Clinical trial NCT04292899
Conditions: COVID-19
Sponsor: Gilead Sciences
Start date: 2020-03-06; Completion date: 2020-06-30
Enrollment: 4891 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the efficacy of 2 remdesivir (RDV) regimens with respect to clinical status assessed by a 7-point ordinal scale on Day 14.

Detailed description:

Arms: arm 1: Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2, 3, 4, and 5. arm 2: Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2, 3, 4, 5, 6, 7, 8, 9, and 10. arm 3: Part B (Extension) will enroll participants after enrollment to Part A is complete. Participants will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2-10. arm 4: Participants on mechanical ventilation will receive continued standard of care therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg on Days 2-10
Interventions: intervention 1: Remdesivir intervention 2: Standard of Care
Intervention descriptions: intervention 1: Administered as an intravenous infusion intervention 2: Standard of Care Treatment for COVID-19 Infection

Protocol documents:
SAP_002.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 3 Randomized Study to Evaluate the Safety and 
Antiviral Activity of Remdesivir (GS-5734™) in Participants 
with Severe COVID-19
Name of Test Drug:
Remdesivir (RDV; GS-5734™)
Study Number:
GS-US-540-5773
Protocol Version (Date):
Amendment 3.0 (12 April 2020)
Analysis Type:
Part B Final Analysis 
Analysis Plan Version:
Version 1.0
Analysis Plan Date:
23 September 2020
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(r) GILEAU 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF ABBREVIATIONS........................................................................................................................................4
1.
INTRODUCTION ................................................................................................................................................5
1.1.
Study Objectives ......................................................................................................................................5
1.2.
Study Design............................................................................................................................................5
1.3.
Sample Size and Power............................................................................................................................7
2.
TYPE OF PLANNED ANALYSIS ......................................................................................................................9
2.1.
Interim Analyses ......................................................................................................................................9
2.1.1.
Data Monitoring Committee Analysis....................................................................................9
2.1.2.
Primary Analysis....................................................................................................................9
2.1.3.
Part A Final Analysis .............................................................................................................9
2.2.
Final Analysis ..........................................................................................................................................9
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................10
3.1.
Analysis Sets..........................................................................................................................................10
3.1.1.
All Enrolled Analysis Set.....................................................................................................10
3.1.2.
Expanded RDV Analysis Set ...............................................................................................10
3.2.
Subject Grouping ...................................................................................................................................10
3.3.
Strata and Covariates..............................................................................................................................10
3.4.
Examination of Subject Subgroups........................................................................................................11
3.4.1.
Subject Subgroups for Efficacy Analyses ............................................................................11
3.4.2.
Subject Subgroups for Safety Analyses ...............................................................................11
3.5.
Multiple Comparisons............................................................................................................................11
3.6.
Missing Data and Outliers......................................................................................................................12
3.6.1.
Missing Data ........................................................................................................................12
3.6.2.
Outliers.................................................................................................................................12
3.7.
Data Handling Conventions and Transformations .................................................................................12
3.8.
Analysis Visit Windows.........................................................................................................................13
3.8.1.
Definition of Study Day .......................................................................................................13
3.8.2.
Analysis Visit Windows.......................................................................................................13
3.8.3.
Selection of Data in the Event of Multiple Records for an Analysis Visit 
Day.......................................................................................................................................14
4.
SUBJECT DISPOSITION ..................................................................................................................................15
4.1.
Subject Enrollment and Disposition.......................................................................................................15
4.2.
Extent of Study Drug Exposure .............................................................................................................15
4.2.1.
Exposure to Study Drug .......................................................................................................15
4.3.
Protocol Deviations................................................................................................................................15
5.
BASELINE CHARACTERISTICS....................................................................................................................16
5.1.
Demographics and Baseline Characteristics ..........................................................................................16
5.2.
Other Baseline Characteristics ...............................................................................................................16
5.3.
Medical History......................................................................................................................................16
6.
EFFICACY ANALYSES ...................................................................................................................................17
6.1.
Primary Efficacy Endpoint.....................................................................................................................17
6.2.
Efficacy Endpoints of Interest................................................................................................................17
6.2.1.
Analysis of Efficacy Endpoints of Interest...........................................................................18
6.3.
Changes from Protocol-Specified Efficacy Analyses ............................................................................19


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7.
SAFETY ANALYSES........................................................................................................................................20
7.1.
Endpoint of Interest................................................................................................................................20
7.2.
Adverse Events and Deaths....................................................................................................................20
7.2.1.
Adverse Event Dictionary ....................................................................................................20
7.2.2.
Adverse Event Severity........................................................................................................20
7.2.3.
Relationship of Adverse Events to Study Drug....................................................................20
7.2.4.
Serious Adverse Events........................................................................................................20
7.2.5.
Treatment-Emergent Adverse Events...................................................................................21
7.2.5.1.
Definition of Treatment-Emergent Adverse Events .......................................21
7.2.5.2.
Incomplete Dates ............................................................................................21
7.2.6.
Summaries of Adverse Events and Deaths...........................................................................21
7.2.7.
Additional Analysis of Adverse Events ...............................................................................22
7.2.7.1.
Renal Events...................................................................................................22
7.2.7.2.
Hepatic Events................................................................................................23
7.3.
Laboratory Evaluations ..........................................................................................................................23
7.3.1.
Summaries of Numeric Laboratory Results .........................................................................23
7.3.2.
Graded Laboratory Values ...................................................................................................24
7.3.2.1.
Treatment-Emergent Laboratory Abnormalities.............................................24
7.3.2.2.
Summaries of Laboratory Abnormalities........................................................24
7.4.
Body Weight, and Vital Signs................................................................................................................24
7.5.
Prior and Concomitant Medications.......................................................................................................25
7.6.
Other Safety Measures ...........................................................................................................................26
7.7.
Subject Subgroup for Safety Endpoints .................................................................................................26
7.8.
Changes from Protocol-Specified Safety Analyses................................................................................26
8.
PHARMACOKINETIC ANALYSES ................................................................................................................27
9.
REFERENCES ...................................................................................................................................................28
10.
SOFTWARE.......................................................................................................................................................29
11.
SAP REVISION..................................................................................................................................................30
12.
APPENDICES ....................................................................................................................................................31
Appendix 1.
Study Procedures Table..........................................................................................................32
Appendix 2.
Programming Specifications...................................................................................................33
Appendix 3.
Renal Events...........................................................................................................................38
Appendix 4.
Hepatic Events........................................................................................................................40
LIST OF IN-TEXT TABLES
Table 3-1.
Analysis Windows for Hematology and Chemistry Laboratory Tests (hemoglobin, 
hematocrit, platelet count, WBC, ALT, AST, total bilirubin, glucose, serum 
creatinine, and creatinine clearance).......................................................................................14


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LIST OF ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BMI
body mass index
CI
confidence interval
CRF
case report form
CSR
clinical study report
DAIDS
Division of AIDS
ECMO
extracorporeal membrane oxygenation
eCRF
electronic case report form
GLPS
Global Patient Safety
HLGT
high-level group term
HLT
high-level term
ID
identification/identifier
IWRS
interactive web response system
LLN
lower limit of normal
LLT
lowest level term
LOQ
limit of quantitation
MedDRA
Medical Dictionary for Regulatory Activities
PaO2
partial pressure of oxygen, arterial
PCR
polymerase chain reaction
PK
pharmacokinetic
PT
preferred term
Q1, Q3
first quartile, third quartile
RDV
remdesivir
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SE
standard error
SMQ
standardized MedDRA queries
SOC
system organ class
SpO2
oxygen saturation
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
ULN
upper limit of normal
WBC
white blood cell


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1.
INTRODUCTION
This Phase 3 study is conducted in two parts. In Part A, approximately 400 participants who met 
all eligibility criteria and who were not mechanically ventilated were randomized to one of 
two treatment groups. Part B starts after Part A is completed and includes up to approximately 
5600 participants.
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) for the analysis of Part B of 
Study GS-US-540-5773.
This SAP is based on the study protocol Amendment 3.0 dated 12 April 2020 and the electronic 
case report form (eCRF). The SAP will be finalized prior to data finalization. Any changes made 
after the finalization of the SAP will be documented in the clinical study report (CSR).
1.1.
Study Objectives
The purpose of this study is to provide remdesivir (RDV) to participants with severe COVID-19.
The primary objective of this study is as follows:

To evaluate the efficacy of 2 RDV regimens with respect to clinical status assessed by a 
7-point ordinal scale on Day 14.
The secondary objective of this study is as follows:

To evaluate the safety and tolerability of RDV.
1.2.
Study Design
This is a Phase 3 randomized, open-label, multicenter study of RDV therapy in participants with 
severe COVID-19.
Groups
For Part A, approximately 400 participants who met all eligibility criteria and who were not 
mechanically ventilated were randomized in a 1:1 ratio into one of the following treatment 
groups:

Treatment Group 1: 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, and 5

Treatment Group 2: 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


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Part B will enroll new participants on mechanical ventilation and, after enrollment to Part A is 
complete, any additional participants. In Part B, up to an additional approximately 
5600 participants who meet all of the eligibility criteria will be enrolled, based on whether they 
are mechanically ventilated at enrollment, to receive:
Mechanically Ventilated 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
Extension 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
Key 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

Oxygen saturation (SpO2) ≤94% on room air or requiring supplemental oxygen at screening

Radiographic evidence of pulmonary infiltrates
Schedule of Assessments
The date of randomization or enrollment is considered Day 1 and it is expected that all 
randomized or enrolled participants receive their initial dose of RDV on Day 1.
On Days 1 through 14 or until discharge, whichever is earlier, 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 standard of care practice with 
results for white blood cell (WBC) count, hemoglobin and/or hematocrit, platelets, creatinine, 
creatinine clearance, glucose, total bilirubin alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), and any SARS-CoV-2 testing being reported to the Sponsor. Clinical 
status will be recorded on the 7-point ordinal scale for each day.
In addition, even if not performed as standard of care, WBC 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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For Part A, participants who met eligibility criteria were randomized in a 1: 1 ratio to 1 of 
2 treatment groups on Day 1 using an interactive web response system (IWRS) and assigned a 
subject number. Randomization was not stratified. Part B is not randomized. 
Up to approximately 160 centers globally. 
Duration of Treatment 
Part A participants received study treatment with RDV for 5 days (Treatment Group 1) or 
10 days (Treatment Group 2). In Part B, participants in the Mechanically Ventilated Group and 
Extension Group will receive RDV for 10 days. If the participant is discharged, RDV treatment 
will end at that time. 
Discontinuation Criteria 
Study drug dosing in an individual participant 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 serious adverse event (SAE) or~ Grade 3 AE suspected to be related to RDV. 
• 
Any elevations in ALT > 5 x ULN; or ALT > 3 x ULN and total bilirubin > 2 x ULN, 
confinned by i1mnediate repeat testing. 
• 
Creatinine clearance< 30 mL/min 
End of Study 
The end of the study will be the last participant's last observation ( or visit). 
1.3. 
Sample Size and Power 
In Part A, a total of approximately 400 participants were randomized in a 1: 1 ratio to 2 groups 
(200 participants per group). 
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The sample size computation was based on an assumed distribution of the 7-point ordinal scale 
on Day 14 for Part A Treatment Group 1. The odds ratio represents the odds of improvement in 
the ordinal scale for Treatment Group 2 relative to Treatment Group 1. 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 400 participants (200 in each group) achieves > 85% power to detect an odds 
ratio of 1.75 using a two-sided significance level of 0.05. In this sample size calculation, it is 
assumed that the probability distribution of the ordinal scale at Day 14 for Treatment Group 1 is 
as follows:
1. Death, 2%
2. Hospitalized, on invasive mechanical ventilation or ECMO, 4%
3. Hospitalized, on non-invasive ventilation or high flow oxygen devices, 7%
4. Hospitalized, requiring low flow supplemental oxygen, 13%
5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care 
(COVID-19 related or otherwise), 16%
6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 
(other than per protocol RDV administration), 20%
7. Not hospitalized, 38%
The sample size calculation was performed using the software PASS (Version 14.0).
The sample size for Part B is based on the anticipated need for RDV and current trends in the 
COVID-19 epidemic.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
2.1.1.
Data Monitoring Committee Analysis 
The data monitoring committee reviewed the results from the analysis of the Part A Day 14
snapshot.
2.1.2.
Primary Analysis
The primary analysis was performed after participants in Part A either completed 14 days or 
prematurely terminated from Part A on or prior to Day 14.
2.1.3.
Part A Final Analysis
The final analysis for participants in Part A was performed after all participants in Part A 
completed the study or prematurely terminated from the study.
2.2.
Final Analysis
The final analysis for this study will be performed after all participants have completed Part B of 
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. This SAP describes 
the statistical analysis methods and data presentations to be used for the analysis of Part B.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of participants in each category will be presented; for continuous 
variables, the number of participants (n), mean, standard deviation (SD) or standard error (SE), 
median, first quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
By-subject listings will be presented for all participants in the All Enrolled Analysis Set unless 
otherwise specified, and sorted by subject ID number, visit date, and time (if applicable). Data 
collected on log forms, such as AEs, will be presented in chronological order within a 
participant. The group to which participants were categorized at baseline per Section 3.2 will be 
used in the listings. 
3.1.
Analysis Sets
Analysis sets define the participants to be included in an analysis. Analysis sets and their 
definitions are provided in this section. Participants included in each analysis set will be 
determined before database finalization. The analysis set will be included as a subtitle of each 
table, figure, and listing. A summary of the number and percentage of participants in each
analysis set will be provided by group and in total.
3.1.1.
All Enrolled Analysis Set
The All Enrolled Analysis Set will include all participants who are enrolled into Part B of the 
study. This is the primary analysis set for by-subject listings.
3.1.2.
Expanded RDV Analysis Set
The primary analysis set for efficacy and safety analysis is defined as the Expanded 
RDV-Treated Analysis Set, which will include all participants who (1) are enrolled into Part B
of the study and (2) have received at least 1 dose of RDV. Part B participants will be grouped 
according to their baseline ordinal scale (Mechanically Ventilated or Extension Group).
3.2.
Subject Grouping
Part B participants will be grouped according to their baseline ordinal scale (Mechanically 
Ventilated Group [baseline ordinal scale  2] or Extension Group [baseline ordinal scale > 2]).
This grouping may differ from the categorization at enrollment in the IWRS.
3.3.
Strata and Covariates
No formal statistical testing will be performed in the analysis of Part B of the study; therefore, no 
covariates are planned.


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3.4.
Examination of Subject Subgroups
3.4.1.
Subject Subgroups for Efficacy Analyses
Selected efficacy endpoints will be analyzed for the following subject subgroups: 

Age (years): (a) < 65 and (b) ≥65

Sex at birth: (a) male and (b) female 

Baseline oxygen support status (based on the 7-point ordinal scale): (a) invasive mechanical 
ventilation, (b) high flow oxygen, (c) low flow oxygen, and (d) room air (See Appendix 2), 
where (a) only applies to the Mechanically Ventilated Group and (b) - (d) apply to the 
Extension Group

Race: (a) Asian, (b) Black, (c) White and (d) Other. Other includes all races (including 
Not Permitted) other than Asian, Black, and White

Region: (a) North America, (b) Europe, and (c) Asia.
3.4.2.
Subject Subgroups for Safety Analyses
Incidence of all treatment-emergent AEs (TEAEs) and survival will be summarized for the 
following subject subgroups: 

Age (years): (a) < 65 and (b) ≥65

Sex at birth: (a) male and (b) female 

Baseline oxygen support status based on the 7-point ordinal scale: (a) invasive mechanical 
ventilation, (b) high flow oxygen, (c) low flow oxygen, and (d) room air (See Appendix 2), 
where (a) only applies to the Mechanically Ventilated Group and (b) - (d) apply to the 
Extension Group

Race: (a) Asian, (b) Black, (c) White and (d) Other. Other includes all races (including 
Not Permitted) other than Asian, Black and White

Region: (a) North America, (b) Europe, and (c) Asia.
3.5.
Multiple Comparisons
Adjustments for multiplicity will not be made, because no formal statistical testing will be 
performed in the analysis of Part B of the study.


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3.6.
Missing Data and Outliers
3.6.1.
Missing Data
Missing data can have an impact upon the interpretation of the trial data. In general, values for 
missing data will not be imputed, unless methods for handling missing data are specified.
In this study, a missing pre-treatment laboratory result will be treated as normal (ie, no toxicity 
grade) for the laboratory abnormality summary. The handling of missing or incomplete dates for 
AE onset is described in Section 7.2.5.2, and for prior and concomitant medications in 
Section 7.5.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no
sensitivity analyses will be done to evaluate the impact of outliers on efficacy or safety
outcomes, unless specified otherwise. All data will be included in the analyses.
3.7.
Data Handling Conventions and Transformations
In general, age collected at Day 1 (in years) will be used for analyses and presented in listings. If 
age at Day 1 is not available for a participant, then age derived based on date of birth and the 
first dose date will be used instead. If an enrolled participant was not dosed with any study drug, 
the enrollment date will be used instead of the Day 1 visit date. For screen failures, the date the 
first informed consent was signed will be used for the age derivation.
Laboratory data that are continuous in nature but are less than the lower limit of quantitation
(LOQ) or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “x” (where x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate summary statistics. An exception to this rule is any value reported as < 1 or < 0.1, 
etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used to 
calculate summary statistics.

A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.

The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).


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3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study Day 1 is defined as the first dosing date of study drug.
Study Days are calculated relative to Study Day 1 and derived as follows:

For postdose study days: Assessment Date First Dosing Date + 1

For days prior to the first dose: Assessment Date First Dosing Date
Therefore, Study Day 1/ First Dose Date is the day of first dose of study drug administration, as 
recorded on the Study Drug Administration eCRF form.
Last Dose Date is defined as the maximum, nonmissing, nonzero dose end date of treatment
recorded on the Study Drug Administration eCRF form with “Study Drug Permanently 
Withdrawn” box checked for participants who prematurely discontinued or completed study drug 
according to the Study Drug Completion eCRF. Refer to Appendix 2 for missing date
imputation, if necessary.
Last Study Date is the latest of the study drug start dates and end dates, the clinic visit dates, 
and the laboratory visit dates, including the 28-day follow-up visit date, and the death date
(if applicable, only for participants who prematurely discontinued study according to the Study 
Completion eCRF). 
Baseline value is defined as the last value obtained on or prior to the first dose date (and time, 
if available) unless otherwise specified (see Section 3.8.3). 
3.8.2.
Analysis Visit Windows
Participant visits might not occur on protocol-specified days. Therefore, for the purposes of 
analysis, observations will be assigned to analysis windows. The study day as defined in 
Section 3.8.1 will be used when data are summarized by visit.
Vital signs were to be collected daily; therefore, windows are not assigned, and results will be 
summarized for each Study Day, except for Study Day 28. For Study Day 28, the nominal day is 
Study Day 28, the lower limit is Study Day 15 and there is no upper limit. 
Ordinal scale results were to be recorded prior to dosing on Study Day 1. The worst result for 
each day from Day 1 (after first dose) through the earliest of discharge date or Day 14 was to be 
recorded. For participants who were discharged after Day 14, changes in score category were to 
be recorded each day from Day 15 to the earliest of discharge date or Day 28. For the ordinal 
scale, baseline is defined as the value recorded prior to dosing, or the last value obtained prior to 
the first dose date if the predose value was not recorded on the day of dosing. Results will be 
summarized for each Study Day without windows. If more than one result was reported on the 
same day, the worst result will be selected.


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The analysis windows for hematology and chemistry laboratory parameters are presented in 
Table 3-1.
Table 3-1.
Analysis Windows for Hematology and Chemistry Laboratory Tests
(hemoglobin, hematocrit, platelet count, WBC, ALT, AST, total 
bilirubin, glucose, serum creatinine, and creatinine clearance)
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1 (predose)*
Day 3
3
1 (postdose)*
3
Day 5
5
4
6
Day 8
8
7
8
Day 10
10
9
11
Day 14
14
12
15
Post Day 14**
28
16
*
For Baseline, the upper limit includes values collected at or prior to the first dose date/time. For Day 3, the lower limit 
includes values collected after the first dose date/time on Day 1.
**
Post Day 14 laboratory values will be considered for treatment emergent laboratory presentations only.
3.8.3.
Selection of Data in the Event of Multiple Records for an Analysis Visit Day 
Depending on the statistical analysis method, single values may be required for each Study Day
or analysis window. For example, change from baseline by visit usually requires a single value, 
whereas a time-to-event analysis does not require 1 value per Study Day or analysis window.
If multiple valid, nonmissing measurements exist for a Study Day/analysis window, records will 
be chosen based on the following rules if a single value is needed:

For baseline, the last nonmissing value on or prior to the first dosing date (and time, 
if available) of study drug will be selected, unless specified differently. If there are multiple 
records with the same time or no time recorded on the same day, the baseline value will be 
the average of the measurements for continuous data, or the measurement with the lowest 
severity for categorical data.

For postbaseline values:
For windows spanning multiple days, the record(s) collected on the day closest to the 
nominal day will be selected. If there are 2 days equidistant from the nominal day, the 
later day will be selected.
■
For laboratory values and SpO2 and partial pressure of oxygen, arterial (PaO2), if 
there is more than 1 record on the selected day, the worst value will be selected.
See Appendix 2 for definition of worst value.
■
For other parameters, if there is more than 1 record on the selected day, the average 
will be taken for continuous data and the worst severity will be taken for categorical 
data, unless otherwise specified.


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
The number and percentage of participants enrolled at each investigator site will be summarized
by group and overall using the Expanded RDV-Treated Analysis Set. The denominator for this 
calculation will be the number of participants in the Expanded RDV-Treated Analysis Set.
The summary of subject disposition will be provided by group and overall for all screened 
participants. This summary will include the number of participants screened, screen failure 
participants who were not enrolled, participants who met all eligibility criteria and were not 
enrolled, participants enrolled, participants enrolled but never treated, and participants in the
Expanded RDV-Treated Analysis Set.
In addition, the number and percentage of the participants in the following categories will be 
summarized:

Completed 10-day treatment on study drug as recorded on the Study Drug Completion form

Prematurely discontinuing study drug prior to completion of 10 days of dosing with summary 
of reasons for discontinuing study drug as recorded on the Study Drug Completion form

Completed study

Prematurely discontinuing from study with summary of reasons for discontinuing study as 
recorded on the Study Completion form
The denominator for the percentages of participants in each category will be the number of 
participants in the Expanded RDV-Treated Analysis Set. 
A data listing of reasons for study drug/study discontinuation will be provided.
4.2.
Extent of Study Drug Exposure 
4.2.1.
Exposure to Study Drug
Number of doses received will be summarized by group for the Expanded RDV-Treated
Analysis Set.
4.3.
Protocol Deviations 
A listing will be provided for all enrolled participants who violated at least 1 inclusion or 
exclusion criterion. The listing will include the criteria not met.
Protocol deviations occurring after participants entered the study are documented during routine 
monitoring. The number and percentage of participants with important protocol deviations by 
deviation reason and the total number of important protocol deviations by deviation reason
(eg, nonadherence to study drug, violation of select inclusion/exclusion criteria) will be 
summarized by group for the Expanded RDV-Treated Analysis Set. A by-subject listing will be 
provided for those participants with important protocol deviations.


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Participant demographic data (eg, sex, race/ethnicity, and age) and baseline characteristics 
(eg, body weight, height, and body mass index [BMI]) will be summarized by group and overall 
using descriptive statistics (n, mean, SD, median, Q1, Q3, minimum, and maximum) for 
continuous data and by the number and percentage of participants for categorical data. The 
summaries of demographic data and baseline participant characteristics will be provided for the 
Expanded RDV-Treated Analysis Set.
Age group (< 65 and ≥ 65) will be summarized by group and overall.
A by-subject demographic listing will be provided.
5.2.
Other Baseline Characteristics
The following baseline disease characteristics will be summarized by group and overall using 
descriptive statistics:

Clinical status (7-point ordinal scale)

Duration of hospitalization prior to first dose of RDV

Duration of symptoms prior to first dose of RDV

AST

ALT

Oxygen support status based on the 7-point ordinal scale (invasive mechanical ventilation, 
high flow oxygen, low flow oxygen, room air)

Region (North America, Europe, Asia)
5.3.
Medical History
Any medical condition or clinically significant laboratory abnormality with an onset date before 
the consent form is signed and not related to a protocol-associated procedure is considered to be 
preexisting and should be documented as medical history. General medical history data will be 
collected at screening and coded using the Medical Dictionary for Regulatory Activities
(MedDRA). A summary table will present the percentages of participants reporting each medical 
history preferred term, sorted first in alphabetical order by system organ class (SOC) and then by 
preferred term (PT) in descending order of total frequency within SOC. Preferred terms with the 
same total frequency will be sorted in alphabetical order.


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6.
EFFICACY ANALYSES
6.1.
Primary Efficacy Endpoint
The primary efficacy endpoint was analyzed for Part A of the study and is not described in this 
SAP.
6.2.
Efficacy Endpoints of Interest
Efficacy endpoints of interest include endpoints based on clinical status assessed by a 7-point 
ordinal scale. The endpoint will be derived by combining the available death, hospital discharge
alive and ordinal scale assessment reported by the site, where death supersedes discharge alive
and discharge alive supersedes the ordinal scale score reported by the site.
Sites were instructed to report the worst ordinal scale category for each day. Therefore, the 
ordinal scale result on the day the participant was discharged alive does not necessarily reflect 
Not hospitalized ( 7). The definition of clinical status based on the 7-point ordinal scale is 
defined as follows:

If a participant dies while hospitalized (as recorded on the Death eCRF and Hospitalization 
eCRF), the endpoint on the day of death and all subsequent days through Day 28 will be set 
to Death ( 1)

If the participant is discharged alive, the endpoint on the day of discharge alive and all 
subsequent days through Day 28 will be set to Not hospitalized ( 7)

If the participant is discharged alive and dies on the same day or a later day (as recorded on 
the Death eCRF and Hospitalization eCRF), the endpoint on the day of discharge alive and 
all subsequent days until the day of death will be set to Not hospitalized ( 7). On the day of 
death and all subsequent days through Day 28, the endpoint will be set to Death ( 1),
Every effort will be made to obtain clinical status data for all participants prior to discharge 
alive. The last known clinical status will be used for days with missing clinical status (eg, where 
the reason for Hospital Discharge is not “Discharged Alive” and the participant has not died). All 
post-baseline days with missing ordinal scale score, from Day 2 to Day 14 and Day 28, will use 
the previous last known clinical status.
Efficacy endpoints of interest include

Clinical status on Days 1 to 14, Day 28 and last available assessment

Change in clinical status on Days 5, 7, 11, 14, 28, and last available assessment

Time to clinical improvement (days): Clinical improvement is defined as a ≥ 2-point 
improvement from baseline clinical status or discharged alive on the 7-point ordinal scale 
using the definition specified above. 

Percentage of participants with a ≥ 2-point improvement or discharged alive based on the 
7-point ordinal scale using the definition specified above on Day 5, Day 7, Day 11, Day 14,
Day 28, and last available assessment


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
Time to ≥ 1-point improvement (days) from baseline clinical status on the 7-point ordinal 
scale using the definition specified above. 

Percentage of participants with a ≥ 1-point improvement based on the 7-point ordinal scale 
using the definition specified above on Day 5, Day 7, Day 11, Day 14, Day 28 and last 
available assessment

Time to recovery based on the 7-point ordinal scale using the definition above, where 
recovery is defined as an improvement 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

Percentage of participants with recovery based on the 7-point ordinal scale using the 
definition specified above on Day 5, Day 7, Day 11, Day 14, Day 28 and last available 
assessment

Number of days of oxygen support while hospitalized through discharge alive, death or 
Day 14 based on the 7-point ordinal scale reported values (See Appendix 2). This summary 
will present results separately for participants who died on or prior to Day 14 and those who 
were discharged alive on or prior to Day 14 and will include: 
Days on invasive mechanical ventilation 
Days on high flow oxygen devices 
Days requiring low flow supplemental oxygen
Because oxygen support status was collected only while the participant was in the hospital, 
if a participant was discharged alive and died afterwards, the participant will be included 
only in the summary for participants discharged alive.

Shift in oxygen support status from baseline to Days 5, 7, 11, 14, 28 and last available 
assessment

Duration of hospitalization (days) (duration from hospital admission and duration from 
Day 1). Duration of hospitalization is calculated through Day 28 for participants who were 
discharged alive on or prior to Day 28. If participants were rehospitalized for COVID-19 
related reasons, the hospitalization discharge information is entered in the eCRF database 
using the latest hospitalization admission. 

All-cause mortality
6.2.1.
Analysis of Efficacy Endpoints of Interest
The number and percentage of participants in each clinical status category for each day from 
Baseline through Day 14 and at Day 28 and using the last available assessment will be 
summarized by group. These results will be summarized using (1) the clinical status definition in 
Section 6.2 and (2) with the definition specified in Section 6.2 but excluding days with missing 
ordinal scale score not due to death or discharge alive. In addition, stacked bar charts by study 
day (Baseline through Day 14 and at Day 28) will be produced by group using the definition 
specified in Section 6.2.


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The number and percentage of participants in each clinical status category for each day from 
Baseline through Day 14 and at Day 28 and last available assessment will be summarized within 
each subgroup defined in Section 3.4.1.
The change from baseline in clinical status category on Days 5, 7, 11, 14, 28 and last available 
assessment will be summarized by group using descriptive statistics.
Number of days of oxygen support status modes (invasive mechanical ventilation, high flow 
oxygen, low flow oxygen) will be calculated as the number of days oxygen support was reported 
on the 7-point ordinal scale eCRF through death, discharge alive, or Day 14 and presented for 
each group using descriptive statistics.
A shift table of baseline oxygen support status (death, invasive mechanical ventilation, high flow 
oxygen, low flow oxygen, room air, discharge alive) to Days 5, 7, 11, 14, 28 and the last 
available status will be provided for each group. 
Duration of hospitalization will be calculated only for participants who are discharged alive on or 
prior to Day 28 and will be summarized for each group using descriptive statistics.
All-cause mortality will be estimated for each group using the Kaplan-Meier product limit 
method with all available data. Participants who did not die will be censored at the last study 
day.
Days to clinical improvement and days to recovery will be estimated for each group using a 
competing risk analysis approach, with death as the competing risk. Participants without 
recovery will be censored on the day of the last non-missing ordinal scale assessment.
Forest plots by subgroup will be presented for all-cause mortality Kaplan-Meier estimates on 
Day 28 and cumulative incidence of recovery on Day 28.
The number and percent of participants in each group with ≥ 1-point improvement, ≥2-point 
improvement, and recovery will be presented with 95% confidence intervals on Day 5, Day 7, 
Day 11, Day 14, Day 28 and last available assessment.
Analyses will be performed using the Expanded RDV-Treated Analysis Set.
6.3.
Changes from Protocol-Specified Efficacy Analyses
There are no changes from the protocol-specified efficacy analyses.


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7.
SAFETY ANALYSES
Safety data will be summarized for the participants in the Expanded RDV-Treated Analysis Set. 
All safety data collected on or after the date that study drug was first dispensed through 30 days 
after last dose will be summarized by group for the Expanded RDV-Treated Analysis Set, unless 
specified otherwise. All safety data will be included in data listings.
7.1.
Endpoint of Interest
The percentage of participants in the Mechanically Ventilated Treatment Group and the 
Extension Treatment Group with any treatment-emergent adverse events, an endpoint of interest,
will be summarized for each group.
7.2.
Adverse Events and Deaths
7.2.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using MedDRA. SOC, high-level 
group term (HLGT), high-level term (HLT), PT, and lowest-level term (LLT) will be provided in 
the AE dataset.
7.2.2.
Adverse Event Severity
The severity of AEs will be graded using the Division of AIDS (DAIDS) Table for Grading the
Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017. For each episode, 
the highest grade attained should be reported as defined in the grading scale. The DAIDS scale is
available at the following location:
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf
Adverse events are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 
(severe), Grade 4 (life threatening) or Grade 5 (fatal) according to toxicity criteria specified in 
the document above. The severity grade of events for which the investigator did not record 
severity will be left as “missing” for data listings.
7.2.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE eCRF to the 
question of “Related to Study Treatment.” Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.2.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definition 
of SAE specified in the study protocol. Serious adverse events captured and stored in the clinical 


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database will be reconciled with the SAE database from the Gilead Global Patient Safety (GLPS)
before data finalization.
7.2.5.
Treatment-Emergent Adverse Events
7.2.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the study drug start date and no later than 30 days
after permanent discontinuation of study drug

Any AEs leading to premature discontinuation of study drug.
7.2.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The month and year (or year) of the AE onset is the same as or after the month and year 
(or year) of the first dosing date of study drug, and

The month and year (or year) of the AE onset is the same as or before the month and year 
(or year) of the date corresponding to 30 days after the date of the last dose of study drug
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date marked as ongoing or on or after the first dosing date of study drug, will be considered to be 
treatment emergent. In addition, an AE with the onset date missing and incomplete stop date 
with the same or later month and year (or year alone if month is not recorded) as the first dosing 
date of study drug will be considered treatment emergent.
7.2.6.
Summaries of Adverse Events and Deaths
The number and percentage of participants who experienced at least 1 TEAE will be provided 
and summarized by SOC, HLT, PT, and group. For other AEs described below, summaries will 
be provided by SOC, PT, and group using the Expanded RDV-Treated Analysis Set:

Grade 3 or higher treatment-emergent AEs

All treatment-emergent study drug-related AEs 

Grade 3 or higher treatment-emergent study drug-related AEs

All treatment-emergent SAEs

All treatment-emergent study drug-related SAEs


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
All treatment-emergent AEs that caused premature discontinuation from study drug

Treatment-emergent deaths
A brief, high-level summary of AEs described above will be provided by group and by the 
number and percentage of participants who experienced the above AEs. Treatment-emergent 
deaths observed in the study will also be included in this summary.
Treatment-emergent death refers to deaths that occurred between the first dose date and the 
last dose date plus 30 days (inclusive).
Multiple events will be counted only once per participant in each summary. Adverse events will 
be summarized and listed first in alphabetic order of SOC and HLT within each SOC 
(if applicable), and then by PT in descending order of total frequency within each SOC. For 
summaries by severity grade, the most severe grade will be used for those AEs that occurred 
more than once in an individual participant during the study.
In addition to the above summary tables, all treatment-emergent AEs, treatment-emergent AEs
with Grade 3 or higher, treatment-emergent study drug-related AEs, treatment-emergent study 
drug-related AEs with Grade 3 or higher, and treatment-emergent SAEs will be summarized by 
PT only, in descending order of total frequency. Preferred terms with the same total frequency 
will be sorted in alphabetical order. Treatment-emergent AEs and study-drug related treatment-
emergent AEs will also be summarized by highest grade.
Data listings will be provided for the following:

All AEs

Study-Drug-Related AEs

AEs with severity of Grade 3 or higher

SAEs

Study-Drug-Related SAEs

Deaths

AEs leading to premature discontinuation of study drug
7.2.7.
Additional Analysis of Adverse Events
7.2.7.1.
Renal Events
Preferred terms for renal events are from the acute renal failure Standardised MedDRA Query
(SMQ). The selected PT listing was provided by Gilead GLPS and reviewed by Gilead medical 
monitors (see details in Appendix 3).


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Treatment-emergent renal AEs will be summarized by PT only, in descending order of total 
frequency. In addition, treatment-emergent renal AEs will be listed.
7.2.7.2.
Hepatic Events
Liver function test increased events include ALT increased, AST increased, hepatic enzyme 
increased, hypertransaminasaemia, liver function test increased, and transaminaseses increased. 
Preferred terms for hepatic events are from the search term list ‘Acute and non-infectious liver 
events.’ The selected PT listing was provided by Gilead GLPS and reviewed by Gilead medical 
monitors (see details in Appendix 4).
Treatment-emergent liver function test increased AEs and hepatic events will be summarized by 
PT only, in descending order of total frequency. An overall summary of treatment-emergent 
hepatic AEs will be provided. In addition, treatment-emergent hepatic AEs will be listed.
7.3.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Expanded RDV-Treated Analysis Set and will include data collected up to the last dose of study 
drug plus 30 days. The analysis will be based on values reported in conventional units. When 
values are below the LOQ, they will be listed as such, and the closest imputed value will be used 
for the purpose of calculating summary statistics as specified in Section 3.7. 
A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, serum chemistry, and PCR separately. Values falling 
outside of the reference range and/or having a severity grade of 1 or higher on the DAIDS 
Grading Scale will be flagged in the data listings, as appropriate.
7.3.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by group for each laboratory test as follows:

Baseline values

Values at each postbaseline analysis window

Change from baseline at each postbaseline analysis window
A baseline laboratory value will be defined as the last nonmissing value obtained on or prior to 
the date (and time, if applicable) of first dose of study drug. Change from baseline to a 
postbaseline visit will be defined as the postbaseline value minus the baseline value. The mean, 
median, Q1, Q3, minimum, and maximum values will be displayed to the number of digits
indicated in Appendix 2.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.


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7.3.2.
Graded Laboratory Values
The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Event, Version 2.1 
(July 2017) will be used for assigning toxicity grades (0 to 4) to laboratory results for analysis. 
Grade 0 includes all values that do not meet the criteria for an abnormality of at least Grade 1. 
For laboratory tests with criteria for both increased and decreased levels, analyses for each 
direction (ie, increased, decreased) will be presented separately.
7.3.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of 
last dose of study drug plus 30 days. If the relevant baseline laboratory value is missing, any 
abnormality of at least Grade 1 observed within the time frame specified above will be 
considered treatment emergent.
7.3.2.2.
Summaries of Laboratory Abnormalities
The following summaries (number and percentage of participants) for treatment-emergent 
laboratory abnormalities will be provided by laboratory test and group; participants will be 
categorized according to the most severe postbaseline abnormality grade for a given laboratory
test:

Treatment-emergent laboratory abnormalities

Treatment-emergent Grade 3 and 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of participants
with nonmissing postbaseline values up to 30 days after last dosing date.
A by-subject listing of laboratory abnormalities and Grade 3 or 4 laboratory abnormalities will 
be provided by subject ID number and visit in chronological order.
7.4.
Body Weight, and Vital Signs
Descriptive statistics will be provided by group for body weight, and vital signs (including 
heart rate, respiratory rate, blood pressure) as follows:

Baseline value

Values at each postbaseline visit

Change from baseline at each postbaseline visit
A baseline value will be defined as the last available value collected on or prior to the date/time 
of first dose of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value.


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In the case of multiple values on one Study Day, data will be selected for analysis as described in
Section 3.8.3. 
Temperature will not be summarized due to different methods of measuring temperature. SpO2
and PaO2 will not be summarized due to multiple measures through varying oxygen 
supplementation methods. 
A by-subject listing of body weight, BMI, and vital signs (including heart rate, respiratory rate, 
temperature, and blood pressure) will be provided by subject ID number and visit in 
chronological order. Similarly, a by-subject listing of oxygen saturation (including oxygen 
delivery mode, oxygen concentration, oxygen flow, SpO2, and PaO2) will be provided.
7.5.
Prior and Concomitant Medications
Concomitant use of traditional herbal treatments including herb sho-saiko-to 
(or Xiao-Shai-Hu-Tang) or investigational agents with putative antiviral activity for COVID-19 
including approved HIV protease inhibitors like lopinavir/ritonavir, chloroquine, interferon, etc 
is prohibited in participants receiving RDV.
Concomitant use of investigational agents such as approved HIV protease inhibitors like 
lopinavir/ritonavir, chloroquine, interferon, 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.
Concomitant medications are defined as medications taken while a participant took study drug.
Use of concomitant medications will be summarized by preferred name using the number and 
percentage of participants for each group. A participant reporting the same medication more than 
once will be counted only once when calculating the number and percentage of participants who 
received that medication. The summary will be ordered by preferred name in descending overall 
frequency. For drugs with the same frequency, sorting will be done alphabetically.
For the purposes of analysis, any medications with a start date prior to or on the first dosing date 
of study drug and continued to be taken after the first dosing date, or started after the first dosing 
date but prior to or on the last dosing date of study drug will be considered concomitant 
medications. Medications started and stopped on the same day as the first dosing date or the 
last dosing date of study drug will also be considered concomitant. Medications with a stop date 
prior to the date of first dosing date of study drug or a start date after the last dosing date of study 
drug will be excluded from the concomitant medication summary. If a partial stop date is 
entered, any medication with the month and year (if day is missing) or year (if day and month are 
missing) prior to the date of first study drug administration will be excluded from the 
concomitant medication summary. If a partial start date is entered, any medication with the 
month and year (if day is missing) or year (if day and month are missing) after the study drug 
stop date will be excluded from the concomitant medication summary. Medications with year 
missing from start date (but with day and/or month) will be considered concomitant unless the 
stop date is prior to the first dosing date. Medications with completely missing start and stop 
dates will be included in the concomitant medication summary, unless otherwise specified. 
Summaries of concomitant medications will be provided for the Expanded RDV-Treated 
Analysis Set. Participants with any prior and/or concomitant medications will be listed. 


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7.6.
Other Safety Measures
A data listing will be provided for participants experiencing pregnancy during the study.
7.7.
Subject Subgroup for Safety Endpoints
Incidence of all treatment-emergent AEs will be repeated within each subgroup defined in 
Section 3.4.2 using the Expanded RDV-Treated Analysis Set.
7.8.
Changes from Protocol-Specified Safety Analyses
There are no changes from the protocol-specified safety analysis.


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CCI
CCI
CCII 


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9.
REFERENCES
Whitehead J. Sample size calculations for ordered categorical data. Stat Med 1993;12 (24):2257-
71.


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10.
SOFTWARE
SASVersion 9.4 (SAS Institute Inc., Cary, NC.) is to be used for all programming of tables, 
listings, and figures.
PASS Version 14 (NCSS, LLC, Kaysville, Utah) was used for planned sample size and power 
calculation.


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11.
SAP REVISION
Revision Date
Section
Summary of Revision
Reason for Revision


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12.
APPENDICES
Appendix 1.
Study Procedures Table
Appendix 2.
Programming Specifications
Appendix 3.
Renal Events
Appendix 4.
Hepatic Events


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Appendix 1.
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
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 at rest, and body weight. Body weight collected on screening and Day 1 and otherwise if available.
b
Assessments need not be repeated if performed the same calendar day as screening procedures.; data collection other than adverse events should stop Day 14 or discharge
whichever is earlier.
c
Day 28 evaluations completed if the visit is conducted in person. Only AEs, ordinal scale, and concomitant medication review completed if visit conducted by phone.
CCI
CCI
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Appendix 2.
Programming Specifications
1) If the age from the Day 1 eCRF is not available, age will be calculated as follows:
Only year is provided for the date of birth (DOB). Use July 1 for the month and day.
a) AGE (years) is calculated from the number of days between the DOB and Study Day 1,
b) Use the SAS INTCK function to determine the number of “1st-of-month days” 
(eg, January 1st, February 1st, March 1st) between DOB and Day 1 (inclusive),
c) Divide the result in (b) by 12,
AGE  the integer of the result in (c),
Age for laboratory test reference range will be based on the age at the sample collection 
date.
2) All screened participants refer to all participants who are screened (ie, with non-missing 
screening date) and have a screening number. For summaries the same participant is counted 
only once.
3) Screen failure participants are the participants who were screened and answered “No” for any 
inclusion criteria or “Yes” for any exclusion criteria regardless of which version of protocol 
the participant was consented to.
4) Participants in the enrolled analysis set are defined as participants enrolled into the study. 
IXRSRAND is the source to determine whether the participant is enrolled (ie, participant
with non-missing ENRDTN in the IXRSRAND dataset), and confirmed by the eCRF 
ENROLL dataset (ie, ENROLLYN  “Yes” in ENROLL dataset).
5) Treatment (ie, TRT01P in ADSL) is derived from IXRSRAND, while actual treatment 
received (ie, TRT01A in ADSL) is based on the baseline ordinal scale reported at the 
pre-dose timepoint. If the participant was never dosed, actual treatment received will be 
assigned as “Never Dosed.”
6) In the disposition table, the reasons for premature discontinuation are displayed in the order 
as they appear on the eCRF.
7) Body mass index (BMI) 
BMI will be calculated only at baseline as follows:
BMI
 (weight [kg]) / (height [meters]2)
Baseline height and weight will be used for this calculation if available.


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8) Definition of worst values for laboratory, SpO2 and PaO2 results.
Test
Result
ALT
Highest result
AST
Highest result
Creatinine
Highest result
Glucose
Highest result if any >ULN and none <LLN
Lowest result if any <LLN and none >ULN
Otherwise use the average
Total bilirubin
Highest result
Creatinine Clearance
Lowest result
Hemoglobin
Lowest result
Hematocrit
Lowest result
Platelet count
Lowest result
WBC
Lowest result
SpO2
Lowest result
PaO2
Lowest result
If there are 2 values with the same “worst” numerical result on the same day, the later value is 
chosen.
9) For demographics tables, “Not Permitted”, “Unknown”, or missing categories will be 
excluded from percentage with the exception of Race Category where “Not Permitted” is 
included in “Other.”
10) Confidence Interval for single percentage
The 95% CI for percentage estimate for each group is calculated based on the 
Clopper-Pearson exact method.
proc freq;
by trt;
tables event/ binomial;
exact binomial;
run;
11) Competing risk analysis
EVENT  1 if the participant had the event; EVENT  2 if the participant died prior to 
having the event, and EVENT  0 if the participant did not have the event and did not die.
SAS code to obtain a cumulative incidence function plot and dataset for further processing
for time to first event table: 
proc lifetest outcif outcif plots cif;
strata trt;
time days*event(0) / failcode  1; *Note: this produces data for the event of interest only;
run;


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SAS code to obtain support tables: 
proc univariate;
by trt event;
var days;
output pctlpre P_ min min max max pctlpts  10, 25, 50, 75, 90;
run;
12) TEAE
Events with Missing Onset Day and/or Month
An event is considered treatment emergent if any of the following 3 criteria are met:
i.
The month and year (or year) of onset date is the same as or after the month and year 
(or year) of the first dose of study drug, and
ii.
The month and year (or year) of the onset date is the same as or before the month and 
year (or year) of the 30th day after the date of the last dose of study drug, and
iii.
End date is as follows: 
The (complete) end date is on or after the first dose date, or
The month and year (or year) of end date is the same or after the month and year 
(or year) of the first dose of study drug, or
End date is completely missing 
Events with Completely Missing Onset Date
An AE with a completely missing onset date is defined as TEAE if end date meets any of the 
3 criteria specified above.
13) The precision in reporting numerical values should be as follows:
Raw measurements will be reported the same as the data captured electronically or on the 
eCRF for all but hematology and chemistry values.
The precision for reporting numerical values for hematology and chemistry is as follows:
Laboratory 
category
Laboratory parameter
Number of digits after the decimal place for mean, 
median, minimum, Q1, Q3, maximum
Hematology
Hemoglobin (g/dL)
1
Hematology
Hematocrit (%)
1
Hematology
Platelet count (x10^9/L)
0
Hematology
WBC (x10^9/L)
2
Chemistry
ALT (U/L)
0
Chemistry
AST (U/L)
0
Chemistry
Total bilirubin (mg/dL)
2
Chemistry
Glucose (mg/dL)
0
Chemistry
Serum creatinine (mg/dL)
2
Chemistry
Creatinine Clearance by 
Cockcroft Gault (mL/min)
1


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Standard deviation and standard error will be reported to one more significant decimal place 
than the raw measurement.
Mean, median, minimum, Q1, Q3, and maximum will be reported to the same number of 
decimal places of the raw measurements. 
Exceptions may be considered; for example, if more than 4 significant digits are provided for 
the measurement.
14) Last dose date is not expected to be missing. However, if last dose date is missing, it will be 
imputed using the maximum of non-missing, non-zero dose, study drug start and stop dates.
15) Incomplete death dates will be imputed as the maximum of the study drug start dates (lasfdt), 
study drug end dates (lasldt), clinic visit dates (lvis28dt), laboratory visit dates (llab28dt), 
including the 28-day follow-up visit date plus 1, ie dthdt  
max(lasfdt,lasldt,lvis28dt,llab28dt) + 1.
16) Ordinal scale and oxygen support status
The oxygen support status is derived from the ordinal scale: 
Ordinal Scale
Oxygen Support Status
1
Death
Death
2
Hospitalized, on invasive mechanical ventilation or ECMO
Invasive Mechanical Ventilation
3
Hospitalized, on non invasive ventilation or high flow oxygen devices
High Flow Oxygen
4
Hospitalized, requiring low flow supplemental oxygen
Low Flow Oxygen
5
Hospitalized, not requiring supplemental oxygen requiring ongoing 
medical care (COVID 19 related or otherwise)
Room Air
6
Hospitalized, not requiring supplemental oxygen no longer requires 
ongoing medical care (other than per protocol RDV administration)
Room Air
7
Not hospitalized
Discharge
17) Censoring rules
Time to death: participants are censored at the last known date alive (last study day)
Time to ≥ 2-point improvement, time to ≥ 1-point improvement, time to recovery; if a 
participant does not experience the event of interest and does not die, the participant is 
censored at the last non-missing ordinal scale assessment date.


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18) Graded Laboratory Abnormalities Summary
The following labels will be used for laboratory abnormalities and Grade 3 or 4 laboratory 
abnormalities summary tables and listings:
Battery
Lab Test Label
Used in l-labtox Listing
Toxicity 
Direction
Lab Test Label
Used in t-labtox Table
Hematology
Hemoglobin
Decrease
Hemoglobin (Decreased)
Platelets
Decrease
Platelets (Decreased)
WBC
Decrease
WBC (Decreased)
Chemistry
ALT
Increase
ALT (Increased)
AST
Increase
AST (Increased)
Creatinine
Increase
Creatinine (Increased)
Creatinine Clearance
Decrease
Creatinine Clearance (Decreased)
Serum Glucose
Increase
Serum Glucose (Hyperglycemia)
Serum Glucose
Decrease
Serum Glucose (Hypoglycemia)
Total Bilirubin
Increase
Total Bilirubin (Hyperbilirubinemia)


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Appendix 3.
Renal Events
An adverse event record will be flagged as a renal event if its MedDRA PT is included in this
pre-specified PT list, which includes all PTs from the broad and narrow search of the acute renal 
failure SMQ under MedDRA v22.1 provided by Gilead GLPS (search name: Acute Renal 
Failure (SMQ)) and reviewed by Gilead medical monitors.
SMQ Source
Preferred Term
Acute Renal Failure (SMQ)
Albuminuria
Anuria
Azotaemia
Blood creatinine abnormal
Blood creatinine increased
Blood urea abnormal
Blood urea increased
Creatinine renal clearance decreased
Glomerular filtration rate abnormal
Glomerular filtration rate decreased
Haemodialysis
Nephritis
Nephropathy toxic
Oliguria
Peritoneal dialysis
Proteinuria
Renal failure
Renal failure neonatal
Renal transplant
Renal tubular disorder
Renal tubular necrosis
Urea renal clearance decreased
Tubulointerstitial nephritis
Oedema due to renal disease
Renal impairment neonatal
Neonatal anuria
Renal tubular dysfunction
Blood urea nitrogen/creatinine ratio increased
Haemofiltration


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SMQ Source
Preferred Term
Protein urine present
Creatinine urine decreased
Urine output decreased
Dialysis
Renal function test abnormal
Renal impairment
Hypercreatininaemia
Continuous haemodiafiltration
Creatinine renal clearance abnormal
Kidney injury molecule-1
Acute kidney injury
Acute phosphate nephropathy
Creatinine urine abnormal
Crystal nephropathy
Prerenal failure
Intradialytic parenteral nutrition
Fractional excretion of sodium
Hyponatriuria
Renal tubular injury
Foetal renal impairment
Subacute kidney injury
Neutrophil gelatinase-associated lipocalin increased


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Appendix 4.
Hepatic Events
An adverse event record will be flagged as a hepatic event if its MedDRA PT is included in this
pre-specified PT list, which includes the following 152 PTs for acute and non-infectious liver 
events under MedDRA v22.1 provided by Gilead GLPS (search name: Acute and non-infectious 
liver events_simple) and reviewed by Gilead medical monitors.
Search Term
Preferred Term
Acute and Non-infectious Liver Events
5'nucleotidase increased
Acute hepatic failure
Alanine aminotransferase abnormal
Alanine aminotransferase increased
Ammonia abnormal
Ammonia increased
Aspartate aminotransferase abnormal
Aspartate aminotransferase increased
Asterixis
Autoimmune hepatitis
Bilirubin conjugated increased
Biopsy liver abnormal
Blood bilirubin increased
Blood bilirubin unconjugated increased
Blood cholinesterase abnormal
Blood cholinesterase decreased
Blood fibrinogen abnormal
Blood fibrinogen decreased
Blood thrombin abnormal
Blood thrombin decreased
Blood thromboplastin abnormal
Blood thromboplastin decreased
Bromosulphthalein test abnormal
Cholestasis
Coagulation factor decreased
Coagulation factor IX level decreased
Coagulation factor V level decreased
Coagulation factor VII level decreased
Coagulation factor X level decreased


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Search Term
Preferred Term
Coma hepatic
Gamma-glutamyl transferase abnormal
Gamma-glutamyl transferase increased
Hepaplastin abnormal
Hepaplastin decreased
Hepatic encephalopathy
Hepatic failure
Hepatic function abnormal
Hepatic necrosis
Hepatic pain
Hepatitis
Hepatitis acute
Hepatitis cholestatic
Hepatitis fulminant
Hepatitis toxic
Hepatocellular injury
Hepatomegaly
Hepatorenal failure
Hepatorenal syndrome
Hepatosplenomegaly
Hepatotoxicity
Hyperammonaemia
Hyperbilirubinaemia
Hypocoagulable state
Hypoprothrombinaemia
Icterus index increased
International normalised ratio abnormal
International normalised ratio increased
Jaundice
Jaundice cholestatic
Jaundice hepatocellular
Leucine aminopeptidase increased
Liver disorder


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Search Term
Preferred Term
Liver function test abnormal
Liver tenderness
Protein C decreased
Prothrombin level abnormal
Prothrombin level decreased
Prothrombin time abnormal
Prothrombin time prolonged
Prothrombin time ratio increased
Ultrasound liver abnormal
Yellow skin
Cholaemia
Glutamate dehydrogenase increased
Antithrombin III decreased
Urine bilirubin increased
Protein S decreased
Hypofibrinogenaemia
Thrombin time abnormal
Guanase increased
Bile output decreased
Bile output abnormal
Thrombin time prolonged
Protein S abnormal
Hepatopulmonary syndrome
Foetor hepaticus
Perihepatic discomfort
Transaminases increased
X-ray hepatobiliary abnormal
Subacute hepatic failure
Ocular icterus
Blood bilirubin abnormal
Hypothrombinaemia
Hypothromboplastinaemia
Blood alkaline phosphatase increased


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Search Term
Preferred Term
Blood alkaline phosphatase abnormal
Galactose elimination capacity test abnormal
Galactose elimination capacity test decreased
Hepatic enzyme increased
Bilirubin excretion disorder
Coagulation factor IX level abnormal
Coagulation factor V level abnormal
Coagulation factor VII level abnormal
Coagulation factor X level abnormal
Prothrombin time ratio abnormal
Liver scan abnormal
Hepatobiliary disease
Hepatic enzyme abnormal
Transaminases abnormal
Cholestatic pruritus
Total bile acids increased
Hepatic infiltration eosinophilic
Mitochondrial aspartate aminotransferase increased
Hepatobiliary scan abnormal
Hepatic encephalopathy prophylaxis
Mixed liver injury
Molar ratio of total branched-chain amino acid to tyrosine
Liver injury
Bilirubin conjugated abnormal
Cholestatic liver injury
Hypertransaminasaemia
Child-Pugh-Turcotte score increased
Acquired protein S deficiency
Urobilinogen urine increased
Acute yellow liver atrophy
Allergic hepatitis
Deficiency of bile secretion
Drug-induced liver injury


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Search Term
Preferred Term
Parenteral nutrition associated liver disease
Acquired antithrombin III deficiency
Hyperfibrinolysis
Portal tract inflammation
Liver palpable
Minimal hepatic encephalopathy
Hepatic hypertrophy
Liver dialysis
Child-Pugh-Turcotte score abnormal
Model for end stage liver disease score abnormal
Model for end stage liver disease score increased
Acute on chronic liver failure
Bilirubin urine present
Anti factor X activity abnormal
Anti factor X activity increased
Liver function test increased
Computerised tomogram liver abnormal
Immune-mediated hepatitis
Hepatic lymphocytic infiltration
Acquired factor VIII deficiency
Acquired factor XI deficiency
Acquired factor IX deficiency
AST/ALT ratio abnormal
Magnetic resonance imaging liver abnormal


GS-US-540-5773_Part_B_SAP
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
24-Sep-2020
16:00:10
Clinical Research eSigned 25-Sep-2020
05:27:22
PPD
PPD-

Prot_000.pdf: 
CLINICAL STUDY PROTOCOL
Study Title:
A Phase 3 Randomized Study to Evaluate the Safety and Antiviral 
Activity of Remdesivir (GS-5734™) in Participants with Severe
COVID-19
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
147753
2020-000841-15
NCT04292899
Indication:
COVID-19
Protocol ID:
GS-US-540-5773
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:
20 March 2020
Amendment 3.0: 
12 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 ..............................................................................................................................................13
1.1.
Background ............................................................................................................................................13
1.2.
Remdesivir (RDV, GS-5734).................................................................................................................13
1.2.1.
General Information .............................................................................................................14
1.2.2.
Preclinical Pharmacology and Toxicology...........................................................................14
1.3.
Rationale for This Study ........................................................................................................................14
1.4.
Rationale for Dose Selection of Remdesivir ..........................................................................................15
1.4.1.
Pediatric Dosing ...................................................................................................................16
1.5.
Risk/Benefit Assessment for the Study..................................................................................................16
1.6.
Compliance ............................................................................................................................................18
2.
OBJECTIVES.....................................................................................................................................................19
3.
STUDY DESIGN................................................................................................................................................20
3.1.
Endpoints ...............................................................................................................................................20
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...................................................................................................................................24
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) ..............................................................................................30
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 ........................................................................................................36
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events.......................................................................................................................................37
7.3.1.
Requirements for Collection Prior to Study Drug Initiation.................................................37
7.3.2.
Adverse Events.....................................................................................................................37
7.3.3.
Serious Adverse Events........................................................................................................37
7.4.
Gilead Reporting Requirements.............................................................................................................38
7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or 
Serious Adverse Events..........................................................................................................................39
7.6.
Special Situations Reports......................................................................................................................39
7.6.1.
Definitions of Special Situations..........................................................................................39
7.6.2.
Instructions for Reporting Special Situations.......................................................................40
8.
STATISTICAL CONSIDERATIONS................................................................................................................42
8.1.
Analysis Objectives and Endpoints........................................................................................................42
8.1.1.
Analysis Objectives..............................................................................................................42
8.1.2.
Primary Endpoint .................................................................................................................42
8.1.3.
Secondary Endpoint .............................................................................................................42
8.1.4.
Other Endpoints of Interest ..................................................................................................42
8.2.
Planned Analyses ...................................................................................................................................43
8.2.1.
Interim Analysis ...................................................................................................................43
8.2.2.
Primary Analysis..................................................................................................................43
8.2.3.
Final Analysis.......................................................................................................................43
8.3.
Analysis Conventions.............................................................................................................................43
8.3.1.
Analysis Sets ........................................................................................................................43
8.3.2.
Data Handling Conventions .................................................................................................44
8.4.
Demographic and Baseline Characteristics Analysis .............................................................................44
8.5.
Efficacy Analysis ...................................................................................................................................44
8.5.1.
Primary Analysis..................................................................................................................44
8.5.2.
Secondary Analyses .............................................................................................................45
8.6.
Safety Analysis.......................................................................................................................................45
8.6.1.
Extent of Exposure...............................................................................................................45
CCI
CCI
-


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8.6.2.
Adverse Events.....................................................................................................................45
8.6.3.
Laboratory Evaluations ........................................................................................................46
8.8.
Adjustments for Multiplicity..................................................................................................................46
8.9.
Sample Size............................................................................................................................................46
8.10.
Data Monitoring Committee ..................................................................................................................47
9.
RESPONSIBILITIES..........................................................................................................................................48
9.1.
Investigator Responsibilities ..................................................................................................................48
9.1.1.
Good Clinical Practice..........................................................................................................48
9.1.2.
Financial Disclosure.............................................................................................................48
9.1.3.
Institutional Review Board/Independent Ethics Committee Review and 
Approval...............................................................................................................................48
9.1.4.
Informed Consent (or Assent) ..............................................................................................48
9.1.5.
Confidentiality......................................................................................................................49
9.1.6.
Study Files and Retention of Records ..................................................................................49
9.1.7.
Case Report Forms...............................................................................................................50
9.1.8.
Investigator Inspections........................................................................................................51
9.1.9.
Protocol Compliance............................................................................................................51
9.2.
Sponsor Responsibilities ........................................................................................................................51
9.2.1.
Protocol Modifications.........................................................................................................51
9.2.2.
Study Report and Publications .............................................................................................51
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................52
9.3.1.
Payment Reporting...............................................................................................................52
9.3.2.
Access to Information for Monitoring..................................................................................52
9.3.3.
Access to Information for Auditing or Inspections ..............................................................52
9.3.4.
Study Discontinuation..........................................................................................................52
10.
REFERENCES ...................................................................................................................................................53
11.
APPENDICES ....................................................................................................................................................54
Appendix 1.
Investigator Signature Page....................................................................................................55
Appendix 2.
Study Procedures Table..........................................................................................................56
Appendix 3.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................57
LIST OF IN-TEXT TABLES
Table 1.
Data Entry Requirements When Only One Result of Multiple Results Is Recorded 
for a Given Day ......................................................................................................................32
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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-5734™) in Participants 
with Severe COVID-19
IND Number:
EudraCT Number:
Clinical Trials.gov Identifier:
147753
2020-000841-15
NCT04292899
Study Centers Planned:
Up to approximately 160 centers globally
Objectives:
The purpose of this study is to provide remdesivir (RDV) to 
participants with severe COVID-19.
The primary objective of this study is as follows:

To evaluate the efficacy of 2 RDV regimens with respect to 
clinical status assessed by a 7-point ordinal scale on 
Day 14
The secondary objective of this study is as follows: 

To evaluate the safety and tolerability of RDV
Study Design:
This is a Phase 3 randomized, open-labeled, multi-center study 
of RDV therapy in participants with severe COVID-19.
The study will be conducted in two parts. In Part A, 
approximately 400 participants who meet all eligibility criteria
and who are not mechanically ventilated may be randomized in 
a 1:1 ratio into one of the following treatment groups:
Treatment Group 1: 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, and 5
Treatment Group 2: 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


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Part B will enroll participants on mechanical ventilation and, 
after enrollment to Part A is complete, any additional 
participants. In Part B, up to an additional approximately 
5600 participants who meet all of the eligibility criteria will be 
enrolled, based on whether they are mechanically ventilated at 
enrollment, to receive:
Mechanically Ventilated 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
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 the 5-day dosing regimen used in Treatment Group 1 of 
Part A is selected for Part B, 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 6000
Target Population:
Participants with severe 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, or 
with a legal representative who can provide informed 
consent, or enrolled under ICH E6(R2) 4.8.15 emergency 
use provisions as deemed necessary by the investigator 
(age ≥18), or willing and able to provide assent (age ≥12 to 
<18, where locally and nationally approved) prior to 
performing study procedures

Hospitalized

SpO2 ≤94 % on room air or requiring supplemental 
oxygen at screening

Radiographic evidence of pulmonary infiltrates 


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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 testing will be performed; if this testing has been 
performed within the previous 4 days, no repeat testing is 
required.
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 2 treatment groups in a 1:1 ratio to 
receive:
Treatment Group 1: 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, and 5
Treatment Group 2: 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
In Part B, after screening procedures, eligible participants will
be assigned to receive:
Mechanically Ventilated 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
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.


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Test Product, Dose, and 
Mode of Administration: 
Reference Therapy, Dose, 
and Mode of 
Administration: 
Criteria for Evaluation: 
Safety: 
Efficacy: 
CONFIDENTIAL 
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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 perfonned 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 perfonned as standard of care, white 
blood cell count, hemoglobin and/or hematocrit, platelets, 
creatinine, creatinine clearance, glucose, total bilirubin, ALT, 
AST will be perfonned at Days 1, 3, 5, 8, 10, and 14 or m1til 
discharge, whichever is earlier. 
Remdesivir (GS-5734) for injection, 100 mg, for IV 
administration 
None 
Incidence of treatment-emergent AEs and treatment-emergent 
clinical laboratory abnonnalities 
Clinical status assessed by a 7-point ordinal scale on Day 14 
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Statistical Methods: 
FINAL 
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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 the 
two treatment groups (i.e., whether the common odds ratio is 
equal to 1 ). The odds ratio and 95% confidence interval will 
be provided. 
Treatment-emergent AEs and laboratory abnonnalities will 
be summarized using descriptive statistics and listed by 
subject. 
Sample Size: 
In Part A, a total of approximately 400 participants will be 
randomized in a 1: 1 ratio to 2 groups (200 participants per 
group) 
A sample size of 400 participants (200 participants in each 
group) achieves > 85 % power to detect an odds ratio of 1. 7 5 
using a two-sided significance level of 0.05. 
The sample size for 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. 
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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
°F
Fahrenheit
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUCtau
area under plasma concentration-time curve over dosing interval
BLQ
below the limit of quantitation
CDC
Centers for Disease Control and Prevention
CoV
Coronavirus
CRF
case report form
CRO
contract/clinical research organization
CSR
clinical study report
d
deciliter
DAIDS
Division of AIDS
DMC
data monitoring committee
EBOV
Ebola virus
eCCGs
eCRF Completion Guidelines
eCRF
electronic case report form
EDC
electronic data capture
EGFR
epidermal growth factor receptor
eSAE
Electronic Serious Adverse Event
EU
European Union
EudraCT
European Clinical Trials Database
FAS
Full Analysis Set
FDA
Food and Drug Administration
FSH
follicle-stimulating hormone
g
grams
GCP
Good Clinical Practice
Gilead
Gilead Sciences
HIV
human immunodeficiency virus
HLGT
high-level group term
HLT
high-level term
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
IND
investigational new drug
IRB
institutional review board
IUD
intrauterine device


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IV
intravenous
IWRS
interactive web response system
J
Joule
kg
kilogram
LAM
lactational amenorrhea method
LLOQ
lower limit of quantitation
LLT
lower-level term
LPV
lopinavir
LPV/RTV-IFNb
LPV/RTV + interferon-beta
MARV
Marburg virus
MedDRA
Medical Dictionary for Regulatory Activities
MERS
Middle East Respiratory Syndrome
min
minute
NHPs
nonhuman primates
OAT
organic anion transporter
PBMC
peripheral blood mononuclear cell
PBPK
physiologically-based pharmacokinetic 
PCR
polymerase chain reaction
PK
pharmacokinetic(s)
PT
preferred term
PVE
Pharmacovigilance and Epidemiology
QT
electrocardiographic interval between the beginning of the Q wave and termination of the T 
wave, representing the time for both ventricular depolarization and repolarization to occur
RDV
remdesivir
RNA
ribonucleic acid
RSV
respiratory syncytial virus
RT
reverse transcriptase
RTV
ritonavir
SADR
serious adverse drug reaction
SAE
serious adverse event
SARS
Severe Acute Respiratory Syndrome
SBECD
sulfobutylether β-cyclodextrin sodium
SDV
source data verification
SOC
system organ class
SOP
standard operating procedure
SUSAR
suspected unexpected serious adverse reaction
TM
test method
ULN
upper limit of normal
US
United States
V-A ECMO
Veno-arterial extracorporeal membrane oxygenation


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V-V ECMO
Veno-venous extracorporeal membrane oxygenation
WHO
World Health Organization


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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 highly pathogenic human 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 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 selection of a preferred 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.
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 


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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 adult dose, the efficacious dose of RDV against SARS-CoV-2 remains to be established. 
Dose selection of remdesivir (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 remdesivir 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 remdesivir (ie, the adult dosage regimen) should be 
administered. Use of the adult dose in these pediatric patients is expected to maintain exposures 
of both remdesivir and GS-441524 generally within those expected at the therapeutic doses and 
which were previously observed to be well tolerated in healthy volunteers.
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 a 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.


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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 ULN 

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.


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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 
COVID-19 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 severe COVID-19.
The primary objective of this study is as follows:

To evaluate the efficacy of 2 RDV regimens with respect to clinical status assessed by a 
7-point ordinal scale on Day 14
The secondary objective of this study is as follows:

To evaluate the safety and tolerability of RDV


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3.
STUDY DESIGN
Part A of this study is a randomized, open-label, multicenter study of RDV in participants with 
severe COVID-19 infection. Part B is a two treatment group multicenter study of RDV in 
participants with severe COVID-19 infection. Treatment group assignment is based on whether 
the participant is on mechanical ventilation at treatment assignment. All participants will 
continue to receive SOC therapy according to local guidelines.
3.1.
Endpoints
The primary endpoint of this study is:

Clinical status assessed by a 7-point ordinal scale on Day 14
The secondary endpoint of this study is:

The proportion of participants with treatment emergent AEs
Other endpoints of interest are:

Time to SpO2 > 94% on room air

Time to first negative SARS-CoV-2 polymerase chain reaction (PCR)

Duration of oxygen therapy (days)

Duration of hospitalization (days)

All cause mortality at Day 28

Time to clinical improvement (days): Clinical improvement is defined as a ≥ 2-point 
improvement from Day 1 on a 7-point ordinal scale

The proportion of participants in the Mechanically Ventilated Treatment Group and 
Extension Treatment Group with treatment-emergent AEs
3.2.
Study Design
Part A of this study is a randomized, open-label, multicenter study of RDV in participants with 
severe COVID-19 infection. Eligible participants will be randomized in equal proportions to 1 of 
2 treatment groups. No stratification will be performed. Part B is a two treatment group 
multicenter study of RDV in participants with severe COVID-19 infection.
CCII 


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3.3.
Study Treatments
In Part A, approximately 400 participants who meet all eligibility criteria and who are not 
mechanically ventilated may be randomized in a 1:1 ratio into 1 of the following treatment 
groups:
Treatment Group 1: 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, and 5
Treatment Group 2: 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
In Part B, an additional approximately 5600 participants who meet all of the eligibility criteria 
may receive:
Mechanically Ventilated 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
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 the 
5-day dosing regimen used in 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), 10 days 
(Treatment Group 2), 10 days (Mechanically Ventilated Treatment Group), 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 < 30mL/min


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Discontinuation of study medication is not a seriousness criterion.
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 400 participants will be randomized in a 1:1 ratio into 1 of 2 treatment 
groups. In Part B, up to approximately 5600 participants may be assigned to 1 of 2 treatment 
groups. 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, or with a legal representative who can 
provide informed consent, or enrolled under ICH E6(R2) 4.8.15 emergency use provisions as 
deemed necessary by the investigator (participants ≥ 18 years of age), or willing and able to 
provide assent (participants ≥ 12 and < 18 years of age, where locally and nationally 
approved) 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 test ≤4 days before randomization
4) Currently hospitalized
5) SpO2 ≤94% on room air or requiring supplemental oxygen 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.


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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 treatment for COVID-19
2) Concurrent treatment with other agents with actual or possible direct acting antiviral activity 
against SARS-CoV-2 < 24 hours prior to study drug dosing
3) Evidence of multiorgan failure
4) Mechanically ventilated (including V-V ECMO) ≥ 5 days, or any duration of V-A ECMO
5) ALT or AST > 5 ULN
6) 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
7) Positive pregnancy test (Appendix 3)
8) Breastfeeding woman
9) 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 ratio to 1 of 2 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 Mechanically Ventilated Treatment Group will 
receive 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. Participants in the Extension Treatment Group will also receive 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 the 5-day dosing 
regimen used in 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. 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 14 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 with a legal representative who can provide informed 
consent, or enrolled under ICH E6(R2) 4.8.15 emergency use provisions as deemed 
necessary by the investigator (participants ≥ 18 years of age), or obtain assent (participants 
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


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Oxygen supplementation: room air, low flow 0 2 (L/min and %), high flow 0 2 (L/min and 
%), CPAP/BIPAP (Fi02 or%), mechanical ventilation (Fi0 2 or %), ECMO 
Oxygenation: Sp02 or Pa02 
Radiographic findings 
• 
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 SAEs and all AEs related to protocol-mandated procedures occurring after 
signing of the consent ( or assent) fonn. 
Study subjects who qualify should be nmnediately 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 (Part A) or treatment assigmnent 
(Part B) on the Day 1 visit. If the screening and Day 1 visits occur within one day, 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 (Fi02 or %), mechanical ventilation (Fi0 2 or %), ECMO 
Oxygenation: Sp02 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 
• 
Review the Ordinal Scale (see Section 6.9) 
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6.3. 
Daily Study Assessments (Days 2-14) 
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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 0 2 (L/min and %), high flow 0 2 (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 of 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 until 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 
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) 
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
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. All laboratory testing will be completed 
by local laboratories. From Day 1 to Day 14, at specified timepoints, the sponsor will be 
provided with results for the following analytes: 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 RT-qPCR to detect or quantify SARS-CoV-2 or virus 
sequencing results. If feasible, oropharyngeal, saliva, sputum, stool, and/or blood samples may
be collected and assayed using RT-qPCR 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 if possible.
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 
available. When more than 1 result is available in a calendar day, at minimum, results should be 
reported as indicated in Table 1. All SARS-CoV-2 results should be provided.


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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 Schwarz 
Lowest result 
preferred) 
6.7. 
Physical Examination 
A targeted physical examination and vital signs (heart rate, respiratory rate, temperature, blood 
pressure, Sp0 2 or Pa02) should be perfonn ed 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 
(i.e. lowest ordinal) score from the previous day will be recorded. i.e. on Day 3, the lowest 
ordinal score from Day 2 is obtained and recorded for Day 2. The scale is as follows: 
1. Death 
2. Hospitalized, on invasive mechanical ventilation or ECMO 
3. Hospitalized, on non-invasive ventilation or high flow oxygen devices 
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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 
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The end of the study will occur when the last participant's last observation ( or visit). 
6.13. 
Post Study Care 
The long-tenn care of the participant will remain the responsibility of their primary treating 
physician. Remdesivir is being supplied with curative intent. There is no provision for post-study 
availability. 
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. No samples will be obtained or retained by Gilead . 
• 
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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.)

In-patient hospitalization or prolongation of existing hospitalization

Persistent or significant disability/incapacity

A congenital anomaly/birth defect


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
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)
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


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7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events 
7.3.1.
Requirements for Collection Prior to Study Drug Initiation
After informed consent, but prior to initiation of study medication, the following types of events 
must be reported on the applicable eCRFs: all SAEs and AE 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 should be followed up 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 30-days of 
the last dose of study drug, regardless of causality, should also be reported.
Investigators are not obligated to actively seek SAEs after the protocol-defined follow-up period; 
however, if the investigator learns of any SAEs that occur after the protocol-defined follow-up 
period has concluded and the event is deemed relevant to the use of study drug, the investigator
should promptly document and report the event to Gilead PVE.
All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guidelines.  
7.3.3.1.
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.


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
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.
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. 
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7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, and 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.
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 
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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 the 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.
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.
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A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Sections 7.3.3. 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 or other 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 the 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.
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
The purpose of this study is to provide RDV to participants with severe COVID-19.
8.1.1.
Analysis Objectives
The analysis objectives of this study are as follows: 

To evaluate the efficacy of 2 RDV regimens with respect to clinical status assessed by a 
7-point ordinal scale on Day 14

To evaluate the safety and tolerability of RDV
8.1.2.
Primary Endpoint
The primary endpoint of this study is:

Clinical status assessed by a 7-point ordinal scale on Day 14
8.1.3.
Secondary Endpoint
The secondary endpoint of this study is:

The proportion of participants with treatment emergent AEs
8.1.4.
Other Endpoints of Interest
Other endpoints of interest are:

Time to SpO2 > 94% on room air

Time to first negative SARS-CoV-2 PCR

Duration of oxygen therapy (days)

Duration of hospitalization (days)

All cause mortality at Day 28

Time to clinical improvement (days): Clinical improvement defined a ≥ 2-point improvement
from Day 1 on a 7-point ordinal scale

The proportion of participants in the Mechanically Ventilated Treatment Group and 
Extension Treatment Group with treatment-emergent AEs 
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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 and efficacy data on a regular basis.
8.2.2.
Primary Analysis
The primary analysis will be performed after all participants have completed 14 days in Part A of 
the study or prematurely terminated from Part A of the study prior to 14 days. 
8.2.3.
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.
8.3.
Analysis Conventions
8.3.1.
Analysis Sets
8.3.1.1.
Efficacy
The primary analysis set for efficacy analysis is defined as the full analysis set (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 RDV. 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 RDV. Participants will be grouped according to the treatment to which they were 
randomized for Part A (5-day dosing group or 10-day dosing group) and according to the 
treatment to which they were assigned for Part B (Mechanically Ventilated Treatment Group or 
Extension Treatment Group).


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The Expanded RDV-Treated Analysis Set will include participants who have received at least 
1 dose of RDV in either the Mechanically Ventilated Treatment Group or 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 
8.4. 
Demographic and Baseline Characteristics Analysis 
Demographic and baseline measurements will be smmnarized using standard descriptive 
methods. Demographic smmnaries will include sex, race/ethnicity, and age. For categorical 
demographic and baseline characteristics, a Cochran Mantel Haenszel test will be used to 
compare treatment groups in Part A. For continuous demographic and baseline characteristics, a 
Wilcoxon rank sum test will be used to compare treatment groups in Part A. 
8.5. 
8.5.1. 
Efficacy Analysis 
Primary Analysis 
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 the 
two treatment groups (ie, whether the co1mnon odds ratio is equal to 1 ). The odds ratio and 
95% confidence interval will be provided. 
The proportion of subjects in each category will be smmnarized by treatment group. The validity 
of the proportionality assumption will be evaluated. 
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If a participant is discharged prior to Day 14, the Day 14 ordinal scale category is considered to 
be not hospitalized. Every effort will be made to obtain clinical status data for all subjects prior 
to discharge. Subjects who have missing clinical status information on Day 14 will be excluded 
from the primary analysis. 
8.5.2.
Secondary Analyses
The secondary endpoint of proportion of participants with treatment emergent AEs will be 
compared between the 2 treatment groups in Part A using a Fisher’s Exact test. The point 
estimate of the treatment difference and the associated 95% confidence intervals will be 
provided. Secondary or 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. 
Endpoints that are measured as time to first event will be compared between treatment groups 
using the Log-Rank test and continuous endpoints will be compared between treatment groups 
using a Wilcoxon rank sum test or analysis of variance model.
For Part B, summaries of the 7-point scale ordinal scale and other efficacy endpoints of interest
will be provided by group (Mechanically Ventilated Treatment Group or Extension Treatment 
Group).
8.6.
Safety Analysis
All safety data collected on or after the date that study drug was first dispensed through the 
Day 28 follow-up visit will be summarized by treatment group (according to the study drug 
received). Data for the pretreatment period will be included in data listings.
Summaries will be provided by group: 5-day dosing group or 10-day dosing group for Part A and 
Mechanically Ventilated Treatment Group or Extension Treatment Group for Part B.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug data will be generated from the study drug
administration data. Exposure data will be summarized by group. 
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 Term (HLGT), 
High-Level Term (HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be attached to 
the clinical database.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
AE will be defined as any AE that begins on or after the date of first dose of study drug up to the 
date of last dose of study drug plus 30 days, or up to Day 28, whichever is the later date.
Summaries (number and percentage of participants) of treatment-emergent AEs (by SOC, and 
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Selected laboratory data will be smmnarized using only observed data. Data and change from 
baseline at all scheduled time points will be summarized. 
Graded laboratory abnonnalities will be defined using the grading scheme in DAIDS Table for 
Grading the Severity of Adult and Pediatric Adverse Event, 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 and including the date of last dose 
of study drug plus 30 days 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. 
8.8. 
Adjustments for Multiplicity 
No adjustments for multiple comparisons are planned. 
8.9. 
Sample Size 
The sample size computation is based on an assmn ed distribution of the 7-point ordinal scale on 
Day 14 for Part A Treatment Group 1. The odds ratio represents the odds of improvement in the 
ordinal scale for Treatment Group 2 relative to Treatment Group 1. The sample size needed to 
detect a given odds ratio for a 1: 1 randomization using a 2-tailed test at level a is given by: 
Where 0 is the log odds ratio, Pi is the overall probability (combined over both treatment groups) 
of being in the ith category of the ordinal outcome, and Za 12 and 213 are the 1- a /2 and p quantiles 
of the standard nonnal distribution {Whitehead 1993}. 
A sample size of 400 participants (200 in each group) achieves > 85% power to detect an odds 
ratio of 1.75 using a two-sided significance level of 0.05. In this sample size calculation, it is 
assumed that the probability distribution of the ordinal scale at Day 14 for Group 1 is as follows: 
1. Death, 2% 
2. Hospitalized, on invasive mechanical ventilation or ECMO, 4% 
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3. Hospitalized, on non-invasive ventilation or high flow oxygen devices, 7%
4. Hospitalized, requiring low flow supplemental oxygen, 13%
5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care 
(COVID-19 related or otherwise), 16%
6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 
(other than per protocol RDV administration), 20%
7. Not hospitalized, 38%
The sample size calculation was done using software PASS (Version 14.0).
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 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 
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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 from the participant, or
with a legal representative who can provide informed consent, or enrolled under ICH E6(R2) 
4.8.15 emergency use provisions as deemed necessary by the investigator (participants ≥ 18 
years of age), or obtaining 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 
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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.
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);


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
Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol-specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of study drug, including dates of dispensing and 
return;

Record of all AEs and other safety parameters (start and end date, and including causality 
and severity), and documentation that adequate medical care has been provided for any AE;

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (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


Remdesivir (RDV; GS-5734T") 
Protocol GS-US-540-5773 
Gilead Sciences, Inc. 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGMENT 
FINAL 
Amendment 3.0 
A Phase 3 Randomized Study to Evaluate the Safety and Antiviral Activity of Remdesivir 
(GS-5734™) in Participants with Severe COVID-19 
Protocol Amendment 3.0 12 April 2020 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
PD 
[PPD 
Signature 
12 April 2020 
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 perso1mel 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 
CONFIDENTIAL 
Page 55 
12 April 2020 


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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
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 should stop at Day 14 or discharge 
whichever is earlier.
c
Day 28 evaluations completed if the visit is conducted in person.  Only AEs, ordinal scale, and concomitant medication review completed if visit conducted by phone.
 
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 IB 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 1 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 1 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.

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 3 Randomized Study to Evaluate the Safety and 
Antiviral Activity of Remdesivir (GS-5734™) in Participants 
with Severe COVID-19
Name of Test Drug:
Remdesivir (RDV; GS-5734™)
Study Number:
GS-US-540-5773
Protocol Version (Date):
Amendment 3.0 (12 April 2020)
Analysis Type:
Part A Final Analysis 
Analysis Plan Version:
Version 2
Analysis Plan Date:
18 May 2020
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
(r) GILEAU 


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF ABBREVIATIONS........................................................................................................................................4
1.
INTRODUCTION ................................................................................................................................................5
1.1.
Study Objectives ......................................................................................................................................5
1.2.
Study Design............................................................................................................................................5
1.3.
Sample Size and Power............................................................................................................................7
2.
TYPE OF PLANNED ANALYSIS ......................................................................................................................9
2.1.
Interim Analyses ......................................................................................................................................9
2.1.1.
DMC Analysis........................................................................................................................9
2.1.2.
Primary Analysis....................................................................................................................9
2.1.3.
Part A Final Analysis .............................................................................................................9
2.2.
Final Analysis ..........................................................................................................................................9
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................10
3.1.
Analysis Sets..........................................................................................................................................10
3.1.1.
All Randomized Analysis Set...............................................................................................10
3.1.2.
Full Analysis Set ..................................................................................................................10
3.1.3.
Safety Analysis Set...............................................................................................................10
3.2.
Subject Grouping ...................................................................................................................................10
3.2.1.
Subject Subgroups for Efficacy Analyses ............................................................................11
3.2.2.
Subject Subgroups for Safety Analyses ...............................................................................11
3.3.
Multiple Comparisons............................................................................................................................11
3.4.
Missing Data and Outliers......................................................................................................................11
3.4.1.
Missing Data ........................................................................................................................11
3.4.2.
Outliers.................................................................................................................................12
3.5.
Data Handling Conventions and Transformations .................................................................................12
3.6.
Analysis Visit Windows.........................................................................................................................12
3.6.1.
Definition of Study Day .......................................................................................................12
3.6.2.
Analysis Visit Windows.......................................................................................................13
3.6.3.
Selection of Data in the Event of Multiple Records for an Analysis Visit 
Day.......................................................................................................................................14
4.
SUBJECT DISPOSITION ..................................................................................................................................15
4.1.
Subject Enrollment and Disposition.......................................................................................................15
4.2.
Extent of Study Drug Exposure .............................................................................................................15
4.2.1.
Exposure to Study Drug .......................................................................................................15
4.3.
Protocol Deviations................................................................................................................................16
5.
BASELINE CHARACTERISTICS....................................................................................................................17
5.1.
Demographics and Baseline Characteristics ..........................................................................................17
5.2.
Other Baseline Characteristics ...............................................................................................................17
5.3.
Medical History......................................................................................................................................18
6.
EFFICACY ANALYSES ...................................................................................................................................19
6.1.
Primary Efficacy Endpoint.....................................................................................................................19
6.1.1.
Definition of the Primary Efficacy Endpoint .......................................................................19
6.1.2.
Statistical Hypothesis for the Primary Efficacy Endpoint....................................................19
6.1.3.
Primary Analysis of the Primary Efficacy Endpoint ............................................................20
6.1.4.
The FAS will be the primary analysis set for efficacy endpoint evaluation. 
Secondary Analyses of the Primary Efficacy Endpoint .......................................................20


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6.2.
Other Endpoints of Interest ....................................................................................................................21
6.2.1.
Analysis of Other Endpoints of Interest ...............................................................................22
6.3.
Changes from Protocol-Specified Efficacy Analyses ............................................................................23
7.
SAFETY ANALYSES........................................................................................................................................24
7.1.
Secondary Endpoint ...............................................................................................................................24
7.2.
Adverse Events and Deaths....................................................................................................................24
7.2.1.
Adverse Event Dictionary ....................................................................................................24
7.2.2.
Adverse Event Severity........................................................................................................24
7.2.3.
Relationship of Adverse Events to Study Drug....................................................................24
7.2.4.
Serious Adverse Events........................................................................................................25
7.2.5.
Treatment-Emergent Adverse Events...................................................................................25
7.2.5.1.
Definition of Treatment-Emergent Adverse Events .......................................25
7.2.5.2.
Incomplete Dates ............................................................................................25
7.2.6.
Summaries of Adverse Events and Deaths...........................................................................25
7.3.
Laboratory Evaluations ..........................................................................................................................27
7.3.1.
Summaries of Numeric Laboratory Results .........................................................................27
7.3.2.
Graded Laboratory Values ...................................................................................................27
7.3.2.1.
Treatment-Emergent Laboratory Abnormalities.............................................28
7.3.2.2.
Summaries of Laboratory Abnormalities........................................................28
7.3.3.
Liver-Related Laboratory Evaluations .................................................................................28
7.4.
Body Weight, and Vital Signs................................................................................................................28
7.5.
Prior and Concomitant Medications.......................................................................................................29
7.6.
Other Safety Measures ...........................................................................................................................30
7.7.
Subject Subgroup for Safety Endpoints .................................................................................................30
7.8.
Changes from Protocol-Specified Safety Analyses................................................................................30
8.
REFERENCES ...................................................................................................................................................31
9.
SOFTWARE.......................................................................................................................................................32
10.
SAP REVISION..................................................................................................................................................33
11.
APPENDICES ....................................................................................................................................................34
Appendix 1.
Study Procedures Table..........................................................................................................35
Appendix 2.
Programming Specifications...................................................................................................36
LIST OF IN-TEXT TABLES
Table 3-1.
Analysis Windows for PCR and Hematology and Chemistry Laboratory Tests 
(hemoglobin, hematocrit, platelet count, WBC, ALT, AST, total bilirubin, glucose, 
serum creatinine, and eGFR)..................................................................................................14


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LIST OF ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BMI
body mass index
CI
confidence interval
CMH
Cochran-Mantel-Haenszel
CRF
case report form
CSR
clinical study report
DMC
data monitoring committee
ECMO
extracorporeal membrane oxygenation
eCRF
Electronic case report form
FAS
Full Analysis Set
HLT
high-level term
LLN
lower limit of normal
LLT
lowest level term
LOQ
limit of quantitation
MedDRA
Medical Dictionary for Regulatory Activities
PCR
polymerase chain reaction
PT
preferred term
Q1, Q3
first quartile, third quartile
RDV
remdesivir
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SE
standard error
SOC
system organ class
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
ULN
upper limit of normal


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1.
INTRODUCTION
This Phase 3 study is conducted in two parts. In Part A, approximately 400 participants who 
meet all eligibility criteria and who are not mechanically ventilated are randomized to one of two 
treatment groups.  Part B starts after Part A is completed and includes up to approximately 
5600 participants.  
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) for the analysis of Part A of Study 
GS-US-540-5773. This SAP is based on the study protocol Amendment 3.0 dated 12 April 2020
and the electronic case report form (eCRF). The SAP will be finalized prior to data finalization.
Any changes made after the finalization of the SAP will be documented in the clinical study 
report (CSR).
1.1.
Study Objectives
The purpose of this study is to provide remdesivir (RDV) to participants with severe COVID-19.
The primary objective of this study is as follows:

To evaluate the efficacy of 2 RDV regimens with respect to clinical status assessed by a 
7-point ordinal scale on Day 14.
The secondary objective of this study is as follows:

To evaluate the safety and tolerability of RDV.
1.2.
Study Design
This is a Phase 3 randomized, open-labeled, multi-center study of RDV therapy in participants 
with severe COVID-19.
Treatment Groups
For Part A, approximately 400 participants who meet all eligibility criteria and who are not 
mechanically ventilated may be randomized in a 1:1 ratio into one of the following treatment 
groups:

Treatment Group 1: 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, and 5

Treatment Group 2: 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


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Part B will enroll participants on mechanical ventilation and, after enrollment to Part A is 
complete, any additional participants. In Part B, up to an additional approximately 
5600 participants who meet all of the eligibility criteria will be enrolled, based on whether they 
are mechanically ventilated at enrollment, to receive:
Mechanically Ventilated 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
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 the 5-day dosing regimen used in Treatment Group 1 of Part A is selected for Part B, all 
participants in the Extension Treatment Group and all new participants will be reassigned to 
receive treatment for a total of 5 days.
Key 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

SpO2 ≤94% on room air or requiring supplemental oxygen at screening

Radiographic evidence of pulmonary infiltrates
Schedule of Assessments
The date of randomization is considered Day 1 and it is expected that all randomized participants 
receive their initial dose of RDV on Day 1.
On Days 1 through 14 or until discharge, whichever is earlier, 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 standard of care 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. Clinical status will be recorded on the 7-point ordinal scale for each day.
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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Participants who meet eligibility criteria are randomized in a 1: 1 ratio to 1 of 2 treatment groups 
on Day 1 using an IWRS and assigned a subject number. Randomization is not stratified. 
Up to approximately 160 centers globally. 
Duration of Treatment 
Participants will receive study treatment with RDV for 5 days (Treatment Group 1) or 10 days 
(Treatment Group 2) in Part A, and 10 days (Mechanically Ventilated Treatment Group), or 
either 5 or 10 days (Extension Treatment Group) in Part B. If the participant is discharged, RDV 
treatment will end at that time. 
Discontinuation Criteria 
Study drug dosing in an individual participant 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 serious adverse event (SAE) or~ Grade 3 AE suspected to be related to RDV. 
• 
Any elevations in ALT > 5 x ULN; or ALT > 3 x ULN and total bilirubin > 2 x ULN, 
confinned by nmnediate repeat testing. 
• 
Creatinine clearance < 30mL/min 
Discontinuation of study medication is not a seriousness criterion. 
End of Study 
The end of the study will be the last participant's last observation ( or visit). 
1.3. 
Sample Size and Power 
In Part A, a total of approximately 400 participants will be randomized in a 1: 1 ratio to 2 groups 
(200 participants per group). 
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The sample size computation is based on an assumed distribution of the 7-point ordinal scale on 
Day 14 for Part A Treatment Group 1. The odds ratio represents the odds of improvement in the 
ordinal scale for Treatment Group 2 relative to Treatment Group 1. 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 400 participants (200 in each group) achieves > 85% power to detect an odds 
ratio of 1.75 using a two-sided significance level of 0.05. In this sample size calculation, it is 
assumed that the probability distribution of the ordinal scale at Day 14 for Treatment Group 1 is 
as follows:
1. Death, 2%
2. Hospitalized, on invasive mechanical ventilation or ECMO, 4%
3. Hospitalized, on non-invasive ventilation or high flow oxygen devices, 7%
4. Hospitalized, requiring low flow supplemental oxygen, 13%
5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care 
(COVID-19 related or otherwise), 16%
6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care 
(other than per protocol RDV administration), 20%
7. Not hospitalized, 38%
The sample size calculation was performed using software PASS (Version 14.0).


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
2.1.1.
DMC Analysis 
The DMC will review the results from the analysis of the Day 14 snapshot.
2.1.2.
Primary Analysis
The primary analysis will be performed after availability of data from participants in Part A of 
the study who have completed 14 days or prematurely terminated from Part A of the study on or 
prior to Day 14.
2.1.3.
Part A Final Analysis
The final analysis for participants randomized in Part A will be performed after all these 
participants have completed Part A of the study or prematurely terminated from Part A of the
study, outstanding data queries have been resolved or adjudicated as unresolvable, and the data 
have been cleaned and finalized. This SAP describes the statistical analysis methods and data 
presentations to be used for the analysis of Part A.
2.2.
Final Analysis
The final analysis for this study will be performed after all participants have completed Part B of 
the study or prematurely terminated from the study (Part A or Part B), outstanding data queries 
have been resolved or adjudicated as unresolvable, and the data have been cleaned and finalized. 


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of participants in each category will be presented; for continuous 
variables, the number of participants (n), mean, standard deviation (SD) or standard error (SE), 
median, first quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
All statistical tests will be 2-sided and performed at the 5% significance level unless otherwise 
specified.
By-subject listings will be presented for all participants in the All Randomized Analysis Set
unless otherwise specified, and sorted by subject ID number, visit date, and time (if applicable). 
Data collected on log forms, such as AEs, will be presented in chronological order within a 
subject. The treatment group to which participants were randomized will be used in the listings. 
3.1.
Analysis Sets
Analysis sets define the participants to be included in an analysis. Analysis sets and their 
definitions are provided in this section. Participants included in each analysis set will be 
determined before database finalization for the primary analysis. The analysis set will be 
included as a subtitle of each table, figure, and listing. A summary of the number and percentage 
of participants in each analysis set will be provided by treatment group and in total.
3.1.1.
All Randomized Analysis Set
The All Randomized Analysis Set will include all participants who are randomized into Part A 
of the study. This is the primary analysis set for by-subject listings.
3.1.2.
Full Analysis Set
The primary analysis set for efficacy analysis is defined as the Full Analysis Set (FAS), which 
will include all participants who (1) are randomized into Part A of the study and (2) have 
received at least 1 dose of RDV. Participants will be grouped according to the treatment to which 
they were randomized.
3.1.3.
Safety Analysis Set
The primary analysis set for safety analyses is defined as the Safety Analysis Set, which will
include all participants who (1) are randomized into Part A of the study and (2) have received at 
least 1 dose of RDV. Participants will be grouped according to the treatment to which they were 
randomized for Part A.
3.2.
Subject Grouping
Participants will be grouped by randomized treatment (RDV for 5 Days and RDV for 10 Days), 
regardless of the actual number of days of treatment.


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3.2.1.
Subject Subgroups for Efficacy Analyses
The primary endpoint will be analyzed for the following subject subgroups: 

Age (years): (a) < 65 and (b) ≥ 65

Sex at birth: (a) male and (b) female 

Oxygen support status based on the 7-point ordinal scale: (a) Invasive mechanical 
ventilation, (b) high flow oxygen, (c) low flow oxygen, and (d) room air (See Appendix 2) 

Country: (a) USA, (b) Italy, and (c) ex-Italy
3.2.2.
Subject Subgroups for Safety Analyses
Incidence of all treatment-emergent AEs (TEAEs) will be summarized for the following subject 
subgroups: 

Age (years): (a) < 65 and (b) ≥ 65

Sex at birth: (a) male and (b) female 

Country: (a) USA,  (b) Italy, and (c) ex-Italy
Survival will be summarized for the following subject subgroups: 

Age (years): (a) < 65, further broken down by (a1) < 50 and (a2) ≥50 to < 65, and (b) ≥ 65,
further broken down by (b1) ≥ 65 to < 75 and (b2) ≥75

Sex at birth: (a) male and (b) female 

Country: (a) USA, (b) Italy, and (c) ex-Italy
3.3.
Multiple Comparisons
No prespecified multiplicity adjustments are planned for confidence intervals or statistical tests.
3.4.
Missing Data and Outliers
3.4.1.
Missing Data
Missing data can have an impact upon the interpretation of the trial data. In general, values for 
missing data will not be imputed, unless methods for handling missing data are specified.
In this study, a missing pre-treatment laboratory result would be treated as normal (ie, no toxicity 
grade) for the laboratory abnormality summary. The handling of missing or incomplete dates for 
AE onset is described in Section 7.2.5.2, and for prior and concomitant medications in 
Section 7.5.


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3.4.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no
sensitivity analyses will be done to evaluate the impact of outliers on efficacy or safety
outcomes, unless specified otherwise. All data will be included in the analyses.
3.5.
Data Handling Conventions and Transformations
The following conventions will be used for the imputation of date of birth when it is partially 
missing or not collected:

If only month and year of birth is collected, then “15” will be imputed as the day of birth

If only year of birth is collected, then “01 July” will be imputed as the day and month of birth

If year of birth is missing, then date of birth will not be imputed
In general, age collected at Day 1 (in years) will be used for analyses and presented in listings. If 
age at Day 1 is not available for a subject, then age derived based on date of birth and the first 
dose date will be used instead. If a randomized subject was not dosed with any study drug, the 
randomization date will be used instead of the Day 1 visit date. For screen failures, the date the 
first informed consent was signed will be used for the age derivation.  
Laboratory data that are continuous in nature but are less than the lower limit of quantitation
(LOQ) or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “x” (where x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate summary statistics. An exception to this rule is any value reported as < 1 or < 0.1, 
etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used to 
calculate summary statistics.

A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.

The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).
3.6.
Analysis Visit Windows
3.6.1.
Definition of Study Day
Study Day 1 is defined as the first dosing date of study drug.


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Study Days are calculated relative to Study Day 1 and derived as follows:

For postdose study days: Assessment Date First Dosing Date + 1

For days prior to the first dose: Assessment Date First Dosing Date
Therefore, Study Day 1/ First Dose Date is the day of first dose of study drug administration, as 
recorded on the Study Drug Administration eCRF form.
Last Dose Date is defined as the maximum, nonmissing, nonzero dose end date of treatment
recorded on the Study Drug Administration eCRF form with “Study Drug Permanently 
Withdrawn” box checked for participants who prematurely discontinued or completed study drug 
according to the Study Drug Completion eCRF. Refer to Appendix 2 for missing date
imputation, if necessary.
Last Study Date is the latest of the study drug start dates and end dates, the clinic visit dates, 
and the laboratory visit dates, including the 28-day follow-up visit date, for participants who 
prematurely discontinued study according to the Study Completion eCRF. 
Baseline value is defined as the last value obtained on or prior to the first dose date (and time, 
if available) unless otherwise specified (see Section 3.6.3). 
3.6.2.
Analysis Visit Windows
Subject visits might not occur on protocol-specified days. Therefore, for the purposes of analysis,
observations will be assigned to analysis windows. The study day as defined in Section 3.6.1 will 
be used when data are summarized by visit.
Vital signs were to be collected daily; therefore, windows are not assigned and results will be 
summarized for each Study Day, except for Study Day 28. For Study Day 28, the nominal day is 
Study Day 28, the lower limit is Study Day 15 and there is no upper limit. 
Ordinal scale results were to be recorded prior to dosing on Study Day 1. The worst result for 
each day from Day 1 through the earliest of discharge date or Day 14 was to be recorded. For
subjects who were discharged after Day 14, changes in score category were to be recorded each 
day from Day 15 to the earliest of discharge date or Day 28. For the ordinal scale, baseline is 
defined as the value recorded prior to dosing, or the last value obtained prior to the first dose date
if the predose value was not recorded on the day of dosing. Results will be summarized for each 
Study Day without windows. If more than one result was reported on the same day, the worst 
result will be selected.
SARS-CoV-2 PCR results were to be reported (if collected) each day. However, the windows in 
Table 3-1 will be assigned to account for missing data.
The analysis windows for hematology and chemistry laboratory parameters and PCR are 
presented in Table 3-1.


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Table 3-1.
Analysis Windows for PCR and Hematology and Chemistry 
Laboratory Tests (hemoglobin, hematocrit, platelet count, WBC, 
ALT, AST, total bilirubin, glucose, serum creatinine, and eGFR)
Visit ID
Nominal Day
Lower Limit
Upper Limit
Baseline
1
1 (pre dose)*
Day 3
3
1 (post dose)*
3
Day 5
5
4
6
Day 8
8
7
8
Day 10
10
9
11
Day 14
14
12
15
Post Day 14**
28
16
*
For Baseline, the upper limit includes values collected at or prior to the first dose date/time. For Day 3, the lower limit 
includes values collected after the first dose date/time on Day 1.
**
Post Day 14 laboratory values will be considered for treatment emergent laboratory presentations only.
3.6.3.
Selection of Data in the Event of Multiple Records for an Analysis Visit Day 
Depending on the statistical analysis method, single values may be required for each Study Day
or analysis window. For example, change from baseline by visit usually requires a single value, 
whereas a time-to-event analysis does not require 1 value per Study Day or analysis window.
If multiple valid, nonmissing measurements exist for a Study Day/analysis window, records will 
be chosen based on the following rules if a single value is needed:

For baseline, the last nonmissing value on or prior to the first dosing date (and time, if 
available) of study drug will be selected, unless specified differently. If there are multiple 
records with the same time or no time recorded on the same day, the baseline value will be 
the average of the measurements for continuous data, or the measurement with the lowest 
severity for categorical data.

For postbaseline values:
For windows spanning multiple days, the record(s) collected on the day closest to the 
nominal day will be selected. If there are 2 days equidistant from the nominal day, the 
later day will be selected.
■
For PCR, if there is more than 1 record on the selected day, the latest value will be 
selected. If there are multiple records with the same time or no time recorded on the 
same day, the selected value will be the highest severity (ie, highest value or positive 
result).
■
For laboratory values (other than PCR) and SpO2 and PaO2, if there is more than 
1 record on the selected day, the worst value will be selected. See Appendix 2 for 
definition of worst value.
■
For other parameters, if there is more than 1 record on the selected day, the average 
will be taken for continuous data and the worst severity will be taken for categorical 
data, unless otherwise specified.


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
The number and percentage of participants randomized at each investigator site will be 
summarized by treatment group and overall using the Safety Analysis Set. The denominator for 
this calculation will be the number of participants in the Safety Analysis Set.
The summary of subject disposition will be provided by treatment group and overall for all 
screened participants. This summary will include the number of participants screened, screen 
failure participants who were not randomized, participants who met all eligibility criteria and 
were not randomized, participants randomized, participants randomized but never treated, 
participants in the Safety Analysis Set, and participants in the FAS.
In addition, the number and percentage of the participants in the following categories will be 
summarized:

Completed randomized 5-day or 10-day treatment on study drug as recorded on the Study 
Drug Completion form

Prematurely discontinuing study drug prior to completion of 5 days of dosing (Treatment 
Group 1) or 10 days of dosing (Treatment Group 2) with summary of reasons for 
discontinuing study drug as recorded on the Study Drug Completion form

Still on study up to the data cut date (if applicable)

Completed study

Prematurely discontinuing from study (prior to the data cut date for the primary analysis 
only) with summary of reasons for discontinuing study as recorded on the Study Completion 
form
The denominator for the percentages of participants in each category will be the number of 
participants in the Safety Analysis Set. 
No inferential statistics will be generated. A data listing of reasons for study drug/study 
discontinuation will be provided.
4.2.
Extent of Study Drug Exposure 
4.2.1.
Exposure to Study Drug
Number of doses received will be summarized by treatment group for the Safety Analysis Set.


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Time to premature discontinuation of study drug will be analyzed using the Kaplan-Meier 
method by treatment group. Subjects who completed study drug will be censored at the last dose 
date.
4.3.
Protocol Deviations 
A listing will be provided for all randomized participants who violated at least 1 inclusion or 
exclusion criterion. The listing will include the criteria not met.
Protocol deviations occurring after participants entered the study are documented during routine 
monitoring. The number and percentage of participants with important protocol deviations by 
deviation reason and the total number of important protocol deviations by deviation reason
(eg, nonadherence to study drug, violation of select inclusion/exclusion criteria) will be 
summarized by treatment group for the FAS. A by-subject listing will be provided for those 
participants with important protocol deviations.


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5.
BASELINE CHARACTERISTICS  
5.1.
Demographics and Baseline Characteristics
Subject demographic data (eg, sex, race/ethnicity, and age) and baseline characteristics (eg, body 
weight, height, and body mass index [BMI]) will be summarized by treatment group and overall 
using descriptive statistics (n, mean, SD, median, Q1, Q3, minimum, and maximum) for 
continuous data and by the number and percentage of participants for categorical data. The 
summaries of demographic data and baseline subject characteristics will be provided for the 
Safety Analysis Set.
Age groups (< 50, ≥ 50 to < 65, ≥ 65 to < 75 and ≥ 75) will be summarized by treatment group 
and overall.
For categorical data, the Cochran-Mantel-Haenszel (CMH) test (ie, general association statistic 
for nominal data and row mean scores for ordinal data [age groups]) will be used to compare the 
2 treatment groups. For continuous data, the 2-sided Wilcoxon rank sum test will be used to 
compare the 2 treatment groups.
Similar summaries will be produced for the following subgroups: USA, Italy and ex-Italy.
A by-subject demographic listing will be provided.
5.2.
Other Baseline Characteristics
The following baseline disease characteristics will be summarized by treatment group and 
overall using descriptive statistics:

Clinical status (7-point ordinal scale)

Duration of hospitalization prior to first dose of RDV

Duration of symptoms prior to first dose of RDV

Aspartate aminotransferase (AST)

Alanine aminotransferase (ALT)

Oxygen support status based on the 7-point ordinal scale (invasive mechanical ventilation, 
high flow oxygen, low flow oxygen, room air)
For categorical data, the CMH test (row means scores differ statistic for ordinal data [oxygen 
support status]) will be used to compare the 2 treatment groups. For clinical status and 
continuous data, the 2-sided Wilcoxon rank sum test will be used to compare the 2 treatment 
groups.


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Similar summaries will be produced for the following subgroups: USA, Italy and ex-Italy.
5.3.
Medical History
Any medical condition or clinically significant laboratory abnormality with an onset date before 
the consent form is signed and not related to a protocol-associated procedure is considered to be 
preexisting and should be documented as medical history. General medical history data will be 
collected at screening. It will be coded using the current version of MedDRA. A summary table 
will present the percentages of participants reporting each medical history preferred term, sorted 
first in alphabetical order by system organ class (SOC) and then by preferred term (PT) in 
descending order of total frequency within SOC.


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6.
EFFICACY ANALYSES
6.1.
Primary Efficacy Endpoint
6.1.1.
Definition of the Primary Efficacy Endpoint
The primary efficacy endpoint is clinical status assessed by a 7-point ordinal scale on Day 14. 
The endpoint will be derived by combining the available death, hospital discharge alive and
ordinal scale assessment reported by the site, where death supersedes discharge alive and 
discharge alive supersedes the ordinal scale score reported by the site. The proportion of 
participants for each ordinal scale category endpoint by treatment group is expressed as 
percentages for presentation purpose.
Sites were instructed to report the worst ordinal scale category for each day. Therefore, the 
ordinal scale result on the day the participant was discharged alive does not necessarily reflect 
Not hospitalized ( 7). The definition of the 7-point ordinal scale endpoint for the efficacy 
analyses is defined as follows:

If a participant dies while hospitalized (as recorded on the Death eCRF and Hospitalization 
eCRF), the endpoint on the day of death and all subsequent days through Day 28 will be set 
to Death ( 1)

If the participant is discharged alive, the endpoint on the day of discharge alive and all 
subsequent days through Day 28 will be set to Not hospitalized ( 7)

If the participant is discharged alive and dies on the same day or a later day (as recorded on 
the Death eCRF and Hospitalization eCRF), the endpoint on the day of discharge alive and 
all subsequent days until the day of death will be set to Not hospitalized ( 7). On the day of 
death and all subsequent days through Day 28, the endpoint will be set to Death ( 1),
Every effort will be made to obtain clinical status data for all participants prior to discharge
alive.  The last known clinical status will be used for days with missing clinical status (eg , where 
the reason for Hospital Discharge is not “Discharged Alive” and the subject has not died). All 
post-baseline days with missing ordinal scale score, from Day 2 to Day 14 and Day 28, will use 
the previous last known clinical status.
6.1.2.
Statistical Hypothesis for the Primary Efficacy Endpoint
Null hypothesis: The odds of improvement for the 5-day treatment group (Treatment Group 1) 
is the same as the odds of improvement for the 10-day treatment group (Treatment Group 2) with 
respect to clinical status assessed by a 7-point ordinal scale on Day 14. 
Alternative hypothesis: The odds of improvement for the 5-day treatment group (Treatment 
Group 1) is different from the odds of improvement for the 10-day treatment group (Treatment 
Group 2) with respect to clinical status assessed by a 7-point ordinal scale on Day 14.


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6.1.3.
Primary Analysis of the Primary Efficacy Endpoint
The primary endpoint will be analyzed using a proportional odds model including treatment as 
the independent variable and baseline score as a continuous covariate. The odds ratio and 
95% confidence interval will be provided. The corresponding SAS code is as following:
proc logistic data example;
class trt/ param ref order data;
model outcome(descending)  trt baseline;
run;
The percentage of participants in each category will be summarized by treatment group. The 
assumption of odds proportionality will be assessed using a score test and reported. It will be 
concluded that 10-day treatment is superior to 5-day treatment if the lower bound of the 2-sided 
95% CI of the odds ratio (10-day / 5-day) on Day 14 is more than 1. 
6.1.4.
The FAS will be the primary analysis set for efficacy endpoint evaluation.
Secondary Analyses of the Primary Efficacy Endpoint
As supportive analyses of the primary endpoint, the following will be conducted:

The primary endpoint will be analyzed using a proportional odds model including treatment 
as the independent variable (dropping baseline score as a covariate). 

The clinical status at Day 14 will be compared between treatment groups using a 2-sided 
Wilcoxon Rank sum test, stratified on baseline clinical status.
The change from baseline in clinical status category on Days 5, 7, 11, 14, 28 and last available 
assessment will be summarized by treatment groups using descriptive statistics. Change from 
baseline will be compared between the treatment groups using a 2-sided Wilcoxon Rank sum 
test. This analysis will use the definition specified in Section 6.1.1.
The number and percentage of participants in each clinical status category for each day from 
Baseline through Day 14 and at Day 28 and using the last available assessment will be 
summarized by treatment group. These results will be summarized using the clinical status
definition in Section 6.1.1 and two methods: (1) with the definition specified in Section 6.1.1 and 
(2) with the definition specified in Section 6.1.1 but excluding days with missing ordinal scale 
score not due to death or discharge alive. In addition, stacked bar charts by study day (Baseline 
through Day 14 and at Day 28) will be produced by treatment group using the definition 
specified in Section 6.1.1.
The number and percentage of participants in each clinical status category for each day from 
Baseline through Day 14 and at Day 28 and last available assessment will be summarized within 
each subgroup defined in Section 3.2.1. These results will use the definition specified in 
Section 6.1.1.
The above analyses will be conducted using the FAS.


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6.2.
Other Endpoints of Interest
The other endpoints of interest include:

Number of subjects with negative PCR on Days 5 and 10

Number of days of oxygen support while hospitalized through discharge alive, death or 
Day 14 based on the 7-point ordinal scale reported values (See Appendix 2). This summary 
will present results separately for subjects who died on or prior to Day 14 and those who 
were discharged alive on or prior to Day 14 and will include: 
Days on invasive mechanical ventilation 
Days on high flow oxygen devices 
Days requiring low flow supplemental oxygen
Because oxygen support status was collected only while the subject was in the hospital, if a 
subject was discharged alive and died afterwards, the subject will be included only in the 
summary for subjects discharged alive.

Shift in oxygen support status from baseline to Days 5, 7, 11, 14, 28 and last available 
assessment

Duration of hospitalization (days) (duration from hospital admission and duration from 
Day 1). For the primary analysis, duration of hospitalization through Day 14 is calculated for 
subjects who were discharged alive on or prior to Day 14. For the final Part A analysis, 
duration of hospitalization is calculated through Day 28 for subjects who were discharged 
alive prior to Day 28. If subjects were rehospitalized for COVID-19 related reasons, the 
hospitalization discharge information is entered in the eCRF database using the latest 
hospitalization admission. 

All-cause mortality

Time to clinical improvement (days): Clinical improvement is defined as a ≥ 2-point
improvement from baseline clinical status or discharged alive on the 7-point ordinal scale
using the definition specified in Section 6.1.1. 

Percentage of subjects with a ≥ 2-point improvement or discharged alive based on the 7-point 
ordinal scale using the definition specified in Section 6.1.1 on Day 5, Day 7, Day 11, Day 14,
Day 28, and last available assessment

Time to ≥ 1-point improvement (days) from baseline clinical status on the 7-point ordinal 
scale using the definition specified in Section 6.1.1.

Percentage of subjects with a ≥ 1-point improvement based on the 7-point ordinal scale using 
the definition specified in Section 6.1.1 on Day 5, Day 7, Day 11, Day 14, Day 28 and last 
available assessment


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
Time to recovery based on the 7-point ordinal scale using the definition specified in 
Section 6.1.1, where recovery is defined as an improvement 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

Percentage of subjects with recovery based on the 7-point ordinal scale using the definition 
specified in Section 6.1.1 on Day 5, Day 7, Day 11, Day 14, Day 28 and last available
assessment

Time to modified recovery based on the 7-point ordinal scale using the definition specified in 
Section 6.1.1, where modified recovery is defined as an improvement 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

Percentage of subjects with modified recovery based on the 7-point ordinal scale using the 
definition specified in Section 6.1.1 on Day 5, Day 7, Day 11, Day 14, Day 28 and last 
available assessment

Time to room air (for subjects not on room air at baseline) based on the 7-point ordinal scale
using the definition specified in Section 6.1.1, defined as an improvement from a baseline 
score of 2 through 4 to a score of 5, 6 or 7

Percentage of subjects with improvement to room air based on the 7-point ordinal scale using 
the definition specified in Section 6.1.1 on Day 5, Day 7, Day 11, Day 14, Day 28 and last 
available assessment
6.2.1.
Analysis of Other Endpoints of Interest
The number and percent of subjects with negative PCR on Days 5 and 10 will be summarized.
The point estimate of the treatment difference and the associated 95% confidence intervals will 
be constructed based on an unconditional exact method using 2 inverted 1-sided tests.
Number of days of oxygen support status modes (invasive mechanical ventilation, high flow 
oxygen, low flow oxygen) will be compared between the treatment groups using the Wilcoxon 
Rank sum test. Number of days will be calculated as the number of days oxygen support was 
reported on the 7-point ordinal scale eCRF through death, discharge alive, or Day 14.
A shift table of baseline oxygen support status (death, invasive mechanical ventilation, high flow 
oxygen, low flow oxygen, room air, discharge alive) to Days 5, 7, 11, 14, 28 and the last 
available status will be provided. For the primary analysis, the last available assessment on or 
prior to Day 14 will be included.
Duration of hospitalization will be calculated only for participants who are discharged alive on or 
prior to Day 28 and will be compared between the treatment groups using the Wilcoxon Rank 
sum test.


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All-cause mortality will be estimated using the Kaplan-Meier product limit method with all 
available data. The treatment groups will be compared using the log-rank test stratified by 
baseline clinical status. The hazard ratio and 95% confidence interval will be provided based on 
a stratified proportional hazards model. Participants who did not die will be censored at the last 
study day.
Days to clinical improvement will be estimated using a competing risk analysis approach, with 
death as the competing risk. Baseline score will be included in the model as a continuous 
covariate. The hazard ratio and 95% confidence interval will be provided. Subjects without 
clinical improvement will be censored on the day of the last non-missing ordinal scale 
assessment.
Days to recovery, days to modified recovery and days to room air will be estimated using a 
competing risk analysis approach, with death as the competing risk. Baseline score will be 
included in the model as a continuous covariate. The hazard ratio and 95% confidence interval 
will be provided. Subjects without recovery will be censored on the day of the last non-missing 
ordinal scale assessment.
The number and percent of subjects with  ≥ 1-point improvement, ≥ 2-point improvement, 
recovery, modified recovery, and improvement to room air will be presented with 95% 
confidence intervals on Day 5, Day 7, Day 11 and Day 14. The point estimate of the treatment 
difference and the associated 95% confidence intervals will be provided. For the number of 
subjects on room air, only subjects on room air at baseline will be included.
Point estimates of treatment differences in percentages and 95% confidence intervals will be 
calculated based on stratum-adjusted Mantel-Haenszel proportion where the stratum is baseline 
clinical status {Koch 1989} (see Appendix 2). Comparisons between treatment groups will be 
performed using the CMH test stratified on baseline clinical status.
Analyses will be performed using the FAS.
6.3.
Changes from Protocol-Specified Efficacy Analyses
The protocol stated that participants who have missing clinical status information on Day 14 will 
be excluded from the primary analysis; however death and discharge alive information as well as 
last known clinical status will be used for Day 14 (see Section 6.1.1). 
The protocol stated that endpoints that are measured as time to first event will be compared 
between treatment groups using the log-rank test; however, a competing risk approach (with 
death as the competing risk) will be used. Treatment groups will be compared using the hazard 
ratio with 95% confidence interval.
The endpoint of interest of time to SpO2 > 94% on room air was changed to time to room air 
because SpO2 was not collected routinely for participants on room air.
The endpoint of interest of time to first negative PCR was updated to the number of subjects with 
negative PCR on Days 5 and 10 because PCR was not collected on a routine basis.


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7.
SAFETY ANALYSES
Safety data will be summarized for the participants in the safety analysis set. All safety data 
collected on or after the date that study drug was first dispensed through 30 days after last dose
will be summarized by treatment group for the Safety Analysis Set, unless specified otherwise.
All safety data will be included in data listings.
7.1.
Secondary Endpoint
The secondary endpoint of the percentage of participants with any treatment emergent adverse 
events will be compared between the 2 groups using the CMH test stratified on baseline clinical 
status. The point estimate of the treatment difference and the associated 95% confidence 
intervals will be calculated based on stratum-adjusted Mantel-Haenszel proportion where the 
stratum is baseline clinical status (see Appendix 2).
7.2.
Adverse Events and Deaths
7.2.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the current version of 
MedDRA. SOC, high-level group term (HLGT), high-level term (HLT), PT, and lowest-level 
term (LLT) will be provided in the AE dataset.
7.2.2.
Adverse Event Severity
The severity of AEs will be graded using the Division of AIDS (DAIDS) Table for Grading the
Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017. For each episode, 
the highest grade attained should be reported as defined in the grading scale. The DAIDS scale is
available at the following location:
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf
Adverse events are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 
(severe), Grade 4 (life threatening) or Grade 5 (fatal) according to toxicity criteria specified in 
the document above. The severity grade of events for which the investigator did not record 
severity will be left as “missing” for data listings.
7.2.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE eCRF to the 
question of “Related to Study Treatment.” Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.


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7.2.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definitions 
of SAE specified in the study protocol. Serious adverse events captured and stored in the clinical 
database will be reconciled with the SAE database from the Gilead Pharmacovigilance and
Epidemiology Department before data finalization.
7.2.5.
Treatment-Emergent Adverse Events
7.2.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the study drug start date and no later than 30 days
after permanent discontinuation of study drug

Any AEs leading to premature discontinuation of study drug.
7.2.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The month and year (or year) of the AE onset is the same as or after the month and year 
(or year) of the first dosing date of study drug, and

The month and year (or year) of the AE onset is the same as or before the month and year 
(or year) of the date corresponding to 30 days after the date of the last dose of study drug
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date marked as ongoing or on or after the first dosing date of study drug, will be considered to be 
treatment emergent. In addition, an AE with the onset date missing and incomplete stop date 
with the same or later month and year (or year alone if month is not recorded) as the first dosing 
date of study drug will be considered treatment emergent.
7.2.6.
Summaries of Adverse Events and Deaths
The number and percentage of participants who experienced at least 1 TEAE will be provided 
and summarized by SOC, HLT, PT, and treatment group. For other AEs described below, 
summaries will be provided by SOC, PT, and treatment group using the Safety Analysis Set:

Grade 3 or higher treatment-emergent AEs

All treatment-emergent study drug-related AEs 

Grade 3 or higher treatment-emergent study drug-related AEs


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
All treatment-emergent SAEs

All treatment-emergent study drug-related SAEs

All treatment-emergent AEs that caused premature discontinuation from study drug

Treatment-emergent deaths
A brief, high-level summary of AEs described above will be provided by treatment group and by 
the number and percentage of participants who experienced the above AEs. Treatment-emergent 
deaths observed in the study will be also included in this summary.
For each of the categories, the percentage of participants reporting AEs will be compared 
between the 2 groups using the CMH test stratified on baseline clinical status. The point estimate 
of the treatment difference and the associated 95% confidence intervals will be calculated based 
on stratum-adjusted Mantel-Haenszel proportion where the stratum is baseline clinical status 
(see Appendix 2).
Treatment-emergent death refers to deaths that occurred between the first dose date and the last 
dose date plus 30 days (inclusive).
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC and HLT within each SOC (if applicable), 
and then by PT in descending order of total frequency within each SOC. For summaries by 
severity grade, the most severe grade will be used for those AEs that occurred more than once in 
an individual subject during the study.
In addition to the above summary tables, all treatment-emergent AEs, treatment-emergent AEs
with Grade 3 or higher, treatment-emergent study drug-related AEs, treatment-emergent study 
drug-related AEs with Grade 3 or higher, and treatment-emergent SAEs will be summarized by 
PT only, in descending order of total frequency. Treatment-emergent AEs and study-drug related 
treatment-emergent AEs will also be summarized by highest grade.
Data listings will be provided for the following:

All AEs

Study-Drug-Related AEs

AEs with severity of Grade 3 or higher

SAEs

Study-Drug-Related SAEs

Deaths

AEs leading to premature discontinuation of study drug


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7.3.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected up to the last dose of study drug plus 30 days. 
The analysis will be based on values reported in conventional units. When values are below the 
LOQ, they will be listed as such, and the closest imputed value will be used for the purpose of 
calculating summary statistics as specified in Section 3.2.2. 
A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, serum chemistry, and PCR separately. Values falling 
outside of the reference range and/or having a severity grade of 1 or higher on the DAIDS 
Grading Scale will be flagged in the data listings, as appropriate.
7.3.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for each laboratory test as follows:

Baseline values

Values at each postbaseline analysis window

Change from baseline at each postbaseline analysis window

Percentage change from baseline to each postbaseline analysis window (if specified)
A baseline laboratory value will be defined as the last nonmissing value obtained on or prior to 
the date (and time, if applicable) of first dose of study drug. Change from baseline to a 
postbaseline visit will be defined as the postbaseline value minus the baseline value. The mean, 
median, Q1, Q3, minimum, and maximum values will be displayed to the reported number of 
digits; SD values will be displayed to the reported number of digits plus 1. Baseline and change 
from baseline will be compared between the treatment groups using the 2-sided Wilcoxon rank 
sum test.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.6.3.
7.3.2.
Graded Laboratory Values
The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Event, Version 2.1 
(July 2017) will be used for assigning toxicity grades (0 to 4) to laboratory results for analysis. 
Grade 0 includes all values that do not meet the criteria for an abnormality of at least Grade 1. 
For laboratory tests with criteria for both increased and decreased levels, analyses for each 
direction (ie, increased, decreased) will be presented separately.


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7.3.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last 
dose of study drug plus 30 days. If the relevant baseline laboratory value is missing, any 
abnormality of at least Grade 1 observed within the time frame specified above will be 
considered treatment emergent.
7.3.2.2.
Summaries of Laboratory Abnormalities
Laboratory data that are categorical will be summarized using the number and percentage of 
participants in the study with the given response at baseline and each scheduled postbaseline 
visit.
The following summaries (number and percentage of participants) for treatment-emergent 
laboratory abnormalities will be provided by laboratory test and treatment group; participants
will be categorized according to the most severe postbaseline abnormality grade for a given 
laboratory test:

Treatment-emergent laboratory abnormalities

Treatment-emergent Grade 3 and 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of participants
with nonmissing postbaseline values up to 30 days after last dosing date.
A by-subject listing of laboratory abnormalities and Grade 3 or 4 laboratory abnormalities will 
be provided by subject ID number and visit in chronological order.
7.3.3.
Liver-Related Laboratory Evaluations
Subjects with AST or ALT > 3 × ULN will be listed.
7.4.
Body Weight, and Vital Signs
Descriptive statistics will be provided by treatment group for body weight, and vital signs
(including heart rate, respiratory rate, blood pressure) as follows:

Baseline value

Values at each postbaseline visit

Change from baseline at each postbaseline visit
A baseline value will be defined as the last available value collected on or prior to the date/time 
of first dose of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value. 


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In the case of multiple values on one Study Day, data will be selected for analysis as described in
Section 3.6.3. No formal statistical testing is planned.
Temperature will not be summarized due to different methods of measuring temperature. SpO2
and PaO2 will not be summarized due to multiple measures through varying oxygen 
supplementation methods. 
A by-subject listing of body weight, BMI, and vital signs (including heart rate, respiratory rate, 
temperature, blood pressure, SpO2 and PaO2) will be provided by subject ID number and visit in 
chronological order.
7.5.
Prior and Concomitant Medications
Concomitant use of traditional herbal treatments including herb sho-saiko-to 
(or Xiao-Shai-Hu-Tang) or investigational agents with putative antiviral activity for COVID-19 
including approved HIV protease inhibitors like lopinavir/ritonavir, chloroquine, interferon, etc 
is prohibited in participants receiving RDV.
Concomitant use of investigational agents such as approved HIV protease inhibitors like 
lopinavir/ritonavir, chloroquine, interferon, 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.
Concomitant medications are defined as medications taken while a subject took study drug. Use 
of concomitant medications will be summarized by preferred name using the number and 
percentage of participants for each treatment group. A subject reporting the same medication 
more than once will be counted only once when calculating the number and percentage of 
participants who received that medication. The summary will be ordered by preferred name in 
descending overall frequency. For drugs with the same frequency, sorting will be done 
alphabetically.
For the purposes of analysis, any medications with a start date prior to or on the first dosing date 
of study drug and continued to be taken after the first dosing date, or started after the first dosing 
date but prior to or on the last dosing date of study drug will be considered concomitant 
medications. Medications started and stopped on the same day as the first dosing date or the last 
dosing date of study drug will also be considered concomitant. Medications with a stop date prior 
to the date of first dosing date of study drug or a start date after the last dosing date of study drug 
will be excluded from the concomitant medication summary. If a partial stop date is entered, any 
medication with the month and year (if day is missing) or year (if day and month are missing) 
prior to the date of first study drug administration will be excluded from the concomitant 
medication summary. If a partial start date is entered, any medication with the month and year 
(if day is missing) or year (if day and month are missing) after the study drug stop date will be 
excluded from the concomitant medication summary. Medications with completely missing start 
and stop dates will be included in the concomitant medication summary, unless otherwise 
specified. 


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Summaries of concomitant medications will be provided for the Safety Analysis Set. Participants
with any concomitant medications will be listed. No inferential statistics will be provided.
7.6.
Other Safety Measures
A data listing will be provided for participants experiencing pregnancy during the study.
7.7.
Subject Subgroup for Safety Endpoints
Incidence of all treatment-emergent AEs will be repeated within each subgroup defined in 
Section 3.2.2 using the safety analysis set.
7.8.
Changes from Protocol-Specified Safety Analyses
The protocol stated that the secondary endpoint of particpants with treatment emergent AEs 
would be compared between the treatment groups using a Fisher’s Exact test. However, a CMH 
test stratified on baseline clinical status will be used to account for differences in baseline 
clinical status.


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8.
REFERENCES
Koch GG, Carr GJ, Amara IA, Stokes ME, Uryniak TJ. Categorical Data Analysis. Chapter 13 in 
Berry, D.A. (ed.).  Statistical Methodology in the Pharmaceutical Sciences. New 
York: Marcel Dekker, Inc., 1989:pp. 414-21. 
Whitehead J. Sample size calculations for ordered categorical data. Stat Med 1993;12 (24):2257-
71.


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9.
SOFTWARE
SASVersion 9.4 (SAS Institute Inc., Cary, NC.) is to be used for all programming of tables, 
listings, and figures.
PASS Version 14 (NCSS, LLC, Kaysville, Utah) was used for planned sample size and power 
calculation.


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10.
SAP REVISION
Revision Date
Section
Summary of Revision
Reason for Revision
15 May 2020
3.6.2, 7.4
SpO2 and PaO2 summaries 
removed
Removed because they were 
collected under various oxygen 
support statuses
3.6.3, 4.1, 6.1.3
Minor updates to wording and 
formats
Clarity and consistency
5,1
Age groups added to list of 
baseline variables to be 
summarized
Clarity and consistency
6.1.4
Day 28 and last available 
assessment were added to 
summaries
Omission
6.2
Other endpoints of interest 
were clarified
Clarity and consistency
6.2.1, 7.1, 7.8, Appendix 2
Analyses adjusting for 
baseline clinical status were 
added
Clarity and consistency
7.3.2.2
Description of listing was 
updated
Clarity and consistency
7.3.3
Listing added
Omission


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11.
APPENDICES
Appendix 1.
Study Procedures Table
Appendix 2.
Programming Specifications


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Appendix 1.
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
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 at rest, and body weight. Body weight collected on screening and Day 1 and otherwise if available.
b
Assessments need not be repeated if performed the same calendar day as screening procedures.; data collection other than adverse events should stop Day 14 or discharge
whichever is earlier.
c
Day 28 evaluations completed if the visit is conducted in person. Only AEs, ordinal scale, and concomitant medication review completed if visit conducted by phone.
CCI
CCII 


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Appendix 2.
Programming Specifications
1) If the age from the Day 1 eCRF is not available, age will be calculated as follows:
Only year is provided for the date of birth (DOB). Use July 1 for the month and day.
a) AGE (years) is calculated from the number of days between the DOB and Study Day 1,
b) Use the SAS INTCK function to determine the number of “1st-of-month days” 
(eg, January 1st, February 1st, March 1st) between DOB and Day 1 (inclusive),
c) Divide the result in (b) by 12,
AGE  the integer of the result in (c),
Age for laboratory test reference range will be based on the age at the sample collection 
date.
2) All screened participants refer to all participants who are screened (ie, with non-missing 
screening date) and have a screening number. For summaries the same subject is counted 
only once.
3) Screen failure participants are the participants who were screened and answered “No” for any 
inclusion criteria or “Yes” for any exclusion criteria regardless of which version of protocol 
the subject was consent to.
4) Participants in the randomized analysis set are defined as participants randomized into the 
study. IXRSRAND is the source to determine whether the subject is randomized (ie, subject 
with non-missing RGMNDTN in the IXRSRAND dataset), and confirmed by the eCRF 
ENROLL dataset (ie, ENROLLYN  “Yes” in ENROLL dataset).
5) Randomized treatment (ie, TRT01P in ADSL) is derived from IXRSRAND, while actual 
treatment received (ie, TRT01A in ADSL) is assigned as the randomized treatment if subject 
took at least 1 dose of study drug and assigned as blank if the subject was never dosed.
6) In the disposition table, the reasons for premature discontinuation are displayed in the order 
as they appear on the eCRF.
7) Body mass index (BMI) 
BMI will be calculated only at baseline as follows:
BMI
 (weight [kg]) / (height [meters]2)
Baseline height and weight will be used for this calculation if available.


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8) Definition of worst values for laboratory and SpO2 and PaO2 results.
Test
Result
ALT
Highest result
AST
Highest result
Creatinine
Highest result
Glucose
Highest result if  any >ULN and none <LLN
Lowest result if any  <LLN and none >ULN
Otherwise use the average
Total bilirubin
Highest result
GFR/Creatinine Clearance
Lowest result
Hemoglobin
Lowest result
Hematocrit
Lowest result
Platelet count
Lowest result
WBC
Lowest result
SpO2
Lowest result
PaO2
Lowest result
If there are 2 values with the same “worst” numerical result on the same day, the later value is 
chosen.
9) SAS codes for the treatment comparison for demographics and baseline characteristics tables.
CMH test for nominal variable (Y), the p-value from the general association test should be
used for nominal variables:
proc freq;
tables trt * Y /cmh; /*general association test*/
run;
CMH test for ordinal variable (Y), the p-value from the row mean score test should be used 
for ordinal variables:
proc freq;
tables trt * Y / cmh2 ; /*row mean score test*/
run;
Wilcoxon rank sum test for continuous variable (Y), the p-value from the normal 
approximation two-sided test should be used for continuous variables:
proc npar1way wilcoxon;
class trt; 
var Y;
run;


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10) Please note, “Not Permitted”, “Unknown”, or missing categories will be excluded from 
percentage calculation and also excluded for p-value generation for categorical data analysis 
(eg, CMH test or Fisher exact test).
11) Proportional Odds
A proportional odds model is used for the primary efficacy endpoint:
proc logistic;
class trt/ param ref order data;
model outcome(descending)  trt baseline;
run;
where outcome is the ordinal scale response at Day 14.
12) Confidence Interval for single percentage
The 95% CI for percentage estimate for each treatment is calculated based on the 
Clopper-Pearson exact method.
proc freq;
by trt;
tables event/ binomial;
exact binomial;
run;
13) Treatment difference in percentages not adjusted by baseline clinical status
The percentage difference between two treatment groups and its 95% CIs are calculated 
based on the unconditional exact method using 2 inverted 1-sided tests in SAS v9.3 or above. 
The following SAS code will be used to compute cell counts and p-values. 
data example;
input  grp trt $  outcome $ count ;
datalines;
1       Treat-A        2-Fail        x     
1       Treat-A        1-Succ      xxx     
1       Treat-B        2-Fail        x     
1       Treat-B        1-Succ      xxx     
run;
proc freq data  example;
table trt*outcome /riskdiff(CL (exact)) alpha 0.05;
weight count; exact RISKDIFF(METHOD SCORE);
output out ciexact(keep _RDIF1_ XL_RDIF1 XU_RDIF1 _RSK11_  _RSK21) riskdiff;
run;


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data final(keep A1 B1 Estimate LowerCL UpperCL ocharc1);
set ciexact;
label Estimate "Percentage Difference"
LowerCL  "95% Lower Confidence Limit"
UpperCL  "95% Upper Confidence Limit"
A1  "Percentage of Success in Treat-A"
B1  "Percentage of Success in Treat-B";
Estimate 100* RDIF1 ;
LowerCL  100*XL RDIF1;
UpperCL  100*XU_RDIF1;
A1  100* RSK11 ;
B1  100* RSK21 ;
ocharc1  right(compress(put(Estimate,8.1)) || '% (' || compress(put(LowerCL,8.1)) || '% 
to ' || compress(put(UpperCL,8.1)) || '%)');
run;
The 95% CI for percentage estimate for each treatment is calculated based on the 
Clopper-Pearson exact method.
proc freq;
by trt;
tables event/ binomial;
exact binomial;
run;
14) Treatment difference in percentages adjusted by baseline clinical status
The baseline stratum weighted difference in rate (P1
P2) and its 95% CI will be calculated 
based on stratum-adjusted Mantel-Haenszel (MH) proportion as described as follows {Koch 
1989}, where the stratification factor is baseline clinical status:
P1
P2 Z(1 α/2 ) * SE(P1
P2),
where 

(P1 P2)  

h
h
h
w
d
w
, is the stratum-adjusted MH proportion difference, where 
h
d
h
h
p
p
2
1
is the difference in the response rate between the 
Treatment Groups 1 and 2 in stratum h (h  1 to 4). 

h
w
 
h
h
h
h
n
n
n
n
2
1
2
1

, is the weight based on the harmonic mean of sample size per treatment 
group for each stratum where 
h
n1 and 
h
n2 are the sample sizes of the 
Treatment Groups 1 and 2 in stratum h. 


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
SE(P1 P2)  
2
2
*
2
*
2
1
*
1
*
1
2
)
(
1
)
1(
1
)
1(









h
h
h
h
h
h
h
h
w
n
p
p
n
p
p
w
, where 
1
5.0
1
1
*
1


h
h
h
n
m
p
and 
1
5.0
2
2
*
2


h
h
h
n
m
p
.
h
m1 and 
h
m2
are the number of subjects with the event in Treatment 
Groups 1 and 2 in stratum h. 

α  0.05

Z(1 α/2 )
 Z0.975
 1.96 is the 97.5th percentile of the normal distribution
Note that if the computed lower confidence bound is less than 1, the lower bound is defined 
as 1. If the computed upper confidence bound is greater than 1, the upper bound is defined 
as 1.
15) CMH test for difference in percentages
The following SAS code will be used to test percentages adjusting for baseline status:
proc freq;
      tables base*trt*response/cmh; * p-value from general association;
run;
16) Log-rank test
Log-rank test for time to death between treatment groups: 
proc lifetest;
strata base;
time days*censor(0);
test trt;
run;
The binary indicator variable (CENSOR) with a value of 1 indicates the time to the event of 
interest is complete or 0 indicates the time to the event is censored. DAYS is a time to event 
variable.
17) Hazard ratio
The following SAS code will be used to compute hazard ratio (HR) and its 95% CI:
proc phreg;
class trt;
model days*censor(0)  trt;
hazardratio ’10 vs 4’ trt;
strata base;
~ - -


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run;
18) Competing risk analysis
The following SAS code will be used to generate the cause-specific hazard ratio and 95% 
confidence intervals for the competing risk analysis:
proc phreg;
class trt;
model days*event(0, 2)  trt base/ rl;
hazardratio “Cause-specific hazard” trt;
run;
where EVENT  1 if the participant had the event; EVENT  2 if the participant died prior to 
having the event, and EVENT  0 if the subject did not have the event and did not die. BASE 
 baseline value.
SAS code to obtain a cumulative incidence function plot and dataset for further processing
for time to first event table: 
proc lifetest outcif outcif plots cif;
strata trt;
time days*event(0) / failcode  1; *Note: this produces data for the event of interest only;
run;
SAS code to obtain support tables: 
proc univariate;
by trt event;
var days;
output pctlpre P_ min min max max pctlpts  10, 25, 50, 75, 90;
run;
19) SAS code for stratified 2-sided Wilcoxon Rank sum test (stratified on baseline result)
proc freq;
   table base*trt*aval/cmh2 scores modridit;
run;
where BASE is the baseline value.
20) TEAE
Events with Missing Onset Day and/or Month
An event is considered treatment emergent if the following 3 criteria are met:
i.
The month and year (or year) of onset date is the same as or after the month and year 
(or year) of the first dose of study drug, and


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ii.
The month and year (or year) of the onset date is the same as or before the month and 
year (or year) of the 30th day after the date of the last dose of study drug, and
iii.
End date is as follows: 
The (complete) end date is on or after the first dose date, or
The month and year (or year) of end date is the same or after the month and year 
(or year) of the first dose of study drug, or
End date is completely missing 
Events with Completely Missing Onset Date
An AE with a completely missing onset date is defined as TEAE if end date meets any of the 
3 criteria specified above.
21) The number of decimal places in reporting p-values should be as follows:
a) values less than 0.001 < 0.001
b) values 0.001 to less than 1.000 4 decimal places (no rounding)
22) The precision in reporting numerical values should be as follows:
Raw measurements will be reported the same as the data captured electronically or on the 
eCRF.
Standard deviation and standard error will be reported to one more significant decimal place 
than the raw measurement.
Mean, median, minimum, Q1, Q3, maximum, 95% CIs will be reported to the same number 
of decimal places of the raw measurements. 
Exceptions may be considered; for example, if more than 4 significant digits are provided for 
the measurement.
23) Last dose date is not expected to be missing. However, if last dose date is missing due to data 
issues, it will be imputed using the maximum of non-missing, non-zero dose, study drug start 
and stop dates.


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24) Ordinal scale and oxygen support status
The oxygen support status is derived from the ordinal scale: 
Ordinal Scale
Oxygen Support Status
1
Death
Death
2
Hospitalized, on invasive mechanical ventilation or ECMO
Invasive Mechanical Ventilation 
3
Hospitalized, on non-invasive ventilation or high flow oxygen 
devices
High Flow Oxygen
4
Hospitalized, requiring low flow supplemental oxygen
Low Flow Oxygen
5
Hospitalized, not requiring supplemental oxygen - requiring ongoing 
medical care (COVID-19 related or otherwise)
Room Air
6
Hospitalized, not requiring supplemental oxygen - no longer 
requires ongoing medical care (other than per protocol RDV 
administration)
Room Air
7
Not hospitalized
Discharge
25) Censoring rules
Time to death: subjects are censored at the last known date alive (last study day)
Time to ≥ 2 point improvement, time to  ≥ 1 point improvement, time to recovery; time to 
modified recovery; time to room air: if a subject does not experience the event of interest and 
does not die, the subject is censored at the last non-missing ordinal scale assessment date.
26) Graded Laboratory Abnormalities Summary
The following labels will be used for laboratory abnormalities and Grade 3 or 4 laboratory 
abnormalities summary tables and listings:


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Battery
Lab Test Label
Used in l-labtox Listing
Toxicity 
Direction
Lab Test Label
Used in t-labtox Table
Hematology
Hemoglobin
Decrease
Hemoglobin (Decreased)
Platelets
Decrease
Platelets (Decreased)
WBC
Decrease
WBC (Decreased)
Chemistry
ALT
Increase
ALT (Increased)
AST
Increase
AST (Increased)
Creatinine
Increase
Creatinine (Increased)
Creatinine Clearance
Decrease
Creatinine Clearance (Decreased)
Serum Glucose
Increase
Serum Glucose (Hyperglycemia)
Serum Glucose 
Decrease
Serum Glucose (Hypoglycemia)
Total Bilirubin
Increase
Total Bilirubin (Hyperbilirubinemia)


GS-US-540-5773_Part_A_SAP
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Regulatory Affairs eSigned 19-May-2020
02:51:23
Biostatistics eSigned
19-May-2020
03:20:19
Clinical Research eSigned 19-May-2020
16:57:30
PPD
PPD
PPD-