
must be present to 
calculate domain score 
Chest/Respiratory 
Trouble breathing 
Chest congestion 
Chest tightness 
Dry or hacking cough 
Wet or loose cough 
Coughing 
Coughed up mucus or 
phlegm 
Arithmetic mean of 7 items 
within Chest/Respiratory 
domain 
Daily score for 5 of 7 items 
must be present to 
calculate domain score 
Gastrointestinal 
Felt nauseous 
Stomach ache 
How many times did you 
vomit? 
How many times did you 
have diarrhea? 
Arithmetic mean of 4 items 
within Gastrointestinal 
domain 
Daily score for 3 of 4 items 
must be present to 
calculate domain score 
Body/Systemic 
Headache 
Head congestion 
Felt dizzy 
Lack of appetite 
Sleeping more than usual 
Arithmetic mean of 
11 items within 
Body/Systemic domain 
Daily score for 8 of 
11 items must be present to 
calculate domain score 


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Domain 
Items 
Scoring 
Minimum Data 
Requirement 
Body aches or pains 
Weak or tired 
Chills or shivering 
Felt cold 
Felt hot 
Sweating 
Sense*
Loss Smell
Loss Taste
Arithmetic mean of 2 items 
within Sense domain
Daily score for 1 of 2 items 
must be present to 
calculate domain score
Total 
All above 34 items 
Arithmetic mean of all 
34 items within FLU-PRO 
In the presence of missing 
data, the above conditions 
for the calculation of all 
domain scores must be met 
in order to calculate the 
FLU-PRO total score. 
*
Added for COVID-19
18) Symptom alleviation and time to baseline symptom alleviation
1. Baseline symptoms: Baseline symptoms are the symptoms collected prior to dosing and 
score ≥1. 
■
Item 1 to 34 of the FLUPRO are symptoms.  Global assessments (last 6 items in the 
questionnaire) are not symptoms.
■
Each subject's baseline symptoms including number of symptoms likely are different. 
■
For alleviation of baseline symptoms, only need to follow the symptoms presented 
(≥1) at baseline
○
If a participant has 5 baseline symptoms, only the 5 symptoms will be followed to 
derive alleviation.
○
If a symptom (e.g. coughing) is not one of the baseline symptoms and has a score 
>1 post baseline, the symptom will be not considered to derive the subject's 
baseline symptom alleviation. 
○
If participant has not symptom ≥1 at baseline, alleviation status for the participant 
is missing for all visit. 
○
Baseline symptoms ≥1, symptoms from Day 2 and later are all missing, the 
alleviation status for the symptom is missing for all visits.
2. Alleviation of a symptom: 
■
Symptom scored as 2 or higher at baseline are scored as 0 or 1 at postbaseline
■
Symptom scored as 1 at baseline are scored as 0 at postbaseline


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■
for two consecutive days - need to be confirmed with 2 visits
○
one missing day between two visits (that meets the alleviation definition) is 
allowed, but 2 or more days of missing is not considered reach alleviation
○
for Day 14 (or last assessment on Day x), if the symptom meets definition of 
alleviation, and day 13 (or Day x -1) also meets the definition of alleviation, then 
it is considered as confirmed. One missing day is allowed for the confirmation of 
Day 14 or last assessment, i.e if day 13 (or Day x-1 ) is missing and Day 12 (or 
Day x-2) meets the definition of alleviation, then it is considered as confirmed. 
Examples:
Day 
Alleviation for 
a symptom on 
day 
Example
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1
2
2
2
1
1
1
0
0
0
0
0
0
0
0
4
baseline 2 or higher 
needs to be 1 or 0
2
2
2
2
0
1
1
0
0
0
0
0
0
0
0
4
baseline 2 or higher 
needs to be 1 or 0
3
2
2
2
0
2
1
1
0
0
0
0
0
0
0
6
day 4 is not confirmed
4
3
2
2
1
1
1
0
2
1
1
0
0
0
0
4
still on day 4 if worsen 
after confirmation
5
1
1
1
0
0
0
1
0
1
1
0
0
0
0
4
Worsening on day7
6
1
1
1
1
0
0
0
0
0
0
0
0
0
0
5
baseline 1 needs to be 0
7
2
2
2
1
.
1
0
0
0
0
0
0
0
0
4
allow one missing 
8
2
2
2
1
.
.
1
1
.
0
0
0
0
0
7
day 4 is not confirmed 
if there are two or more 
days’ response missing, 
re-start the check for 
confirmation
9
2
2
2
2
2
2
2
2
4
2
2
2
2
1
14
censor
10
2
2
2
2
2
2
2
2
2
2
2
2
1
.
13
censor
11
2
2
2
2
2
2
2
2
2
2
2
2
1
1
13
Confirmed on day 13 
and 14
12
2
2
2
2
2
2
2
2
1
.
.
.
.
.
9
censor
13
2
2
2
2
2
2
2
2
1
1
.
.
.
.
9
Confirmed on day 9 
and 10
Yellow - Confirmed alleviation, Tan -  Not confirmed, Blue - Worsening
3. Alleviation of baseline symptoms for a participant
The alleviation status for a participant at each visit is 
■
Yes, if all confirmed baseline symptom alleviation status are Yes.
■
if > 25% of symptoms are missing, then alleviation status is No, else ignore missing.
■
No, if any baseline symptom alleviation status is No.


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4. Tim to alleviation of baseline symptoms
First day of participant level alleviation status equals Yes.  If a participant has not achieved 
symptom alleviation at last FLuPRO assessment, the participant will be censored at the date of 
last FLUpro assessment. For symptom alleviation of a domain, the last assessment date is only 
among those baseline symptoms within the domain. 
19) Covid-19 medications include: 
Chloroquine, Hydroxychloroquine, IV remdesivir, Bamlanivimab, Casirivimab/Imdevimab, 
Molnupiravir, Lopinavir-ritonavir, Ribavirin.  Details of COVID-19 medications are provided in 
table below. 
Drug name
ATC Code
WHODRUG Preferred Term
Chloroquine
P01BA
CHLOROQUINE
Hydroxychloroquine
P01BA
HYDROXYCHLOROQUINE
Lopinavir/ritonavir
J05AR
LOPINAVIR/RITONAVIR
Ribavirin
J05AP
RIBAVIRIN
Remdesivir
J05AB
REMDESIVIR
Bamlanivimab
--
BAMLANIVIMAB
Casirivimab/Imdevimab
--
CASIRIVIMAB/IMDEVIMAB
Molnupiravir
--
MOLNUPIRAVIR
ATC = anatomical therapeutic chemical
Additional medication may be included during final review of Concomitant medications prior to 
data finalization.
20) Baseline risk factor
Selected medical history will be summarized as baseline risk factor and be included as subgroups 
in analysis.  A risk factor for a participant is defined as a medical history of one of these 
diseases:
At least 1 ongoing medical history record with MedDRA PT (mh.MDRPT) in the 
following selected PT listing for the corresponding disease with start date on or prior to 
the first dose date. 
At least 1 ongoing AE record with MedDRA PT (ae.MDRPT) in the following selected 
PT listing for the corresponding disease with start date on or prior to the first dose date 
If the start date is incomplete but the month and year (or year alone) of the start date is the same 
as or before the month and year (or year alone) of the first dosing date of study drug, the event 
will be included. If the start date is completely missing, the event will be included.


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A variable for each of the risk factors will be added to raw Medical History and Adverse Events 
datasets. A medical history or an AE record will be flagged for a risk factor if its MedDRA PT 
included in the prespecified PT list for the corresponding disease of interest, which include all 
PTs from the narrow or broad search of the following SMQs under MedDRA 24.0 provided by 
Gilead GLPS and reviewed by Gilead medical monitors.
Disease of Interest
SMQ or MedDRA HLT Source
Chronic lung disease
HLT of bronchospasm and obstruction
Hypertension
Hypertension (SMQ)
Cardiovascular or 
cerebrovascular disease
Ischaemic central nervous system vascular conditions (SMQ); Myocardial 
infarction (SMQ);
Other ischaemic heart disease (SMQ)
Diabetes mellitus
Hyperglycaemia/new onset diabetes Mellitus (SMQ)  
Immunocompromised state
HLGT for “Immunodeficiency syndromes”
Chronic mild or moderate 
kidney disease
Chronic kidney disease (SMQ)   
Chronic liver disease
search name “Chronic liver disease excluding transient_acute events and 
nonspecific signs_symptoms
Current cancer  
Malignancies (SMQ)
Sickle cell disease
HLGT “Haemoglobinopathies”
Risk factor of obesity will be defined as BMI >=30 kg/m^2 at baseline based on CRF data. 
21) Common COVID-19 symptoms at baseline:  
Common COVID-19 symptoms at baseline for each symptom will be considered as present if 
any of the corresponding FLU-PRO questionnaire items score 1 or higher at baseline.  
Common COVID-19 symptoms
FLU-PRO questionnaire item
Stuffy or runny nose
Runny or dripping nose
Congested or stuffy nose
 Sore throat
Sore or painful throat
 Shortness of breath (difficulty breathing)
Trouble breathing
 Cough
Coughing
 Low energy or tiredness
Weak or tired
 Muscle or body aches
Body aches or pains
 Headache
Headache
 Chills or shivering
Chills or shivering
 Feeling hot or feverish
Felt hot


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 Nausea
Felt nauseous (feeling like you wanted to throw-up)
 Vomit
How many times did you vomit?
 Diarrhea
How many times did you have diarrhea?
 Loss of Smell
Loss of smell
 Loss of taste
Loss of taste
22) SpO2 and respiration rate:  - 
Summary of SpO2 and respiration rate will include measurements obtained while 
participants are on room air.  SpO2 and respiration rate obtained while participants are on 
supplemental oxygen will be listed.
23) Glucose:  
Fasting is not required per protocol for collecting Glucose sample, mixed fasting Glucose 
and non-fasting Glucose results are presented in the dataset.  Lab abnormality for 
Glucose will be summarized as follows:
○
if fasting glucose is collected at baseline, max TE lab toxicity grade is selected for 
post-baseline fasting glucose, max post-baseline toxicity grade (i.e. not TE 
toxicity grade) is selected for the post-baseline glucose regardless of fasting 
status.
○
if non-fasting glucose is collected at baseline, TE lab toxicity grade is selected for 
post-baseline non-fasting glucose, max post-baseline toxicity grade is selected for 
the post-baseline glucose regardless of fasting status.
○
Max TE lab toxicity grade for fasting glucose and non-fasting glucose, max 
post-baseline toxicity grade for fasting glucose and non-fasting glucose will be 
summarized separately for Hyperglycemia, and Serum Glucose (regardless fasting 
or non-fasting status) for Hypoglycemia in the lab abnormality summary table.
○
In the any TE lab toxicity section of the lab abnormality table, max post-baseline 
toxicity grade will be included. 
24) SARs-CoV2 PCR data
a) For numeric SARS-CoV2 summary (e.g, mean viral load, change from baseline etc.), 
“Inconclusive” SARs-CoV2 result is set to missing. 
b) For categorical SARS-CoV2 summary, 3 categories will be included if appropriate, i.e. 
Positive, Inconclusive, Negative.
i)
Positive = any numeric result or “<LLOQ SARSCoV2 detected” - LLOQ could vary 
by sample type


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ii) Negative = “No SARS-CoV2 detected”
iii) Inconclusive = “Inconclusive” 
c) For Negative SARS-CoV2 confirmation, “Inconclusive” SARs-CoV2 result will not be 
considered as missing thus a “Negative” followed by a “Inconclusive” is NOT confirmed. 
d) 2 negative results from the same day do not equal confirmation.
e) if last PCR sample is negative for participants completed the study or for participant 
withdrawn early from the study, then one negative PCR of last sample is considered as 
confirmed negative.
f)
Categorical SARS-CoV2 and SARS-CoV2 negative summary will be separated out by 
sample type. There will be no combined Positive or negative category using 2 or more 
sample types.
25)  SAS code for Cox model with Covariates
proc phreg;
class trt01p (ref="Placebo to match RDV") strat1 strat2 strat3;
model aval*cnsr(1) = trt01p strat1 strat2 strat3 /risklimits = wald;
ods output  ParameterEstimates=Est1 ModelANOVA = pvout1;
run;
Hazard ratio is the hazardratio, 95% Cis are HRLowerCL and HRUpperCL where Parameter = “TRT01P” from 
EST1 dataset;   P-value is ProbChiSq where Effect = “TRT01P” from pvout1 dataset.


GS-US-540-9012 SAP final analysis v1.0
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
12-Aug-2021
20:53:51
Clinical Research eSigned 13-Aug-2021
11:55:23
Clinical Pharmacology
eSigned
13-Aug-2021
17:22:10
PPD
PPD
PPD--