A Phase 3 Randomized Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants With Moderate COVID-19 Compared to Standard of Care Treatment
Phase: PHASE3
Conditions: COVID-19
Sponsor: Gilead Sciences

CLINICAL STUDY PROTOCOL
Study Title:
A Phase 3 Randomized Study to Evaluate the Safety and Antiviral 
Activity of Remdesivir (GS-5734™) in Participants with Moderate 
COVID-19 Compared to Standard of Care Treatment
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
147753
2020-000842-32
NCT04292730
Indication:
COVID-19
Protocol ID:
GS-US-540-5774
Contact Information:
The medical monitor name and contact information will be 
provided on the Key Study Team Contact List.
Protocol 
Version/Date:
Original:
24 February 2020
Amendment 1.0
15 March 2020
Amendment 2.0
29 April 2020
This study will be conducted under US Food & Drug Administration IND regulations 
(21 CFR 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The information contained in this document, particularly unpublished data, is the property or 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-TEXT TABLES........................................................................................................................................4
PROTOCOL SYNOPSIS ..............................................................................................................................................5
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS....................................................................10
1.
INTRODUCTION ..............................................................................................................................................12
1.1.
Background ............................................................................................................................................12
1.2.
Remdesivir (RDV, GS-5734).................................................................................................................12
1.2.1.
General Information .............................................................................................................13
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................13
1.3.
Rationale for This Study ........................................................................................................................13
1.4.
Rationale for Dose Selection of Remdesivir ..........................................................................................14
1.4.1.
Pediatric Dosing ...................................................................................................................15
1.5.
Risk/Benefit Assessment for the Study..................................................................................................16
1.6.
Compliance ............................................................................................................................................17
2.
OBJECTIVES.....................................................................................................................................................18
3.
STUDY DESIGN................................................................................................................................................19
3.1.
Endpoints ...............................................................................................................................................19
3.2.
Study Design..........................................................................................................................................20
3.3.
Study Treatments ...................................................................................................................................21
3.4.
Duration of Treatment............................................................................................................................21
3.5.
Discontinuation Criteria.........................................................................................................................21
3.6.
End of Study...........................................................................................................................................22
3.7.
Post Study Care......................................................................................................................................22
4.
SUBJECT POPULATION..................................................................................................................................23
4.1.
Number of Subjects and Subject Selection ............................................................................................23
4.1.1.
Subject Replacement............................................................................................................23
4.2.
Inclusion Criteria....................................................................................................................................23
4.3.
Exclusion Criteria...................................................................................................................................23
5.
INVESTIGATIONAL MEDICINAL PRODUCTS ...........................................................................................25
5.1.
Randomization, Blinding, and Treatment Codes Access .......................................................................25
5.1.1.
Randomization .....................................................................................................................25
5.1.2.
Blinding................................................................................................................................25
5.2.
Description and Handling of Remdesivir...............................................................................................25
5.2.1.
Formulation..........................................................................................................................25
5.2.2.
Packaging and Labeling .......................................................................................................25
5.2.3.
Storage and Handling...........................................................................................................25
5.3.
Dosage and Administration of Remdesivir ............................................................................................26
5.4.
Accountability for Investigational Medicinal Product ...........................................................................26
5.4.1.
Investigational Medicinal Product Return or Disposal.........................................................26
5.5.
Prior and Concomitant Medications.......................................................................................................27
6.
STUDY PROCEDURES ....................................................................................................................................28
6.1.
Subject Enrollment and Treatment Assignment.....................................................................................28
6.2.
Pretreatment Assessments......................................................................................................................28
6.2.1.
Screening Visit .....................................................................................................................28

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6.2.2.
Baseline/Day 1 Assessments................................................................................................29
6.3.
Daily Study Assessments (Days 2-14) ...................................................................................................30
6.4.
Additional Assessments .........................................................................................................................30
6.5.
Day 28 Follow up Assessment (± 5 Days).............................................................................................31
6.6.
Clinical Laboratory Assessments ...........................................................................................................31
6.7.
Physical Examination.............................................................................................................................32
6.9.
Ordinal Scale..........................................................................................................................................32
6.10.
Post-treatment Assessments ...................................................................................................................33
6.11.
Assessments for Early Discontinuation from Study...............................................................................33
6.11.1.
Criteria for Discontinuation of Study Treatment..................................................................33
6.12.
End of Study...........................................................................................................................................34
6.13.
Post Study Care......................................................................................................................................34
6.14.
Sample Disposition and Storage (Non-PK Samples) .............................................................................34
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 ........................................................................................................37
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
7.3.4.
Electronic Serious Adverse Event (eSAE) Reporting Process .............................................38
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.
Special Situations Reports......................................................................................................................39
7.6.1.
Definitions of Special Situations..........................................................................................39
7.6.2.
Instructions for Reporting Special Situations.......................................................................40
8.
STATISTICAL CONSIDERATIONS................................................................................................................43
8.1.
Analysis Objectives and Endpoints........................................................................................................43
8.1.1.
Analysis Objectives..............................................................................................................43
8.1.2.
Primary Endpoint .................................................................................................................43
8.1.3.
Secondary Endpoints............................................................................................................43
8.1.4.
Other Endpoints of Interest ..................................................................................................43
8.2.
Planned Analyses ...................................................................................................................................44
8.2.1.
Interim Analysis ...................................................................................................................44
8.2.2.
Primary Analysis..................................................................................................................44
8.2.3.
Part A Analysis.....................................................................................................................44
8.2.4.
Final Analysis.......................................................................................................................44
8.3.
Analysis Conventions.............................................................................................................................45
8.3.1.
Analysis Sets ........................................................................................................................45
8.3.2.
Data Handling Conventions .................................................................................................45
8.4.
Demographic and Baseline Characteristics Analysis .............................................................................46
8.5.
Efficacy Analysis ...................................................................................................................................46
8.5.1.
Primary Analysis..................................................................................................................46
8.5.2.
Secondary Analyses .............................................................................................................46
CCI
CCI
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8.6.
Safety Analysis.......................................................................................................................................47
8.6.1.
Extent of Exposure...............................................................................................................47
8.6.2.
Adverse Events.....................................................................................................................47
8.6.3.
Laboratory Evaluations ........................................................................................................47
8.8.
Adjustments for Multiplicity..................................................................................................................48
8.9.
Sample Size............................................................................................................................................48
8.10.
Data Monitoring Committee ..................................................................................................................49
9.
RESPONSIBILITIES..........................................................................................................................................50
9.1.
Investigator Responsibilities ..................................................................................................................50
9.1.1.
Good Clinical Practice..........................................................................................................50
9.1.2.
Financial Disclosure.............................................................................................................50
9.1.3.
Institutional Review Board/Independent Ethics Committee Review and 
Approval...............................................................................................................................50
9.1.4.
Informed Consent (or Assent) ..............................................................................................50
9.1.5.
Confidentiality......................................................................................................................51
9.1.6.
Study Files and Retention of Records ..................................................................................51
9.1.7.
Case Report Forms...............................................................................................................52
9.1.8.
Investigator Inspections........................................................................................................53
9.1.9.
Protocol Compliance............................................................................................................53
9.2.
Sponsor Responsibilities ........................................................................................................................53
9.2.1.
Protocol Modifications.........................................................................................................53
9.2.2.
Study Report and Publications .............................................................................................53
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................54
9.3.1.
Payment Reporting...............................................................................................................54
9.3.2.
Access to Information for Monitoring..................................................................................54
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 Table..........................................................................................................58
Appendix 3.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................59
LIST OF IN-TEXT TABLES
Table 1.
Data Entry Requirements When Only One Result of Multiple Results Is Recorded 
for a Given Day ......................................................................................................................32
CCI

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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3 Randomized Study to Evaluate the Safety and 
Antiviral Activity of Remdesivir (GS-5734TM) in Participants 
with Moderate COVID-19 Compared to Standard of Care 
Treatment
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
147753
2020-000842-32
NCT04292730
Study Centers Planned:
Up to approximately 160 centers globally
Objectives:
The purpose of this study is to provide remdesivir (RDV) to 
participants with moderate COVID-19.
The primary objective of this study is as follows:

To evaluate the efficacy of 2 RDV regimens compared to 
standard of care (SOC), with respect to clinical status 
assessed by a 7-point ordinal scale on Day 11
The secondary objective of this study is as follows: 

To evaluate the safety and tolerability of RDV compared to 
SOC
Study Design:
This is a Phase 3 randomized, open-labeled, multi-center study 
RDV therapy in participants with moderate COVID-19.
The study will be conducted in two parts. In Part A, 
approximately 600 participants who meet all eligibility criteria 
may be randomized in 1:1:1 ratio into one of the following 
treatment groups:
Treatment Group 1: continued SOC therapy together with 
intravenous (IV) RDV 200 mg on Day 1 followed by IV RDV 
100 mg on Days 2, 3, 4, and 5
Treatment Group 2: continued SOC therapy together with IV 
RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2, 
3, 4, 5, 6, 7, 8, 9, and 10

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Treatment Group 3: continued SOC therapy
Part B will be enrolled after enrollment to Part A is complete. In 
Part B, an additional approximately 1000 participants who meet 
all of the eligibility criteria may receive:
Extension Treatment Group: continued standard of care 
therapy together with IV RDV 200 mg on Day 1 followed by IV 
RDV 100 mg on Days 2, 3, 4, 5, 6, 7, 8, 9, and 10
If Treatment Group 1 of Part A is selected for Part B, or if 
treatment for 5 days is selected in a study of more severe 
disease, all participants in the Extension Treatment Group and 
all new participants will be reassigned to receive treatment for a 
total of 5 days. National and local regulatory authorities will be 
informed.
Participants in Part A of the study will be the primary efficacy 
population. Participants enrolled in Part B, will have data 
reported descriptively at study completion.
Number of Subjects 
Planned:
Approximately 1600
Target Population:
Participants with moderate COVID-19
Duration of Treatment:
The duration of treatment with RDV will be up to 10 days
Diagnosis and Main 
Eligibility Criteria:
Participants with COVID-19 confirmed by polymerase chain 
reaction (PCR) who meet the following criteria:

Willing and able to provide written informed consent 
(age ≥18) or assent (age ≥12 to <18, where locally and 
nationally approved) prior to performing study procedures

Hospitalized and requiring medical care for COVID-19

SpO2 > 94% on room air at screening

Radiographic evidence of pulmonary infiltrates
Study Procedures/
Frequency:
At Screening, after the participant has provided informed 
consent or assent, demographic and baseline characteristics, 
medical history, and concomitant medications will be 
documented. Vital signs including temperature, respiratory rate, 
and SpO2 will be recorded. Radiographic imaging will be 
performed if not already available. SARS-CoV-2 testing by PCR 
will be performed; if this testing has been performed within the 
previous 4 days, no repeat testing is required.

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If safety laboratory results from the screening day are not 
already available, laboratory testing including alanine 
aminotransferase (ALT) and aspartate aminotransferase (AST), 
serum creatinine, and creatinine clearance will be performed 
according to local practice.
In Part A, after screening procedures, eligible participants will 
be randomized into 1 of the 3 treatment groups in a 1:1:1 ratio to 
receive:
Treatment Group 1: continued SOC therapy together with IV 
RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2, 
3, 4, and 5
Treatment Group 2: continued SOC therapy together with IV 
RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2, 
3, 4, 5, 6, 7, 8, 9, and 10
Treatment Group 3: continued SOC therapy
In Part B, after screening procedures, eligible participants will be
assigned to receive:
Extension Treatment Group: continued standard of care 
therapy together with IV RDV 200 mg on Day 1 followed by IV 
RDV 100 mg on Days 2, 3, 4, 5, 6, 7, 8, 9, and 10 as determined 
by review of the data. Treatment may be reduced to a total of 
5 days following analysis of the data from Part A.
The date of randomization will be considered Day 1 and all 
participants randomized to receive RDV should receive their 
initial dose on Day 1.
On study Days 1 through 14 or until discharge, whichever is 
earlier, 7-point ordinal scale of clinical status, vital signs 
including respiratory status will be measured and adverse events 
(AEs) and concomitant medications will be documented. 
Laboratory testing will be performed according to SOC practice 
with results for white blood cell count, hemoglobin and/or 
hematocrit, platelets, creatinine, creatinine clearance, glucose, 
total bilirubin, ALT, AST, and any SARS-CoV-2 testing being 
reported to the Sponsor. 
In addition, even if not performed as standard of care, white 
blood cell count, hemoglobin and/or hematocrit, platelets, 
creatinine, creatinine clearance, glucose, total bilirubin, ALT, 
AST will be performed at Days 1, 3, 5, 8, 10, and 14 or until 
discharge, whichever is earlier.

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Test Product, Dose, and 
Mode of Administration: 
Reference Therapy, Dose, 
and Mode of 
Administration: 
Criteria for Evaluation: 
Safety: 
Efficacy: 
Statistical Methods: 
CONFIDENTIAL 
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Additional SARS-Co V -2 testing may be conducted at selected 
sites. At participating sites, nasopharyngeal swab samples will 
be collected at Days 1, 3, 5, 8, 10, and 14, sent to a central 
laboratory, and assayed using quantitative reverse transcriptase 
PCR to quantify SARS-CoV-2 viral load. Pretreatment and 
posttreatment samples with detectable SARS-CoV-2 may be 
sequenced for resistance monitoring of the viral polymerase 
gene. 
Remdesivir (GS-5734) for injection, 100 mg, for IV 
administration 
Treatment with SOC according to local practice 
Incidence of treatment-emergent AEs and treatment-emergent 
clinical laboratory abnonnalities 
Clinical status assessed by a 7-point ordinal scale on Day 11 
The primary endpoint will be analyzed using a proportional odds 
model. The null hypothesis being tested is whether the odds of 
improvement on the ordinal scale is the same for either RDV or 
SOC treatment groups (ie, whether the co1mnon odds ratio is 
equal to 1 ). The odds ratio and 95% confidence interval will be 
provided. 
Treatment-emergent AEs and laboratory abnonnalities will be 
smmnarized using descriptive statistics and listed by subject. 
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Sample Size: 
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In Part A, a total of approximately 600 participants will be 
randomized in a 1: 1: 1 ratio to 3 groups (200 participants per 
group). 
A sample size of 200 participants in each of 2 groups achieves 
> 85% power to detect an odds ratio of 1.8 using a two-sided 
alpha level of 0.05. 
The sample size of Part B is based on the anticipated need for 
RDV and current trends in the COVID-19 epidemic. 
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents. 
CONFIDENTIAL 
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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUCtau
area under plasma concentration-time curve over dosing interval
CDC
Centers for Disease Control and Prevention
CoV
Coronavirus
CRF
case report form
CSR
clinical study report
DAIDS
Division of AIDS
DMC
data monitoring committee
EBOV
Ebola virus
eCCGs
eCRF Completion Guidelines
eCRF
electronic case report form
EDC
electronic data capture
EU
European Union
FAS
Full Analysis Set
FDA
Food and Drug Administration
GCP
Good Clinical Practice
Gilead
Gilead Sciences
HIV
human immunodeficiency virus
IB
investigator’s brochure
ICH
International Conference on Harmonisation (of Technical Requirements for 
Pharmaceuticals for Human Use)
IDMC
independent data monitoring committee
IEC
independent ethics committee
IRB
institutional review board
IUD
intrauterine device
IV
intravenous
LLOQ
lower limit of quantitation
LPV
lopinavir
LPV/RTV-IFNb
LPV/RTV + interferon-beta
MERS
Middle East Respiratory Syndrome
OAT
organic anion transporter
PBPK
physiologically-based pharmacokinetic
PCR
polymerase chain reaction
PK
pharmacokinetic(s)
PT
preferred term
PVE
Pharmacovigilance and Epidemiology
RDV
remdesivir

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RNA
ribonucleic acid
RT
reverse transcriptase
qRT-PCR
quantitative reverse transcriptase polymerase chain reaction
RTV
ritonavir
SAE
serious adverse event
SARS
Severe Acute Respiratory Syndrome
SBECD
sulfobutylether β-cyclodextrin sodium
SOC
system organ class
SOP
standard operating procedure
SUSAR
suspected unexpected serious adverse reaction
TEAE
treatment-emergent adverse event
TM
test method
ULN
upper limit of normal
US
United States

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1.
INTRODUCTION
1.1.
Background
In December 2019, a series of pneumonia cases of unknown cause emerged in Wuhan, 
Hubei, China. Sequencing analysis from the patients’ respiratory tract samples indicated a novel 
coronavirus (CoV), which was named COVID-19. As of 23 February 2020, more than 
78,000 confirmed cases have been identified in Wuhan, other provinces in China, and in multiple 
countries outside China {World Health Organisation (WHO) 2020}. More than 2400 deaths 
associated with COVID-19 have been reported, making COVID-19 a major health emergency.
Antiviral drugs that are being evaluated as potential treatments for COVID-19 include 
lopinavir/ritonavir (LPV/RTV; used in the treatment of HIV infection) and remdesivir (RDV, 
GS-5734™). In a study of Severe Acute Respiratory Syndrome (SARS), a significant reduction 
in acute respiratory distress syndrome/mortality was observed in 41 patients treated with the 
combination of LPV/RTV, compared with 111 patients receiving monotherapy ribavirin (2.4 % 
vs 28.8%, p  0.001). However, the use of historical control data does not allow for a reliable 
estimation of efficacy. Additionally, LPV/RTV has multiple known adverse reactions such as 
prolonged QT interval, severe gastrointestinal reactions, abnormal blood glucose, pancreatitis, 
hepatic impairment, and elevated blood lipids. It has multiple drug-to-drug interactions with 
many commonly used drugs in clinical practice; thus, its clinical safety is not determined. 
Remdesivir shows potent in vitro activity against the human pathogenic CoVs Middle East 
Respiratory Syndrome (MERS)-CoV and SARS-CoV in multiple relevant human cell types. In a 
mouse model of MERS-CoV infection, both prophylactic and therapeutic RDV significantly 
improved pulmonary function and reduce lung viral loads and severe lung pathology compared 
with vehicle control animals. In contrast, prophylactic LPV/RTV + interferon-beta 
(LPV/RTV-IFNb) slightly reduced viral loads without impacting other disease parameters. 
Therapeutic LPV/RTV-IFNb improves pulmonary function but did not reduce virus replication 
or severe lung pathology {Sheahan 2020}.
The evaluation of the safety and potential efficacy of RDV in people with COVID-19 is urgently 
needed.
1.2.
Remdesivir (RDV, GS-5734)
Remdesivir is being developed by Gilead Sciences, Inc. (Gilead) and is formulated for
intravenous (IV) administration.

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1.2.1.
General Information
Remdesivir is a nucleotide prodrug that is intracellularly metabolized into an analog of adenosine 
triphosphate that inhibits viral RNA polymerases and has broad spectrum activity against 
members of the filoviruses (eg, Ebola virus [EBOV], Marburg virus [MARV]), CoVs
(eg, SARS-CoV, MERS-CoV), and paramyxoviruses (eg, respiratory syncytial virus [RSV], 
Nipah virus, and Hendra virus). For further information on RDV, refer to the current 
investigator’s brochure (IB) for RDV. Information in the IB includes:

Nonclinical pharmacokinetic (PK) and in vitro metabolism

Nonclinical pharmacology and toxicology

Clinical experience
Additional relevant information regarding RDV are described below.
1.2.2.
Preclinical Pharmacology and Toxicology
Recent results from initial in vitro testing performed at the China CDC in collaboration with 
Gilead showed that RDV has potent antiviral activity against SARS-CoV-2 in Vero cells 
(EC50
0.137 μM).  In another study conducted by the Wuhan Institute of Virology, RDV also 
showed in vitro activity against SARS-CoV-2 in Vero cells (EC50
 0.77 μM) {Wang 2020}. 
Gilead notes that the study from the Wuhan Institute of Virology was conducted externally with 
drug not supplied by Gilead. Researchers in the United States (US) and China are continuing to 
test RDV against clinical isolates of SARS-CoV-2 using drug supplied by Gilead in multiple 
relevant cell types that are known to more efficiently metabolize RDV into its active triphosphate 
form compared with Vero cells.
1.3.
Rationale for This Study
There is currently no approved treatment available for COVID-19 infection. The 
recommendation for using RDV as treatment of COVID-19 is based on the in vitro and in vivo 
activity of RDV against SARS-CoV-2 and other the human highly pathogenic CoVs, 
MERS-CoV and SARS-CoV. 
Remdesivir has acceptable nonclinical tolerability and safety profiles and exhibits in vivo 
prophylactic and therapeutic efficacy against SARS-CoV and MERS-CoV infection in mice and 
MERS-CoV infection in rhesus monkeys. In addition, RDV has been shown to be safe and 
tolerable, with a safety database of over 500 individuals who have received RDV to date. Key 
attributes of the RDV nonclinical and clinical profile supporting its use for emergency treatment 
of COVID-19 are as follows:

Initial in vitro testing performed at the China CDC in collaboration with Gilead showed that 
RDV has potent antiviral activity against SARS-CoV-2 in Vero cells (EC50
 0.137 μM). 
Remdesivir has also shown potent in vitro activity against the human pathogenic CoVs
MERS-CoV and SARS-CoV in multiple relevant human cell types.

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
The PK profile of RDV in nonhuman primates (NHPs) and other relevant animal species 
indicates high and persistent levels of pharmacologically active nucleoside triphosphate 
metabolite in peripheral blood mononuclear cells (PBMCs), supporting once daily IV 
administration as a 30-minuteinfusion.

Remdesivir demonstrated prophylactic and therapeutic efficacy in a mouse model of 
SARS- CoV pathogenesis. Administration of 25 mg/kg RDV subcutaneously twice daily 
beginning 1 day before or 1 day after SARS-CoV inoculation resulted in significantly 
reduced lung viral load and improved clinical signs of disease as well as lung function 
{Sheahan 2017}.

In a mouse model of MERS-CoV pathogenesis, both prophylactic and therapeutic 
administration of 25 mg/kg RDV subcutaneously twice daily improved pulmonary function
and reduced lung viral loads and severe lung pathology. In contrast, prophylactic
LPV/RTV-IFNb slightly reduced viral loads without impacting other disease parameters.
Therapeutic LPV/RTV-IFNb improved pulmonary function but did not reduce virus 
replication or severe lung pathology {Sheahan 2020}.

Remdesivir also showed prophylactic and therapeutic efficacy in MERS-CoV-infected rhesus 
monkeys of Indian origin. Administration of RDV at 10 mg/kg (see RDV IB) or 5 mg/kg 
once daily for 7 days using IV bolus injection beginning 1 day prior to MERS-CoV 
inoculation resulted in a significant reduction of clinical scores, clinical signs of respiratory 
disease, and viral RNA levels compared to vehicle-treated animals. Therapeutic RDV 
treatment of 5 mg/kg once daily using IV bolus injection initiated 12 hours post- inoculation 
also resulted in reduced clinical signs, reduced virus replication in the lungs, and decreased 
presence and severity of lung lesions {De Wit 2020}.
Remdesivir has a favorable clinical safety profile based on approximately 500 individuals who 
received RDV primarily as healthy volunteers in Phase 1 studies and individuals with acute 
EBOV infection.
The design of enrollment in two parts will allow the optimal duration of treatment to be 
determined and then allow continued access to RDV and data collection for eligible participants. 
In addition, further safety data will be obtained.
1.4.
Rationale for Dose Selection of Remdesivir
The proposed regimen for the treatment of established CoV infection, including SARS-CoV and
MERS-CoV, is as follows: single RDV 200 mg IV loading dose on Day 1 of treatment followed 
by 100 mg IV once-daily maintenance doses for a total of up to 10 days of dosing. The proposed 
dosing regimen is based on efficacy studies in MERS-infected rhesus monkeys treated with RDV 
(Studies PC-399-2037 and PC-399-2038) and based on clinical safety data in approximately 
500 patients including healthy volunteers and individuals with acute EBOV infection.

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In the nonclinical studies, RDV was administered at 10 mg/kg (Study PC-399-2038) or 5 mg/kg 
(Study PC-399-2037) once daily for 7 days using IV bolus injection beginning either 1 day prior 
to or 12 hours after (5 mg/kg only) MERS-CoV inoculation. Remdesivir treatment was 
efficacious at reducing viral titers in the lung and alleviating clinical disease signs (RDV IB; {De 
Wit 2020}). Toxicology studies in cynomolgus monkeys and rats and safety and PK studies in 
healthy volunteers support the safety of the proposed dose. Overall, RDV has a favorable PK and 
safety profile that supports evaluation of a 200 mg loading and a 100 mg daily dose that has 
potential to be efficacious in adult patients with COVID-19.
The optimal duration of therapy with RDV remains unknown. However, other agents for acute 
antiviral infection, for example oseltamivir phosphate {TAMIFLU® 2019}, have treatment 
courses ranging from 5 days duration. There is considerable potential patient benefit and societal 
benefit in identifying the minimum duration that will be effective.
1.4.1.
Pediatric Dosing
As with the adult dose, the efficacious dose of RDV against SARS-CoV-2 remains to be 
established. 
Dose selection of RDV in EBOV infected pediatric patients was informed by a physiologically-
based pharmacokinetic (PBPK) model implemented in SimCYP (v.17, Certara). Briefly, a PBPK 
model was developed to characterize the PK of RDV and the primary circulating nucleoside 
metabolite, GS-441524, in adults. The model was verified based on its ability to describe the 
mean and variability of the adult exposures using data from the RDV Phase 1 program 
(GS-US-399-1812). The adult PBPK model was subsequently used to simulate steady-state 
pediatric (age range 0 to 18 years) exposures (AUCtau), accounting for age-dependent changes in 
organ volume/size (liver and kidney), esterase expression, plasma protein binding, and organ 
blood flow.
These simulations do not account for diminished liver or kidney function due to SARS-CoV-2 
infection and/or COVID-19 progression because the impact of infection/disease progression on 
the PK of RDV and GS-441524 is currently unknown.
The results of these simulations indicate: 
For pediatric patients with body weight ≥ 40 kg, a 200 mg loading dose followed by 100 mg 
once-daily maintenance doses of RDV (ie, the adult dosage regimen) should be administered. 
Use of the adult dose in these pediatric patients is expected to maintain exposures of both RDV 
and GS-441524 generally within those expected at the therapeutic doses and which were 
previously observed to be well tolerated in healthy volunteers.   

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1.5.
Risk/Benefit Assessment for the Study
Potential risks associated with the study include unknown adverse events (AEs) and laboratory 
abnormalities. Although not specifically evaluated yet, adolescents with COVID-19 who receive 
RDV are expected to have similar safety profile as adults; no additional safety monitoring is 
required for adolescent participants and no dose adjustments are required. No differing safety 
profile has been reported for the adolescents with EBOV who received RDV in clinical trials. 
Accordingly, the risk:benefit profile, described below, is the same for adolescents and adults.
A pertinent specific risk for participants in this study is the potential for transient, Grade ≤2, 
treatment-emergent elevations in alanine aminotransferase (ALT) and aspartate aminotransferase 
(AST), which were observed after multiple daily RDV administrations in Studies 
GS-US-399-1954 and GS-US-399-5505.
To date in human studies, no serious adverse events (SAEs) have occurred in healthy individuals 
who have received at least 1 dose of RDV. Remdesivir has been tested in healthy volunteers as a 
single ascending dose over a dose range of 3 to 225 mg and in a multi-dose study of 150 mg for 
up to 14 days and at 200 mg loading dose followed by 100 mg for a total of 10 days. 
In nonclinical animal studies, toxicity findings were consistent with dose-dependent and 
reversible kidney injury and dysfunction. The clinical significance of the nephrotoxicity noted in 
animal species is unknown. The etiology of reversible kidney injury observed in rats is consistent 
with the ability of rat renal organic anion transporters (OATs), but not human OATs, to 
efficiently interact with blood metabolites of RDV, particularly GS-704277. This effect may lead 
to proportionally higher intracellular accumulation of drug metabolites in renal rat tubules, 
leading to kidney injury.
The 200 mg loading dose with 8 g of sulfobutylether β-cyclodextrin sodium (SBECD) on Day 1 
will be followed by 100 mg of RDV each day for 4 or 9 days with 4 g of SBECD, which is 
within the range of daily SBECD administration considered safe in humans. A total of 
250 mg/kg/day of SBECD is considered safe by the European Medicines Agency and is therefore 
safe for people with weight over 32 kg. The 100 mg dose prepared in 0.9% saline will be 
hypertonic relative to human serum osmolality but approaches the normal physiological osmolar 
range for humans. The RDV regimen consisting of a loading dose of 200 mg followed by RDV 
100 mg daily for up to 9 days is not anticipated to pose a safety risk to participants enrolled in 
this study.
There are currently no data available on the interaction of RDV and other investigational agents. 
Administering RDV concurrent with other investigational anti-CoV agents may lead to 
antagonism or synergy or have no effect.
The risk mitigation strategy for this study includes restriction of the study population to those 
without a history of significant renal or hepatic disease:

Exclusion of participants with ALT > 5 upper limit of normal (ULN)

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
Exclusion of participants with an estimated glomerular filtration rate (eGFR) < 50 mL/min

Exclusion of coadministration of other investigational agents against COVID-19

Serum chemistry assessments, including liver function testing, will be closely monitored 
during the study period.
There are currently no investigational agents with demonstrated clinical efficacy or approved 
treatments for COVID-19. The timely evaluation of a safe and effective antiviral agent that 
works by directly and selectively blocking the virus replication and is broadly efficacious against 
SARS-CoV-2 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 experimental therapy for the treatment of COVID-19. The benefit-risk balance for this 
study is considered positive.
1.6.
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
The purpose of this study is to provide RDV to participants with moderate COVID-19.
The primary objective of this study is as follows:

To evaluate the efficacy of 2 RDV regimens compared to standard of care (SOC), with 
respect to clinical status assessed by a 7-point ordinal scale on Day 11
The secondary objective of this study is as follows:

To evaluate the safety and tolerability of RDV compared to SOC

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3.
STUDY DESIGN
Part A of this is a Phase 3 randomized, open-labeled, multi-center study RDV therapy in adult 
participants with moderate COVID-19. Part B is a single group multicenter study of RDV in 
participants with moderate COVID-19 infection. All participants will continue to receive SOC
therapy according to local guidelines. Participants randomized to receive RDV will receive this 
in addition to their other care.
3.1.
Endpoints
The primary endpoint of this study is:

Clinical status assessed by a 7-point ordinal scale on Day 11
The secondary endpoint of this study is:

The proportion of participants with treatment emergent adverse events 
Other endpoints of interest are:

The proportion of participants with negative SARS-CoV-2 polymerase chain reaction (PCR)

Time to clinical improvement (days): clinical improvement is defined as a ≥2-point 
improvement in clinical status (7-point ordinal scale) from Day 1 

Time to ≥ 1-point improvement (days) from baseline clinical status

Time to recovery: defined as an improvement in clinical status from a baseline score of 2 
through 5 to a score of 6 or 7, or an improvement from a baseline score of 6 to a score of 7

Time to modified recovery: defined as an improvement in clinical status from a baseline 
score of 2 through 4 to a score of 5, 6, or 7, or an improvement from a baseline score of 5 to a 
score of 6 or 7, or an improvement from a baseline score of 6 to a score of 7

Time to room air: defined as an improvement in clinical status from a baseline score of 2 
through 4 to a score of 5, 6, or 7

Duration of oxygen therapy (days)

Shift in oxygen support status from baseline

Duration of hospitalization (days)

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
The proportion of participants in the Extension Treatment Group with treatment emergent 
adverse events
3.2.
Study Design
Part A of this is a Phase 3 randomized, open-labeled, multi-center study RDV therapy in
participants with moderate COVID-19. Eligible participants will be randomized in equal 
proportions to 1 of 3 treatment groups. No stratification will be performed. Part B is a single 
group multicenter study of RDV in participants with moderate COVID-19 infection. 
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3.3.
Study Treatments
In Part A, approximately 600 participants who meet all eligibility criteria may be randomized in 
a 1:1:1 ratio into 1 of the following treatment groups:
Treatment Group 1: continued SOC therapy together with IV RDV 200 mg on Day 1 followed 
by IV RDV 100 mg on Days 2, 3, 4, and 5
Treatment Group 2: continued SOC therapy together with IV RDV 200 mg on Day 1 followed 
by IV RDV 100 mg on Days 2, 3, 4, 5, 6, 7, 8, 9, and 10
Treatment Group 3: continued SOC therapy
In Part B, an additional approximately 1000 participants who meet all of the eligibility criteria 
may receive:
Extension Treatment Group: continued standard of care therapy together with IV RDV 
200 mg on Day 1 followed by IV RDV 100 mg on Days 2, 3, 4, 5, 6, 7, 8, 9, and 10 unless 
treatment Group 1 of Part A is selected. If treatment for 5 days is selected, all participants in the 
Extension Treatment Group and all new participants will be reassigned to receive treatment for a 
total of 5 days. National and local regulatory authorities will be informed.
Participants in Part A of the study will be the primary efficacy population. Participants enrolled 
in Part B, will have data reported descriptively at study completion.
3.4.
Duration of Treatment
Participants will receive study treatment with RDV for 5 days (treatment group 1), study 
treatment with RDV for 10 days (treatment group 2), no RDV (treatment group 3), or either 5 or 
10 days (Extension Treatment Group). If the participant is discharged, RDV treatment will stop 
at that time.
3.5.
Discontinuation Criteria
Study drug dosing in an individual subject will be placed on hold and may be discontinued, 
following a review of all available clinical data by the medical monitor and discussion with the 
investigator, if any of the following occurs:

Any SAE or ≥ Grade 3 AE suspected to be related to RDV

Any elevations in ALT > 5 ULN; or ALT > 3 ULN and total bilirubin > 2 ULN, 
confirmed by immediate repeat testing

Creatinine Clearance < 30 mL/min
Discontinuation of study medication is not a seriousness criterion.

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Subjects who discontinue the study medication should be encouraged to remain in the study and 
attend study visits as described in Sections 6.3, 6.4, and 6.5.
3.6.
End of Study
The end of the study will be the last participant’s last observation (or visit).
3.7.
Post Study Care
The long-term 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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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
In Part A, approximately 600 participants will be randomized in a 1:1:1 ratio into 1 of 
3 treatment groups. In Part B, up to approximately 1000 participants may be assigned into a 
single treatment group. Rescreening may occur at the investigator’s discretion.
4.1.1.
Subject Replacement
Subjects who discontinue prior to the end of study will not be replaced.
4.2.
Inclusion Criteria
Subjects 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. For 
participants ≥ 12 and < 18 years of age, a parent or legal guardian willing and able to provide
written informed consent prior to performing study procedures
2) Aged ≥ 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 institutional 
review board [IRB] or independent ethics committee [IEC])
3) SARS-CoV-2 infection confirmed by PCR ≤ 4 days before randomization
4) Currently hospitalized and requiring medical care for COVID-19
5) SpO2 > 94% on room air at screening
6) Radiographic evidence of pulmonary infiltrates
7) Men and women 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
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
1) Participation in any other clinical trial of an experimental agent treatment for COVID-19
2) Concurrent treatment or planned concurrent treatment with other agents with actual or
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3)
Requiring mechanical ventilation at screening
4)
ALT or AST > 5 ULN
Note: if per local practice only ALT is routinely measured, exclusion criteria will be 
evaluated on ALT alone
5)
Creatinine clearance < 50 mL/min using the Cockcroft-Gault formula for participants
≥18 years of age {Cockcroft 1976} and Schwartz Formula for participants < 18 years of age
6)
Positive pregnancy test (Appendix 3)
7)
Breastfeeding woman
8)
Known hypersensitivity to the study drug, the metabolites, or formulation excipient

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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding, and Treatment Codes Access
5.1.1.
Randomization
Subjects who meet eligibility criteria will be randomized in a 1:1:1 ratio to 1 of 3 treatment 
groups on Day 1 using an IWRS, and assigned a subject number. Randomization will not be 
stratified.
5.1.2.
Blinding
Blinding of treatment assignments or data will not be performed in this study.
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 GS-5734 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: betadex sulfobutyl ether sodium (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.
5.2.2.
Packaging and Labeling
Remdesivir for injection, 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 fluoro-resin laminated rubber stopper and an aluminum 
overseal with a red, plastic flip-off cap.
Remdesivir for injection, 100 mg, shall be labeled to meet all applicable requirements of the 
US Food and Drug Administration (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, 100 mg, 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.

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Measures that minimize drug contact with the body should always be considered during 
handling, preparation, and disposal procedures.
Remdesivir for injection, 100 mg, is recommended to be reconstituted and diluted on the same 
day as administration. Remdesivir for injection, 100 mg, does not contain any preservative and is 
intended for single-use. Any unused RDV material should be discarded.
5.3.
Dosage and Administration of Remdesivir
Remdesivir for injection, 100 mg, will be provided by Gilead. In Part A, participants in 
Treatment Groups 1 and 2 will receive RDV 200 mg on Day 1 followed by IV RDV 100 mg on 
Days 2, 3, 4, and 5. Participants in Treatment Group 2 will also receive RDV 100 mg on Days 6, 
7, 8, 9, and 10. In Part B, participants in the Extension Treatment Group will receive RDV 
200 mg on Day 1 followed by IV RDV 100 mg on Days 2, 3, 4, 5, 6, 7, 8, 9, and 10. If Treatment 
Group 1 of Part A is selected for Part B, or if treatment for 5 days is selected in a study of more 
severe disease, all participants in the Extension Treatment Group and all new participants will be 
reassigned to receive treatment for a total of 5 days. Remdesivir treatment will be stopped at 
discharge regardless of the scheduled duration of therapy. Remdesivir will be administered over 
30 minutes where possible.
5.4.
Accountability for Investigational Medicinal Product
The investigator is responsible for ensuring adequate accountability of all used and unused study 
drug. 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 kits 

The date, subject number, and the study drug kit number dispensed

The date, quantity of used and unused study drug returned, along with the initials of the 
person recording the information
5.4.1.
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 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 
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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 monitoring visit.
5.5.
Prior and Concomitant Medications
Concomitant use of the following is prohibited in participants receiving RDV:

Traditional herbal treatments including herb sho-saiko-to (or Xiao-Shai-Hu-Tang)

Investigational agents with putative antiviral activity for COVID-19 including approved HIV 
protease inhibitors such as lopinavir/ritonavir, chloroquine, interferon, etc.
Concomitant use of investigational agents such as approved HIV protease inhibitors like 
lopinavir/ritonavir, chloroquine, etc while receiving RDV is prohibited due to lack of evidence 
on additive or synergistic effects and potential for an increased risk of transaminase elevations.
Medications will be assessed only from Day 1 prior to enrollment to Day 28 or discharge,
whichever is earlier.

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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject 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 the 
Gilead or contract research organization (CRO).
6.1.
Subject 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.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 2 days before randomization and dosing to determine eligibility 
for participation in the study. 

Obtain written informed consent or assent (age ≥12 to <18, where locally and nationally 
approved)
After the informed consent the following assessments are performed to determine eligibility 
requirements as specified in the inclusion and exclusion criteria:

Focused medical history including the following information (eg, date of first symptoms, 
overall symptoms, exposure source, demographics, baseline characteristics, allergies and 
medical history

Review and record medications and therapies for this current illness 

Counsel subjects to use adequate birth control methods required during the trial to avoid 
pregnancy

Targeted physical examination including, vital signs (heart rate, temperature, blood pressure), 
body weight, and height

Documentation of respiratory status:
Respiratory Rate
Oxygen supplementation: room air, low flow O2 (L/min and %), high flow O2 (L/min 
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• 
Obtain blood samples if not done in the preceding 48 hours for creatinine, creatinine 
clearance, ALT and AST 
• 
Pregnancy test (for women of childbearing potential) 
• 
Record any serious adverse events and all adverse events related to protocol-mandated 
procedures occurring after signing of the consent (or assent) fonn. 
Study subjects who qualify should be immediately randomized. Randomization and dosing 
should occur on the same day if possible. 
6.2.2. 
Baseline/Day 1 Assessments 
The following evaluations are to be completed at the Day 1 visit. The investigator must have 
confinned eligibility before proceeding with randomization on the Day 1 visit. If the screening 
and Day 1 visits occur within 24 hours, no procedures need to be repeated. Participants must 
complete the following assessments before being administered study drug: 
• 
Physical examination including, vital signs (heart rate, temperature, blood pressure, and body 
weight) 
• 
Documentation of respiratory status: 
Respiratory rate 
Oxygen supplementation: room air, low flow 0 2 (L/min and %), high flow 0 2 (L/min 
and %), CPAP/BIPAP (Fi0 2 or %), mechanical ventilation (Fi02 or %), ECMO 
Oxygenation: SpOi or Pa02 
Radiographic findings (if available) 
• 
Review AEs and document concomitant medications 
• 
Obtain blood samples for white blood cell count, hemoglobin and/or hematocrit, platelets, 
creatinine and creatinine clearance, glucose, total bilirubin, ALT, AST 
I 
• 
SARS-CoV-2 Testing: Collect nasopharyngeal swab sample for subjects/sites participating in 
this portion of the study 
• 
Review Ordinal Scale (Section 6.9) 
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The following evaluations are to be completed daily from Days 2 
14 or until discharge 
whichever comes earlier: 
• 
Vital signs (heart rate, temperature, blood pressure), body weight (if available). 
• 
A symptom-directed (targeted) physical examination will be perfonned to evaluate for any 
possible adverse event 
• 
Documentation of respiratory status: 
Respiratory Rate 
Oxygen supplementation: room air, low flow 02 (L/min and%), high flow 02 (L/min 
and%), CPAP/BIPAP (FiO2 or%), mechanical ventilation (FiO2 or%), ECMO 
Oxygenation: Sp02 or PaO2 
Radiographic findings (if available) 
• 
SARS-CoV-2 testing results if available should be reported 
• 
Review AEs and document concomitant medications 
• 
Review Ordinal Scale (Section 6.9) 
6.4. 
Additional Assessments 
The following evaluations are to be completed at the following visits or m1til discharge, 
whichever comes earlier: 
• 
Safety laboratory tests (white blood cell count, hemoglobin and/or hematocrit, platelets, 
creatinine and creatinine clearance, glucose, total bilirubin, ALT, AST) are to be completed 
at Days 3, 5, 8, 10, and 14 
I 
• 
SARS-CoV-2 Testing: Collect nasopharyngeal swab sample at Days 3, 5, 8, 10, and 14 for 
subjects/sites participating in this portion of the study 
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6.5.
Day 28 Follow up Assessment (± 5 Days)
The following evaluations are to be completed if this visit is conducted in person. For 
participants who have been discharged from hospital, the final evaluation can be made by phone.
Only AE and concomitant medication and ordinal scale (if discharged on or after Day 14) review
are to be completed if visit is conducted by phone.

Physical examination and vital signs (heart rate, temperature, blood pressure)

Documentation of respiratory status:
Respiratory rate
Oxygen supplementation: room air, low flow O2 (L/min and %), high flow O2 (L/min 
and %), CPAP/BIPAP (FiO2 or %), mechanical ventilation (FiO2 or %), ECMO
Oxygenation: SpO2 or PaO2
Radiographic findings (if available)

Review AEs and document concomitant medications

Review the Ordinal Scale (Section 6.9). If subject was not discharged by Day 14, any change 
in category and the date of any change in category from Day 14 to discharge (or Day 28) 
should be recorded
6.6.
Clinical Laboratory Assessments
Clinical laboratory assessments are required at screening, Days 1, 3, 5, 8, 10, and 14 or until 
discharge, whichever comes earlier. Clinical laboratory assessments at other days may be 
conducted if required by clinical need or local practice. From Day 1 to Day 14, at specified 
timepoints, the sponsor will be provided with results for the following analytes completed by 
local laboratories: white blood cell count, hemoglobin and/or hematocrit, platelets, creatinine and 
creatinine clearance, glucose, total bilirubin, ALT, AST, and any SARS-CoV-2 testing.
SARS-CoV-2 testing may include quantitative reverse transcriptase polymerase chain reaction
(qRT-PCR) to detect or quantify SARS-CoV-2 or virus sequencing results. 
Additional SARS-CoV-2 testing may be conducted at selected sites in a subset of participants. At 
participating sites, nasopharyngeal swab samples will be collected at Days 1, 3, 5, 8, 10, and 14, 
sent to a central laboratory, and assayed using qRT-PCR to quantify SARS-CoV-2 viral load. 
Pretreatment and posttreatment samples with detectable SARS-CoV-2 may be sequenced for 
resistance monitoring of the viral polymerase gene.

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For all clinical laboratory tests at Day 1, at least the most recent result before dosing should be 
used. For other tests, preferably enter all results if the most recent result before dosing is not 
possible. When more than 1 result is available in a calendar day, at minimmn , results should be 
reported as indicated in Table 1. All SARS-CoV-2 results should be provided. 
Table 1. 
Data Entry Requirements When Only One Result of Multiple Results 
Is Recorded for a Given Day 
Test Name 
Minimum Data to be Recorded 
Alanine aminotransferase 
Highest result 
Aspartate aminotransferase 
Highest result 
Crea ti nine 
Highest result 
Glucose 
Lowest result (hypoglycemia) 
Highest result (hyperglycemia) if outside normal range 
Total bilirubin 
Highest result 
Hematocrit 
Lowest result 
Hemoglobin 
Lowest result 
Platelets 
Lowest result 
White Blood Cells 
Lowest result 
Creatinine Clearance (Cockcroft-Gault or 
Lowest result 
Schwarz preferred) 
6.7. 
Physical Examination 
A targeted physical examination including vital signs (heart rate, respiratory rate, temperature, 
blood pressure, Sp0 2 or Pa0 2) should be perfonned at least daily. 
6.9. 
Ordinal Scale 
The ordinal scale is an assessment of the clinical status at a given study day. Each day, the worst 
(ie, lowest ordinal) score from the previous day will be recorded, ie, on Day 3, the lowest ordinal 
score from Day 2 is obtained and recorded for Day 2. The scale is as follows: 
1) Death 
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2) Hospitalized, on invasive mechanical ventilation or ECMO
3) Hospitalized, on non-invasive ventilation or high flow oxygen devices
4) Hospitalized, requiring low flow supplemental oxygen
5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care 
(COVID-19 related or otherwise)
6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 
(other than per protocol RDV administration)
7) Not hospitalized
6.10.
Post-treatment Assessments
No assessments are required after Day 28.
6.11.
Assessments for Early Discontinuation from Study
If a subject discontinues study dosing (for example, as a result of an AE or clinically significant 
laboratory abnormality), every attempt should be made to keep the subject in the study and 
continue to perform the required study-related follow-up and procedures (see Section 3.5, 
Discontinuation Criteria). If this is not possible or acceptable to the subject or investigator, the 
subject may be withdrawn from the study.
6.11.1.
Criteria for Discontinuation of Study Treatment
Study medication may be discontinued in the following instances:

Discharge from the hospital/institution

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 subject 
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 subject’s best 
interest

Subject request to discontinue for any reason

Subject noncompliance

Pregnancy during the study; refer to Appendix 3

Discontinuation of the study at the request of Gilead, a regulatory agency or an IRB or IEC

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End of Study 
The end of the study will be the last participant's last observation ( or visit). 
6.13. 
Post Study 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. 
6.14. 
Sample Disposition and Storage (Non-PK Samples) 
Samples will be processed and retained according to local practice and the regulations pertaining 
to each institution. At participating sites, nasopharyngeal swab SARS-CoV-2 sam les will be 
collected and sent to Gilead or its research artner for additional virolo ic testin . 
• 
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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 subject 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 considered related to the 
investigational product. AEs may also include pretreatment or posttreatment complications that 
occur as a result of protocol specified procedures or special situations (Section 7.6).
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 7.6.1)

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 subject 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)

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
Persistent or significant disability/incapacity

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 subject 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 AE 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).

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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:
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf
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-required post treatment 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 occurs after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported on the 
applicable eCRFs and Pharmacovigilance an Epidemiology (PVE) 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 7-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 PVE.

All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guidelines.  

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7.3.4.
Electronic Serious Adverse Event (eSAE) Reporting Process

Site personnel record all SAE data on the applicable eCRFs and from there transmit the SAE 
information to Gilead PVE within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If it is not possible to record and submit the SAE information electronically, because the 
eCRF database cannot be accessed or is not available (including at study-start), record the 
SAE on the paper SAE reporting form and submit within 24 hours to:
Gilead PVE 
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 eCRF 
completion guidelines.

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 subject identification, 
maintaining the traceability of a document to the subject 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 subject’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 European Union (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 
(SADRs), or suspected unexpected serious adverse reactions (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.
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Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the investigator’s brochure 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. 
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 urinalysis) 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 (ie, decreased hemoglobin).
Laboratory abnormalities that do not require medical intervention or action are generally not 
considered AEs.
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.
Special Situations Reports
7.6.1.
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 
with an AE; intercepted medication error; or potential medication error.

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Abuse is defined as persistent or sporadic intentional excessive use of an investigational product 
by a subject.
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 
subject in question). In cases of a discrepancy in drug accountability, overdose will be 
established only when it is clear that the subject has taken the excess dose(s). Overdose cannot 
be established when the subject cannot account for the discrepancy except in cases in which the 
investigator has reason to suspect that the subject 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.
7.6.2.
Instructions for Reporting Special Situations
7.6.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study drug and throughout the study, including the post study drug follow-up period, 
to Gilead PVE using the pregnancy report form within 24 hours of becoming aware of the 
pregnancy.
Gilead PVE
Email:
or
Fax: 
Refer to Section 7.3 and the eCRF completion guidelines 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.
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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 
SAE. The underlying medical reason for this procedure should be recorded as the AE term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Sections 7.3.2. Furthermore, any SAE occurring as an adverse pregnancy outcome post study
must be reported to Gilead PVE.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead PVE 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 PVE. Gilead PVE contact information is as follows: email: 
 and fax: 
Pregnancies of female partners of male study subjects exposed to Gilead study drugs must also 
be reported and relevant information should be submitted to Gilead PVE 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 PVE, fax number 
 or email 
Refer to Appendix 3 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.
7.6.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead PVE 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.
Gilead PVE
Email:
 
or
Fax: 
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 and the eCRF completion guidelines for instructions on special situation 
reporting.
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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.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The purpose of this study is to provide RDV to participants with moderate COVID-19.
The primary objective of this study is as follows:

To evaluate the efficacy of 2 RDV regimens compared to standard of care (SOC), with 
respect to clinical status assessed by a 7-point ordinal scale on Day 11
The secondary objective of this study is as follows:

To evaluate the safety and tolerability of RDV compared to SOC
8.1.2.
Primary Endpoint
The primary endpoint of this study is:

Clinical status assessed by a 7-point ordinal scale on Day 11
8.1.3.
Secondary Endpoints
The secondary endpoint of this study is:

The proportion of participants with treatment emergent adverse events 
8.1.4.
Other Endpoints of Interest
Other endpoints of interest are:

The proportion of participants with negative SARS-CoV-2 PCR

Time to clinical improvement (days): clinical improvement is defined as a ≥2-point 
improvement in clinical status (7-point ordinal scale) from Day 1 

Time to ≥ 1-point improvement (days) from baseline clinical status

Time to recovery: defined as an improvement in clinical status from a baseline score of 2 
through 5 to a score of 6 or 7, or an improvement from a baseline score of 6 to a score of 7

Time to modified recovery: defined as an improvement in clinical status from a baseline 
score of 2 through 4 to a score of 5, 6, or 7, or an improvement from a baseline score of 5 to a 
score of 6 or 7, or an improvement from a baseline score of 6 to a score of 7

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
Time to room air: defined as an improvement in clinical status from a baseline score of 2 
through 4 to a score of 5, 6, or 7

Duration of oxygen therapy (days)

Shift in oxygen support status from baseline

Duration of hospitalization (days)

All-cause mortality at Day 28

The proportion of participants in the Extension Treatment Group with treatment emergent 
adverse events
8.2.
Planned Analyses
8.2.1.
Interim Analysis
Prior to the final analysis, the primary analysis of the primary endpoint will be conducted, 
additional interim analyses may be conducted, and the analyses may be submitted to regulatory 
agencies to seek guidance for the overall clinical development program or for other purposes.
8.2.1.1.
DMC Analysis
The DMC will review safety data on a regular basis. The DMC will review safety and efficacy 
data at the time of the primary analysis.
8.2.2.
Primary Analysis
The primary analysis will be performed after all participants have completed Day 11 of Part A of 
the study or prematurely terminated from the study. 
8.2.3.
Part A Analysis
The analysis for Part A subjects will be performed after all participants have completed Part A of 
the study or prematurely terminated from Part A of the study. 
8.2.4.
Final Analysis
The final analysis will be performed after all participants have completed the study or 
prematurely terminated from the study, outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned and finalized. The final analysis will 
summarize results from Part B of the study.
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8.3. 
8.3.1. 
8.3.1.1. 
Analysis Conventions 
Analysis Sets 
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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 Part A of the study and (2) have 
received at least 1 dose of study treatment if randomized to 1 of the RDV treatment groups. 
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 if randomized to 1 of the RDV treatment groups. Participants will be 
grouped according to the treatment which they received. 
8.3.1.3. 
Extension Analysis Set 
The Extension Analysis Set will include participants who have received at least 1 dose of RDV 
in Extension Treatment Group. This analysis set will be used for both the safety and efficacy 
evaluations for participants enrolled in Part B. 
8.3.2. 
Data Handling Conventions 
Laboratory data that are continuous in nature but are less than the lower limit of quantitation 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 (ie, no toxicity grade) for the laboratory abnormality summary. 
All available data for participants that do not complete the study will be included in data listings. 
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8.4.
Demographic and Baseline Characteristics Analysis
Demographic and baseline measurements will be summarized using standard descriptive 
methods. Demographic summaries will include sex, race/ethnicity, 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 sum test will be used to compare treatment groups.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
The primary endpoint will be analyzed using a proportional odds model including baseline 
clinical status as a covariate. Each RDV group will be compared to the SOC group. The null 
hypothesis being tested is whether the odds of improvement on the ordinal scale is the same for 
the SOC group and either RDV group (ie, whether the common odds ratio is equal to 1). The 
odds ratio and 95% confidence interval for each comparison will be provided. 
The proportion of subjects in each category will be summarized by treatment group. The validity 
of the proportionality assumption will be evaluated. 
If a participant is discharged prior to Day 11, the Day 11 ordinal scale category is considered to 
be not hospitalized. If a participant dies prior to Day 11, the Day 11 ordinal scale category is 
considered to be death. Every effort will be made to obtain clinical status data for all subjects 
prior to discharge. 
8.5.2.
Secondary Analyses
The secondary endpoint of proportion of participants with treatment emergent AEs will be 
compared between each of the RDV groups and standard of care group in Part A using a Fisher’s 
Exact test. The point estimates of the treatment differences and the associated 95% confidence 
intervals will be provided. Other endpoints of interest related to proportion of participants will be 
compared between treatment groups in Part A using a chi-square test or Fisher’s Exact test. 
Efficacy endpoints that are measured as time to first event will be compared between treatment 
groups using a competing risk model (with death as the competing risk) and continuous 
endpoints will be compared between treatment groups using a Wilcoxon rank sum test or 
analysis of variance model.
The 7-point ordinal scale of clinical status and other efficacy endpoint of interest will be 
summarized descriptively for Part B.

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Safety Analysis 
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All safety data collected on or after the randomization date through the Day 28 follow-up visit 
will be smmnarized by treatment group ( according to the study drug received). Data for the 
pretreatment period will be included in data listings. Part A and Part B will be smmnarized 
separately. 
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 smmnarized by treatment group for the RDV groups. 
8.6.2. 
Adverse Events 
Clinical and laboratory AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). System Organ Class (SOC), High-Level Group Tenn (HLGT), 
High-Level Tenn (HLT), Preferred Tenn (PT), and Lower-Level Tenn (LLT) will be attached to 
the clinical database. 
Events will be smmnarized 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, or up to Day 28, whichever is the later date. 
Smmnaries (number and percentage of participants) of treatment-emergent adverse events 
(TEAEs) (by SOC, and PT) will be provided by treatment group. 
8.6.3. 
Laboratory Evaluations 
Selected laboratory data will be smmnarized using only observed data. Data and change from 
baseline at all scheduled time points will be smmnarized. 
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. 
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 subject has 
been discontinued from treatment for more than 30 days will be included in a data listing. 
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8.8.
Adjustments for Multiplicity
The statistical analysis plan will include alpha spending considerations for the primary endpoint. 
No other adjustments for multiple comparisons are planned.
8.9.
Sample Size
The sample size computation is based on an assumed distribution of the 7-point ordinal scale on 
Day 11 for the SOC treatment group. The odds ratio represents the odds of improvement in the
7-point ordinal scale for an RDV treatment group relative to the SOC treatment group. The 
sample size needed to detect a given odds ratio for a 1:1 randomization using a 2-tailed test at 
level α is given by:
12 (∝/
 + )
 / 
(1 −




)
Where θ is the log odds ratio, ρi is the overall probability (combined over both treatment groups) 
of being in the ith category of the ordinal outcome, and zα /2 and zβ are the 1- α /2 and β quantiles 
of the standard normal distribution {Whitehead 1993}.
A sample size of 600 participants (200 in each group) achieves > 85% power to detect an odds 
ratio of 1.8 using a two-sided significance level of 0.05 for comparing each RDV group (n 200) 
to standard of care group (n 200). In this sample size calculation, it is assumed that the 
probability distribution of the ordinal scale at Day 11 for Treatment Group 3 is as follows:
1. Death, 0.5%
2. Hospitalized, on invasive mechanical ventilation or ECMO, 2.5%
3. Hospitalized, on non-invasive ventilation or high flow oxygen devices, 7%
4. Hospitalized, requiring low flow supplemental oxygen, 8%
5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care 
(COVID-19 related or otherwise), 15%
6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 
(other than per protocol RDV administration), 27%
7. Not hospitalized, 40%
The sample size calculation was done using software PASS (Version 14.0).

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8.10.
Data Monitoring Committee
An external Independent Data Monitoring Committee (IDMC) includes independent experts that 
do not have direct involvement in the conduct of the study. The IDMC will review the progress of 
the study and perform interim reviews of efficacy and safety data, and provide recommendation 
to Gilead whether the nature, frequency, and severity of adverse effects 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’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 ICH E6(R2)
addendum to its guideline for GCP and applicable laws and regulations including the principles 
of the Declaration of Helsinki.
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 subject 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 subject 
(such as advertisements, subject information sheets, or descriptions of the study used to obtain 
informed consent) to an IRB/IEC. The investigator will not begin any study subject 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 subject after initial IRB/IEC approval, with the exception of those necessary to 
reduce immediate risk to study subjects.
9.1.4.
Informed Consent (or Assent)
The investigator is responsible for obtaining written informed consent or assent (age ≥12 to <18, 
where locally and nationally approved) 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 subject or the subject’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 requirements.

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9.1.5.
Confidentiality
The investigator must assure that subjects’ 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 form 
or biological sample submitted to Gilead, IRB or IEC. No biological samples will be provided to 
Gilead or any central laboratory during this study. NOTE: The investigator must keep a 
screening log with details for all subjects screened and enrolled in the study, in accordance with 
the site procedures and regulations.  Subject data will be processed in accordance with all 
applicable regulations.
The investigator agrees that all information received from Gilead, including but not limited to the 
investigator’s brochure, this protocol, CRF/eCRF, the study drug, and any other study 
information, remain the sole and exclusive property of Gilead during the conduct of the study 
and thereafter. This information 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 documented and the study data to be subsequently verified. These documents should 
be classified into at least the following 2 categories: (1) investigator’s study file, and (2) subject 
clinical source documents.
The investigator’s study file will contain the protocol/amendments, paper or electronic 
completed subject CRFs, IRB or IEC and governmental approval with correspondence, informed 
consent, drug records, staff curriculum vitae and authorization forms, and other appropriate 
documents and correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification;

Documentation that subject meets eligibility criteria, ie, medical history, physical 
examination, and confirmation of diagnosis (to support inclusion and exclusion criteria);

Documentation of the reason(s) a consented subject is not enrolled;

Participation in study (including study number);

Study discussed and date of informed consent;

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
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 (ie, 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 
subject, appropriate copies should be made for storage away from the site.
9.1.7.
Case Report Forms
For each subject consented, an eCRF casebook will be completed by an authorized study staff 
member whose training for this function is completed in the electronic data capture
(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 eCRF Completion Guidelines (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 

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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 (e.g. 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 subjects, 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.
9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(ies). 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 
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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 subject 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.
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 subjects, 
appropriate regulatory authorities, IRB/IECs. In terminating the study, Gilead and the 
investigator will assure that adequate consideration is given to the protection of the subjects’ 
interests.

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10.
REFERENCES
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16:31-41.
De Wit E, Feldmann F, Cronin J, Jordan R, Okumura A, Thomas T, et al. Prophylactic and 
Therapeutic Remdesivir (GS-5734) Treatment in the Rhesus Macaque Model of 
MERS-CoV Infection. PNAS Latest Articles 2020.
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 2017:1-20.
Sheahan TP, Sims AC, Leist SR, Schafer A, Won J, Brown AJ, et al. Comparative Therapeutic 
Efficacy of Remdesivir and Combination Lopinavir, Ritonavir, and Interferon 
Beta Against MERS-CoV. Nature communications 2020;11:222.
TAMIFLU®, Genentech Inc. TAMIFLU® (oseltamivir phosphate) capsules for oral use, 
TAMIFLU® (oseltamivir phosphate) for oral suspension. U.S. Prescribing 
Information. South San Francisco, CA. Revised August.  2019:
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and Chloroquine Effectively 
Inhibit the Recently Emerged Novel Coronavirus (2019-nCoV) In Vitro. Cell 
research 2020;30:269-71.
Whitehead J. Sample size calculations for ordered categorical data. Stat Med 1993;12 (24):2257-
71.
World Health Organisation (WHO). Coronavirus Disease 2019 (COVID-19) Situation Report -
34. 2020.

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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table
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
A Phase 3 Randomized Study to Evaluate the Safety and Antiviral Activity of Remdesivir 
(GS-5734TM) in Participants with Moderate COVID-19 Compared to Standard of Care Treatment
Protocol Amendment 2.0 29 April 2020
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval.
Signature
Date
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 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study.
Principal Investigator Name (Printed)
Signature
Date
Site Number
29 April 2020
PPD
PPD

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Appendix 2.
Study Procedures Table
Screening
Baseline / 
Day 1b
Day 2
Day 3
Day 4
Day 5
Days 6 
and 7
Day 8
Day 9
Day 10
Days 11, 
12 and 
13
Day 14
Day 28c
Follow-up
(± 5 days)
Written Informed Consent
X
Medical History 
X
Physical Examination
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Vital Signsa
X
X
X
X
X
X
X
X
X
X
X
X
X
Study Laboratory Testing
X
X
X
X
X
X
X
Respiratory Status
X
X
X
X
X
X
X
X
X
X
X
X
X
Ordinal Scale
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy Test 
X
Virologic Testinge
X
X
X
X
X
X
RDV Dosing for Group 1
X
X
X
X
X
RDV Dosing for Group 2
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
a
Includes heart rate, respiratory rate, temperature, blood pressure, SpO2, and body weight. Body weight collected on Screening and Day 1 and otherwise if available.
b
Assessments need not be repeated if performed within 24 hours of screening procedures; data collection other than adverse events and concomitant medications should stop at 
Day 14 or discharge, whichever is earlier.
c
Day 28 evaluations completed if the visit is conducted in person. Only adverse event and concomitant medications review completed if visit conducted by phone.
e
Virologic (SARS CoV 2) testing for subjects/sites participating in this portion of the study on Days 1, 3, 5, 8, 10, and 14.
CCI
CCI
I 

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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 subject 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.  In 
addition, women of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age. Tubal ligation is not considered a method of 
permanent sterilization for the purposes of this study.
b. Definition of Male Fertility
For the purposes of this study, a male born subject is considered of fertile after the initiation of 
puberty unless permanently sterile by bilateral orchidectomy or medical documentation.
2) Contraception Requirements for Female Subjects
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.
Please refer to the latest version of the investigator’s brochure for additional information.

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b. Contraception Requirements for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires using at least an acceptable 
effective contraceptive measure. They must have a negative pregnancy test at Screening. In the 
event of a delayed menstrual period (over one month between menstruations), a pregnancy test 
must be performed to rule out pregnancy. This is applicable also for women of childbearing 
potential with infrequent or irregular periods. They must also agree to one of the following from 
Screening until the last dose of the study drug:  

Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual 
lifestyle.
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 with a barrier method)
Tubal sterilization
Vasectomy in the male partner (provided that the partner is the sole sexual partner and 
had confirmation of surgical success 3 months after procedure)
Barrier methods 
■
Female barriers: Diaphragm with spermicide or Cervical cap with spermicide
■
Male barriers: Male condom (with or without spermicide)
Hormonal methods are restricted to drugs associated with the inhibition of ovulation. 
Each method must be used with a barrier method, preferably male condom. 
Hormonally-based contraceptives permitted for use in this protocol are as follows:
■
Oral contraceptives (either combined or progesterone only)
■
Injectable progesterone
■
Subdermal contraceptive implant
■
Transdermal contraceptive patch
■
Contraceptive vaginal ring

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Contraceptive methods must be locally approved to be permitted.
Female subjects must also refrain from egg donation and in vitro fertilization during treatment 
and until the last study drug dose. 
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.
3) Contraception Requirements for Male Subjects
During the study male subjects 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 (LAM).  A Female condom and a male condom should not be 
used together.
5) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study. Subjects who become pregnant or who suspect that they are pregnant during the study 
must report the information to the investigator and discontinue study drug immediately. Subjects 
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 7.6.2.1.