A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study Evaluating the Efficacy and Safety of Remdesivir in Participants With Severely Reduced Kidney Function Who Are Hospitalized for COVID-19
Phase: PHASE3
Conditions: COVID-19
Sponsor: Gilead Sciences

CLINICAL STUDY PROTOCOL
Study Title:
A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel 
Group, Multicenter Study Evaluating the Efficacy and Safety of 
Remdesivir in Participants with Severely Reduced Kidney Function 
who are Hospitalized for COVID-19
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
147753
2020-005416-22
NCT04745351
Indication:
COVID-19
Protocol ID:
GS-US-540-5912
Contact Information:
The medical monitor name and contact information will be 
provided on the Key Study Team Contact List.
Protocol 
Version/Date:
Original:
07 December 2020
Amendment 1:
28 January 2021
Amendment 2:
02 August 2021
Amendment 3:
27 August 2021
This study will be conducted under United States Food and Drug Administration investigational 
new drug (IND) regulations (21 Code of Federal Regulations Part 312); however, sites located in 
the European Economic Area and Switzerland are not included under the IND and are considered 
non-IND sites.
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable 
institutional review board or independent ethics committee. The information is only to be used 
by you in connection with authorized clinical studies of the investigational drug described in 
the protocol. You will not disclose any of the information to others without written 
authorization from Gilead Sciences, Inc., except to the extent necessary to obtain informed 
consent from those persons to whom the drug may be administered.
GILEAU 

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
FINAL 
Amendment3 
TABLE OF CONTENTS 
TABLE OF CONTENTS ................................................................................................................................................ 2 
LIST OF IN-TEXT TABLES ......................................................................................................................................... 5 
LIST OF IN-TEXT FIGURES ........................................................................................................................................ 5 
PROTOCOL SYNOPSIS ................................................................................................................................................ 6 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................... 15 
1. 
INTRODUCTION ................................................................................................................................................ 18 
1.1. 
Backgrowid .............................................................................................................................................. 18 
1.2. 
Reindesivir ............................................................................................................................................... 19 
1. 2 .1. 
General Infonnation .............................................................................................................. 19 
1.3. 
Rationale for This Study .......................................................................................................................... 20 
1.4. 
Rationale for Dose Selection ofRemdesivir ........................................................................................... 22 
1.5. 
Risk/Benefit Assessment for the Study ................................................................................................... 23 
1.6. 
Coinpliance .............................................................................................................................................. 23 
2. 
OBJECTIVES ....................................................................................................................................................... 24 
3. 
STUDY DESIGN ................................................................................................................................................. 25 
3.1. 
3.2. 
3.3. 
3.4. 
3.5. 
3.6. 
3.7. 
3.8. 
End Points ................................................................................................................................................ 25 
Study Design ........................................................................................................................................... 26 
Study Treatments ..................................................................................................................................... 27 
Duration of Treatment ............................................................................................................................. 27 
Discontinuation Criteria .......................................................................................................................... 27 
End of Study ............................................................................................................................................ 28 
Poststudy Care ......................................................................................................................................... 28 
Sow·ce Data ............................................................................................................................................. 28 
4. 
PARTICIPANT POPULATION .......................................................................................................................... 30 
4.1. 
Number of Participants and Prut icipant Selection ................................................................................... 30 
4.1.1. 
Participant Replacement ........................................................................................................ 30 
4.2. 
Inclusion Criteria ..................................................................................................................................... 30 
4.3. 
Exclusion Criteria .................................................................................................................................... 31 
5. 
INVESTIGATIONAL MEDICINAL PRODUCTS ............................................................................................. 32 
5.1. 
Randomization, Blinding, and Treatment Codes Access ........................................................................ 32 
5.1.1. 
Randoinization ....................................................................................................................... 32 
5.1.2. 
Blinding ................................................................................................................................. 32 
5.1.3. 
Procedw-es for Breaking Treatment Codes ............................................................................ 33 
5.2. 
Description and Handling ofRemdesivir ................................................................................................ 33 
5.2.1. 
Fo1mulation ........................................................................................................................... 33 
5.2.2. 
Packaging and Labeling ........................................................................................................ 33 
5.2.3. 
Storage and Handling ............................................................................................................ 34 
5.3. 
Dosage and Administrntion ofRemdesivir ............................................................................................. 34 
5.4. 
Infusion-related Reaction ........................................................................................................................ 34 
5.5. 
Prior and Concomitant Medications ........................................................................................................ 34 
5.6. 
Accountability for Investigational Medicinal Product ............................................................................ 35 
CONFIDENTIAL 
Page2 
27 August 2021 

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
FINAL 
Amendment3 
5.6.1. 
Investigational Medicinal Product Retum or Disposal ......................................................... 36 
6. 
STUDY PROCEDURES ...................................................................................................................................... 37 
6.1. 
6.2. 
6.4. 
6.5. I 
6.8. 
6.9. 
6.10. 
6.11. 
6.12. 
6.13. -
Participant Enrollment and Treatment Assignment ................................................................................ 37 
Preti·eatinent Assessments ....................................................................................................................... 37 
6.2.1. 
Screening Visit ...................................................................................................................... 37 
6.2.2. 
Baseline/Da 1 Assess1nents ................................................................................................. 38 
Assess1nents (Days 2 Through 29) .......................................................................................................... 39 
Additional Assessments .......................................................................................................................... .40 
Virology Assessments ............................................................................................................................ .42 
Ordinal Scale .......................................................................................................................................... .42 
Post.treatment Assess1nents ..................................................................................................................... .42 
Assessments for Early Discontinuation from Study ............................................................................... .43 
6.11.1. 
Criteria for Discontinuation of Study Treatment. ................................................................. .43 
End of Study ........................................................................................................................................... .43 
Poststud Care ......................................................................................................................................... 44 
7. 
ADVERSE EVENTS AND TOXICITY MANAGEMENT ............................................................................... .45 
7.1. 
Definitions of Adverse Events and Serious Adverse Events .................................................................. .45 
7 .1.1. 
Adverse Events ..................................................................................................................... .45 
7 .1. 2. 
Serious Adverse Events ........................................................................................................ .45 
7 .1.3. 
Investigational Drngs and Gilead Concomitant Therapy Special Situations 
Repoits .................................................................................................................................. .46 
7.2. 
Assessment of Adverse Events and Serious Adverse Events .................................................................. 47 
7.2.1. 
Assessment of Causality for Investigational Drngs and Procedw-es .................................... .47 
7.2.2. 
Assess1nent of Severity ......................................................................................................... .47 
7.3. 
Investigator Repo1ting Requirements and Instrnctions .......................................................................... .48 
7 .3 .1. 
Requirements for Collection Prior to Investigational Drng Initiation .................................. .48 
7.3.2. 
Adverse Events ..................................................................................................................... .48 
7.3.3. 
Serious Adverse Events ........................................................................................................ .48 
7 .3 .4. 
Investigational Drng Special Situations Repo11s .................................................................. .48 
7.3.5. 
Conco1nitant Therapy Reports .............................................................................................. .49 
7.4. 
Repo11ing Process for Serious Adverse Events and Special Situation Repoits ...................................... .49 
7.4.1. 
Serious Adverse Event Rep01ting Process ........................................................................... .49 
7.4.2. 
Special Situations Repo1ting Process .................................................................................... 50 
7.5. 
Gilead Repo11ing Requirements .............................................................................................................. 51 
7.6. 
Clinical Laborato1y Abnonnalities and Other Abno1mal Assessments as Adverse Events or 
Serious Adverse Events ........................................................................................................................... 52 
7.7. 
Toxicity Mana.geinent .............................................................................................................................. 52 
7. 7 .1. 
Grade 1 and 2 Laborato1y Abno1malities .............................................................................. 53 
7.7.2. 
Grade 3 Laborato1y Abnoimalities ........................................................................................ 53 
7.7.3. 
Grade 4 Laborato1y Abnoimalities ........................................................................................ 53 
8. 
STATISTICAL CONSIDERATIONS ................................................................................................................. 55 
8.1. 
Analysis Objectives and End Points ........................................................................................................ 55 
8.1.1. 
Analysis Objectives ............................................................................................................... 55 
8.1.2. 
Pri1nruy End Point ................................................................................................................. 56 
8.1.3. 
Secondru End Points ............................................................................................................ 56 
-
8.2. 
Planned Analyses ..................................................................................................................................... 57 
CONFIDENTIAL 
Page 3 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 4
27 August 2021
8.2.1.
Interim Analysis ....................................................................................................................57
8.2.2.
Primary Analysis ...................................................................................................................58
8.2.3.
Final Analysis........................................................................................................................58
8.3.
Analysis Conventions..............................................................................................................................58
8.3.1.
Analysis Sets .........................................................................................................................58
8.3.2.
Data Handling Conventions ..................................................................................................59
8.4.
Demographic and Baseline Characteristics Analysis..............................................................................59
8.5.
Efficacy Analysis.....................................................................................................................................59
8.5.1.
Primary Analysis ...................................................................................................................59
8.5.2.
Secondary Analyses...............................................................................................................59
8.6.
Safety Analysis........................................................................................................................................60
8.6.1.
Extent of Exposure ................................................................................................................60
8.6.2.
Adverse Events......................................................................................................................60
8.6.3.
Laboratory Evaluations .........................................................................................................60
8.7.
Adjustments for Multiplicity ...................................................................................................................61
8.9.
Sample Size .............................................................................................................................................61
8.10.
Data Monitoring Committee....................................................................................................................62
9.
RESPONSIBILITIES...........................................................................................................................................63
9.1.
Investigator Responsibilities ...................................................................................................................63
9.1.1.
Good Clinical Practice...........................................................................................................63
9.1.2.
Financial Disclosure ..............................................................................................................63
9.1.3.
Institutional Review Board/Independent Ethics Committee Review and 
Approval................................................................................................................................63
9.1.4.
Informed Consent ..................................................................................................................63
9.1.5.
Confidentiality.......................................................................................................................64
9.1.6.
Study Files and Retention of Records ...................................................................................64
9.1.7.
Case Report Forms ................................................................................................................66
9.1.8.
Investigator Inspections.........................................................................................................66
9.1.9.
Protocol Compliance .............................................................................................................66
9.2.
Sponsor Responsibilities .........................................................................................................................67
9.2.1.
Protocol Modifications ..........................................................................................................67
9.2.2.
Study Report and Publications ..............................................................................................67
9.3.
Joint Investigator/Sponsor Responsibilities ............................................................................................67
9.3.1.
Payment Reporting ................................................................................................................67
9.3.2.
Access to Information for Monitoring...................................................................................68
9.3.3.
Access to Information for Auditing or Inspections ...............................................................68
9.3.4.
Study Discontinuation ...........................................................................................................68
10.
REFERENCES.....................................................................................................................................................69
11.
APPENDICES......................................................................................................................................................72
Appendix 1.
Investigator Signature Page.....................................................................................................73
Appendix 2
Pandemic Risk Assessment and Mitigation Plan ....................................................................74
Appendix 3.
Study Procedures Table...........................................................................................................77
Appendix 4.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements....................................................................................................80
Appendix 5.
Toxicity Grading Scale for Severity of Adverse Events and Laboratory 
Abnormalities ..........................................................................................................................83
Appendix 6.
Management of Clinical and Laboratory Adverse Events.......................................................84
Appendix 7.
eGFR Automated Calculators..................................................................................................85
CCI

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 5
27 August 2021
LIST OF IN-TEXT TABLES
Table 1.
Development of AKI Stages 2 or 3 in ACTT-1 Study, by Treatment Group..........................21
Table 2.
Death Among Those With AKI Stage 3 in ACTT-1 Study, by Treatment Group..................21
Table 3.
Development of AKI Stages 2 or 3 in ACTT-1 Study Who Were Not Receiving 
Mechanical Ventilation at Baseline, by Treatment Group ......................................................21
Table 4.
Death Among Those With AKI Stage 3 in ACTT-1 Study Who Were Not Receiving 
Mechanical Ventilation at Baseline, by Treatment Group ......................................................21
Table 5.
Gatekeeping and Boundaries for Efficacy Analysis................................................................61
LIST OF IN-TEXT FIGURES
Figure 1.
Study Schema ..........................................................................................................................27

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 6
27 August 2021
PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel 
Group, Multicenter Study Evaluating the Efficacy and Safety of 
Remdesivir in Participants with Severely Reduced Kidney Function 
who are Hospitalized for COVID-19
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
147753
2020-005416-22
NCT04745351
Study Centers 
Planned:
Approximately 150 centers globally
Objectives:
The primary objective of this study is as follows:

To evaluate whether remdesivir (RDV, GS-5734™) reduces the
composite risk of death or invasive mechanical ventilation
(IMV) through Day 29 in participants with severely reduced
kidney function who are hospitalized for coronavirus disease
2019 (COVID-19)
The secondary objectives of this study are as follows:

To evaluate whether RDV reduces the risk of death through
Day 29

To evaluate whether RDV reduces the risk of IMV through
Day 29

To evaluate the time to recovery (defined as satisfying category
1, 2, or 3 by the 8-point ordinal scale)

To evaluate the effect of RDV on clinical status assessed by an
8-point ordinal scale at Day 15 and Day 29

To evaluate the effect of RDV on renal replacement therapy
(RRT)-free days (among those without end-stage kidney disease
[ESKD]) through Day 29

To evaluate the effect of RDV on recovery through Day 29

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
Study Design: 
CONFIDENTIAL 
FINAL 
Amendment3 
• 
To evaluate the safety and tolerability of RDV in paiiicipants 
with severely reduced kidney function who ai·e hospitalized for 
COVID-19 
This is a Phase 3 randomized, double-blind, placebo-contrnlled, 
parallel-group, multicenter study evaluating the efficacy and safety 
of RDV therapy in paiiicipants with severely reduced kidney 
function who are hospitalized for COVID-19. 
In this study, prima1y and seconda1y end points will be evaluated 
through Day 29. Following screening, eligible paiiicipants will be 
randomized in a 2:1 ratio to receive RDV or saline as placebo 
according to the following treatment regimen, in addition to 
standai·d of care (SOC) therapy: 
• 
Treatment Group A: Intravenous (IV) RDV 200 mg on Day 1 
followed by IV RDV 100 mg once daily from Day 2 up to Day 5 
• 
Treatment Group B: IV saline as placebo on Day 1 followed by 
IV saline as placebo once daily from Day 2 up to Day 5 
Page7 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 8
27 August 2021
Randomization will be stratified by:

ESKD requiring chronic dialysis

High-flow oxygen requirement

Region (United States [US] versus ex-US)
Number of 
Participants 
Planned:
Approximately 1116
Target Population:
Participants with severely reduced kidney function who are 
hospitalized for COVID-19
Duration of 
Treatment:
The duration of treatment with RDV or saline as placebo will be up 
to 5 days
Study Duration:
Up to 29 days (not including screening window or Day 60 phone 
follow-up)
Diagnosis and Main 
Eligibility Criteria:
Participants who meet the following criteria:

SARS-CoV-2 positive as determined by polymerase chain 
reaction (PCR) or other commercially available or public health 
assay (eg, nucleic acid amplification test and antigen tests) in 
any respiratory specimen

Hospitalized for COVID-19

Age ≥ 12 years and weighing at least 40 kg

O2 saturation ≤ 94% on room air or requiring O2 
supplementation OR radiographic evidence of pulmonary 
infiltrates for COVID-19

Have either:
Severely reduced kidney function (estimated glomerular 
filtration rate [eGFR] < 30 mL/min/1.73 m2), using the 
Chronic Kidney Disease Epidemiology Collaboration 
(CKD-EPI) and revised Schwartz equations for adults and 
adolescents, respectively, including people with ESKD 
requiring chronic dialysis but not people requiring RRT for 
AKI, OR
Ongoing AKI: defined as a 50% increase in SCr within a 
48-hour period that is sustained (ie, requires confirmatory 
SCr) for ≥ 6 hours despite supportive care

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 9
27 August 2021

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) prior to 
performing study procedures

The interval between COVID-19 symptoms onset and 
randomization is no more than 10 days

Male participants and female participants of childbearing 
potential who engage in heterosexual intercourse must agree to 
use protocol-specified method(s) of contraception as described 
in Appendix 4
Key Exclusion 
Criteria: 
Participants who meet any of the following criteria at screening:

Received any investigational drug, RDV, or other antiviral 
treatment for COVID-19

Alanine aminotransferase or aspartate aminotransferase 
> 5 × the upper limit of normal

IMV, noninvasive mechanical ventilation, extracorporeal 
membrane oxygenation, or RRT for AKI

Positive serum pregnancy test at screening for women of 
childbearing potential or currently breastfeeding

Known hypersensitivity to the investigational drug, metabolites, 
or formulation SBECD
Study Procedures/
Frequency:
At screening, after the participant has provided informed consent 
(or assent), demographic and baseline characteristics, focused 
medical history, complete physical examination findings, vital signs 
(including temperature, respiratory rate, and oxygen saturation), 
RRT status, 8-point ordinal scale of clinical status and concomitant 
medications will be documented. Women of childbearing potential 
will have a serum pregnancy test. Pulmonary radiographic imaging 
may be performed, if not already available from the past 72 hours 
and if needed to satisfy eligibility criteria. SARS-CoV-2 testing will 
be performed; if this testing has been performed within the last 
4 calendar days, no repeat testing is required.
If safety laboratory results from within 48 hours prior are not 
already available, laboratory analyses (chemistry, hematology, SCr, 
coagulation, urinalysis, and serum pregnancy test) will be 
performed according to local practice.

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
CONFIDENTIAL 
FINAL 
Amendment3 
After screening procedures, eligible participants will be randomized 
into 1 of the 2 tr·eatment groups in a 2:1 ratio to receive: 
• 
Continued SOC therapy together with IV RDV 200 mg on 
Day 1 followed by IV RDV 100 mg once daily from Day 2 up to 
Day5 
• 
Continued SOC therapy together with IV saline as placebo on 
Day 1 followed by IV saline as placebo once daily from Day 2 
up to Day 5 
The date of randomization will be considered Day 1, and all 
participants randomized to receive RDV or saline as placebo should 
receive their initial dose on Day 1. 
On Days 1 through 29 or until discharge from inpatient 
hospitalization, whichever is earlier, need for RRT, 8-point ordinal 
scale of clinical status, vital signs, respirato1y status measurement, 
adverse events (AEs ), and concomitant medications will be 
documented. Following discharge from inpatient hospitalization, 
RRT status, 8-point ordinal scale of clinical status, AEs, 
concomitant medications, and m01iality will also be collected during 
the Day 29 and Day 60 phone follow-up. Laborato1y testing during 
hospitalization will be perfo1med according to SOC practice with 
results for chemistry , hematology, and any SARS-CoV-2 testing 
being repo1ied to the sponsor. 
Even if not perfo1med as SOC, SCr will be completed at screening, 
and on Days 1 through 29, or until discharge, whichever is earlier. 
In addition, even if not perfo1med as SOC, chemistry, hematology, 
and coagulation will be completed at screening and on Days 1, 3, 5, 
8, 12, 16, 20, 24, and 29 or until discharge, whichever is earlier. 
Page 10 
27 August 2021 

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
Test Product, Dose, 
and Mode of 
Administration: 
Reference Therapy, 
Dose, and Mode of 
Administration: 
Criteria for 
Evaluation: 
Safety: 
CONFIDENTIAL 
FINAL 
Amendment3 
Remdesivir for injection, 100 mg, for IV administrntion (lyophilized 
preparation) 
Saline as placebo 
The safety of RDV will be assessed during the study through the 
repo1ting of treatment-emergent AEs and serious adverse events 
(SAEs), as well as treatment-emergent clinical laborato1y 
abnonnalities. 
Page 11 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 12
27 August 2021
A data monitoring committee (DMC) will meet regularly to evaluate 
all available safety data accumulated during the study, including 
kidney injury. The DMC will have 2 formal (unblinded data review) 
meetings. The first formal DMC meeting will be based on data 
collected after the first 100 participants complete the Day 29 
assessment. The second formal DMC meeting will be based on data 
collected after 50% of participants complete the Day 29 assessment 
and will include review of safety, efficacy, and futility. The DMC 
will make a recommendation of stopping enrollment to the study at 
the second formal DMC meeting if the prespecified efficacy or 
futility stopping criteria are met. The DMC will also receive blinded 
safety listings for review up to every week for the first 2 weeks 
followed by every 2 weeks until the second DMC meeting occurs 
after 50% of participants complete the Day 29 assessment.
Efficacy:
Primary efficacy end point:

The composite of all-cause mortality or IMV through Day 29
Key (α-controlled) secondary end point:

All-cause mortality through Day 29
Other secondary end points:

IMV through Day 29

Time to recovery (defined as satisfying category 1, 2, or 3 by the 
8 point ordinal scale)

Clinical status assessed by an 8-point ordinal scale on Day 15 
and Day 29

RRT-free days (among those without ESKD at randomization) 
through Day 29

Recovery through Day 29
CCI
I 
I 
I 

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
Statistical Methods: 
CONFIDENTIAL 
I 
I 
I 
I 
I 
I 
FINAL 
Amendment3 
The primaiy analysis set for efficacy analyses is the Full Analysis 
Set, which includes all paiiicipants who were randomized and 
received at least 1 dose of investigational chug. The primaiy clinical 
end point is the composite of all-cause mo1iality or IMV from date 
of first dose through Day 29. 
The primaiy end point will be analyzed using a stratified log-rank 
test. The hazard ratio and 95% confidence interval will be provided. 
Treatment-emergent AEs and laborato1y abno1malities will be 
Sllllllllai·ized using descriptive statistics and listed by participant. 
Page 13 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 14
27 August 2021
Sample Size:
A total of approximately 1116 participants will be randomized in a 
2:1 ratio to 2 groups (744 in the RDV group and 372 in the saline as 
placebo group). This sample size achieves approximately 85% 
power to detect a hazard ratio of 0.70 at a two-sided alpha level 
of 0.05. In the sample size calculation, it is assumed that the event 
rate in the saline as placebo group is 35%. The hazard ratio and 
event rate in the saline as placebo group are based on the most 
conservative estimates of the primary end point (composite of 
all-cause mortality or IMV) and key α-controlled secondary end 
point (all-cause mortality) through Day 29 among a subset of 
participants with eGFR < 60 mL/min in the Division of 
Microbiology and Infectious Diseases Protocol 20-0006 Adaptive 
COVID-19 Treatment Trial (ACTT)-1 (hazard ratio of 0.67 and 
placebo rate of 33%). An unblinded interim analysis of efficacy and 
futility is planned after 50% of participants complete the Day 29 
assessment.
This study will be conducted in accordance with the guidelines of Good Clinical Practice, 
including archiving of essential documents.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 15
27 August 2021
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
z
terminal elimination rate constant, estimated by linear regression of the terminal 
elimination phase of the log concentration of drug versus time curve of the drug
ACE2
angiotensin-converting enzyme 2
ADME
absorption, distribution, metabolism, and excretion
AE
adverse event
AKI
acute kidney injury
ALT
alanine aminotransferase
AST
aspartate aminotransferase
ATP
adenosine triphosphate
AUC
area under the curve
AUCtau
area under the concentration versus time curve over the dosing interval
BIPAP
bilevel positive airway pressure
CDC
Centers for Disease Control and Prevention
CI
confidence interval
CK
creatine kinase
CKD
chronic kidney disease
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
Clast
last observed quantifiable concentration of the drug
Cmax
maximum observed plasma drug concentration
CoV
coronavirus
COVID-19
coronavirus disease 2019
CPAP
continuous positive airway pressure
CRF
case report form
CRO
contract research organization
Ctau
observed drug concentration at the end of the dosing interval
CVVH
continuous venovenous hemofiltration
DAIDS
Division of AIDS
DMC
data monitoring committee
DNA
deoxyribonucleic acid
EC
ethics committee
ECMO
extracorporeal membrane oxygenation
eCRF
electronic case report form
EDC
electronic data capture
eGFR
estimated glomerular filtration rate
EMA
European Medicines Agency
ESKD
end-stage kidney disease
EU
European Union
FDA
Food and Drug Administration
FIO2
fraction of inspired oxygen

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 16
27 August 2021
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GLPS
Global Patient Safety
HIV
human immunodeficiency virus
IB
investigator’s brochure
ICF
informed consent form
ICH
International Council for Harmonisation (of Technical Requirements for 
Pharmaceuticals for Human Use)
ICU
intensive care unit
IEC
independent ethics committee
IMV
invasive mechanical ventilation
IND
investigational new drug
IRB
institutional review board
IUD
intrauterine device
IV
intravenous
LPV
lopinavir
MedDRA
Medical Dictionary for Regulatory Activities
mRNA
messenger RNA
NIAID
National Institute of Allergy and Infectious Diseases
OR
odds ratio
PCR
polymerase chain reaction
PI
principal investigator
PK
pharmacokinetic(s)
RDV
remdesivir (GS-5734™)
RNA
ribonucleic acid
RRT
renal replacement therapy
RTV
ritonavir
SAE
serious adverse event
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SBECD
sulfobutylether-beta-cyclodextrin 
SCr
serum creatinine
SDV
source data verification
SmPC
Summary of Product Characteristics
SOC
standard of care
SOP
standard operating procedure
SpO2
oxygen saturation
SSR
special situation report
SUSAR
suspected unexpected serious adverse reaction
t1/2
estimate of the terminal elimination half-life of the drug, calculated by dividing the 
natural log of 2 by the terminal elimination rate constant (z)

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 17
27 August 2021
Tlast
time (observed time point) of Clast
Tmax
time to maximum observed concentration
ULN
upper limit of normal
US
United States
USPI
United States prescribing information
WHO
World Health Organization

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 18
27 August 2021
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), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 
resulting in a novel infectious disease called coronavirus disease 2019 (COVID-19). On 
30 January 2020, the International Health Regulations Emergency Committee of the World 
Health Organization (WHO) declared the SARS-CoV-2 outbreak a public health emergency of 
international concern and a pandemic on 11 March 2020 {World Health Organization (WHO) 
2020}. As of 11 July 2021, more than 186 million cases have been identified globally, with a 
death toll of over 4 million{World Health Organization (WHO) 2021}.
The clinical manifestations of COVID-19 are broad, ranging from mild symptoms to severe 
respiratory failure. However, the SARS-CoV-2 also manifests in several extrapulmonary organs 
by using angiotensin-converting enzyme 2 (ACE2) to enter human cells. ACE2 is expressed in 
the lung, heart, intestine, and kidney, and provides a probable mechanism for the systemic 
manifestations observed with this disease {Gupta 2020} Many patients with severe COVID-19 
demonstrate signs of kidney damage that manifest as proteinuria, hematuria, and elevated serum 
creatinine (SCr) levels. Acute kidney injury (AKI) is a common complication of COVID-19 that 
is associated with high mortality rates, especially among people requiring renal replacement 
therapy (RRT) {Robbins-Juarez 2020}. Acute kidney injury is also more common among 
patients with respiratory failure, and most patients who require RRT also require mechanical 
ventilation, {Hirsch 2020}. Among those who require mechanical ventilation and develop AKI, 
about half have onset of AKI within 24 hours of intubation. In addition to need for ventilation 
and vasopressor medications, risk factors for AKI are similar to those at risk for severe 
COVID-19, including older age, diabetes mellitus, cardiovascular disease, black race, and 
hypertension {Hirsch 2020}.
The most common cause of AKI is likely related to acute tubular necrosis from the indirect 
effects of severe COVID-19, including alterations in systemic hemodynamics, inflammation, and 
immune function {Nadim 2020}. Several direct effects of SARS-CoV-2 have also been observed 
and are likely important mechanisms for AKI, including endothelial dysfunction, coagulopathy, 
and complement activation. The pathologic manifestations of these direct viral effects in the 
kidney include endothelial damage and capillary occlusions, deposition of complement complex 
on tubules, and glomerular lesions {Gupta 2020, Nadim 2020}. Several postmortem studies 
imply direct infection of the kidney by detection of SARS-CoV-2 mRNA and protein in 
glomerular and tubular cells, as well as visualization by electron microscopy of viral inclusion 
particles with distinctive spikes in podocytes, proximal tubular epithelial cells, and endothelial 
cells of the glomerular capillary loops {Farkash 2020, Puelles 2020, Su 2020, Varga 2020}. 
Finally, collapsing glomerulopathy associated with COVID-19 (an entity termed 
COVID-19-associated nephropathy, or COVAN) {Velez 2020} manifests as an aggressive 
morphological variant of focal segmental glomerulosclerosis, particularly among patients of 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 19
27 August 2021
African ancestry, in whom the presence of high-risk APOL1 alleles serve as a genetic risk factor 
{Nasr 2020}.
In addition to the direct and indirect acute effects of COVID-19 kidney function, preexisting 
kidney disease is a strong risk factor for severe COVID-19 and poor outcomes {Centers for 
Disease Control and Prevention (CDC) 2020}. Patients with chronic kidney disease (CKD) and 
end-stage kidney disease (ESKD) are particularly vulnerable to severe COVID-19 due to their 
older age and high burden of comorbid conditions including diabetes and hypertension {Alberici 
2020, Williamson 2020}. In one study of critically-ill patients with COVID-19 across 
68 intensive care units (ICUs; N = 4264), half of dialysis and CKD patients died within 28-days 
of ICU admission versus 35% of patients without preexisting kidney disease {Flythe 2020}. 
Among those with prehospitalization CKD who do not die, many require dialysis at hospital 
discharge {Ng 2020}. Despite the greater risk of adverse outcomes with COVID-19 among those 
with preexisting kidney disease, patients with CKD are being excluded from almost half of all 
registered clinical trials for COVID-19 {Major 2020}.
Remdesivir is approved for the treatment of COVID-19 in the United States (US), European 
Union (EU), Japan, and other countries for populations including adults and pediatric patients 
(12 years and older and weighing at least 40 kg). However, in the current US prescribing 
information (USPI) and EU Summary of Product Characteristics (SmPC), RDV is currently not 
recommended in people with severely reduced kidney function (glomerular filtration rate 
< 30 mL/min), leaving no alternative treatment options for those with COVID-19. The unmet 
need in this population remains large in the context of their poor outcomes with COVID-19, and 
providers around the world have expressed strong interest in treating these patients with RDV 
{Adamsick 2020}.
1.2.
Remdesivir
Remdesivir is being developed by Gilead Sciences, Inc. (Gilead) and is formulated for 
intravenous (IV) administration.
1.2.1.
General Information
Remdesivir is an adenosine nucleotide prodrug that distributes into cells where it is metabolized 
to form the pharmacologically active nucleoside triphosphate metabolite. Metabolism of RDV to 
RDV triphosphate has been demonstrated in multiple cell types. Remdesivir triphosphate acts as 
an analog of adenosine triphosphate (ATP) and competes with the natural ATP substrate for 
incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent RNA polymerase, 
which results in delayed chain termination during replication of the viral RNA.
For further information on RDV, refer to the USPI and investigator’s brochure (IB) for RDV.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 20
27 August 2021
1.3.
Rationale for This Study
The restriction for RDV dosing among those with severely reduced kidney function is due 
primarily to the excipient betadex sulfobutyl ether sodium, also called 
sulfobutylether-beta-cyclodextrin (SBECD), which is renally cleared and accumulates in patients 
with decreased kidney function. Thus, administration of drugs formulated with SBECD, such as 
RDV, is not recommended in patients with estimated glomerular filtration rate (eGFR) < 30 mL 
per minute {VEKLURY 2020} (Veklury USPI). In terms of the renal tubular vacuolation 
associated with SBECD, it was observed in nonclinical studies in animals treated for 1 to 
6 months with exposures that were 50- to 100-fold higher than would be expected for a 5- to 
10-day course of RDV, and this change was largely reversible after cessation of treatment. For 
example, the amount of SBECD in a 5-day course of RDV (lyophilized formulation, 200 mg on 
Day 1 and 100 mg from Day 2 [Veklury USPI] {VEKLURY 2020}) would be 18 grams 
(SBECD:RDV is 30:1), or 257.1 mg/kg total and an average of 51.4 mg/kg/day over 5 days for a 
70 kg adult, which is well below the maximum recommended safety dose of 250 mg/kg/day by 
the European Medicines Agency (EMA) safety review.
In addition, the clinical effects and pharmacokinetics (PK) of SBECD are well known from its 
use in other agents like IV voriconazole, which also requires this carrier to address its limited 
water solubility. Short courses of voriconazole have been well tolerated without significant 
adverse events (AEs) despite documented accumulation in some patients. For example, plasma 
exposures (AUC) increased 4-fold following intravenously administered SBECD to participants 
with moderate renal dysfunction (creatinine clearance 30-50 mL/min) {VFEND 2020}. In 
addition, SBECD is readily removed by dialysis (up to 100% of SBECD can be removed through 
continuous RRT and approximately 46% through high-flux hemodialysis), and liver function test 
elevation due to SBECD has been rare in patients with kidney failure. Finally, although tubular 
injury with RDV has been observed in nonclinical studies, the mechanism for nonclinical tubular 
injury is not understood, and RDV-related kidney injury has not been observed clinically in an 
Ebola trial {Mulangu 2019} or in COVID-19 trials (GS-US-540-5773, GS-US-540-5774, and 
Adaptive COVID-19 Treatment Trial [ACTT-1] conducted by National Institute of Allergy and 
Infectious Diseases [NIAID]).
To further explore the impact of RDV for COVID-19 in patients with reduced kidney function, 
Gilead performed a post hoc analysis on the ACTT-1 data. Although patients with baseline 
eGFR < 30 mL/min/1.73 m2 were not included, the development of AKI with COVID-19 may 
provide some insights into the potential risk versus benefit of RDV treatment among those with 
lower levels of kidney function. We have the following preliminary findings:
1) The risk of developing AKI stage 2 or 3 may be lower in RDV-treated patients (Table 1; 
odds ratio [OR] 0.73 [95% CI, 0.48 to 1.10]; P = 0.13).
2) Among those who develop AKI stage 3, the risk of death at Day 15 also may be nominally 
lower in RDV-treated patients (Table 2; OR 0.66 [0.17, 2.40]; Fisher exact P = 0.57).

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 21
27 August 2021
Table 1.
Development of AKI Stages 2 or 3 in ACTT-1 Study, by Treatment 
Group
RDV (N = 512)
SOC (N = 500)
Stage 2 or 3 AKI
43
56
None
469
444
AKI staging: Stage 1, Increase in serum creatinine (SCr) 1.5- to 2-fold from baseline; Stage 2, Increase in SCr > 2- to 3-fold from 
baseline; Stage 3, Increase in SCr > 3-fold from baseline, or SCr ≥ 4.0 mg/dL with an acute increase of at least 0.5 mg/dL, or 
initiation of RRT {Kellum 2012}.
Table 2.
Death Among Those With AKI Stage 3 in ACTT-1 Study, by 
Treatment Group
Stage 3 AKI
RDV (N = 28)
SOC (N = 34)
Died
6
10
AKI staging: Stage 1, Increase in serum creatinine (SCr) 1.5- to 2-fold from baseline; Stage 2, Increase in SCr > 2- to 3-fold from 
baseline; Stage 3, Increase in SCr > 3-fold from baseline, or SCr ≥ 4.0 mg/dL with an acute increase of at least 0.5 mg/dL, or 
initiation of RRT {Kellum 2012}.
3) Among participants who were not receiving mechanical ventilation at baseline, the risk of 
developing AKI stage 2 or 3 seems lower in RDV-treated participants (Table 3; OR 0.61 
[0.34, 1.09]; P = 0.10), and
4) The risk of death at Day 15 among those not receiving mechanical ventilation at baseline and 
having developed stage 3 AKI also seems lower in RDV-treated participants (Table 4; OR 
0.13 [0.00, 1.25]; Fisher exact P = 0.056).
Table 3.
Development of AKI Stages 2 or 3 in ACTT-1 Study Who Were Not 
Receiving Mechanical Ventilation at Baseline, by Treatment Group
RDV (N = 382)
SOC (N = 349)
Stage 2 or 3 AKI
20
29
None
362
320
AKI staging: Stage 1, Increase in serum creatinine (SCr) 1.5- to 2-fold from baseline; Stage 2, Increase in SCr > 2- to 3-fold from 
baseline; Stage 3, Increase in SCr > 3-fold from baseline, or SCr ≥ 4.0 mg/dL with an acute increase of at least 0.5 mg/dL, or 
initiation of RRT {Kellum 2012}.
Table 4.
Death Among Those With AKI Stage 3 in ACTT-1 Study Who Were 
Not Receiving Mechanical Ventilation at Baseline, by Treatment 
Group
Stage 3 AKI
RDV (N = 13)
SOC (N = 20)
Died
1
8
AKI staging: Stage 1, Increase in serum creatinine (SCr) 1.5- to 2-fold from baseline; Stage 2, Increase in SCr > 2- to 3-fold from 
baseline; Stage 3, Increase in SCr > 3-fold from baseline, or SCr ≥ 4.0 mg/dL with an acute increase of at least 0.5 mg/dL, or 
initiation of RRT {Kellum 2012}.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 22
27 August 2021
No differences in rate of AKI or death were observed in patients on mechanical ventilation at 
baseline (data not shown). With this context, the potential benefits of treatment with RDV, 
particularly before the need for mechanical ventilation, may outweigh the potential risks of its 
administration in patients with severely reduced kidney function.
1.4.
Rationale for Dose Selection of Remdesivir
As the reduction in kidney function was commonly observed in COVID-19 patients at hospital 
admission, patients with eGFR ≥ 30 mL/min (mild to moderate renal disease) were included in 
the Phase 3 clinical development program and received RDV for treatment of COVID-19 with 
no dose adjustment.
Remdesivir is a prodrug. The metabolism of RDV, including metabolic routes leading to 
elimination and activation were characterized in vitro and in human mass balance studies. Inside 
the cell, RDV undergoes metabolic activation to form the intracellular active triphosphate 
metabolite, GS-443902, and ultimately, plasma terminal metabolite, GS-441524, that is not 
efficiently re-phosphorylated to the active triphosphate. The results of the RDV absorption, 
distribution, metabolism, and excretion (ADME) study showed that the mean total recovery of 
the radioactive dose was > 92%, consisting of approximately 74% and 18% recovered in urine 
and feces, respectively (GS-US-399-4231 clinical study report). Elimination through urine was 
the major elimination pathway for total radioactivity with the majority of the RDV dose 
recovered in urine being GS-441524 (48.6%) metabolite (little to no antiviral activity), while 
10.3% was recovered as RDV. These data indicate that renal clearance is the major elimination 
pathway for GS-441524 and that renal impairment is likely to alter the PK of GS-441524. 
Considering that most of RDV elimination is via the nonrenal route, substantial increases in 
RDV PK, and corresponding active metabolite, GS-443902, are not expected. Available 
nonclinical and clinical data suggested that RDV, dosed once daily, is necessary to provide the 
active metabolite at the site of action; as such, dose interval modifications or RDV dose 
reduction to decrease GS-441524 exposure in this patient population are not deemed appropriate.
As such, the proposed dose for this study (hospitalized COVID-19 patients with 
eGFR < 30 mL/min/1.73 m2) is a clinical dosing regimen approved for treatment of COVID-19 
patients age ≥ 12 weighing ≥ 40 kg; single RDV 200 mg IV loading dose on Day 1 followed by 
RDV 100 mg IV once daily maintenance doses on Days 2 through 5 (EU SmPC) {VEKLURY 
2020}. For participants on intermittent hemodialysis, if dosing falls on the same day as the 
hemodialysis session, RDV will be administered prior to initiation of the hemodialysis.
A dosing duration of up to 5 days will be evaluated in this study. The 5 days dosing duration is 
the recommended IV RDV duration for treatment of COVID-19 requiring hospitalization and not 
requiring invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation 
(ECMO) {VEKLURY 2020}. Moreover, patients with COVID-19 who do not require 
mechanical ventilation, 5 days of RDV showed similar efficacy to a 10-day regimen. Similarly, 
5 days treatment of RDV in participants with moderate COVID-19 was associated with a 
significant improvement in clinical status compared with standard of care (SOC) and 
approximately a third of participants were discharged prior to completion of 5 days RDV 
therapy.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 23
27 August 2021
In order to fully characterize the relationship between kidney function and RDV disposition, an 
additional Phase 1 study in non-COVID-19 participants with chronic renal impairment (mild, 
moderate, severe chronic impairment, and end-stage renal disease) is ongoing 
(GS-US-540-9015). PK and safety data from both studies will be used to inform the 
recommendations for the use of RDV in COVID-19 patients with varying degrees of renal 
impairment.
1.5.
Risk/Benefit Assessment for the Study
In addition to the established risks associated with IV RDV, potential risks associated with the 
study include unknown AEs and laboratory abnormalities associated with this study population. 
Intravenous RDV is approved for the treatment of COVID-19 in the US, Japan, and the EU.
An infectious disease pandemic may pose additional risks to investigational drug availability, 
study visit schedule, and adherence to protocol-specified safety monitoring or laboratory 
assessments. Refer to Appendix 2 for further details on the risks and risk mitigation strategy.
There are currently no approved antiviral therapies for hospitalized patients with COVID-19 and 
severely reduced renal function (ie, eGFR< 30 mL/min). The timely evaluation of a safe and 
effective antiviral agent with previously demonstrated efficacy in patients with 
eGFR > 30 mL/min addresses a serious unmet need. The risk-benefit 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.

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
2. 
OBJECTIVES 
The prirmuy objective of this study is as follows: 
FINAL 
Amendment3 
• 
To evaluate whether RDV reduces the composite risk of death or IMV through Day 29 in 
paiiicipants with severely reduced kidney function who ai·e hospitalized for COVID-19 
The secondaiy objectives of this study are as follows: 
• 
To evaluate whether RDV reduces the risk of death through Day 29 
• 
To evaluate whether RDV reduces the risk of IMV through Day 29 
• 
To evaluate the time to recove1y ( defined as satisfying catego1y 1, 2, or 3 by the 8-point 
ordinal scale) 
• 
To evaluate the effect of RDV on clinical status assessed by an 8-point ordinal scale at 
Day 15 and Day 29 
• 
To evaluate the effect of RDV on RRT-free days (among those without ESKD) through 
Day29 
• 
To evaluate the effect of RDV on recove1y through Day 29 
• 
To evaluate the safety and tolerability of RDV in paiticipants with severely reduced kidney 
function who ai·e hospitalized for COVID-19 
I 
I 
I 
I 
I 
CONFIDENTIAL 
Page 24 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 25
27 August 2021
3.
STUDY DESIGN
This is a Phase 3 randomized, double-blind, placebo-controlled, parallel-group, multicenter study 
evaluating the efficacy and safety of RDV therapy in participants with severely reduced kidney 
function who are hospitalized for COVID-19.
In this study, primary and secondary end points will be evaluated through Day 29. Following 
screening, eligible participants will be randomized in a 2:1 ratio to receive RDV or saline as 
placebo, according to the following treatment regimen, in addition to SOC therapy:

Treatment Group A: IV RDV 200 mg on Day 1 followed by IV RDV 100 mg once daily 
from Day 2 up to Day 5

Treatment Group B: IV saline as placebo on Day 1 followed by IV saline as placebo once 
daily from Day 2 up to Day 5
Randomization will be stratified by:

ESKD requiring chronic dialysis

High-flow oxygen requirement

Region (US vs ex-US)
Study participants will receive RDV in a double-blind fashion as a 200 mg IV loading dose on 
Day 1, followed by 100 mg once daily IV maintenance doses up to a 5-day total treatment course 
(ie, Days 2 through 5) while hospitalized.
3.1.
End Points
The primary efficacy end point of this study is as follows:

The composite of all-cause mortality or IMV through Day 29
The key (α-controlled) secondary end point of this study is as follows:

All-cause mortality through Day 29
Other secondary end points include:

IMV through Day 29

Time to recovery (defined as satisfying category 1, 2, or 3 by the 8-point ordinal scale)

Clinical status assessed by an 8-point ordinal scale on Day 15 and Day 29

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
• 
RRT-free days (among those without ESKD at randomization) through Day 29 
• 
Recove1y through Day 29 
FINAL 
Amendment3 
• 
Serious adverse events (SAEs) and AEs leading to investigational diug discontinuation 
I 
I 
I 
I 
I 
I 
I 
I 
I 
3.2. 
Study Design 
This is a double-blind, placebo-controlled study. 
Approximately 1116 paiiicipants aged~ 12 yeai·s of age, weighing at least 40 kg will be emolled 
as described below: 
CONFIDENTIAL 
Page 26 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 27
27 August 2021
Figure 1.
Study Schema
3.3.
Study Treatments

Continued SOC therapy together with IV RDV 200 mg on Day 1 followed by IV RDV 
100 mg once daily from Day 2 up to Day 5

Continued SOC therapy together with IV saline as placebo on Day 1 followed by IV saline as 
placebo once daily from Day 2 up to Day 5
3.4.
Duration of Treatment
Participants will be treated with RDV or saline as placebo for up to 5 days.
3.5.
Discontinuation Criteria
Investigational 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 SAE or ≥ Grade 3 AE suspected to be related to RDV
Any elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 × the 
upper limit of normal (ULN), confirmed by immediate repeat testing

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 
participant may resume study dosing at the discretion of the investigator
n=1,116 
Day 
1 
a - 744 
, :1 
'-----~n~=-3~7~2~ 
RDV x up to 5 days 
(200 mg IV day 1, 
100 mg IV days 2-5) 
Saline as placeoo x 
up to 5 days 
5 
10 
14 
Primary 
endpoint 
Composite of invasive 
mechanical ventilation 
or death through 
day 29 
"Day 60 follow-up phone call 

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
FINAL 
Amendment3 
• 
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 paiiicipant's 
best interest 
• 
Paiiicipant request to discontinue for any reason 
All participants will be requested to continue assessments during study hospitalization and any 
subsequent re-hospitalization to the same institution during Days 1 through 29 and attend the 
Day 60 phone follow-up (whether hospitalized or as an outpatient). 
3.6. 
End of Study 
The end of the study will be the last paiiicipant's last observation (or visit). 
3.7. 
Poststudy Care 
The long-tenn cai·e of the paiiicipant will remain the responsibility of their primaiy treating 
physician. Remdesivir is being supplied with curative intent. There is no provision for poststudy 
availability. 
3.8. 
Source Data 
The source data for this study will be obtained from electronic data capture (EDC), centrnl 
laborato1y , local laborato1y, and specialty laborato1y -
and/or phaimacodynamic data). 
CONFIDENTIAL 
Page 28 
27 August 2021 

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
-
CONFIDENTIAL 
Page 29 
FINAL 
Amendment3 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 30
27 August 2021
4.
PARTICIPANT POPULATION
4.1.
Number of Participants and Participant Selection
Approximately 1116 participants with severely reduced kidney function, who are hospitalized for 
COVID-19 will be enrolled into this study.
4.1.1.
Participant Replacement
Participants who discontinue before the end of study will not be replaced.
4.2.
Inclusion Criteria
Participants must meet all of the following inclusion criteria to be eligible for participation in this 
study:
1) SARS-CoV-2 positive as determined by polymerase chain reaction (PCR) or other 
commercially available or public health assay (eg, nucleic acid amplification test and antigen 
tests) in any respiratory specimen
2) Hospitalized for COVID-19
3) Age ≥ 12 years and weighing at least 40 kg
4) O2 saturation ≤ 94% on room air or requiring O2 supplementation OR radiographic evidence 
of pulmonary infiltrates for COVID-19
5) Have either:
a) Severely reduced kidney function (eGFR < 30 mL/min/1.73 m2), using the Chronic 
Kidney Disease Epidemiology Collaboration (CKD-EPI) and revised Schwartz equations 
for adults and adolescents, respectively, including people with ESKD requiring chronic 
dialysis but not people requiring RRT for AKI {Levey 2009, Schwartz 2009}
Adults: eGFR (mL/min/1.73 m²) 141 × min(SCr/κ, 1)α × max(SCr/κ, 1)-1 209 × 0.993Age × 
1.018 [if female] × 1.159 [if African American]
κ = 0.7 for females; 0.9 for males
α = -0.329 for females; -0.411 for males 
Adolescents (age 12–17 years): eGFR (mL/min/1.73 m²) = (0.41 × Height in cm) / SCr  
SCr in mg/dL, age in years
(See Appendix 7 for web links to adult and adolescent eGFR calculators), OR

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 31
27 August 2021
b) Ongoing AKI: defined as a 50% increase in SCr within a 48-hour period that is sustained 
(ie, requires confirmatory SCr) for ≥ 6 hours despite supportive care
6) Willing and able to provide written informed consent, or with a legal representative who can 
provide informed consent, or enrolled under International Council for Harmonisation (of 
Technical Requirements for Pharmaceuticals for Human Use) (ICH) E6(R2) 4.8.15 
emergency use provisions as deemed necessary by the investigator (age ≥ 18) prior to 
performing study procedures
7) The interval between COVID-19 symptoms onset and randomization is no more than 10 days
8) Male participants and female participants of childbearing potential who engage in 
heterosexual intercourse must agree to use protocol-specified method(s) of contraception as 
described in Appendix 4
4.3.
Exclusion Criteria
Participants who meet any of the following exclusion criteria at screening and randomization are 
not eligible to be enrolled in this study:
1) Received any investigational drug, RDV, or other antiviral treatment for COVID-19
2) ALT or AST > 5 × ULN
3) IMV, noninvasive mechanical ventilation, ECMO, or RRT for AKI
4) Positive serum pregnancy test at screening for women of childbearing potential or currently 
breastfeeding
5) Known hypersensitivity to the investigational drug, metabolites, or formulation SBECD

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 32
27 August 2021
5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding, and Treatment Codes Access
5.1.1.
Randomization
Participants who meet screening and randomization eligibility criteria will be randomized in a 
2:1 ratio to RDV or saline as placebo starting on Day 1 and assigned a participant number. 
Randomization will be stratified by:

ESKD requiring chronic dialysis

High-flow oxygen requirement

Region (US vs ex-US)
No more than 20% of enrolled participants will have ESKD requiring chronic dialysis.
5.1.2.
Blinding
This is a double-blind, placebo-controlled study.
During the randomized phase, participants and all personnel directly involved in the conduct of 
the study will be blinded to treatment assignment. Specified personnel may be unblinded based 
on their study role. Study drug will be dispensed by the unblinded study pharmacist, or designee, 
in a blinded fashion to the blinded study care team. The Pharmacokinetics File Administrator, or 
designee, in Bioanalytical Operations and/or Clinical Data Management who facilitates the data 
transfer of PK files between Gilead and vendors will remain unblinded. Individuals in clinical 
virology performing sample selection for resistance analysis may be unblinded. Individuals in 
Clinical Packaging and Labeling or Clinical Supply Management who have an Unblinded 
Inventory Manager role in the interactive voice/web response system for purposes of 
investigational drug inventory management will remain unblinded. Individuals in Gilead Global 
Patient Safety (GLPS) responsible for safety signal detection, investigational new drug (IND) 
safety reporting, and/or expedited reporting of suspected unexpected serious adverse reactions 
(SUSARs) may be unblinded to individual case data and/or group-level summaries. A limited 
number of Gilead Clinical Operations personnel will be unblinded for specific unblinded study 
activities. The team performing the unblinded data reviews will be separate from the ongoing 
blinded study team. No Gilead personnel involved in the day-to-day conduct of the study will 
have access to any unblinded data. External (ie, contract research organizations [CROs]) 
biostatisticians and programmers will be unblinded for the data monitoring committee (DMC) 
and IND safety reporting. Regulatory Quality and Compliance personnel in Research and 
Development may also be unblinded for purposes of supporting Quality Assurance activities 
and/or regulatory agency inspections.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 33
27 August 2021
5.1.3.
Procedures for Breaking Treatment Codes
In the event of a medical emergency where breaking the blind is required to provide medical care 
to the participant, the investigator may obtain treatment assignment directly from the interactive 
voice/web response system for that participant. The designated Site Unblinder may record an 
emergency unblinding transaction to immediately receive the participant’s randomized treatment 
assignment. Gilead recommends but does not require that the investigator contact the Gilead 
medical monitor before breaking the blind. Treatment assignment should remain blinded unless 
that knowledge is necessary to determine participant emergency medical care. The rationale for 
unblinding must be clearly explained in source documentation along with the date on which the 
treatment assignment was obtained. The investigator is requested to contact the Gilead medical 
monitor promptly in case of any treatment unblinding.
Blinding of study treatment is critical to the integrity of this clinical study. Therefore, if a 
participant’s treatment assignment is disclosed to the investigator, the participant will have study 
treatment discontinued. All participants will be followed until study completion unless consent to 
do so is specifically withdrawn by the participant.
5.2.
Description and Handling of Remdesivir
5.2.1.
Formulation
Remdesivir for injection, 100 mg, is a preservative-free, white to off-white or yellow, lyophilized 
solid containing 100 mg of RDV that is to be reconstituted with sterile water for injection and 
diluted into 0.9% saline prior to administration by IV infusion.
In addition to the active ingredient, remdesivir for injection, 100 mg, contains the following 
inactive ingredients: SBECD, water for injection, hydrochloric acid, and sodium hydroxide. 
Hydrochloric acid and sodium hydroxide are used to adjust the formulation to a pH of 3.0 to 4.0.
The 0.9% normal saline will be used as placebo for remdesivir for injection, 100 mg. The 0.9% 
normal saline is identical in physical appearance to RDV once diluted into 0.9% normal saline as 
described above.
Compounding needs to be performed by the unblinded pharmacist and should remain blinded to 
the study care team.
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 
seal with a red, plastic flip-off cap. The total amount of SBECD in a 5-day course of RDV 
(lyophilized) is 18 grams (SBECD:RDV is 30:1); 6 grams of SBECD on Day 1 (loading dose) 
followed by 3 grams of SBECD on each day from Day 2 through Day 5 (maintenance dose).

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 34
27 August 2021
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), 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 investigational drug 
should be stored in a securely locked area, accessible only to authorized site personnel. Storage 
of investigational RDV should be kept separate from commercial RDV.
To ensure the sterility, stability, and proper identification, study drug(s) should not be stored in a 
container other than the container in which they were supplied.
Measures that minimize drug contact with the body should always be considered during 
handling, preparation, and disposal procedures.
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 materials that have been prepared for infusion should be 
discarded.
5.3.
Dosage and Administration of Remdesivir
Remdesivir for injection, 100 mg, will be provided by Gilead.
Participants in Treatment Group A will receive IV RDV 200 mg on Day 1 followed by IV RDV 
100 mg once daily on Day 2 up to Day 5. Participants in Treatment Group B will receive IV 
saline as placebo on Day 1 followed by IV saline as placebo once daily on Day 2 up to Day 5.
Remdesivir will be administered via IV infusion over 30 to 120 minutes. Refer to the pharmacy 
manual for details. For participants on intermittent hemodialysis, if dosing falls on the same day 
as the hemodialysis session, RDV will be administered before initiation of the hemodialysis.
5.4.
Infusion-related Reaction
Please refer to Section 7.7.
5.5.
Prior and Concomitant Medications
Concomitant use of the following is prohibited during or within 30 days of the start of the study:

Investigational medications for COVID-19 that have not received emergency use 
authorization or regulatory approval such as HIV protease inhibitors (eg, the combination of 
lopinavir [LPV]/ritonavir [RTV]), chloroquine, hydroxychloroquine, ivermectin, and 
interferon.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 35
27 August 2021

This excludes medications that have received emergency use authorization or regulatory 
approval and are broadly recommended for the treatment of COVID-19 (eg, monoclonal 
antibodies).
Concomitant use of the following is prohibited during the study:

Strong inducers of P-glycoprotein (eg, rifampin, rifabutin, carbamazepine, phenytoin, or 
herbal medications)
Prior medications:

Any use of RDV prior to screening
Concomitant use of the following is allowed during the study:

Parenteral drugs with SBECD as an excipient should be used with caution while participants 
are in the study, particularly during the 5-day dosing period (eg, EMA maximum 
recommended safety dose is 250 mg/kg/day)

Medications that have emergency use authorization or regulatory approval and are broadly 
recommended for the treatment of hospitalized patients with COVID-19, and in the clinical 
opinion of the investigator, can be used in patients with severely reduced kidney function. 
Examples include tocilizumab and systemic corticosteroids.
5.6.
Accountability for Investigational Medicinal Product
The unblinded pharmacist or designated unblinded personnel is responsible for ensuring 
adequate accountability of all used and unused investigational drug vials. This includes 
acknowledgment of receipt of each shipment of investigational drug vials (quantity and 
condition).
Each study site must keep accountability records that capture:

The date received and quantity of investigational drug vials

The date, participant number, and the investigational drug lot number dispensed

The date, quantity of used and unused investigational drug vials returned, along with the 
initials of the person recording the information

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 36
27 August 2021
5.6.1.
Investigational Medicinal Product Return or Disposal
Gilead recommends that used investigational drug supplies be destroyed at the site. If the site has 
an appropriate standard operating procedure (SOP) for drug destruction as determined by Gilead, 
the site may destroy used (empty or partially empty) investigational drug supplies in accordance 
with that site’s approved SOP. A copy of the site’s approved SOP will be obtained for electronic 
trial master file. If investigational drug is destroyed at the site, the unblinded pharmacist or 
designated personnel must maintain accurate records for all investigational drugs destroyed. 
Records must show the identification and quantity of each unit destroyed, the method of 
destruction, and the person who disposed of the investigational drug. Upon study completion, 
copies of the investigational drug accountability records must be filed at the site. Another copy 
will be returned to Gilead.
If the site does not have an appropriate SOP for drug destruction, used investigational drug 
supplies are to be sent to the designated disposal facility for destruction. The unblinded study 
monitor will provide instructions for return.
The unblinded study monitor will review investigational drug supplies and associated records at 
periodic intervals with the unblinded pharmacist or designated personnel during remote or 
on-site monitoring visits.
For both disposal options listed above, the unblinded study monitor should first perform drug 
accountability during a remote or on-site monitoring visit.

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
6. 
STUDY PROCEDURES 
FINAL 
Amendment3 
The study procedures to be conducted for each paiiicipant enrolled in the study are presented in 
tabulai· f01m in Appendix 3 and described in the text that follows. 
The investigator must doclllllent any deviation from the protocol procedures and notify Gilead or 
the CRO. 
NOTE: Samples for laborato1y safety assessments should be collected before dialysis on the day 
of dialysis for paiiicipants on intennittent RRT during the study. 
6.1. 
Participant Enrollment and Treatment Assignment 
Enny into screening does not gt1ai·antee 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. 
6.2.1. 
Pretreatment Assessments 
Screening Visit 
Paiiicipants will be screened within 2 days before randomization to dete1mine eligibility for 
paii icipation in the study. The following will be perfo1med and doclllllented at screening: 
• 
Obtain written info1med consent (pa1i icipant 
18 years of age) or assent from parent or legal 
guai·dian (paiiicipants < 18 yeai·s of age, where locally and nationally approved) 
• 
Detennine eligibility requirements as specified in the inclusion and exclusion criteria 
• 
Focused medical histo1y will include date of first symptoms, overall symptoms, exposure 
source, demographics, baseline characteristics, concomitant medications, kidney or other 
u·ansplant histo1y, and allergies 
• 
Complete physical examination, including vital signs (heaii rate, temperature, blood 
pressure), actual body weight, and height 
• 
Doclllllentation of respirato1y status: 
-
Respirato1y rate 
-
Oxygenation: oxygen saturation (Sp02) , room air, low-flow 0 2, high-flow 0 2 
CONFIDENTIAL 
Page 37 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 38
27 August 2021

Documentation of SARS-CoV-2 infection by PCR via 1 validated assay at a local laboratory, 
if not performed within the last 4 calendar days

Document COVID-19 vaccine status (Note: It should be documented whether participant is 
fully or partially vaccinated, including any booster[s] received, if applicable.)

Record the 8-point ordinal scale (see Section 6.9)

Record any SAEs and all AEs related to protocol-mandated procedures occurring after 
signing of the informed consent (or assent) form

IMV (yes/no; if yes, provide date when mechanical ventilation was started)

RRT assessment

If available, up to 3 SCr values prior to COVID-19 illness (eg, within the previous 6 months)

Counsel participants of childbearing potential to use adequate birth control methods required 
during the trial to avoid pregnancy. See Appendix 4

Laboratory evaluations: The following tests will be performed at screening. Results from 
within 48 hours prior to screening are acceptable; the entire panel of tests should be 
performed for all study participants if not done in the preceding 48 hours (see Section 6.5):
Chemistry, hematology, SCr, and coagulation
Urinalysis (participants who are oliguric are not required to provide a urine sample)
Pregnancy test (serum, for females of childbearing potential)
All other untoward medical occurrences observed during the screening period, including 
exacerbation or changes in medical history, are to be considered medical history. See Section 7, 
Adverse Events and Toxicity Management, for additional details.
6.2.2.
Baseline/Day 1 Assessments
The following evaluations are to be completed at the Day 1 visit. The investigator must have 
confirmed eligibility (all inclusion/exclusion criteria must be met prior to randomization) before 
proceeding with Day 1 visit procedures.
Participants must complete the following assessments before being administered investigational 
drug:

Vital signs (heart rate, temperature, blood pressure)

Confirmed negative pregnancy test from screening visit (for women of childbearing age)

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
• 
Documentation of respirato1y status: 
-
Respirato1y rate 
FINAL 
Amendment3 
Oxygenation: Sp02, room air, low-flow 0 2, high-flow 0 2, and target fraction of inspired 
oxygen (FI02). The target FI02 value applies to all fonns of 0 2 nasal and mask delive1y 
(nasal prongs, masks, CP AP/BIP AP) as well as mechanical ventilation. 
• 
IMV (yes/no; if yes, provide date when mechanical ventilation was staiied) 
• 
Assessment of need for RRT 
• 
Record the 8-point ordinal scale twice (see Section 6.9) 
• 
Review AEs and document concomitant medications 
• 
Laborato1y evaluations: Chemistry, hematology, coagulation, and SCr (see Section 6.5) 
hai:yngeal swab sample for SARS-CoV-2 RT-qPCR testing -
(see Section 6.8) 
6.4. 
Assessments (Days 2 Through 29) 
The following evaluations are to be completed daily (unless othe1w ise noted in indicated 
sections and Appendix 3) from Day 2 through Day 29 or until discharge from inpatient 
hospitalization, whichever is eai·lier. If the paiticipant is readmitted to the hospital prior to 
Day 29, evaluation for RR T, ordinal scale and AEs ai·e to be completed daily through Day 29. 
Paiiicipants must complete the following assessments before being administered investigational 
diug: 
• 
Vital signs (heaii rate, temperature, blood pressure) 
• 
Documentation of respirato1y status: 
-
Respirato1y rate 
-
Oxygenation: Sp02, room air, low-flow 0 2, high-flow 0 2, CPAP/BIPAP, mechanical 
ventilation, venovenous ECMO, venoaiierial ECMO, and tai·get FI0 2. The target FI02 
value applies to all fonns of 0 2 nasal and mask delive1y (nasal prongs, masks, 
CP AP/BIPAP) as well as mechanical ventilation 
CONFIDENTIAL 
Page 39 
27 August 2021 

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
• 
IMV (yes/no; if yes, provide date when mechanical ventilation was staiied) 
• 
Assessment of need for RRT 
• 
Record the 8-point ordinal scale (see Section 6.9) 
• 
Review AEs and document concomitant medications 
FINAL 
Amendment3 
• 
Laborato1y evaluations: Chemistry, hematology, coagulation, and SCr (see Section 6.5) 
I 
I 
• ~
yngeal swab sample for SARS-CoV-2 RT-qPCR testing-
-
(see Section 6.8) 
6.5. 
Additional Assessments 
Laborato1y testing dming hospitalization will be perfonned according to SOC practice with 
results for chemistry, hematology, and any SARS-CoV-2 testing being reported to the sponsor. 
In addition, even if not perfo1med as SOC, the following will be completed at screening and on 
Days 1, 3, 5, 8, 12, 16, 20, 24, and 29 or until discharge, whichever is earlier: 
• 
Laborato1y evaluations: Chemistry, hematology, coagulation 
In addition, even if not perfo1med as SOC, the following will be completed at screening and on 
Days 1 through 29, or until discharge, whichever is earlier: 
• 
Laborato1y evaluations: SCr 
CONFIDENTIAL 
Page40 
27 August 2021 

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
I 
I 
I 
I 
I 
I 
I 
I 
CONFIDENTIAL 
Page 41 
FINAL 
Amendment3 
27 August 2021 

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
6.8. 
Virology Assessments 
-
haiyngeal swab samples for SARS-CoV-2 RT-qPCR testing 
will be collected from all paiiicipants on Days 1, 3, 5, 7, 14, 21, an 
whichever is earlier 
6.9. 
Ordinal Scale 
FINAL 
Amendment3 
The ordinal scale is an assessment of the clinical status of a given study day. Each day, the worst 
(ie, highest ordinal) score from the previous day will be recorded (ie, on Day 3, the highest 
ordinal score from Day 2 is obtained and recorded for Day 2). The ordinal scale needs to be 
completed twice on Day 1 : prior to randomization ( for baseline predose score) and the worst 
score on Day 1. 
The scale is as follows: 
8) 
Death 
7) 
Hospitalized, on IMV or ECMO 
6) 
Hospitalized, on noninvasive ventilation or high-flow oxygen devices 
5) 
Hospitalized, supplemental oxygen 
4) 
Hospitalized, not requiring supplemental oxygen- requiring ongoing medical care for 
COVID-19- specific medical care ( other than per-protocol RDV administration) 
3) 
Hospitalized, not requiring supplemental oxygen- no longer requires ongoing medical 
care ( other than per-protocol RDV /saline as placebo administration) 
2) 
Not hospitalized, limitation on activities and/or requiring home oxygen 
1) 
Not hospitalized, no limitations on activities 
6.10. 
Posttreatment Assessments 
Upon dischai·ge from inpatient hospitalization, the following assessments will be required at the 
Day 29 and Day 60 phone follow-up (see Appendix 3): 
• 
Assessment of need for RRT 
• 
Record the 8-point ordinal scale (see Section 6.9) 
• 
Review AEs and document concomitant medications 
CONFIDENTIAL 
Page42 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 43
27 August 2021

Mortality

IMV (yes/no if yes, provide date when mechanical ventilation was started)

Hospital readmission rate
6.11.
Assessments for Early Discontinuation from Study
If a participant discontinues study dosing (eg, as a result of an AE), every attempt should be 
made to keep the participant in the study and continue to perform the required study-related 
follow-up and procedures (see Section 6.11.1, Criteria for Discontinuation of Study Treatment). 
If this is not possible or acceptable to the participant or investigator, the participant may be 
withdrawn from the study.
6.11.1.
Criteria for Discontinuation of Study Treatment
Study medication may be discontinued in the following instances:

Any SAE or ≥ Grade 3 AE suspected to be related to RDV

Any elevations in ALT or AST > 5  ULN

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the 
participant may resume study dosing at the discretion of the investigator

Unacceptable toxicity or toxicity that, in the judgment of the investigator, compromises the 
ability to continue study-specific procedures or is considered to not be in the participant’s 
best interest

Participant request to discontinue for any reason

Participant noncompliance

Pregnancy during the study (refer to Appendix 4)

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board (IRB) or independent ethics committee (IEC)
6.12.
End of Study
The end of the study will be the last participant’s last observation (or visit).

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
6.13. 
Poststudy Care 
FINAL 
Amendment3 
The long-tenn care of the paiiicipant will remain the responsibility of their primaiy treating 
physician. Remdesivir is being supplied with cmative intent. There is no provision for poststudy 
availability . 
• 
CONFIDENTIAL 
Page44 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 45
27 August 2021
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events and Serious Adverse Events
7.1.1.
Adverse Events
An AE is any untoward medical occurrence in a clinical study participant administered an 
investigational drug, 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 drug, whether or not the AE is considered related to 
the investigational drug. Adverse events may also include pretreatment or posttreatment 
complications that occur as a result of protocol-specified procedures or special situations 
(Section 7.1.3).
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 7.1.3)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the informed consent form (ICF) is signed and not related to a protocol-associated 
procedure is not an AE but rather considered to be preexisting and should be documented as 
medical history.
Preexisting events that increase in severity or change in nature after investigational drug 
initiation or during or as a consequence of participation in the clinical study will also be 
considered AEs.
7.1.2.
Serious Adverse Events
An SAE is defined as an event that, at any dose, results in the following:

Death

A life-threatening situation (Note: The term “life-threatening” in the definition of “serious” 
refers to an event in which the participant was at risk of death at the time of the event; it does 
not refer to an event that hypothetically might have caused death if it were more severe.)

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 46
27 August 2021

Inpatient hospitalization or prolongation of existing hospitalization

Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: Such events may not be immediately life 
-threatening or result in death or hospitalization but may jeopardize the participant or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse.
7.1.3.
Investigational Drugs and Gilead Concomitant Therapy Special Situations 
Reports
Special situation reports (SSRs) 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 or 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 drug 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 drug by 
a participant.
Misuse is defined as any intentional and inappropriate use of an investigational drug that is not in 
accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of an 
investigational drug given per administration or cumulatively which is above the maximum 
recommended dose as per protocol or in the product labeling (as it applies to the daily dose of the 
participant in question). In cases of a discrepancy in drug accountability, overdose will be 
established only when it is clear that the participant has taken the excess dose(s). Overdose 
cannot be established when the participant cannot account for the discrepancy, except in cases in 
which the investigator has reason to suspect that the participant has taken the additional dose(s).
Occupational exposure is defined as exposure to an investigational drug as a result of one’s 
professional or nonprofessional occupation.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 47
27 August 2021
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 drug.
Counterfeit or falsified medicine: Any investigational drug with a false representation of (a) its 
identity, (b) its source, or (c) its history.
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 Investigational Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to 
investigational drug using clinical judgment and the following considerations:

No: Evidence exists that the AE has an etiology other than the investigational drug. For 
SAEs, an alternative causality must be provided (eg, preexisting condition, underlying 
disease, intercurrent illness, concomitant medication).

Yes: There is reasonable possibility that the AE may have been caused by the investigational 
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) Toxicity Grading 
Scale, Version 2.1. For each episode, the highest grade attained should be reported as defined in 
the Toxicity Grading Scale (Appendix 5).

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 48
27 August 2021
7.3.
Investigator Reporting Requirements and Instructions
7.3.1.
Requirements for Collection Prior to Investigational Drug Initiation
After informed consent, but prior to initiation of study medication, the following types of events 
must be reported on the applicable eCRFs: all SAEs and AEs related to protocol-mandated 
procedures.
7.3.2.
Adverse Events
Following initiation of study medication, collect all AEs, regardless of cause or relationship, 
throughout the duration of the study, including the protocol-required posttreatment follow-up 
period. This must be reported on the eCRFs as instructed.
All AEs and clinically significant laboratory abnormalities should be followed until resolution or 
until the AE is stable, if possible. Gilead may request that certain AEs be followed beyond the 
protocol-defined follow-up period.
7.3.3.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occur after the participant first consents to 
participate in the study (ie, signing the ICF) and throughout the duration of the study, including 
the posttreatment follow-up visit, must be reported on the applicable eCRFs and Gilead GLPS 
(formerly known as Pharmacovigilance and Epidemiology) as instructed below in this section. 
This also includes any SAEs resulting from protocol-associated procedures performed after the 
ICF is signed.
Any SAEs and deaths that occur after the posttreatment follow-up visit but within 30 days of the 
last dose of investigational 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 investigational drug, the 
investigator should promptly document and report the event to Gilead GLPS.
Instructions for reporting SAEs are described in Section 7.4.1.
7.3.4.
Investigational Drug Special Situations Reports
All investigational drug SSRs that occur from investigational drug initiation and throughout the 
duration of the study, including the posttreatment follow-up visit, must be reported to Gilead 
GLPS (Section 7.4.2). Adverse events and SAEs resulting from SSRs must be reported in 
accordance to the AE and SAE reporting guidance (Section 7.3).

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 49
27 August 2021
7.3.5.
Concomitant Therapy Reports
7.3.5.1.
Gilead Concomitant Therapy Special Situations Report
Special situation reports involving a Gilead concomitant therapy (not considered investigational 
drug), that occurs after the participant first consents to participate in the study (ie, signing the 
informed consent) and throughout the duration of the study, including the posttreatment 
follow-up visit, must be reported to Gilead GLPS utilizing the paper SSR (Section 7.4.2.2).
7.3.5.2.
Non-Gilead Concomitant Therapy Report
Special situations involving non-Gilead concomitant medications do not need to be reported on 
the SSR form; however, for special situations that result in AEs due to a non-Gilead concomitant 
medication, the AE should be reported on the AE form.
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.
All clinical sequelae in relation to these SSRs 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.
7.4.
Reporting Process for Serious Adverse Events and Special Situation Reports
7.4.1.
Serious Adverse Event Reporting Process

For fatal or life-threatening events, copies of hospital case reports, autopsy reports, and other 
documents are also to be transmitted by email or fax when requested and applicable. 
Transmission of such documents should occur without personal participant identification, 
maintaining the traceability of a document to the participant identifiers.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the participant’s eCRF and the SAE narrative section of the Safety 
Report Form eCRF.
7.4.1.1.
Electronic Serious Adverse Event Reporting Process

Electronic Serious Adverse Event Reporting Process Site personnel will record all SAE data 
on the applicable eCRFs and from there transmit the SAE information to Gilead GLPS within 
24 hours of the investigator’s knowledge of the event from ICF signature throughout the 
duration of the study, including the protocol-required posttreatment follow-up period.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 50
27 August 2021

If it is not possible to record and transmit the SAE information electronically, record the SAE 
on the paper SAE reporting form and transmit within 24 hours:
Gilead GLPS
Email: 
 
or
Fax: 

If an SAE has been reported via a paper form because the eCRF database has been locked, no 
further action is necessary. If the database is not locked, any SAE reported via paper must be 
transcribed as soon as possible on the applicable eCRFs and transmitted to Gilead GLPS.
7.4.2.
Special Situations Reporting Process
7.4.2.1.
Paper Special Situations Reporting Process for Investigational Drug

All SSRs will be recorded on the special situations report form and transmitted by emailing 
or faxing the report form within 24 hours of the investigator’s knowledge of the event to the 
attention of Gilead GLPS from investigational drug initiation throughout the duration of the 
study, including the protocol-required posttreatment follow-up period.
Gilead GLPS
Email: 
 
or
Fax: 
7.4.2.2.
Reporting Process for Gilead Concomitant Medications

Special situations that involve Gilead concomitant medications that are not considered 
investigational drug must be reported within 24 hours of the investigator’s knowledge of the 
event to Gilead GLPS utilizing the paper special situations report form to:
Gilead GLPS
Email: 
 
or
Fax: 

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.

Special situations involving non-Gilead concomitant medications do not need to be reported 
on the SSR form; however, special situations that result in AEs due to a non-Gilead 
concomitant medication, must be reported as an AE.
PPD
PPD
PPD
PPD
PPD
PPD

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 51
27 August 2021
7.4.2.3.
Pregnancy Reporting Process

The investigator should report pregnancies in female study participants and/or female 
partners of male participants that are identified after initiation of investigational drug and 
throughout the study, including the postinvestigational drug follow-up period, to Gilead 
GLPS using the pregnancy report form within 24 hours of becoming aware of the pregnancy. 
Contact details for transmitting the pregnancy report form are as follows:
Gilead GLPS
Email: 
 
or
Fax: 

The pregnancy itself is not considered an AE, nor is an induced elective abortion to terminate 
a pregnancy without medical reasons.

All other premature terminations 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, as described in Section 7.4.1. The underlying medical reason for this 
procedure should be recorded as the AE term.

A spontaneous abortion is always considered to be an SAE and will be reported as described 
in Section 7.4.1. Furthermore, any SAE occurring as an adverse pregnancy outcome 
poststudy must be reported to the Gilead GLPS.

The participant should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome of the pregnancy/partner pregnancy should be reported to Gilead 
GLPS using the pregnancy outcome report form. If the end of the pregnancy/partner 
pregnancy occurs after the study has been completed, the outcome should be reported 
directly to Gilead GLPS. Gilead GLPS contact information is as follows: 
email: 
 and fax: 

Refer to Appendix 4 for Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements.
7.5.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA 
Administration Code of Federal Regulations, the EU Clinical Trials Directive (2001/20/EC) and 
relevant updates, and other country-specific legislation or regulations, Gilead may be required to 
expedite to worldwide regulatory agencies reports of SAEs, which may be in the form of 
line-listings, serious adverse drug reactions, or SUSARs. In accordance with the EU Clinical 
Trials Directive (2001/20/EC), Gilead or a specified designee will notify worldwide regulatory 
agencies and the relevant IEC in concerned Member States of applicable SUSARs as outlined in 
current regulations.
PPD
PPD
PPD
PPD

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 52
27 August 2021
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the IB or relevant local label as applicable.
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any investigational drug. The investigator should notify the IRB or IEC of SUSAR reports 
as soon as is practical, where this is required by local regulatory agencies, and in accordance 
with the local institutional policy.
7.6.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities without clinical significance are not to be recorded as AEs or SAEs. 
However, laboratory abnormalities (eg, clinical chemistry, hematology, urinalysis) that require 
medical or surgical intervention or lead to investigational 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).
Severity should be recorded and graded according to the DAIDS Toxicity Grading Scale, 
Version 2.1. 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.
7.7.
Toxicity Management
Infusion-related reactions have been observed during and following administration of RDV. 
Signs and symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, 
fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion 
rates, with a maximum infusion time of up to 120 minutes, can be considered to potentially 
prevent these signs and symptoms. If signs and symptoms of a severe infusion-related reaction 
occur, immediately discontinue administration of RDV and initiate appropriate treatment. 
Remdesivir infusions will be administered to participants at the site under close supervision. 
Healthcare professionals administering RDV infusions must have the appropriate medication 
available for immediate use in case of hypersensitivity or infusion-related reactions. The 
participant should be treated according to the SOC for management of hypersensitivity reaction 
or infusion-related reactions. Participants should be monitored for at least 2 hours after the RDV 
infusion is completed.
All clinical events and clinically significant laboratory toxicities will be managed according to 
uniform guidelines detailed in Appendix 6, and as outlined below.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 53
27 August 2021
Grade 3 or 4 clinically significant laboratory abnormalities that were not present at baseline 
should be confirmed by repeat testing as soon as possible, and preferably within 3 calendar days 
after receipt of the original test results.
The Gilead medical monitor should be consulted prior to investigational drug discontinuation 
when medically feasible.
7.7.1.
Grade 1 and 2 Laboratory Abnormalities
Continue investigational drug at the discretion of the investigator.
7.7.2.
Grade 3 Laboratory Abnormalities
For a Grade 3 clinically nonsignificant laboratory abnormality (eg, clinically insignificant 
Grade 3 cholesterol, triglyceride abnormalities, or creatine kinase (CK) elevations) that were not 
present at baseline, the investigational drug may be continued if the event is considered to be 
unrelated to the investigational drug.
For a Grade 3 clinically significant laboratory abnormality confirmed by repeat testing (as soon 
as possible, and preferably within 3 calendar days after receipt of the original test results), that 
was not present at baseline and considered to be related to the investigational drug, the 
investigational drug should be permanently discontinued and the participant managed according 
to local practice. The Gilead medical monitor should be consulted prior to investigational drug 
discontinuation when medically feasible.
7.7.3.
Grade 4 Laboratory Abnormalities
For a Grade 4 clinically significant laboratory abnormality by repeat testing (as soon as possible, 
and preferably within 3 calendar days after receipt of the original test results), that was not 
present at baseline and considered to be related to the investigational drug, the investigational 
drug should be permanently discontinued and the participant managed according to local 
practice. The Gilead medical monitor should be consulted prior to investigational drug 
discontinuation when medically feasible. The participant should be followed as clinically 
indicated until the laboratory abnormality returns to baseline or is otherwise explained, 
whichever occurs first. A clinically significant Grade 4 laboratory abnormality that is not 
confirmed by repeat testing should be managed according to the algorithm for the new toxicity 
grade.
Investigational drug may be continued without dose interruption for a clinically nonsignificant 
Grade 4 laboratory abnormality (eg, Grade 4 CK elevation after strenuous exercise, triglyceride 
elevation that is nonfasting or that can be medically managed) or a clinical event considered 
unrelated to the investigational drug.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 54
27 August 2021
Treatment-emergent toxicities will be noted by the investigator and brought to the attention of 
the Gilead medical monitor, and the appropriate course of action will be discussed and decided. 
Whether or not considered treatment related, all participants experiencing AEs must be 
monitored periodically until symptoms subside, any abnormal laboratory values have resolved or 
returned to baseline levels or they are considered irreversible, or until there is a satisfactory 
explanation for the changes observed.
Any questions regarding toxicity management should be directed to the Gilead medical monitor.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 55
27 August 2021
8.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and End Points
8.1.1.
Analysis Objectives
The primary objective of this study is as follows:

To evaluate whether RDV reduces the composite risk of death or IMV through Day 29 in 
participants with severely reduced kidney function who are hospitalized for COVID-19
The secondary objectives of this study are as follows:

To evaluate whether RDV reduces the risk of death through Day 29

To evaluate whether RDV reduces the risk of IMV through Day 29

To evaluate the time to recovery (defined as satisfying category 1, 2, or 3 by the 8-point 
ordinal scale)

To evaluate the effect of RDV on clinical status assessed by an 8-point ordinal scale at 
Day 15 and Day 29

To evaluate the effect of RDV on RRT-free days (among those without ESKD) through 
Day 29

To evaluate the effect of RDV on recovery through Day 29

To evaluate the safety and tolerability of RDV in participants with severely reduced kidney 
function who are hospitalized for COVID-19
CCI
I 
I 
I 
I 

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
I 
I 
I 
I 
8.1.2. 
Primary End Point 
• 
The composite of all-cause mortality or IMV through Day 29 
8.1.3. 
Secondary End Points 
The key (a-contrnlled) secondaiy end point of this study is as follows: 
• 
All-cause m01iality through Day 29 
Other secondaiy end points include: 
• 
IMV through Day 29 
FINAL 
Amendment3 
• 
Time to recove1y (defined as satisfying catego1y 1, 2, or 3 by the 8-point ordinal scale) 
• 
Clinical status assessed by an 8-point ordinal scale on Day 15 and Day 29 
• 
RRT-free days (among those without ESKD at randomization) through Day 29 
• 
Recove1y through Day 29 
• 
SAEs and AEs leading to investigational dmg discontinuation 
-
I 
I 
I 
CONFIDENTIAL 
Page 56 
27 August 2021 

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
I 
I 
I 
I 
I 
I 
8.2. 
8.2.1. 
Planned Analyses 
Interim Analysis 
FINAL 
Amendment3 
Prior to the final analysis, interim analyses will be conducted and the analyses may be submitted 
to regulato1y agencies to seek guidance for the overall clinical development program. 
8.2.1.1. 
Data Monitoring Committee Analysis (Safety Analysis) 
The first DMC meeting will be based on data collected after the first 100 paiiicipants complete 
the Day 29 assessment and will include safety data, including renal and hepatic toxicity. No 
fo1mal efficacy evaluations are planned for this meeting. 
8.2.1.2. 
Data Monitoring Committee Analysis (Efficacy and Futility Interim 
Analysis) 
The second DMC meeting will be based on data collected after 50% of paiiicipants complete the 
Day 29 assessment and will include review of safety, and fonnal evaluation of futility and 
efficacy. The DMC may provide recommendation on stopping enrollment to the study if the 
prespecified boundai·ies for efficacy (outlined in Section 8.7) or futility ai·e crossed. If the 
conditional power (ie, the probability of obtaining a statistically significant result after all 
paiiicipants have completed the Day 29 assessment assuming the trend of treatment effect 
observed at interim is retained for the remainder of the study) is 15% or less, consideration 
should be given to stopping the study for futility. An interim analysis communication plan will 
be created. 
CONFIDENTIAL 
Page 57 
27 August 2021 

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
8.2.2. 
Primary Analysis 
FINAL 
Amendment3 
The prirmuy analysis will be perfonned after all paiiicipants have completed Day 29 of the study 
or prematurely discontinued from the study before Day 29. The analysis of the primaiy end point 
of all-cause mo1iality or IMV through Day 29 and key a-controlled secondaiy end point of 
all-cause mo1iality through Day 29 will be conducted at the time of the interim analysis (after 
50% of paii icipants complete the Day 29 assessment) and will only be evaluated in this analysis 
based on results observed at the interim analysis (see Section 8.7 for prespecified boundai·ies). 
The overall Type I enor rate will be controlled at the two-sided 0.05 significance level. 
8.2.3. 
Final Analysis 
The final analysis will be perfonned after all paiiicipants have completed the study, outstanding 
data queries have been resolved or adjudicated as unresolvable, and the data have been cleaned 
and finalized. 
8.3. 
8.3.1. 
8.3.1.1. 
Analysis Conventions 
Analysis Sets 
Efficacy 
The prirmuy analysis set for efficacy analysis is defined as the Full Analysis Set, which will 
include all participants who (1) ai·e randomized into the study and (2) have received at least 
1 dose of study treatment. Paii icipants will be grouped according to the treatment to which they 
were randomized. 
8.3.1.2. 
Safety 
The prirmuy analysis set for safety analyses is defined as the Safety Analysis Set, which will 
include all participants who (1) ai·e randomized into the study and (2) have received at least 
1 dose of study treatment. Paii icipants will be grouped according to the treatment which they 
received. -
8.3.1.4. 
Bio marker 
The biomarker analysis set will include all randomized paii icipants who received at least 1 dose 
of study treatment and for whom biomarker sainples ai·e available. 
CONFIDENTIAL 
Page 58 
27 August 2021 

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
8.3.2. 
Data Handling Conventions 
FINAL 
Amendment3 
Laborato1y 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 (ie, if the result of a continuous laborato1y test is 
< 20, a value of 19 will be assigned). 
Missing data can have an impact upon the inte1p retation of the trial data. In general, values for 
missing data will not be imputed. However, a missing pretreatment laborato1y result would be 
treated as nonnal (ie, no toxicity grade) for the laborato1y abnonnality summa1y. 
All available data for paiiicipants 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 summarized using standard descriptive 
methods. Demographic summaries will include sex, race/ethnicity, randomization stratification 
group, and age. For categorical demographic and baseline characteristics, a 
Cochran-Mantel-Haenszel test will be used to compare treatment groups. For continuous 
demographic and baseline chai·acteristics, a Wilcoxon rank sum test will be used to compai·e 
treatment groups. 
8.5. 
8.5.1. 
Efficacy Analysis 
Primary Analysis 
The primaiy clinical end point is the composite of all-cause mo1iality or IMV from date of first 
dose through Day 29. 
The prima1y end point will be analyzed using a stratified log-rank test stratified by the 
randomization stratum. The hazai·d ratio and 95% confidence interval will be provided. The null 
hypothesis being tested is that there is no difference between treatment groups in the probability 
of death or IMV through Day 29. 
Paiiicipants with missing outcomes for the primaiy end point due to premature discontinuation 
of the study on or prior to Day 29 will be censored at the date of last contact. 
8.5.2. 
Secondary Analyses 
The secondaiy end points of all-cause mo1iality through Day 29 ( a-controlled) and of recove1y 
through Day 29 will be analyzed in a similai· manner to the primaiy end point 
CONFIDENTIAL 
Page 59 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 60
27 August 2021
The clinical status assessed by an 8-point ordinal scale on Day 15 and Day 29 will be analyzed 
using a proportional odds model including treatment as the independent variable to compare the 
treatment groups.
Other end points related to proportion of participants will be compared between treatment groups 
using a chi-square test or Fisher exact test. End points that are measured as time to first event 
will be compared between treatment groups using the log-rank test and continuous end points 
will be compared between treatment groups using a Wilcoxon rank sum test or analysis of 
variance model.
8.6.
Safety Analysis
All safety data collected on or after first investigational drug dose date through 30 days after the 
date of the last investigational drug dose will be summarized by treatment group (according to 
the investigational drug received). Data for the pretreatment period and after the date of last 
investigational drug dose plus 30 days will be included in data listings.
8.6.1.
Extent of Exposure
A participant’s extent of exposure to investigational drug data will be generated from the 
investigational drug administration data. Exposure data will be summarized by treatment group.
8.6.2.
Adverse Events
Clinical and laboratory AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). System organ class, high-level group term, high-level term, preferred 
term, and lower-level term will be attached to the clinical database.
Events will be summarized on the basis of the date of onset for the event. A treatment-emergent 
AE will be defined as any AE that begins on or after the first dose date up to the date of last dose 
of investigational drug plus 30 days.
Summaries (number and percentage of participants) of treatment-emergent AEs (by system 
organ class and preferred term) will be provided by treatment group.
8.6.3.
Laboratory Evaluations
Selected laboratory data will be summarized using only observed data. Data and change from 
baseline at all scheduled time points will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme in DAIDS Table for 
Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017.
Incidence of treatment-emergent laboratory abnormalities, defined as values that increase at least 
1 toxicity grade from baseline at any time after baseline up to and including the date of last dose 
of investigational drug plus 30 days will be summarized by treatment group. If baseline data are 
missing, then any graded abnormality (ie, at least a Grade 1) will be considered 
treatment-emergent.

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
FINAL 
Amendment3 
Laborato1y abnonnalities that occur before the first dose of investigational diug or after the 
paii icipant has been discontinued from treatment for 30 days will be included in a data listing. 
8.7. 
Adjustments for Multiplicity 
The overall two-sided Type I en or rate of 0.05 for the primaiy and key a-controlled seconda1y 
end points will be controlled using the Lan-DeMets approach with O'Brien-Fleming type 
spending function accompanying a gatekeeping testing strategy (ie, the primaiy efficacy end 
point will be tested first and the key a-controlled secondaiy end point will be tested only if the 
primaiy efficacy end point is met). The a-spending and gatekeeping details ai·e specified in 
Table 5. 
Table 5. 
Gatekeeping and Boundaries for Efficacy Analysis 
Key a-controlled Secondary End Point (Will 
be Tested ONLY IF Primary End Point is 
Efficacy Analysis 
Prima1-y End Point 
Met) 
Interim Analysis 
(50% of Participants 
0.0031 
0.0031 
Completed Day 29) 
Prima1y Analysis 
0.0490 
(All Pa1ticipants Completed 
(will be tested ONLY IF the 
0.0490 
prima1y end point is NOT met 
Day29) 
at interim) 
Note: P-values are based on two-sided stratified log-rank test. 
8.9. 
Sample Size 
A total of approximately 1116 pa1i icipants will be randomized in a 2:1 ratio to 2 groups (744 in 
the RDV group and 372 in the saline as placebo group). This sample size achieves approximately 
85% power to detect a hazai·d ratio of 0.70 at a two-sided alpha level of 0.05. In the sample size 
calculation, it is assumed that the event rate in the saline as placebo group is 35%. The hazard 
ratio and event rate in the saline as placebo group are based on the most conservative estimates 
of the prima1y end point ( composite of all-cause mo1iality or IMV) and key a-controlled 
secondaiy end point (all-cause mortality) through Day 29 among a subset of paii icipants with 
eGFR < 60 mL/min in the Division of Microbiology and Infectious Diseases Protocol 20-0006 
Adaptive COVID-19 Treatment Trial (ACTT)-1 (hazard ratio of 0.67 and placebo rate of 33% ). 
The sample size calculation was done using softwai·e EAST (Version 6.5, module for log-rank 
test given accmal duration [120 days] and study duration [149 days] and 1 interim analysis using 
the Lan-DeMets approach with O'Brien-Fleming type spending function). 
CONFIDENTIAL 
Page 61 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 62
27 August 2021
8.10.
Data Monitoring Committee
An external multidisciplinary DMC will review the progress of the study, perform interim 
reviews of safety data and provide recommendation to Gilead whether the nature, frequency, and 
severity of AEs associated with study treatment warrant the early termination of the study in the 
best interests of the participants, whether the study should continue as planned, or whether the 
study should continue with modifications. The DMC will have 2 formal (unblinded data review) 
meetings. The first formal meeting will review safety data after the first 100 participants 
complete the Day 29 assessment. The second formal meeting will review safety, efficacy and 
futility data after 50% of participants complete the Day 29 assessment. The DMC may make a 
recommendation of stopping enrollment to the study if the prespecified efficacy or futility 
stopping criteria are met. The DMC will also receive blinded safety listings for review up to 
every week for the first 2 weeks followed by every 2 weeks until the second DMC meeting 
occurs after 50% of participants complete the Day 29 assessment. The DMC may also provide 
recommendations as needed regarding study design.
The DMC’s specific activities will be defined by a mutually agreed charter, which will define the 
DMC’s membership, conduct, and meeting schedule.
While the DMC will be asked to advise Gilead regarding future conduct of the study, including 
possible early study termination, Gilead retains final decision-making authority on all aspects of 
the study.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 63
27 August 2021
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.
9.1.2.
Financial Disclosure
The investigator and subinvestigators will provide prompt and accurate documentation of their 
financial interest or arrangements with Gilead or proprietary interests in the investigational drug 
during the course of a clinical study. This documentation must be provided prior to the 
investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last participant completes the protocol-defined activities.
9.1.3.
Institutional Review Board/Independent Ethics Committee Review and 
Approval
The investigator (or Gilead as appropriate according to local regulations) will submit this 
protocol, ICF, and any accompanying material to be provided to the participant (such as 
advertisements, participant information sheets, or descriptions of the study used to obtain 
informed consent) to an IRB/IEC. The investigator will not begin any study participant activities 
until approval from the IRB/IEC has been documented and provided as a letter to the 
investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/IEC any modifications made to the protocol or any accompanying material to be 
provided to the participant after initial IRB/IEC approval, with the exception of those necessary 
to reduce immediate risk to study participants.
9.1.4.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study before undertaking any study-related procedures. The investigator 
must use the most current IRB- or IEC-approved ICF for documenting written informed consent. 
Each ICF (or assent as applicable) will be appropriately signed and dated by the participant or 
the participant’s legally authorized representative, the person conducting the consent discussion, 
and an impartial witness (if required by IRB or IEC or local requirements).

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
samples will not be given to the paiiicipant or the investigator. 
9.1.5. 
Confidentiality 
FINAL 
Amendment3 
The investigator must ensure that paiiicipants' anonymity will be strictly maintained and that 
their identities ai·e protected from unauthorized paiiies. Only an identification code and any other 
unique identifier(s) as allowed by local law (such as year of bi1ih) will be recorded on any fo1m 
or biological sample submitted to Gilead or the laborato1y. Laborato1y specimens must be 
labeled in such a way as to protect paiiicipant identity while allowing the results to be recorded 
to the proper pa1iicipant. Refer to specific laborato1y. NOTE: The investigator must keep a 
screening log with details for all paiiicipants screened and emolled in the study, in accordance 
with the site procedures and regulations. Paiiicipant data will be processed in accordance with all 
applicable regulations. 
The investigator agrees that all info1mation received from Gilead, including but not limited to the 
IB, this protocol, case repo1i fonns (CRFs)/eCRFs, investigational dmg info1mation, and any 
other study info1mation, remain the sole and exclusive property of Gilead during the conduct of 
the study and thereafter. This infonnation is not to be disclosed to any third pai·ty ( 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 fmiher agrees to take all reasonable 
precautions to prevent the disclosure by any employee or agent of the study site to any third 
paiiy or othe1w ise 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 docUillents should 
be classified into at least the following 2 categories: (1) investigator's study file and 
(2) paiiicipant clinical source docUillents. 
The investigator's study file will contain the protocol/amendments, CRFs/eCRFs, governmental 
approval with conespondence, the ICF(s), dmg records, staff cmTiculUill vitae and authorization 
fo1ms, and other appropriate docUillents and conespondence. 
CONFIDENTIAL 
Page 64 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 65
27 August 2021
The required source data should include sequential notes containing at least the following 
information for each participant:

Participant identification

Documentation that participant meets eligibility criteria, ie, medical history, physical 
examination, and confirmation of diagnosis (to support inclusion and exclusion criteria)

Documentation of the reason(s) a consented participant is not enrolled

Participation in study (including study number)

Study discussed and date of informed consent

Dates of all visits

Documentation that protocol-specific procedures were performed

Results of efficacy parameters, as required by the protocol

Start and end date (including dose regimen) of investigational drug, including dates of 
dispensing and return

Record of all AEs and other safety parameters (start and end date; causality and severity) and 
documentation that adequate medical care has been provided for any AE

Concomitant medication (start and end dates; 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 for 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, the US, the EU, 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, for 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.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 66
27 August 2021
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
participant, appropriate copies should be made for storage away from the site.
9.1.7.
Case Report Forms
For each participant consented, an eCRF casebook will be completed by an authorized study 
staff member whose training for this function is completed in the EDC system. The eCRF 
casebook will only capture the data required per the protocol schedule of events and 
procedures. The Inclusion/Exclusion Criteria and Enrollment eCRFs should be completed only 
after all data related to eligibility have been received. Data entry should be performed in 
accordance with the CRF Completion Guidelines provided by the sponsor. Subsequent to data 
entry, a study monitor will perform source data verification 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, site coordinator, or other designee is 
responsible for responding to the queries in a timely manner, within the system, either by 
confirming the data as correct or updating the original entry, and providing the reason for the 
update (eg, data entry error). Original entries as well as any changes to data fields will be stored 
in the audit trail of the system. At a minimum, prior to any interim time points or database lock 
(as instructed by Gilead), the investigator will use his/her login 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.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 67
27 August 2021
9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study participants, 
may be made only by Gilead. The investigator must submit all protocol modifications to the IRB 
in accordance with local requirements and receive documented IRB approval before 
modifications can be implemented.
9.2.2.
Study Report and Publications
A clinical study report will be prepared and provided to the regulatory agency. Gilead will ensure 
that the report meets the standards set out in the ICH Guideline for Structure and Content of 
Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in certain 
cases.
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly media only after the following conditions have been met:

The results of the study in their entirety have been publicly disclosed by or with the consent 
of Gilead in an abstract, manuscript, or presentation form or the study has been completed at 
all study sites for at least 2 years.

The investigator will submit to Gilead any proposed publication or presentation along with 
the respective scientific journal or presentation forum at least 30 days before submission of 
the publication or presentation.

No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.5).

The investigator will comply with Gilead’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol (eg, attendance at investigator meetings). If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to federal and state agencies any 
expenses paid or reimbursed for such services, including any clinical study payments, meal, 
travel expenses or reimbursements, consulting fees, and any other transfer of value.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 68
27 August 2021
9.3.2.
Access to Information for Monitoring
The monitor is responsible for routine review of the CRF/eCRF at regular intervals throughout 
the study to verify adherence to the protocol and the completeness, consistency, and accuracy of 
the data being entered on them. The monitor should have access to any participant records 
needed to verify the entries in the CRF/eCRF. The investigator agrees to cooperate with the 
monitor to ensure that any problems detected through any type of monitoring (central, on-site) 
are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead medical monitor immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, and 
personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both Gilead and the investigator reserve the right to terminate the study at any time. Should this 
be necessary, both parties will arrange discontinuation procedures and notify the participants, 
appropriate regulatory authorities and IRB. In terminating the study, Gilead and the investigator 
will ensure that adequate consideration is given to the protection of the participants’ interests.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 69
27 August 2021
10.
REFERENCES
Adamsick ML, Gandhi RG, Bidell MR, Elshaboury RH, Bhattacharyya RP, Kim AY, et al. 
Remdesivir in Patients with Acute or Chronic Kidney Disease and COVID-19. J 
Am Soc Nephrol 2020;31 (7):1384-6.
Alberici F, Delbarba E, Manenti C, Econimo L, Valerio F, Pola A, et al. A report from the 
Brescia Renal COVID Task Force on the clinical characteristics and short-term 
outcome of hemodialysis patients with SARS-CoV-2 infection. Kidney Int 
2020;98 (1):20-6.
Centers for Disease Control and Prevention (CDC). Coronavirus Disease 2019 (COVID-19). If 
You Are at Higher Risk. Available at: https://www.cdc.gov/coronavirus/2019-
ncov/specific-groups/high-risk-complications.html. Accessed: 18 March 2020. 
Last Reviewed: 12 March.  2020:
Farkash EA, Wilson AM, Jentzen JM. Ultrastructural Evidence for Direct Renal Infection with 
SARS-CoV-2. J Am Soc Nephrol 2020;31 (8):1683-7.
Flythe JE, Assimon MM, Tugman MJ, Chang EH, Gupta S, Shah J, et al. Characteristics and 
Outcomes of Individuals With Pre-existing Kidney Disease and COVID-19 
Admitted to Intensive Care Units in the United States [Uncorrected Proof]. Am J 
Kidney Dis 2020.
Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, et al. Extrapulmonary 
manifestations of COVID-19. Nat Med 2020;26 (7):1017-32.
Hirsch JS, Ng JH, Ross DW, Sharma P, Shah HH, Barnett RL, et al. Acute kidney injury in 
patients hospitalized with COVID-19. Kidney Int 2020;98 (1):209–18.
Kellum JA, Lameire N, Aspelin P, Barsoum RS, Burdmann EA, Goldstein SL, et al. Kidney 
disease: Improving global outcomes (KDIGO) acute kidney injury work group. 
KDIGO clinical practice guideline for acute kidney injury. Kidney International 
Supplements 2012;2 (1):1-138.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 3rd, Feldman HI, et al. A new 
equation to estimate glomerular filtration rate. Ann Intern Med 2009;150 (9):604-
12.
Major R, Selvaskandan H, Makkeyah YM, Hull K, Kuverji A, Graham-Brown M. The Exclusion 
of Patients with CKD in Prospectively Registered Interventional Trials for 
COVID-19-a Rapid Review of International Registry Data. J Am Soc Nephrol 
2020;31 (10):2250-2.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 70
27 August 2021
Mulangu S, Dodd LE, Davey RT, Jr., Tshiani Mbaya O, Proschan M, Mukadi D, et al. A 
Randomized, Controlled Trial of Ebola Virus Disease Therapeutics. N Engl J 
Med 2019;381 (24):2293-303.
Nadim MK, Forni LG, Mehta RL, Connor MJ, Jr., Liu KD, Ostermann M, et al. COVID-19-
associated acute kidney injury: consensus report of the 25th Acute Disease 
Quality Initiative (ADQI) Workgroup. Nature reviews. Nephrology 2020.
Nasr SH, Kopp JB. COVID-19-Associated Collapsing Glomerulopathy: An Emerging Entity. 
Kidney Int Rep 2020;5 (6):759-61.
Ng JH, Hirsch JS, Hazzan A, Wanchoo R, Shah HH, Malieckal DA, et al. Outcomes Among 
Patients Hospitalized With COVID-19 and Acute Kidney Injury [Journal Pre-
proof]. Am J Kidney Dis 2020.
Puelles VG, Lutgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, et al. 
Multiorgan and Renal Tropism of SARS-CoV-2. N Engl J Med 2020;383 (6):590-
2.
Robbins-Juarez SY, Qian L, King KL, Stevens JS, Husain SA, Radhakrishnan J, et al. Outcomes 
for Patients With COVID-19 and Acute Kidney Injury: A Systematic Review and 
Meta-Analysis. Kidney Int Rep 2020;5 (8):1149-60.
Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, et al. New equations to 
estimate GFR in children with CKD. J Am Soc Nephrol 2009;20 (3):629-37.
Su H, Yang M, Wan C, Yi LX, Tang F, Zhu HY, et al. Renal histopathological analysis of 26 
postmortem findings of patients with COVID-19 in China. Kidney Int 2020;98 
(1):219-27.
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. 
Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020;395 
(10234):1417-8.
VEKLURY, Gilead Sciences Inc. VEKLURY® (remdesivir) for injection, for intravenous use. 
VEKLURY® (remdesivir) injection, for intravenous use. U.S. Prescribing 
Information. Foster City, CA. Revised October.  2020:
Velez JCQ, Caza T, Larsen CP. COVAN is the new HIVAN: the re-emergence of collapsing 
glomerulopathy with COVID-19. Nature reviews. Nephrology 2020;16 (10):565-
7.
VFEND, Pfizer. VFEND® (voriconazole) Tablets for Oral Use. VFEND® (voriconazole) for 
Oral Suspension, VFEND® (voriconazole) for Injection, for Intravenous Use. 
U.S. Prescribing Information. New York, NY. Revised September.  2020:

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 71
27 August 2021
Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, et al. Factors associated 
with COVID-19-related death using OpenSAFELY. Nature 2020;584 (7821):430-
6.
World Health Organization (WHO). Statement on the Second Meeting of the International 
Health Regulations (2005) Emergency Committee Regarding the Outbreak of 
Novel Coronavirus (2019-nCoV). Available at: https://www.who.int/news-
room/detail/30-01-2020-statement-on-the-second-meeting-of-the-international-
health-regulations-%282005%29-emergency-committee-regarding-the-outbreak-
of-novel-coronavirus-%282019-ncov%29. Accessed: 10 February. 30 January.  
2020:
World Health Organization (WHO). Weekly operational update on COVID-19 - 12 July 2021. 
Issue No. 63.  July, 2021.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 72
27 August 2021
11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2
Pandemic Risk Assessment and Mitigation Plan
Appendix 3.
Study Procedures Table
Appendix 4.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 5.
Toxicity Grading Scale for Severity of Adverse Events and Laboratory 
Abnormalities
Appendix 6.
Management of Clinical and Laboratory Adverse Events
Appendix 7.
eGFR Automated Calculators

Remdesivir (GS-5734™) 
GS-US-540-5912 
FINAL 
Gilead Sciences, Inc. 
Amendment 3 
Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGMENT 
A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study 
Evaluating the Efficacy and Safety ofRemdesivir in Participants with Severely Reduced Kidney 
Function who are Hospitalized for COVID- 19 
Protocol Amendment 3: 27 August 2021 
This protocol has been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
[PPD 
PPD 
Medical Monitor 
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. l will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
Page 73 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 74
27 August 2021
Appendix 2
Pandemic Risk Assessment and Mitigation Plan
During an ongoing pandemic, potential risks associated with participants being unable to attend 
study visits have been identified for this study.
These risks can be summarized as follows:
1) Study treatment supplies to participants and sites:
a) Participants may be unable to return to the site for a number of visits to get the 
investigational drug, or the site may be unable to accept any participant visits. Without 
investigational drugs, the participant would not be able to stay on the investigational drug 
as planned per protocol.
Mitigation plan: Investigational drug supplies may be provided to the participant from the 
site without a clinic visit, once it is confirmed that the participant may safely continue on 
investigational drug as determined by the principal investigator (PI). A virtual study visit, 
via phone or video conferencing, must be performed prior to remote investigational drug 
resupply. At the earliest opportunity, the site will schedule in-person participant visits and 
return to the protocol’s regular schedule of assessments. A qualified courier may be 
utilized to ship the investigational drug from sites to study participants if permitted by 
local ethics committee (EC)/institutional review boards (IRB)/Regulatory Authority as 
applicable and with sponsor's approval.
b) Shipments of investigational drug could be delayed because of transportation issues. 
Without investigational drug participant would not be able to stay on the investigational 
drug as planned per protocol.
Mitigation plan: The sites' investigational drug inventory should be closely monitored. 
Site staff should notify the sponsor or delegate if they foresee shortage in investigational 
drug inventory or if there is any interruption in local shipping service. The sponsor will 
continue to monitor inventory at the investigational drug depot and study sites. Manual 
shipments will be triggered as necessary.
2) Participant safety monitoring and follow-up:
a) Participants may be unable or unwilling to come to the study site for their scheduled 
study visits as required per protocol.
Mitigation plan: For participants who may be unable or unwilling to visit the study site 
for their scheduled study visits as required per protocol, the PI or qualified delegate will 
conduct a virtual study visit, via phone or video conferencing, to assess the participant 
within target visit window date whenever possible. During the virtual study visit, the 
following information at minimum will be reviewed:
i)
Confirm if participant has experienced any AEs/SAEs/special situations (including 
pregnancy) and follow-up on any unresolved AE/SAEs.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 75
27 August 2021
ii) Review current list of concomitant medications and document any new concomitant 
medications.
iii) If applicable, confirm electronic diary questionnaires and patient-reported outcomes 
have been completed and transmitted.
iv) If applicable, confirm participants investigational drug supply is sufficient to last until 
the next planned visit date. If investigational drug resupply is needed it will be 
provided as described above in (1).
v) If applicable, remind participant to maintain current dosing and to keep all dispensed 
investigational drug kits for return at the next on-site visit.
b) Participants may be unable or unwilling to travel to the site for planned assessments 
(eg, safety blood draws); hence samples may not be sent for central lab analyses.
Mitigation plan: Local labs may be utilized as appropriate to monitor participant safety 
until the participant can return to the site for their regular follow-up per protocol. Any 
laboratory assessments conducted at a local lab due to the pandemic will be documented 
accordingly. Pregnancy testing may be performed using a home urine pregnancy test if 
local lab pregnancy testing is not feasible.
Participants may be unable or unwilling to attend the study visit to sign an updated ICF 
version.
Mitigation plan: The site staff will follow their approved consent process and remain in 
compliance with local EC/IRB and national laws and regulations. Remote consent will be 
allowed if has been approved by the local EC/IRB. The consent process will be 
documented and confirmed by normal consent procedure at the earliest opportunity.
3) Protocol and monitoring compliance:
a) Protocol deviations may occur, in case scheduled visits cannot occur as planned per 
protocol.
Mitigation plan: If it is not possible to complete a required procedure, an unscheduled 
visit should be conducted as soon as possible when conditions allow. The situation should 
be recorded and explained as a protocol deviation. Any missed participant visits or 
deviation to the protocol due to the pandemic must be reported in the eCRF and described 
in the clinical study report. Any virtual study visits that are conducted in lieu of clinic 
visits due to the pandemic will be documented as a protocol deviation related to the 
pandemic.
b) Monitors may be unable to carry out source data review or source data verification 
(SDV), or investigational drug accountability or assess protocol and GCP compliance. 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 76
27 August 2021
This may lead to delays in SDV, an increase in protocol deviations, or under reporting of 
AEs.
Mitigation plan: The study monitor is to remain in close communication with the site to 
ensure data entry and query resolution. In compliance with Gilead policy, a remote SDV 
should not be arranged. The study monitor is to reference the Study Monitoring Plan for 
guidance on how to conduct a remote monitoring visit. The study staff is to save and 
document all relevant communication in the study files. The status of sites that cannot 
accept monitoring visits and/or participants on site, must be tracked centrally and updated 
on a regular basis.
4) Missing data and data integrity:
a) There may be an increased amount of missing data due to participants missing 
visits/assessments. This could have an impact on the analysis and the interpretation of 
clinical trial data.
Mitigation plan: Implications of a pandemic on methodological aspects for the study will 
be thoroughly assessed and documented, and relevant actions will be taken as appropriate 
(ie, modification of the statistical analysis plan) and in compliance with regulatory 
authorities’ guidance. Overall, the clinical study report will describe the impact of the 
pandemic on the interpretability of study data.
Risks will be assessed continuously, and temporary measures will be implemented to mitigate 
these risks as part of a mitigation plan, as described above. These measures will be 
communicated to the relevant stakeholders as appropriate and are intended to provide alternate 
methods that will ensure the evaluation and assessment of the safety of participants who are 
enrolled in this study.
Since these potential risks are considered mitigated with the implementation of these measures, 
the expected benefit-risk assessment of [investigational drug(s)] in study participants remains 
unchanged.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 77
27 August 2021
Appendix 3.
Study Procedures Table
Screening
Baseline/ 
Day 1
Day 
2
Day 
3
Day 
4
Day 
5
Day 
6
Day 
7
Day 
8
Day 
9, 10, 
11
Day 
12
Day 
13
Day 
14
Day 
15
Day 
16
Day 
17, 
18, 
19
Day 
20
Day 
21
Day 
22, 23
Day 
24
Day 
25, 26, 
27, 28
Day 
29*
Day 29 
and 
Day 60 
Phone 
Follow-up 
Visits
(+ 5 days)
Written Informed 
Consent
X
Inclusion/Exclusion 
Criteria
X
Focused Medical 
History, including 
SCr valuesa 
X
Documentation of 
SARS-CoV-2 
Infectionb
X
Complete Physical 
Examination
X
Height
X
Weight
X
Vital Signsc 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Respiratory Statusd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Invasive 
Mechanical 
Ventilationq
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pulmonary 
Radiographic 
Imaginge
X
8-Point Ordinal 
Scalef
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pregnancy Testg
X
Chemistryh,r
X
X
X
X
X
X
X
X
X
X
Hematologyi,r
X
X
X
X
X
X
X
X
X
X

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 78
27 August 2021
Screening
Baseline/ 
Day 1
Day 
2
Day 
3
Day 
4
Day 
5
Day 
6
Day 
7
Day 
8
Day 
9, 10, 
11
Day 
12
Day 
13
Day 
14
Day 
15
Day 
16
Day 
17, 
18, 
19
Day 
20
Day 
21
Day 
22, 23
Day 
24
Day 
25, 26, 
27, 28
Day 
29*
Day 29 
and 
Day 60 
Phone 
Follow-up 
Visits
(+ 5 days)
Coagulationj,r
X
X
X
X
X
X
X
X
X
X
Serum Creatininer,s
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysist
X
RRT Assessmentk
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Virologic Testingl
X
X
X
X
X
X
X
Investigational 
Drug Dosing
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
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
X
X
X
X
X
X
X
X
X
X
Mortality
X
Hospital 
Readmission Rate
X
*
All assessments to be completed through Day 29, or until discharge, whichever is earlier. If participant is discharged prior to Day 29, a phone follow-up is to be completed at 
Day 29 and Day 60.
CCI
CCICCI

Remdesivir (GS-5734™) 
Protocol GS-US-540-5912 
Gilead Sciences, Inc. 
FINAL 
Amendment3 
a 
Focused medical histo1y will include date of first symptoms, overall symptoms, exposme sotu·ce, demographics, baseline characteristics, concomitant medications, kidney or 
other transplant histo1y, and allergies. If available, up to 3 SCr values prior to COVID-19 illness (eg, within the previous 6 months) should be provided. Doctuuent COVID-19 
vaccine status. (Note: It should be documented whether participant is fully or partially vaccinated, including any booster[ s] received, if applicable.) 
b 
Positive as detenuined by PCR via 1 validated assay at a local laborato1y, if not pe,fonued within the last 4 calendar days. 
c 
Includes heart rate, temperature, and blood pressm·e. 
d 
Respirato,y status includes respiratory rate and oxygenation: see Sections 6.2.1, 6.2.2, and 6.4. 
e 
Puhuona,y radiographic imaging may be performed within 72 hotu·s, if not already available and if needed to satisfy eligibility criteria. 
f 
Ordinal scale to be pe1fo1med twice on Day 1: prior to randomization (for baseline predose score) and the worst score on Day 1. 
g 
Serum pregnancy test will only be done for women of childbearing potential. Women < 54 years of age with amenoffhea of:C:: 12 months may also be considered 
postmenopausal if their follicle stimulating hormone (FSH) level is in the postmenopausal range > 40 IU/L and they are not using hormonal contraception or ho,monal 
replacement therapy. Results from within 48 homs prior to screening are acceptable. 
h 
Chemistiy: alkaline phosphatase, AST, ALT, total bilimbin, total protein, albumin, lactate dehydrogenase, creatine phosphokinase, bicarbonate, blood mea nih'ogen, calcimu, 
chloride, creatinine, glucose, lipase, magnesium, phosphorus, potassium, sodium, tu-ic acid. Results from within 48 homs p1-ior to screening are acceptable. 
Hematology: complete blood count with differential, hemoglobin and/or hematocrit, platelets. Results from within 48 homs p1-ior to screening are acceptable. 
Coagulation performed by centl'al lab: international n01malized ratio, prothrombin time, activated partial thromboplastin time, D-dimer, fibrinogen. Results from within 
48 homs p1-ior to screening are acceptable. 
k 
RRT will be measmed at screening through Day 29 or until discharge from inpatient hospitalization, as well as at the Day 60 phone follow-up. 
1 
Naso ha1 
geal swab collection for virologic SARS-CoV-2 testing for a,tici ants on Da s 1 3 5 7 14 21 and 29 or until discharoe whichever is earlier. 
' 
I 
q 
I on mvas,ve mec an,ca vent, ation at scre.enmg, pa1t1c1pant s ou 
e exc u e 
·om e stu y. 
r 
For participants on intenruttent RRT, laborato,y safety assessments should be drawn before dialysis on the day of dialysis. 
s 
Refer to Inclusion Criterion #5 to dete1mine the need for a confirmatory SCr evaluation. 
Pa,ticipants who are oliguric are not required to provide a tu-ine sample. 
CONFIDENTIAL 
Page 79 
27 August 2021 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 80
27 August 2021
Appendix 4.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definition
a. Definition of Childbearing Potential
For the purposes of this study, a female born participant is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming postmenopausal unless the 
participant is permanently sterile or has medically documented ovarian failure.
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 < 54 years of 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 participant of any age.
b. Definition of Male Fertility
For the purposes of this study, a male born participant is considered fertile after the initiation of 
puberty unless the participant is permanently sterile by bilateral orchidectomy or medical 
documentation.
2) Contraception Requirements for Female Participants
a. Investigational Drug Effects on Pregnancy and Hormonal Contraception
Data from clinical PK interaction studies of RDV have demonstrated that a clinically relevant 
interaction with contraceptive steroids was observed or suspected, but the effect is considered to 
be of limited clinical significance. In addition, nonclinical toxicity studies of RDV have 
demonstrated no adverse effect on fertility or embryo-fetal development. However, there is no 
clinical data available for RDV in pregnant women. Before enrolling into studies with RDV, 
women of childbearing potential must have pregnancy testing performed at screening. Refer to 
the latest version of the IB for additional information.
b. Contraception Requirements for Female Participants of Childbearing Potential
The inclusion of non-pregnant female participants of childbearing potential requires the use of at 
least 1 acceptable contraceptive measure. They must have a negative serum pregnancy test at 
screening and a confirmed negative pregnancy test from screening visit on Day 1, prior to 
randomization. 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 also applicable 
for women of childbearing potential with infrequent or irregular periods.
Duration of required contraception for female participants in this clinical trial should start from 
screening visit until 30 days after last dose of investigational drug.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 81
27 August 2021
Female participants must agree to 1 of the following contraceptive methods:

Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the participant’s preferred and usual 
lifestyle.
Or

Consistent and correct use of 1 of the following methods of birth control listed below:
Non-hormonal intrauterine device (IUD)
Hormonal IUD (must be used in conjunction with a barrier method)
Bilateral tubal occlusion (upon medical assessment of surgical success)
Vasectomy in the male partner (upon medical assessment of surgical success)
Or

Female participants who wish to use a hormonally-based method must use it in conjunction 
with a barrier method, preferably a male condom. Hormonal methods are restricted to those 
associated with the inhibition of ovulation. Hormonally-based contraceptives and barrier 
methods permitted for use in this protocol are as follows:
Hormonal methods (each method must be used with a barrier method, preferably male 
condom)
■
Oral contraceptives (either combined or progesterone only)
■
Injectable progesterone
■
Subdermal contraceptive implant
■
Transdermal contraceptive patch
■
Contraceptive vaginal ring
Barrier methods
■
Male condom (with or without spermicide)
■
Female condom (with or without spermicide)
■
Diaphragm with spermicide
■
Cervical cap with spermicide
■
Sponge with spermicide

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 82
27 August 2021
Inclusion of methods of contraception in this list of permitted methods does not imply that the 
method is approved in any country or region. Methods should only be used if locally approved.
Female participants must also refrain from egg donation and in vitro fertilization during 
treatment and until the end of contraception requirement.
3) Contraception Requirements for Male Participants
During the study, male participants with female partners of childbearing potential must use 
condoms when engaging in intercourse of reproductive potential during treatment and until 
30 days after last dose of investigational drug. If the female partner of childbearing potential is 
not pregnant, additional contraception recommendations should also be considered.
Male participants must also refrain from sperm donation during treatment and until the end of 
contraception requirement.
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhea method. A female condom and a male condom should not be used 
together.
5) Procedures to be Followed in the Event of Pregnancy
Female participants will be instructed to notify the investigator if they become pregnant or 
suspect they are pregnant at any time from start of the study to 30 days after last investigational 
drug dose.
Note: Female participants who become pregnant during the study or are discovered to be 
pregnant after receiving at least 1 dose, may continue investigational drug after discussion with 
the investigator.
Male participants whose partner has become pregnant or suspects she is pregnant from start of 
study to 30 days after last investigational drug dose must also report the information to the 
investigator. Instructions for reporting pregnancy, partner pregnancy, and pregnancy outcome are 
outlined in Section 7.4.2.3.

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 83
27 August 2021
Appendix 5.
Toxicity Grading Scale for Severity of Adverse Events and 
Laboratory Abnormalities
The DAIDS Toxicity Grading Scale Version 2.1 dated July 2017 is available at the following 
location:
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 84
27 August 2021
Appendix 6.
Management of Clinical and Laboratory Adverse Events
Grade 1 
Grade 2 
Grade 3 
Continue study drug dosing at the 
discretion of the investigator 
Repeat lab to confirm toxicity 
grade 
If confirmed, and possibly or probably related to study drug(s): 
If confirmed and 
unrelated to st udy 
drug(s), dosing may 
continue at the 
discretion of the 
investigator. 
1. Withhold study drug(s) until::; Grade 2 
2. Restart all study drug(s) at full dose upon discussion with the 
Gilead Medical Monitor 
If Grade 3 or 4 recurrence is 
confirmed and possibly or 
probably related to study drug(s), 
discontinue all study drug(s) 
permanently, and manage the 
subject according to local practice. 
If Grade 3 or 4 recurrence is 
confirmed and unrelated to 
study drug(s), continue all 
investigational medicinal 
product(s) at the same dose at 
the discretion of the 
investigator. 
Grade 4 
If confirmed, and 
possibly or probably 
related to study 
drug(s), discontinue 
study(s) dosing 
permanently, and 
manage subject 
according to local 
practice. Subject 
should be followed as 
clinically indicated 
until the laboratory 
abnormality returns to 
baseline, or is 
otherwise explained. 

Remdesivir (GS-5734™)
Protocol GS-US-540-5912
FINAL
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 85
27 August 2021
Appendix 7.
eGFR Automated Calculators
Automated calculators are provided by the National Institute of Diabetic and Digestive and 
Kidney Diseases.
Adults: 
https://www.niddk.nih.gov/health-information/professionals/clinical-tools-patient-management/k
idney-disease/laboratory-evaluation/glomerular-filtration-rate-calculators/ckd-epi-adults-convent
ional-units
Adolescents: 
https://www.niddk.nih.gov/health-information/professionals/clinical-tools-patient-management/k
idney-disease/laboratory-evaluation/glomerular-filtration-rate-calculators/children-conventional-
units