Clinical trial NCT04745351
Conditions: COVID-19
Sponsor: Gilead Sciences
Start date: 2021-03-31; Completion date: 2022-05-24
Enrollment: 249 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is 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).

Detailed description:

Arms: arm 1: Participants will receive continued Standard of Care (SOC) therapy together with RDV 200 mg on Day 1 followed by RDV 100 mg from Day 2 up to Day 5. arm 2: Participants will receive continued SOC therapy together with RDV matching placebo on Day 1 followed by RDV matching placebo from Day 2 up to Day 5.
Interventions: intervention 1: Remdesivir intervention 2: RDV Placebo intervention 3: Standard of Care
Intervention descriptions: intervention 1: Administered as Intravenous (IV) infusion once daily intervention 2: Administered as IV saline once daily intervention 3: Standard of Care Treatment for COVID-19 Infection

Protocol documents:
Prot_000.pdf: 
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The information contained in this document, particularly unpublished data, is the property or 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 


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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 
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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 
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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
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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


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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title: 
A Phase 3 Randomized, Double-Blind, Placebo-Controlled, 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™) 
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Study Design: 
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• 
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 
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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 
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
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™) 
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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. 
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Test Product, Dose, 
and Mode of 
Administration: 
Reference Therapy, 
Dose, and Mode of 
Administration: 
Criteria for 
Evaluation: 
Safety: 
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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. 
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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
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Statistical Methods: 
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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. 
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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.


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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


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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)


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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


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1.
INTRODUCTION
1.1.
Background
In December 2019, a series of pneumonia cases of unknown cause emerged in Wuhan, Hubei, 
China. Sequencing analysis from the patients’ respiratory tract samples indicated a novel 
coronavirus (CoV), 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 


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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.


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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).


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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}.


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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 
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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.


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OBJECTIVES 
The prirmuy objective of this study is as follows: 
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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 
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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


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RRT-free days (among those without ESKD at randomization) through Day 29 
• 
Recove1y through Day 29 
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Serious adverse events (SAEs) and AEs leading to investigational diug discontinuation 
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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: 
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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 


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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). 
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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


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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


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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 
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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).


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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 
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
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 
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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.


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STUDY PROCEDURES 
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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 
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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)


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Documentation of respirato1y status: 
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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 
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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 
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Laborato1y evaluations: Chemistry, hematology, coagulation, and SCr (see Section 6.5) 
I 
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• ~
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 
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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 
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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 
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
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).


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Poststudy Care 
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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 . 
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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events and Serious Adverse Events
7.1.1.
Adverse Events
An AE is any untoward medical occurrence in a clinical study participant administered an 
investigational 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.)


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
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 
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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).


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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).


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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.


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
If it is not possible to record and transmit the SAE information electronically, record the SAE 
on the paper SAE reporting form and 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.
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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.
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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.


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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 
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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.


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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
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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 
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• 
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 
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8.2.1. 
Planned Analyses 
Interim Analysis 
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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. 
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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 
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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. 
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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 
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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.


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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). 
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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.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with ICH E6(R2) 
addendum to its guideline for GCP and applicable laws and regulations.
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).


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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. 
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The required source data should include sequential notes containing at least the following 
information for each participant:

Participant identification

Documentation that participant meets eligibility criteria, 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.


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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.


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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.


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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.


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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.


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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:


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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.


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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


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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGMENT 
A Phase 3 Randomized, 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 
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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.


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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. 


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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.


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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


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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
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Remdesivir (GS-5734™) 
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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 
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Amendment 3
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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.


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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


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Inclusion of methods of contraception in this list of permitted methods does not imply that the 
method is approved in any country or region. Methods should only be used if locally approved.
Female participants must also refrain from egg donation and in vitro fertilization during 
treatment and until the end of contraception requirement.
3) Contraception Requirements for Male Participants
During the study, male participants with female partners of childbearing potential 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.


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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


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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. 


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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

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
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
Name of Test Drug:
Remdesivir
Study Number:
GS-US-540-5912
Protocol Version (Date):
Original:
07 December 2020
Amendment 1:
28 January 2021
Amendment 2:
02 August 2021
Amendment 3:
27 August 2021
Analysis Type:
Final Analysis
Analysis Plan Version:
SAP v1.0
Analysis Plan Date:
22 July 2022 
Analysis Plan Author(s):
 & 
 
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
PPD
GILEAU 


Remdesivir (RDV) 
GS-US-540-5912 Statistical Analysis Plan - Final Analysis 
Version 1.0 
TABLE OF CONTENTS 
STATISTICAL ANALYSIS PLAN ............................................................................................................................... 1 
TABLE OF CONTENTS ................................................................................................................................................ 2 
LIST OF IN-TEXT TABLES ........................................................................................................................................ .4 
LIST OF IN-TEXT FIGURES ....................................................................................................................................... .4 
LIST OF ABBREVIATIONS ......................................................................................................................................... 5 
1. 
INTRODUCTION .................................................................................................................................................. 7 
1. 1. 
Study Objectives ........................................................................................................................................ 7 
1.2. 
Study Design ............................................................................................................................................. 8 
1.3. 
Sample Size and Power ............................................................................................................................. 9 
2. 
TYPE OF PLANNED ANALYSIS ...................................................................................................................... 10 
2.1. 
Interi1n Analyses ...................................................................................................................................... 10 
2.2. 
DMC Analyses ........................................................................................................................................ 10 
2.3. 
Final Analysis .......................................................................................................................................... 10 
2.4. 
Change fro1n Protocol-Specified Analyses ............................................................................................. 10 
3. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES ............................................................................. 11 
3.1. 
3.2. 
3.3. 
3.4. 
3.5. 
3.6. 
3.7. 
3.8. 
3.9. 
Analysis Sets ........................................................................................................................................... 11 
3 .1. 1. 
All Randomized Analysis Set ................................................................................................ 11 
3.1.2. 
Full Analysis Set. ................................................................................................................... 11 
3.1.3. 
Safe Anal sis Set ................................................................................................................ 11 
Participant Groupmg ............................................................................................................................... 12 
Strata and Covariates ............................................................................................................................... 12 
Examination of Pa1ticipant Subgroups .................................................................................................... 13 
Multiple Co1nparisons ............................................................................................................................. 13 
Missing Data and Outliers ....................................................................................................................... 14 
3.6.1. 
Missing Data .......................................................................................................................... 14 
3. 6. 2. 
Outliers .................................................................................................................................. 14 
Data Handling Conventions and Transfo1mations .................................................................................. 14 
Analysis Visit Windows .......................................................................................................................... 16 
3.8.1. 
Definition of Study Day ........................................................................................................ 16 
3.8.2. 
Analysis Visit Windows ........................................................................................................ 16 
3.8.3. 
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window ................................................................................................................................. 18 
Change from Protocol-Specified General Considerations ...................................................................... 19 
4. 
PARTICIPANT DISPOSITION .......................................................................................................................... 20 
4.1. 
Participant Enrollment and Disposition ................................................................................................... 20 
4.2. 
Extent of Study Thug Exposw·e ............................................................................................................... 21 
4.3. 
Protocol Deviations ................................................................................................................................. 21 
5. 
BASELINE CHARACTERISTICS ..................................................................................................................... 22 
5.1. 
Demographics and Baseline Characteristics ........................................................................................... 22 
5.2. 
Other Baseline Characteristics ................................................................................................................ 22 
5.3. 
Medical Histoiy ....................................................................................................................................... 23 
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Remdesivir (RDV) 
GS-US-540-5912 Statistical Analysis Plan - Final Analysis 
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6. 
EFFICACY ANALYSES ..................................................................................................................................... 24 
6.1. 
Pri1nruy Efficacy Endpoint ...................................................................................................................... 24 
6.1. 1. 
Definition of the Prima1y Efficacy Endpoint ........................................................................ 24 
6.1.2. 
Statistical Hypothesis for the Primruy Efficacy Endpoint ..................................................... 24 
6.1.3. 
Primruy Analysis of the Prima1y Efficacy Endpoint.. ........................................................... 24 
6.1.4. 
Secondruy Analyses of the Prinia1y Efficacy Endpoint ........................................................ 24 
6.2. 
Secondruy Efficacy Endpoints ................................................................................................................ 25 
6.2.1. 
Anal sis of Secondru Efficac End oints ........................................................................... 25 
6.4. 
Changes from Protocol-Specified Efficacy Analyses ............................................................................. 29 
7. 
SAFETY ANALYSES ......................................................................................................................................... 30 
7 .1. 
Adverse Events and Deaths ..................................................................................................................... 30 
7.1. 1. 
Adverse Event Dictiona1y ..................................................................................................... 30 
7.1.2. 
Adverse Event Severity ......................................................................................................... 30 
7.1.3. 
Relationship of Adverse Events to Study Dmg ..................................................................... 30 
7.1.4. 
Serious Adverse Events ......................................................................................................... 30 
7.1.5. 
Treatinent-Emergent Adverse Events .................................................................................... 30 
7 .1.5.1. 
Definition of Treatinent-Emergent Adverse Events ........................................ 30 
7.1.5.2. 
Inco1nplete Dates ............................................................................................. 31 
7.1.6. 
SUllllllaries of Adverse Events and Deaths ............................................................................ 31 
7.2. 
Laborato1y Evaluations ........................................................................................................................... 32 
7.2.1. 
Sllllllllaries of Numeric Laborat01y Results .......................................................................... 33 
7.2.2. 
Graded Laborato1y Values .................................................................................................... 34 
7 .2.2.1. 
Treatinent-Emergent Laborat01y Abnonnalities ............................................. 34 
7.2.2.2. 
Summaries of Laborat01y Abnonnalities ........................................................ 34 
7.2.3. 
Liver-Related Laborato1y Evaluations .................................................................................. 35 
7.3. 
Vital Signs and Respirato1y Status .......................................................................................................... 35 
7.4. 
Conco1nitant Medications ........................................................................................................................ 36 
7.5. 
Other Safety Measures ............................................................................................................................ 36 
7 .6. 
Changes from Protocol-Specified Safety Analyses ................................................................................. 36 
I 
9. 
REFERENCES ..................................................................................................................................................... 39 
10. SOFTWARE ........................................................................................................................................................ .40 
11. SAP REVISION .................................................................................................................................................. .41 
12. APPENDICES ..................................................................................................................................................... .42 
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LIST OF IN-TEXT TABLES
Table 3-1.
Analysis Visit Windows for Chemistry (Except for SCr), Hematology, and 
Coagulation Laboratory Tests .................................................................................................17
Table 3-3.
Analysis Visit Window for 8-Point Ordinal Scale Collected after Day 44.............................17
LIST OF IN-TEXT FIGURES
Figure 1-1.
Study Schema ............................................................................................................................8
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LIST OF ABBREVIATIONS
AE
adverse event
AKI
acute kidney injury
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BLQ
below the limit of quantitation
BMI
body mass index
BUN
blood urea nitrogen
CI
confidence interval
CKD
chronic kidney disease
CMH
Cochran-Mantel-Haenszel
CoV
coronavirus
COVID-19
coronavirus disease 2019
CRF
case report form
CSR
clinical study report
DAIDS
Division of AIDS
DAVG
Time-weighted average change from baseline
DMC
data monitoring committee
ED
Emergency department
ESKD
end-stage kidney disease
ET
early termination
FAS
Full Analysis Set
Hb
Hemoglobin
HLT
high-level term
HLGT
high-level group term
ICH
International Conference on Harmonization (of Technical Requirements for Registration of 
Pharmaceuticals for Human Use)
IMV
Invasive mechanical ventilation
IV
Intravenous
IXRS
interactive voice or web response system
LLT
lower-level term
LOQ
limit of quantitation
MedDRA
Medical Dictionary for Regulatory Activities
PCR
polymerase chain reaction
PK
pharmacokinetics
PT
preferred term
PTM
Placebo to match
Q1, Q3
first quartile, third quartile
RDV
remdesivir
RRT
renal replacement therapy


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SAE
serious adverse event
SAP
statistical analysis plan
SARS
severe acute respiratory syndrome
SBECD
sulfobutylether-beta-cyclodextrin
SCr
serum creatinine
SD
standard deviation
SI (units)
international system of units
SOC
system organ class
SpO2
oxygen saturation
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
ULN
upper limit of normal
US
United States
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the clinical study report (CSR) 
for Study GS-US-540-5912. This SAP is based on the study protocol Amendment 3 dated 
27 August 2021 and the electronic case report form (eCRF). This SAP will be finalized before 
data finalization and unblinding. Any changes made after the finalization of the SAP will be 
documented in the CSR.
1.1.
Study Objectives
The primary objective of this study is as follows:

To evaluate whether remdesivir (RDV) 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 an 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

To evaluate the safety and tolerability of RDV in participants with severely reduced kidney 
function who are hospitalized for COVID-19  
CCI
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Remdesivir (RDV) 
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I 
I 
I 
I 
I 
I 
I 
1.2. 
Study Design 
Version 1.0 
This is a Phase 3 randomized, double-blind, placebo-controlled, parallel-group, multicenter study 
evaluating the efficacy and safety of RDV therapy in pa1ticipants with severely reduced kidney 
function who are hospitalized for COVID-19. 
Figure 1-1. 
Study Schema 
Day 
1 
RDV x up to 5 days 
(200 mg IV day 1, 
100 mg IV days 2-5) 
Saline as placebo x 
up to 5 days 
5 
10 
14 
29• 
Primary 
endpoint 
Composite of invasive 
mechanical ventilation 
or death through 
day29 
•oay 60 follow-up phone call 
Approximately 1,116 eligible paiticipants ai·e planned to be randomized in a 2: 1 ratio to receive 
RDV or saline as placebo, according to the following ti-eatment regimen, in addition to standai·d 
of care therapy: 
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Treatment Group A (N = 744): 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 (N = 372): 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 (United States [US] vs. ex-US)
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).
The schedule of assessments is provided as an appendix (Appendix 1).
1.3.
Sample Size and Power
A total of approximately 1116 participants are planned to 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 endpoint (composite of all-cause 
mortality or IMV) and the key α-controlled secondary endpoint (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%). 
The sample size calculation was done using software EAST (Version 6.5, module for log-rank 
test given accrual duration [120 days] and study duration [149 days] and 1 interim analysis at 
50% information fraction using the Lan-Demets approach with O’Brien-Fleming type spending 
function).


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
Prior to the final analysis, interim analyses may be conducted, and the analyses may be 
submitted to regulatory agencies to seek guidance for the overall clinical development program.
2.2.
DMC Analyses
Two formal DMC meetings were planned for this study and were specified in protocol 
Sections 8.2 and 8.10. The first meeting has occurred and was conducted after the first 
100 participants completed the Day 29 assessment. The purpose of this meeting was to review 
safety data, including renal and hepatic toxicity. The second meeting was planned after 50% of 
participants completed the Day 29 assessment. The purpose of this meeting was to review safety 
and provide a formal evaluation of futility and efficacy. However, this analysis was not 
performed due to the stop of study enrollment prior to reaching 50% of planned enrollment.  
In addition to the above mentioned 2 formal DMC analyses, the DMC was provided with blinded 
safety listings including Grade 3 or higher AEs and SAEs every week for the first 2 weeks after 
the first participant was enrolled followed by every 2 weeks thereafter. 
All details on DMC analyses are documented in the approved DMC charter. 
2.3.
Final Analysis
The final analysis will be performed after all participants have completed or discontinued from 
the study, outstanding data queries have been resolved or adjudicated as unresolvable, and the 
data have been cleaned and finalized.
The analysis of the primary endpoint of all-cause mortality or IMV through Day 29 and the key 
α-controlled secondary endpoint of all-cause mortality through Day 29 will be conducted at the 
final analysis (see Section 3.5 for prespecified testing strategy). The overall Type I error rate will 
be controlled at the two-sided 0.05 significance level.
2.4.
Change from Protocol-Specified Analyses
The second formal DMC analysis was not performed due to the stop of study enrollment prior to 
reaching 50% of planned enrollment. The reason for stopping enrollment was that it became 
clear the study would not fully enroll in a reasonable timeframe even after implementing 
enrollment mitigation strategies. The decision to stop study enrollment was documented in the 
16 December 2021 Study Management Team meeting minutes.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of participants in each category will be presented; for continuous 
variables, the number of participants (n), mean, standard deviation (SD) or standard error (SE), 
median, first quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
By-participant listings will be presented for all participants in the All Randomized Analysis Set 
and sorted by participant identification (ID) number, visit date, and time (if applicable). Data 
collected on log forms, such as adverse events (AEs), will be presented in chronological order 
for each participant. The treatment group to which participants were randomized will be used in 
the listings. Age, sex at birth, race, and ethnicity will be included in the listings, as space permits.
3.1.
Analysis Sets
Analysis sets define the participants to be included in an analysis. Analysis sets and their 
definitions are provided in this section. Participants included in each analysis set will be 
determined before the study blind is broken for analysis. The analysis set will be identified and 
included as a subtitle of each table, figure, and listing.
For each analysis set, the number and percentage of participants eligible for inclusion will be 
summarized by treatment group.
A listing of reasons for exclusion from analysis sets will be provided by participant.
3.1.1.
All Randomized Analysis Set
All Randomized Analysis Set includes all participants who were randomized in the study.
3.1.2.
Full Analysis Set
The primary analysis set for efficacy analysis is defined as the Full Analysis Set (FAS), which 
will include all participants who (1) are randomized into the study, and (2) have received at least 
1 dose of study drug. 
3.1.3.
Safety Analysis Set
The primary analysis set for safety analyses is defined as the Safety Analysis Set, which will 
include all participants who (1) are randomized into the study and (2) have received at least 
1 dose of study drug. 
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3.1.7. 
Virology Analysis Set 
The Virology Analysis Set will include all participants who (1) are randomized into the study, 
(2) have received at least 1 dose ofRDV, and (3) have positive SARS-CoV-2 viral load at 
baseline (a result of"No SARS-CoV-2 detected" is considered as negative, results of 
Inconclusive, < limit of quantitation (LOQ) SARSCo V2 detected, and numerical results are 
considered as positive). 
3.2. 
Participant Grouping 
For analyses based on the All Randomized Analysis Set and FAS, paii icipants will be grouped 
according to the treatment to which the were randomized. For analyses based on Saf~ 
Anal sis Set 
Virology Analysis Set and-
paiiicipants will be grouped according to the actual treatment they received. 
The actual treatment received will differ from the randomized ti·eatment only when their actual 
ti·eatment differs from randomized ti·eatment for the entire treatment duration. 
3.3. 
Strata and Covariates 
Paiiicipants will be randomly assigned to treatment groups via the interactive voice or web 
response system (IXRS) in a 2: 1 ratio using a sti·atified randomization schedule. Randomization 
will be sti·atified by: 
• 
ESKD requiring chronic dialysis (Yes, No) 
• 
High-flow oxygen requirement (Yes, No) 
• 
Region (US, ex-US) 
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Stratification discrepancies between the IXRS and the clinical database will be reviewed and 
assessed. The values recorded in the clinical database will be used for analyses in case there are 
discrepancies. Based on the assessment of stratification discrepancies, a sensitivity analysis of 
the primary endpoint may be performed.
The primary efficacy endpoint and the key α-controlled secondary efficacy endpoint (see 
Section 6 for definition) will be evaluated in a stratified analysis based on the same 3 factors 
used for randomization, as specified in Section 6. In addition, observed imbalances between 
treatment groups in other baseline characteristics may be considered as covariates in sensitivity 
analyses of efficacy endpoints.  
3.4.
Examination of Participant Subgroups
The primary efficacy endpoint and the key α-controlled secondary efficacy endpoint will be 
examined for the following participant subgroups: 

Kidney disease status (defined as: AKI, CKD and ESKD.)

High-flow oxygen requirement at baseline (Yes, No)

Region (US, ex-US)

Participant’s age (≥18 - < 65,   years) 

Sex at birth: (a) male and (b) female

Race: (a) Asian, (b) Black, (c)White, (d) Other

Baseline risk factor (as applicable):  Chronic lung disease (Yes, No), Hypertension (Yes, 
No), Cardiovascular or cerebrovascular disease (Yes, No), Diabetes mellitus (Yes, No), BMI 
(with categories: < 20, ≥ 20 - < 30, ≥ 30 kg/m^2), Immunocompromised state (Yes, No), 
Chronic liver disease (Yes, No), Current cancer (Yes, No)
In addition, the primary efficacy endpoint will be examined for duration of symptoms prior to 
first dose of study drug (<= 5 days vs >5 days) and baseline oxygen support status. Other 
subgroups may be considered based on imbalances between treatment groups observed in other 
baseline characteristics.
3.5.
Multiple Comparisons
To control the overall Type I error in the evaluation of the primary efficacy endpoint and the key 
secondary efficacy endpoint, the hypothesis testing will be performed in sequential order. 
The primary efficacy endpoint will be tested first at the significance level of 0.05. If the primary 
efficacy endpoint null hypothesis is rejected, the key secondary efficacy endpoint will be tested 
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All other endpoints may be tested using 2-sided tests at the 0.05 significance level without 
multiplicity adjustment as they are considered secondary 
 endpoints. 
3.6.
Missing Data and Outliers
3.6.1.
Missing Data
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document.
In this study, a missing pre-treatment laboratory result would be treated as normal (ie, no toxicity 
grade) for the laboratory abnormality summary. 
For missing last dose date of study drug, imputation rules are described in Section 3.8.1. The 
handling of missing or incomplete dates for AE onset is described in Section 7.1.5.2, and for 
concomitant medications in Section 7.4.
Imputation rules for the secondary efficacy endpoints related to the 8-point ordinal scale score 
are described in Section 6.2.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process. No sensitivity 
analyses to evaluate the impact of outliers on efficacy or safety outcomes are planned. Unless 
specified otherwise, all data will be included in the analyses.
3.7.
Data Handling Conventions and Transformations
In general, age collected at Day 1 (in years) will be used for analyses and presented in listings. If 
age at Day 1 is not available for a participant, then age derived from date of birth and the Day 1 
visit date will be used instead. If an enrolled participant was not dosed with any study drug, the 
randomization date will be used instead of the Day 1 visit date. For screen failures, the date the 
first informed consent was signed will be used for the age derivation. Age required for 
longitudinal and temporal calculations and analyses (e.g., estimates of creatinine clearance, age 
at date of AE) will be based on age derived from date of birth and the date of the measurement or 
event, unless otherwise specified.
The following conventions will be used for the imputation of date of birth when it is partially 
missing or not collected:

If only year of birth is collected, then “01 July” will be imputed as the day and month of birth

If year of birth is missing, then date of birth will not be imputed.
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Laborato1y data that are continuous in nature but are less than the lower LOQ or above the upper 
LOQ will be imputed as follows: 
• 
A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is repo1ied in the fo1m of "< x" (where xis considered the LOQ). For example, if the 
values are repo1ied as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate summaiy statistics. An exception to this mle is any value repo1ied as < 1 or < 0.1, 
etc. For values repo1ied as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used to 
calculate summaiy statistics. 
• 
A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is repo1ied in the fo1m of "> x" (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above. 
• 
The LOQ will be used to calculate descriptive statistics if the datum is repo1ied in the fonn of 
":'.S x" or"::::: x" (where xis considered the LOQ). 
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Natural logai·ithm transfo1m ation will be used for analyzing concentrations. Concentration values 
that are BLQ will be presented as "BLQ" in the concentration data listing. Values that are BLQ 
will be treated as O at predose time points, and one-half the value of the LOQ at postdose time 
points for sUllllllaiy pmposes. 
The following conventions will be used for the presentation of smnmaiy and order statistics: 
• If at least 1 paiiicipant has a concentration value of BLQ for the time point, the minimum 
value will be displayed as "BLQ." 
• If more than 25% of the paiiicipants have a concentration data value of BLQ for a given time 
point, the minimum and Q 1 values will be displayed as "BLQ." 
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
If more than 50% of the participants have a concentration data value of BLQ for a given time 
point, the minimum, Q1, and median values will be displayed as “BLQ.”

If more than 75% of the participants have a concentration data value of BLQ for a given time 
point, the minimum, Q1, median, and Q3 values will be displayed as “BLQ.”

If all participants have concentration data values of BLQ for a given time point, all order 
statistics (minimum, Q1, median, Q3, and maximum) will be displayed as “BLQ.”
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study day will be calculated from the first dosing date of study drug and derived as follows:

For assessment dates on or after the first dosing date: Assessment Date – First Dosing 
Date + 1

For assessment dates prior to the first dosing date: Assessment Date – First Dosing Date 
Therefore, Study Day 1 is the day of first dose of study drug administration.
Last Dose Date is defined as the maximum, nonmissing, nonzero dose end date of treatment 
recorded on the Study Drug Administration eCRF form with “Study Drug Permanently 
Withdrawn” box checked for participants who prematurely discontinued or completed study drug 
according to the Study Drug Completion eCRF.
Last dose date is not expected to be missing. However, if last dose date is missing, it will be 
imputed using the maximum of non-missing, non-zero dose, study drug start and stop dates.
Last Study Date is the latest of study drug start dates and end dates, the in-person or phone visit 
dates, the vital sign and the laboratory collection dates, including the Day 60 phone follow-up 
visit date. For participants who died during the study, the death date will be the Last Study Date. 
For participants who died after completing the study or after prematurely discontinuing the 
study, the death date will not be considered for the Last Study Date.
3.8.2.
Analysis Visit Windows
Participant visits might not occur on protocol-specified days. Therefore, for the purpose of 
analysis, observations will be assigned to analysis windows.
The analysis windows for chemistry (except for SCr), hematology and coagulation laboratory 
tests are provided in Table 3-1. 
 
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Table 3-1.
Analysis Visit Windows for Chemistry (Except for SCr), Hematology, 
and Coagulation Laboratory Tests
Visit Window Study Day
Nominal Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1
(none)
1 (Pre Dose)
Day 3
3
1 (Post Dose)
3
Day 5
5
4
6
Day 8
8
7
10
Day 12
12
11
14
Day 16
16
15
18
Day 20
20
19
22
Day 24
24
23
26
Day 29
29
27
44
The 8-point ordinal scale will be collected daily from Day 1 through Day 29 or discharge, 
whichever is earlier, as well as at the Day 29 and Day 60 phone follow-up. The analysis visit 
window will coincide with each study day up to Day 44 with 1 exception: a Day 1 postdose 
record will be mapped to Analysis Day 2 visit (the 8-point ordinal scale will be collected twice 
on Day 1: predose and the worst score on Day 1 post-dose). If any additional records are 
collected after Day 44, the analysis window is provided in Table 3-3.
Table 3-3.
Analysis Visit Window for 8-Point Ordinal Scale Collected after 
Day 44
Visit Window Study Day
Nominal Visit
Nominal 
Study Day
Lower Limit
Upper Limit
Day 60 
60
45
(none)
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Vital signs, and SCr will be collected daily from Day 1 through Day 29 or discharge, whichever 
is earlier, per protocol; therefore, the analysis visit window will coincide with each study day up 
to Day 29 with 1 exception: a Day 1 postdose record will be mapped to Analysis Day 2 visit. 
3.8.3. 
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window 
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time-to-event analysis would use all data regardless of analysis window. 
If multiple valid, nonmissing measurements exist in an analysis window, records will be chosen 
based on the following mles if a single value is needed: 
• 
For baseline, the last nonmissing value on or prior to the first dosing date (and time, 
if available) of study drng will be selected, unless specified differently. If there are multiple 
records with the same time or no time recorded on the same day, the baseline value will be 
selected as follows: 
-
For continuous data: 
For other continuous data, the average of the measurements will be taken. 
-
For categorical data: 
For SARS-Co V-2 infection status, the highest severity (ie, a positive PCR result) will 
be selected. 
For other categorical data, the lowest severity will be selected. 
For the 8-point ordinal scale, only Screening and Day 1 predose values will be considered for 
baseline value selection. 
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In an analysis window (including baseline window), if both central lab and local lab results are 
available, then centrnl lab results will be used for record selection instead of local lab results; 
local lab results will only be used for record selection if central lab results are missing. 
3.9. 
Change from Protocol-Specified General Considerations 
The multiplicity adjustment specified in the protocol Section 8.7 was changed because the 
interim analysis planned after 50% of pa1t icipants completed the Day 29 assessment was not 
perfo1med due to the stop of study enrollment prior to reaching 50% of planned enrollment. As 
there was no interim analysis, there was no alpha spent and the final analysis is planned at the 
0.05 significance level (see Section 2.3). 
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4.
PARTICIPANT DISPOSITION
4.1.
Participant Enrollment and Disposition
A table of key study dates will be provided, including first participant screened, first participant 
enrolled, last participant enrolled, last participant last visit for the primary endpoint, and last 
participant last visit.
The number and percentage of participants enrolled at each investigator site and country will be 
summarized by treatment group and overall. The denominator for this calculation will be the 
number of participants analyzed for that column.
A similar enrollment table will be provided by randomization stratum. The denominator for the 
percentage of participants in the stratum will be the total number of participants in the Safety 
Analysis Set. If there are discrepancies in the value used for stratification assignment between 
the IXRS and the clinical database, the value collected in the clinical database will be used for 
the summary. A listing of participants with discrepancies in the value used for stratification 
assignment between the IXRS and the clinical database at the time of data finalization will be 
provided.
A summary of participant disposition will be provided by treatment group and overall for all 
screened participants. This summary will include the number of participants screened, screen 
failure participants who were not randomized, participants who met all eligibility criteria but 
were not randomized, participants randomized, participants randomized but never treated, 
participants in the Safety Analysis Set, and Full Analysis Set (FAS). 
In addition, the number and percentage of the participants in the following categories will be 
summarized: 

Completed study drug

Did not complete study drug with reasons for premature discontinuation of study drug

Completed study

Did not complete study with reasons for premature discontinuation of study
The denominator for the percentages of participants in each category will be the number of 
participants in the Safety Analysis Set corresponding to that column. 
No inferential statistics will be generated. A data listing of reasons for premature study 
drug/study discontinuation will be provided.
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4.2.
Extent of Study Drug Exposure
Number of doses received will be summarized by treatment group for the Safety Analysis Set.
4.3.
Protocol Deviations 
A listing will be provided for all randomized participants who violated at least 1 inclusion or 
exclusion criterion. The listing will include the criteria not met.
Protocol deviations occurring after participants entered the study are documented during routine 
monitoring. The number and percentage of participants with important protocol deviations and 
the total number of important protocol deviations by deviation reason (eg, violation of select 
inclusion/exclusion criteria) will be summarized by treatment group for the FAS. A 
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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Participant demographic data (eg, sex, race, race category, ethnicity, age, and age group [< 18, 
≥ 18 - < 65, ≥ 65 years]) and baseline characteristics (eg, body weight, height, body mass index 
[BMI] and BMI group [< 20, ≥ 20 - < 30, ≥ 30 kg/m^2]) will be summarized by treatment group 
and overall using descriptive statistics (n, mean, SD, median, Q1, Q3, minimum, and maximum) 
for continuous data and by the number and percentage of participants for categorical data. The 
summaries of demographic data and baseline characteristics will be provided for the Safety 
Analysis Set.
For categorical data, the Cochran-Mantel-Haenszel (CMH) test (ie, general association statistic 
for nominal data and row mean scores differ statistic for ordinal data) will be used to compare 
the 2 treatment groups. For continuous data, the 2-sided Wilcoxon rank sum test will be used to 
compare the 2 treatment groups. 
Similar summaries will be produced for the following subgroups: kidney disease status (as 
defined in Section 3.4), high-flow oxygen requirement (Yes, No), and region (US vs. ex-US).
A by-participant demographic listing will be provided.
5.2.
Other Baseline Characteristics
The following baseline disease characteristics will be summarized by treatment group and 
overall using descriptive statistics:

Kidney disease status (as defined in Section 3.4)

High-flow oxygen requirement (Yes, No)

Region (US, ex-US)

Clinical status (8-point ordinal scale)

Oxygen support status

RRT at baseline

Duration of hospitalization prior to first dose of study drug

Duration of symptoms prior to first dose of study drug (as a continuous variable, and a 
categorical variable with categories of <= 5 and > 5)

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Alanine aminotransferase (ALT) 
• 
Baseline risk factor ( as defined in Section 3 .4 except BMI) 
• 
COVID-19 vaccine (See Appendix 2) status 
For categorical data, the CMH test (ie, general association statistic for nominal data and row 
mean scores differ statistic for ordinal data) will be used to compare the 2 treatment groups. For 
continuous data, the 2-sided Wilcoxon rank sum test will be used to compare the 2 ti·eatment 
groups. 
Similar summaries will be produced for the following subgroups: kidney disease status (as 
defined in Section 3.4), high-flow oxygen requirement (Yes, No), and region (US vs. ex-US). 
A by-paiiicipant listing will also be provided. 
5.3. 
Medical History 
General medical histo1y data will be collected at screening. It will be coded using the cunent 
version ofMedDRA. 
A summaiy table will present the percentages of paiiicipants repo1iing each medical histo1y 
prefened tenn, sorted first in alphabetical order by system organ class (SOC) and then by 
prefened tenn (PT) in descending order of total frequency within SOC. A listing of medical 
histo1y will be provided. 
A by-paiiicipant listing of kidney ti·ansplant histo1y will also be provided. 
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6.
EFFICACY ANALYSES
6.1.
Primary Efficacy Endpoint
6.1.1.
Definition of the Primary Efficacy Endpoint
The primary endpoint is the composite of all-cause mortality or IMV from date of first dose 
through Day 29. 
6.1.2.
Statistical Hypothesis for the Primary Efficacy Endpoint
Null hypothesis:  There is no difference between treatment groups in the probability of all-cause 
mortality or IMV through Day 29.
Alternative hypothesis:  The probability of all-cause mortality or IMV through Day 29 is 
different between treatment groups.
6.1.3.
Primary Analysis of the Primary Efficacy Endpoint
The primary endpoint will be analyzed using a stratified log-rank test stratified by the 
randomization strata. P value and the proportion of all-cause mortality or IMV at Day 29 from 
Kaplan-Meier estimate will be provided. 
The hazard ratio and 95% confidence interval (CI) will be estimated using a Cox model with 
stratification factors as covariates. 
Participants with missing outcomes for the primary endpoint due to premature discontinuation of 
the study on or prior to Day 29 will be censored at the last study day.  
Additionally, the difference in proportions of all-cause mortality or IMV at Day 29 between 
treatment groups and the 95% CI for the difference will be provided based on the 
stratum-adjusted Mantel-Haenszel (MH) proportion as described in {Koch 1989} in Appendix 2.
The FAS will be the primary analysis set for efficacy endpoint evaluation.
6.1.4.
Secondary Analyses of the Primary Efficacy Endpoint
The primary endpoint will also be analyzed for each of the subgroups defined in Section 3.4.
Sensitivity analyses maybe conducted using the following alternative approaches for the primary 
endpoint. 

A CMH test including stratification factors as strata for the statistical comparison between 
treatment groups. If a participant prematurely discontinues from the study prior to Day 29 
with no event before discontinuation or the IMV/death status is missing, the participant will 
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
In rare occasions, a participant may be unblinded to site for safety considerations (Gilead 
remains blinded). Data for such participants after site unblinding may be censored for a 
sensitivity evaluation.
The sensitivity analyses are for the purposes of evaluating the robustness of the estimates of the 
primary analysis.
6.2.
Secondary Efficacy Endpoints 
The key α-controlled secondary endpoint is all-cause mortality through Day 29. 
Other secondary endpoints include:

Initiation of IMV through Day 29

Time to recovery through Day 29

Clinical status assessed by the 8-point ordinal scale at Day 15 and Day 29

RRT-free days (among those without ESKD at baseline) through Day 29

Proportion of participants with recovery through Day 29
Recovery is defined as achieving category 1, 2, or 3 on the 8-point ordinal scale score, for 
participants with a baseline score ≥ 4.
6.2.1.
Analysis of Secondary Efficacy Endpoints
The key α-controlled secondary endpoint of all-cause mortality through Day 29 will be analyzed 
in a similar manner to the primary endpoint. 
Initiation of IMV through Day 29 and time to recovery through Day 29 will also be analyzed in a 
similar manner to the primary endpoint except that a competing risk analysis approach will be 
used with death as the competing risk.
For analysis on time to recovery through Day 29, two sets of analyses will be conducted: 
(1) Time to recovery through Day 29, in which the first recovery without further worsening in 
the ordinal scale score (ie, a score of > 4) by Day 29 will be considered an event; (2) Time to 
recovery through Day 29, in which the first recovery (regardless of further worsening or not) will 
be considered an event. 
The clinical status assessed by the 8-point ordinal scale at Day 15 and Day 29 will be analyzed 
using a proportional odds model including treatment as the independent variable. Two models 
will be explored; one with baseline score as a continuous covariate and one without baseline 
score as a covariate. The odds ratio and 95% CI will be provided. The percentage of participants 
in each category will be summarized by treatment group. The assumption of odds proportionality 
will be assessed using a score test and reported. Clinical status by study day and change from 
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For participants without ESKD at baseline, the number of RRT-free days will be calculated 
between date of first dose and Day 29. The number of RRT-free days will be calculated as the 
number of full days from Day 1 to Day 29 that the participant was alive and did not receive RRT. 
The number of RRT-free days will be summarized by treatment group, and compared between 
treatment groups using Wilcoxon rank sum test.
The proportion of participants with recovery through Day 29 will be summarized by treatment 
group, and compared between treatment groups using the CMH test stratified by randomization 
strata. Similar for time to recovery analysis, two sets of analyses will be conducted: (1) The 
proportion of participants with recovery through Day 29, in which recoveries without further 
worsening by Day 29 is considered; (2) The proportion of participants with  recovery through 
Day 29, in which recoveries regardless of worsening status by Day 29 is considered. 
The key α-controlled secondary endpoint of all-cause mortality through Day 29 will also be 
analyzed for each of the subgroups defined in Section 3.4. Other secondary endpoints may also 
be analyzed for each of the stratification factor subgroups.
For time to event analysis of secondary endpoints, participants with missing outcomes due to 
premature discontinuation of the study on or prior to Day 29 will be censored at the date of last 
known status for that endpoint.
Clinical status assessed by the 8-point ordinal scale will be derived by combining the available 
death, hospital discharge alive and ordinal scale assessment reported by the site, where death 
supersedes discharge alive and discharge alive supersedes the ordinal scale score reported by the 
site.
Sites were instructed to report the worst ordinal scale category for each day. Therefore, the 
ordinal scale result on the day the participant was discharged alive does not necessarily reflect 
Not hospitalized. The definition of clinical status based on the 8-point ordinal scale is defined as 
follows:

If a participant dies on or prior to Day 29, clinical status on the day of death and all 
subsequent days through Day 29 will be set as 8 (death)

If a participant is discharged alive on or prior to Day 29, clinical status on the day of 
discharge alive will be set to 2 (not hospitalized, limitation on activities and/or requiring 
home oxygen), which is the worst score for a non-hospitalized participant 

If a participant is discharged alive and subsequently re-admitted on or prior to Day 29, and 
the 8-point ordinal score is not reported on the day of re-admission, the clinical status on the 
day of the re-admission will be imputed to 7 (hospitalized, on IMV or ECMO), which is the 
worst score for a hospitalized participant

For other missing ordinal scores from Day 2 through Day 29, the clinical status will be 
imputed using the previous day’s score (either reported score or imputed score as applicable)
The FAS will be the primary analysis set for the secondary efficacy endpoints. 


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6.4. 
Changes from Protocol-Specified Efficacy Analyses 
The prirmuy analysis specified in the protocol Section 8.2.2 and the final analysis will be 
combined into one final analysis due to early study closure with smaller than planned sample 
size. 
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7.
SAFETY ANALYSES
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory AEs will be coded using the current version of MedDRA. System organ 
class (SOC), high-level group term (HLGT), high-level term (HLT), preferred term (PT), and 
lower-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
The severity of AEs will be graded using the Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017. For each episode, 
the highest grade attained should be reported as defined in the grading scale. The DAIDS scale is 
available at the following location:
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf
Adverse events are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 
(severe), Grade 4 (life threatening) or Grade 5 (fatal) according to toxicity criteria specified in 
the document above. The severity grade of events for which the investigator did not record 
severity will be left as “missing” for data listings. 
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE CRF to the 
question of “Related to Study Treatment.” Relatedness will always default to the investigator’s 
choice, not that of the medical monitor. Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-participant data listings will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if the AEs met the 
definitions of SAEs that were specified in the study protocol. SAEs captured and stored in the 
clinical database will be reconciled with the SAE database from the Gilead Global Patient Safety 
(GLPS) Department before data finalization.
7.1.5.
Treatment-Emergent Adverse Events 
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the study drug start date and no later than 30 days 
after permanent discontinuation of study drug

Any AEs leading to premature discontinuation of study drug.


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7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The AE onset date is the same as or after the month and year (or year) of the first dosing date 
of study drug, and

The AE onset date is the same as or before the month and year (or year) of the date 
corresponding to 30 days after the date of the last dose of study drug 
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of study drug, will be considered treatment emergent. In 
addition, an AE with the onset date missing and incomplete stop date with the same or later 
month and year (or year alone if month is not recorded) as the first dosing date of study drug will 
be considered treatment emergent.
7.1.6.
Summaries of Adverse Events and Deaths
TEAEs will be summarized based on the Safety Analysis Set.
A brief, high-level summary of the number and percentage of participants who experienced at 
least 1 TEAE in the categories described below will be provided by treatment group. 
Treatment-emergent deaths observed in the study will also be included in this summary.
Treatment-emergent death refers to deaths that occurred between the first dose date and the last 
dose date plus 30 days (inclusive).
The number and percentage of participants who experienced at least 1 TEAE will be provided 
and summarized by SOC, High level term (HLT), PT, and treatment group.  
For other AEs described below, summaries will be provided by SOC, PT, and treatment group: 

TEAEs with Grade 3 or higher

TE study drug-related AEs

TE study drug-related AEs with Grade 3 or higher

TE SAEs

TE study drug-related SAEs

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Multiple events will be counted only once per participant in each summary. Adverse events will 
be summarized and listed first in alphabetic order of SOC (and HLT within each SOC 
if applicable), and then by PT in descending order of total frequency within each SOC. For 
summaries by severity grade, the most severe grade will be used for those AEs that occurred 
more than once in an individual participant during the study. 
In addition to the above summary tables, all TEAEs, TEAEs with Grade 3 or higher, TE study 
drug-related AEs, TE study drug-related AEs with Grade 3 or higher, and TE SAEs will be 
summarized by PT only, in descending order of total frequency. 
The above summary tables may also be provided for one or more of the following subgroups: 
kidney disease status (as defined in Section 3.4), high-flow oxygen requirement (Yes, No), 
and/or region (US, ex-US). 
In addition, data listings will be provided for the following:

All AEs

All study drug-related AEs 

All AEs with severity of Grade 3 or higher

All SAEs

All study drug-related SAEs 

All Deaths

AEs leading to premature discontinuation of study drug
Listing of renal and hepatic adverse events will be provided. Hypersensitivity including infusion-
related reactions adverse events will also be summarized and listed (See Appendix 2).
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected up to the last dose of study drug plus 30 days. 
The analysis will be based on values reported in conventional units. When values are below or 
above the LOQ, they will be listed as such, and the closest imputed value will be used for the 
purpose of calculating summary statistics as specified in Section 3.7. 


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Because RRT may significantly impact certain lab values such as SCr and BUN, a sensitivity 
analysis will be conducted, in which records and/or participants may be excluded from analysis 
as follows:

SCr and BUN will only be analyzed for participants who are not on RRT at baseline. If RRT 
is used during the study, any records from RRT start to end + 3 days will be excluded from 
analysis. 
RRT started within 3 days before first dose is considered RRT at baseline. 
Anticoagulation medications can impact coagulation lab parameters, such as aPTT, PT, and INR. 
Sensitivity analysis will be conducted for coagulation lab parameters. Any coagulation lab 
records under the influence of these medications will be excluded from analysis. For 
anticoagulation medications in the Warfarin class, coagulation lab records with a date in between 
the start and 5 + the stop date of the medication will be excluded; for other anticoagulation 
medications, records with a date in between the start and 1 + the stop date of the medication will 
be excluded. 
A by-participant listing for laboratory test results will be provided by participant ID number and 
visit in chronological order for hematology, coagulation, serum chemistry,
 
 Values falling outside of the relevant reference range and/or having a severity 
grade of 1 or higher on the DAIDS Grading Scale (see Section 7.2.2) will be flagged in the data 
listings, as appropriate.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for selected laboratory test specified in 
the study protocol as follows:

Baseline values 

Values at each postbaseline analysis visit

Change from baseline at each postbaseline analysis visit

Percentage change from baseline to each postbaseline analysis visit (if specified)
A baseline laboratory value will be defined as the last nonmissing measurement obtained on or 
prior to the date/time of first dose of study drug. Change from baseline to a postbaseline visit will 
be defined as the visit value minus the baseline value. The mean, median, Q1, Q3, minimum, and 
maximum values will be displayed to the reported number of digits; SD values will be displayed 
to the reported number of digits plus 1. Baseline and change from baseline will be compared 
between the treatment groups using the 2-sided Wilcoxon rank sum test.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.
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In an analysis window (including baseline window), if both central lab and local lab results are 
available, then central lab results will be used instead of local lab results; local lab results will 
only be used if central lab results are missing. 
7.2.2.
Graded Laboratory Values
The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Event, Version 2.1 
(July 2017) (see Section 7.1.2) will be used for assigning toxicity grades (0 to 4) to laboratory 
results for analysis. Grade 0 includes all values that do not meet the criteria for an abnormality of 
at least Grade 1. For laboratory tests with criteria for both increased and decreased levels, 
analyses for each direction (i.e., increased, decreased) will be presented separately. 
For baseline, if both central lab and local lab results are available, then central lab results will be 
used to determine baseline toxicity grade; local lab results will only be used if central lab results 
are missing. For postbaseline laboratory abnormalities, both central lab and local lab results will 
be used. 
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last 
dose of study drug plus 30 days. If the relevant baseline laboratory value is missing, any 
abnormality of at least Grade 1 observed within the time frame specified above will be 
considered treatment emergent.
7.2.2.2.
Summaries of Laboratory Abnormalities
Laboratory data that are categorical will be summarized using the number and percentage of 
participants in the study with the given response at baseline and each scheduled postbaseline 
visit.
The following summaries (number and percentage of participants) for treatment-emergent 
laboratory abnormalities will be provided by lab test and treatment group; participants will be 
categorized according to the most severe postbaseline abnormality grade for a given lab test:

Treatment-emergent laboratory abnormalities

Treatment-emergent Grade 3 or 4 laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of participants 
with nonmissing postbaseline values up to 30 days after last dosing date.
A by-participant listing of treatment-emergent Grade 3 or 4 laboratory abnormalities will be 
provided by participant ID number and visit in chronological order. 


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7.2.3.
Liver-Related Laboratory Evaluations
Liver-related abnormalities after initial study drug dosing will be examined and summarized 
using the number and percentage of participants who were reported to have the following 
laboratory test values for postbaseline measurements:

Alanine aminotransferase (ALT): (a) > 3 × ULN, (b) > 5 × ULN, (c) > 10 × ULN, 
(d) > 20 × ULN

Aspartate aminotransferase (AST): (a) > 3 × ULN, (b) > 5 × ULN, (c) > 10 × ULN, 
(d) > 20 × ULN

ALT or AST: (a) > 3 × ULN, (b) > 5 × ULN, (c) > 10 × ULN, (d) > 20 × ULN

Total bilirubin: (a) > 1 × ULN, (b) > 2 × ULN

Alkaline phosphatase (ALP) > 1.5 × ULN

ALT or AST > 3 × ULN and total bilirubin: (a) > 1.5 × ULN, (b) > 2 × ULN

ALT or AST > 3 × ULN and total bilirubin > 2 × ULN and ALP < 2 × ULN
For individual laboratory tests, participants will be counted once based on the most severe 
postbaseline value. For both the composite endpoint of ALT or AST and total bilirubin, and the 
composite endpoint of ALT or AST, total bilirubin, and ALP, participants will be counted once 
when the criteria are met at the same postbaseline visit date. The denominator is the number of 
participants in the Safety Analysis Set with nonmissing postbaseline value of the tests in 
evaluation at the same postbaseline visit date. 
Listings of liver-related laboratory tests will be provided.
7.3.
Vital Signs and Respiratory Status
Descriptive statistics will be provided by treatment group for vital signs (including pulse rate, 
respiratory rate and blood pressure) as follows:

Baseline value

Values at each postbaseline visit

Change from baseline at each postbaseline visit
A baseline value will be defined as the last available value collected on or prior to the date/time 
of first dose of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value. 
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3. No formal statistical testing is planned.


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A by-participant listing of vital signs (including pulse rate, temperature, blood pressure, height, 
weight, and respiratory rate) and respiratory status (including SpO2) will be provided by 
participant ID number and visit in chronological order. 
7.4.
Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the World Health Organization (WHO) Drug dictionary.
Concomitant medications are defined as medications taken while a participant took study drug. 
Use of concomitant medications will be summarized by preferred name using the number and 
percentage of participants for each treatment group. A participant reporting the same medication 
more than once will be counted only once when calculating the number and percentage of 
participants who received that medication. The summary will be ordered by preferred name in 
descending overall frequency. For drugs with the same frequency, sorting will be done 
alphabetically.
For the purposes of analysis, any medications with a start date prior to or on the first dosing date 
of study drug and continued to be taken after the first dosing date, or started after the first dosing 
date but prior to or on the last dosing date of study drug will be considered concomitant 
medications. Medications started and stopped on the same day as the first dosing date or the last 
dosing date of study drug will also be considered concomitant. Medications with a stop date prior 
to the date of first dosing date of study drug or a start date after the last dosing date of study drug 
will be excluded from the concomitant medication summary. If a partial stop date is entered, any 
medication with the month and year (if day is missing) or year (if day and month are missing) 
prior to the date of first study drug administration will be excluded from the concomitant 
medication summary. If a partial start date is entered, any medication with the month and year 
(if day is missing) or year (if day and month are missing) after the study drug stop date will be 
excluded from the concomitant medication summary. Medications with completely missing start 
and stop dates will be included in the concomitant medication summary, unless otherwise 
specified. Summaries will be based on the Safety Analysis Set. No formal statistical testing is 
planned.
7.5.
Other Safety Measures
Renal replacement therapy during the study will be listed.
A data listing will be provided for participants experiencing pregnancy during the study.
7.6.
Changes from Protocol-Specified Safety Analyses
There are no deviations from the protocol-specified safety analyses.


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9.
REFERENCES
Koch GG, Carr GJ, Amara IA, Stokes ME, Uryniak TJ. Categorical Data Analysis. Chapter 13 in 
Berry, D.A. (ed.).  Statistical Methodology in the Pharmaceutical Sciences. New 
York: Marcel Dekker, Inc., 1989:pp. 414-21. 


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10.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.


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


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


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Appendix 1.
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
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
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


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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)
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.
a
Focused medical history will include date of first symptoms, overall symptoms, exposure source, demographics, baseline characteristics, concomitant medications, kidney or 
other transplant history, and allergies. If available, up to 3 SCr values prior to COVID-19 illness (eg, within the previous 6 months) should be provided. Document 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 determined by PCR via 1 validated assay at a local laboratory, if not performed within the last 4 calendar days.
c
Includes heart rate, temperature, and blood pressure.
d
Respiratory status includes respiratory rate and oxygenation: see protocol Sections 6.2.1, 6.2.2, and 6.4.
e
Pulmonary radiographic imaging may be performed within 72 hours, if not already available and if needed to satisfy eligibility criteria.
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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 amenon-hea of:C:: 12 months may also be considered 
postmenopausal if theit· follicle stitnulating hormone (FSH) level is in the postmenopausal range > 40 IU/L and they are not using hormonal contraception or ho1monal 
replacement therapy. Results from within 48 hours prior to screening are acceptable. 
h 
Chemistiy: alkaline phosphatase, AST, ALT, total bilimbin, total protein, albumin, lactate dehydrogenase, creatine phosphokinase, bicarbonate, blood urea nih'ogen, calcium, 
chloride, creatinine, glucose, lipase, magnesium, phosphorus, potassium, sodium, tu-ic acid. Results from within 48 hours p1-ior to screening are acceptable. 
Hematology: complete blood count with differential, hemoglobin and/or hematocrit, platelets. Results from within 48 hours p1-ior to screening are acceptable. 
Coagulation performed by centi'al lab: international n01malized ratio, prothrombin titue, activated partial thromboplastin tune, D-ditner, fibrinogen. Results from within 
48 holU's p1-ior to screening are acceptable. 
k 
RRT will be measured at screening through Day 29 or until discharge from inpatient hospitalization, as well as at the Day 60 phone follow-up. 
1 
Naso Im 
geal swab collection for vit·ologic SARS-CoV-2 testing for a1tici ants on Da s 1 3 5 7 14 21 and 29 or until discharoe whichever is earlier. 
, 
I 
q 
I on mvas1ve mec an1ca vent1 ation at scre.enmg, pa1t1c1pant s ou 
e exc u e 
·om e stu y. 
r 
For participants on intermittent RRT, laborato1y safety assessments should be drawn before dialysis on the day of dialysis. 
s 
Refer to protocol Inclusion C1-ite1-ion #5 to detefll!llle the need for a confin11ato1y SCr evaluation. 
Pa1ticipants who are oliguric are not requit·ed to provide a tu-ine sample. 
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Appendix 2.
Programming Specifications
1) If the age from the Day 1 eCRF is not available, age will be calculated as follows:
Only year is provided for the date of birth (DOB). Use July 1 for the month and day.
a) AGE (years) is calculated from the number of days between the DOB and Study Day 1,
b) Use the SAS INTCK function to determine the number of “1st-of-month days” 
(eg, January 1st, February 1st, March 1st) between DOB and Day 1 (inclusive),
c) Divide the result in (b) by 12,
AGE = the integer of the result in (c),
Age for laboratory test reference range will be based on the age at the sample collection 
date.
2) All screened participants refer to all participants who are screened (ie, with non-missing 
screening date) and have a screening number. For summaries the same participant is counted 
only once.
3) Screen failure participants are the participants who were screened and answered “No” for any 
inclusion criteria or “Yes” for any exclusion criteria regardless of which version of protocol 
the participant was consent to.
4) Participants in the randomized analysis set are defined as participants randomized into the 
study. IXRSRAND is the source to determine whether the participant is randomized (ie, 
participant with non-missing RGMNDTN in the IXRSRAND dataset), and confirmed by the 
eCRF ENROLL dataset (ie, ENROLLYN = “Yes” in ENROLL dataset).
5) Randomized treatment (ie, TRT01P in ADSL) is derived from IXRSRAND, while actual 
treatment received (ie, TRT01A in ADSL) is assigned as the randomized treatment if 
participant took at least 1 dose of study drug and assigned as blank if the participant was 
never dosed.
6) In the disposition table, the reasons for premature discontinuation are displayed in the order 
as they appear on the eCRF.
7) Body mass index (BMI) 
BMI will be calculated only at baseline as follows:
BMI = (weight [kg]) / (height [meters]2)
Baseline height and weight will be used for this calculation if available


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8) TEAE
Events with Missing Onset Day and/or Month
An event is considered treatment emergent if all of the following 3 criteria are met:
i.
The month and year (or year) of onset date is the same as or after the month and year 
(or year) of the first dose of study drug, and
ii.
The month and year (or year) of the onset date is the same as or before the month and 
year (or year) of the 30th day after the date of the last dose of study drug, and
iii.
End date is as follows: 
The (complete) end date is on or after the first dose date, or
The month and year (or year) of end date is the same or after the month and year 
(or year) of the first dose of study drug, or
End date is completely missing 
Events with Completely Missing Onset Date
An AE with a completely missing onset date is defined as TEAE if end date meets any of the 
3 criteria specified above.
9) Baseline risk factor
Selected medical history will be summarized as baseline risk factor and be included as 
subgroups in analysis. The risk factor of “current cancer” for a participant is defined as a 
medical history of one of these diseases:
At least 1 ongoing medical history record with MedDRA PT (mh.MDRPT) in the 
following selected PT listing for the corresponding disease with start date on or prior to 
the first dose date;
At least 1 ongoing AE record with MedDRA PT (ae.MDRPT) in the following selected 
PT listing for the corresponding disease with start date on or prior to the first dose date.
Other risk factors for a participant is defined as a medical history of one of these diseases:
At least 1 medical history record with MedDRA PT (mh.MDRPT) in the following 
selected PT listing for the corresponding disease with start date on or prior to the first 
dose date;
At least 1 AE record with MedDRA PT (ae.MDRPT) in the following selected PT listing 
for the corresponding disease with start date on or prior to the first dose date. If the start 
date is incomplete but the month and year (or year alone) of the start date is the same as 
or before the month and year (or year alone) of the first dosing date of study drug, the 
event will be included. If the start date is completely missing, the event will be included.


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If the ongoing status is missing for an event:
If the end date is completely missing and start date is the same as or before the first 
dosing date of the study drug, the event will be included;
If the end date is completely missing and start date is after the first dosing date of the 
study drug, the event will not be included;
If the end date is incomplete but the month and year (or year alone) of the end date is the 
same as or after the month and year (or year alone) of the first dosing date of study drug, 
the event will be included;
If the end date is incomplete but the month and year (or year alone) of the end date is 
before the month and year (or year alone) of the first dosing date of study drug, the event 
will not be included.
A variable for each of the risk factors will be added to raw Medical History and Adverse Events 
datasets. A medical history or an AE record will be flagged for a risk factor if its MedDRA PT is 
included in the prespecified PT list for the corresponding disease of interest, which includes all 
PTs from the narrow or broad search of the following SMQs under MedDRA 25.0 provided by
Gilead GLPS and reviewed by Gilead medical monitors.
Disease of Interest
SMQ or MedDRA HLT Source
Chronic lung disease
HLT of bronchospasm and obstruction
Hypertension
Hypertension (SMQ)
Cardiovascular or 
cerebrovascular disease
Ischaemic central nervous system vascular conditions (SMQ); Myocardial 
infarction (SMQ);
Other ischaemic heart disease (SMQ)
Diabetes mellitus
Hyperglycaemia/new onset diabetes Mellitus (SMQ)  
Immunocompromised state
HLGT for “Immunodeficiency syndromes”
Chronic liver disease
search name “Chronic liver disease excluding transient_acute events and 
nonspecific signs_symptoms”
Current cancer  
Malignancies (SMQ)
10) Details on SCr and BUN record exclusion for sensitivity analysis
SCr and BUN will only be analyzed for participants who are not on RRT at baseline. 
RRT at baseline:
RRT started within 3 days of first dose is considered RRT at baseline. An RRT record with an 
end date prior to the first dose date - 3 days (or 72 hours if time available) or a start date/time 
after the first dose date/time will not be considered a baseline RRT record; otherwise, the record 
will be considered baseline.  


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SCr/BUN record exclusion (for participants who are not on RRT at baseline):
Any SCr/BUN records from an RRT start to end + 3 days will be excluded from analysis. 
If both date and time are collected for RRT and labs, only date will be used, with 1 exception 
below:
If an SCr/BUN record is collected on the first dose date and prior to first dose time, and the 
participant’s first RRT starts on the first dose date but after first dose time, then this lab record 
will not be excluded.  
RRT date: 
A missing end date of a hemodialysis record will be imputed using the hemodialysis start date.
If an end date is missing for a CVVH record: 

If this record is followed by another RRT (CVVH or hemodialysis) record, then the end date 
of this CVVH record will be imputed as the start date of the subsequent RRT record;

If this record is the last available or the only RRT record for a participant:
If the participant died after the start of this CVVH record, then the end date of this CVVH 
record will be imputed as the death date;
Otherwise, the end date of this CVVH record will not be imputed, and all the SCr and 
BUN records after the start date of this CVVH record will be excluded from analysis. 
11) Details on coagulation lab record exclusion for sensitivity analysis
Any coagulation lab records under the influence of anticoagulation medications will be excluded 
from analysis. For coagulation lab record exclusion, the start/end date of anticoagulation 
medications will be used. An anticoagulation medication may be taken chronically prior to 
and/or during the study.
Anticoagulation medication date:
If a medication end date is missing, the medication will be considered as “ongoing”, and all 
coagulation lab records after the medication start date will be excluded from analysis. 
If a medication start date is missing, all coagulation lab records will be considered after the 
medication start date. 
For a partial medication end date:

If only date is missing, then the date will be imputed as the last date of the month;


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
If both month and date is missing, then the month and date will be imputed as December 31st 
of the year.
For a partial medication start date: 

If only date is missing, then the date will be imputed as the first date of the month;

If both month and date is missing, then the month and date will be imputed as January 1st of 
the year.
12) Treatment difference in percentages not adjusted by stratum
The percentage difference between two treatment groups and its 95% CIs are calculated 
based on the unconditional exact method using 2 inverted 1-sided tests in SAS v9.3 or above. 
The following SAS code will be used to compute cell counts and p-values. 
data example;
input  grp trt $  outcome $ count ;
datalines;
1       Treat-A        2-Fail        x     
1       Treat-A        1-Succ      xxx     
1       Treat-B        2-Fail        x     
1       Treat-B        1-Succ      xxx     
run;
proc freq data = example;
table trt*outcome /riskdiff(CL=(exact)) alpha=0.05;
weight count; exact RISKDIFF(METHOD=SCORE);
output out=ciexact(keep=_RDIF1_ XL_RDIF1 XU_RDIF1 _RSK11_  _RSK21) riskdiff;
run;
data final(keep=A1 B1 Estimate LowerCL UpperCL ocharc1);
set ciexact;
label Estimate ="Percentage Difference"
LowerCL = "95% Lower Confidence Limit"
UpperCL = "95% Upper Confidence Limit"
A1 = "Percentage of Success in Treat-A"
B1 = "Percentage of Success in Treat-B";
Estimate=100*_RDIF1_;
LowerCL = 100*XL_RDIF1;
UpperCL = 100*XU_RDIF1;
A1 = 100*_RSK11_;
B1 = 100*_RSK21_;
ocharc1 = right(compress(put(Estimate,8.1)) || '% (' || compress(put(LowerCL,8.1)) || '% 
to ' || compress(put(UpperCL,8.1)) || '%)');
run;


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13) Difference in proportions between treatment groups adjusted by stratum
The 95% confidence interval for difference in between treatment groups will be calculated based 
on the stratum-adjusted Mantel-Haenszel (MH) proportion as described as follows {Koch 1989}, 
where the stratification factors include ESKD (Yes, No), High-flow oxygen requirement (Yes, 
No), and region (US, ex-US):
P1 – P2  Z(1-α/2 ) * SE(P1 – P2),
where 

(P1 – P2) = 

h
h
h
w
d
w
, is the stratum-adjusted MH proportion difference, where 
hd  = 
h
h
p
p
2
1 
 is the difference in the proportions of  Treatment Groups 1 and 2 in stratum 
h.

hw  = 
h
h
h
h
n
n
n
n
2
1
2
1

, is the weight based on the harmonic mean of sample size per treatment 
group for each stratum where 
h
n1  and 
h
n2  are the sample sizes of the 
Treatment Groups 1 and 2 in stratum h. 

SE(P1 – P2) = 
2
2
*
2
*
2
1
*
1
*
1
)
(
1
)
1(
1
)
1(











h
h
h
h
h
h
h
w
n
p
p
n
p
p
, where 
1
5.0
1
1
*
1



h
h
h
n
m
p
 and 
1
5.0
2
2
*
2



h
h
h
n
m
p
. 
h
m1  and 
h
m2  are the number of participants with event interest at Day 29 
in Treatment Groups 1 and 2 in stratum h. 

α = 0.05 for this study 

Z(1-α/2 ) = Z0.975 = 1.96 is the 97.5th percentile of the normal distribution
Note that if the computed lower confidence bound is less than –1, the lower bound is defined as 
–1. If the computed upper confidence bound is greater than 1, the upper bound is defined as 1. 
i-


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To facilitate SAS macro use, a single stratum variable could be defined as: 
ESKD requiring chronic dialysis
High-flow oxygen requirement
Region
Stratum
Yes
No
US
1
Yes
No
ex-US
2
Yes
Yes
US
3
Yes
Yes
ex-US
4
No
No
US
5
No
No
ex-US
6
No
Yes
US
7
No
Yes
ex-US
8
14) Clarification for SE(P1-P2) Calculation in 13).

if n1h or n2h > 1 the denominator n1h − 1 or n2h − 1 was calculated as indicated in the 
formula;

if n1h or n2h =1, the corresponding n1h or n2h will be adjusted to 2, then corresponding 
denominator [(n1h − 1) or (n2h − 1)] is 1;

if n1h or n2h = 0, then the corresponding stratum will be ignored, will not be included in the 
calculation, thus the proportion difference and 95% CI are still calculable.
15) Kidney disease status definition
Kidney disease data at baseline are collected in this study, including: history of CKD and 
ongoing AKI from the Medical History CRF form, ESKD status at Screening from the 
ENROLLMENT CRF form, and renal transplant history from the Transplant History CRF form. 
Expected data patterns are as follows (renal transplant history can be present or absent for any of 
these combinations):
Ongoing AKI 
(from MH CRF 
question)
History of CKD 
(from MH CRF 
question)
ESKD status at Screening
(from ENROLLMENT 
CRF)
Kidney Disease 
Status
1
Yes
Any
No
AKI
2
No
Yes
No
CKD
3
Any
Any
Yes
ESKD


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Kidney disease status is defined as: 

AKI: the 1st row of the above table, ie, ongoing AKI with or without history of CKD 

CKD: the 2nd row of the above table, ie, history of CKD without ongoing AKI 

ESKD: the 3rd  row of the above table. 
16) For demographics tables, “Not Permitted” will be excluded from percentage for detailed race 
categories summary (ie, race categories collected on eCRF). For combined Race Category 
(e.g. Asian, White, Black, Other), “Not Permitted” is included in “Other” and “Other” will be 
included in the count of percentage.
17) For calculation of peak serum creatinine (SCr) through Day 29 (among those without ESKD 
at baseline), (1) baseline records will not be included; (2) Day 1 postdose is included in the 
calculation; (3) for multiple records within one day, the observed record with max SCr will 
be selected; (4) For multiple days has the same highest value, the earliest will be picked. 
18) Death date imputation
For a partial death date where the year and month are available but the date is missing, the 
following imputation will be performed:

If the latest clinical date (ie, the latest of study drug start dates and end dates, the in-person or 
phone visit dates, the vital sign and the laboratory collection dates, including the Day 60 
phone follow-up visit date) falls into the same year/month of death, then this latest clinical 
date will be used to impute the date of death;

If the latest clinical date falls into the same year, but a prior month of death, then the 1st of 
the month of death will be the imputed date of death;

If the latest clinical date falls into a prior year of death, then the 1st of the month of death will 
be the imputed date of death.
19) The precision in reporting numerical values should be as follows: 
Raw measurements will be reported the same as the data captured electronically or on the 
eCRF.
Standard deviation and standard error will be reported to one more significant decimal place 
than the raw measurement.
Mean, median, minimum, Q1, Q3, maximum, 95% CIs will be reported to the same number 
of decimal places of the raw measurements. 
If records for the same lab use different decimal places, the decimal place with majority 
records would be used.
Exceptions may be considered.  


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20) Graded Laboratory Abnormalities Summary
The following labels will be used for laboratory abnormalities and Grade 3 or 4 laboratory 
abnormalities summary tables and listings:
Battery
Lab Test Label Used in 
l-labtox Listing
Toxicity 
Direction
Lab Test Label Used in 
t-labtox Table
Hemoglobin
Decrease
Hemoglobin (Decreased)
Lymphocytes
Decrease
Lymphocytes (Decreased)
Hematology
Neutrophils
Decrease
Neutrophils (Decreased)
Platelets
Decrease
Platelets (Decreased)
WBC
Decrease
WBC (Decreased)
Albumin
Decrease
Albumin (Decreased)
Alkaline Phosphatase
Increase
Alkaline Phosphatase (Increased)
ALT
Increase
ALT (Increased)
AST
Increase
AST (Increased)
Bicarbonate
Decrease
Bicarbonate (Decreased)
Corrected Calcium
Increase
Corrected Calcium (Hypercalcemia)
Corrected Calcium
Decrease
Corrected Calcium (Hypocalcemia)
Creatine Kinase (CK)
Increase
Creatine Kinase (Increased)
Creatinine
Increase
Creatinine (Increased)
Lipase
Increase
Lipase (Increased)
Magnesium
Decrease
Magnesium (Hypomagnesemia)
Chemistry
Phosphate
Decrease
Phosphate (Hypophosphatemia)
Serum Glucose
Increase
Serum Glucose (Hyperglycemia)
Serum Glucose 
Decrease
Serum Glucose (Hypoglycemia)
Serum Potassium
Increase
Serum Potassium (Hyperkalemia)
Serum Potassium
Decrease
Serum Potassium (Hypokalemia)
Serum Sodium
Increase
Serum Sodium (Hypernatremia)
Serum Sodium
Decrease
Serum Sodium (Hyponatremia)
Total Bilirubin
Increase
Total Bilirubin (Hyperbilirubinemia)
Uric Acid
Increase
Uric Acid (Hyperuricemia)
Prothrombin Intl. 
Normalized Ratio (INR)
Increase
Prothrombin Intl. Normalized Ratio (Increased)
Prothrombin Time (PT)
Increase
Prothrombin Time (Increased)
Coagulation
Activated partial 
thromboplastin time 
(aPTT)
Increase
Activated partial thromboplastin time 
(Increased)


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21) SAS codes for the treatment comparison for demographics and baseline characteristics tables.
CMH test for nominal variable (Y), the p-value from the general association test should be 
used for nominal variables:
proc freq;
tables trt * Y /cmh; /*general association test*/
run;
CMH test for ordinal variable (Y), the p-value from the row mean score test should be used 
for ordinal variables:
proc freq;
tables trt * Y / cmh2 ; /*row mean score test*/
run;
Wilcoxon rank sum test for continuous variable (Y), the p-value from the normal 
approximation two-sided test should be used for continuous variables:
proc npar1way wilcoxon;
class trt; 
var Y;
run;
22) Proportional Odds
A proportional odds model including treatment as the independent variable and baseline score as 
a continuous covariate to compare the treatment groups:
proc logistic;
class trt/ param=ref order=data;
model outcome(descending)= trt baseline;
run; 
A proportional odds model including treatment as the independent variable to compare the 
treatment groups (without covariate):
proc logistic;
class trt/ param=ref order=data;
model outcome(descending)= trt;
run;
where outcome is the ordinal scale response at Day 15 and Day 29.


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23) Cox model :
a) with stratification factors as covariates
proc phreg;
class trt strat1 strat2 strat3;
model aval*cnsr(1) = trt strat1 strat2 strat3 /risklimits = wald;
ods output  ParameterEstimates=Est1 ModelANOVA = pvout1;
run;
b) with no stratification factors as covariates
proc phreg;
class trt;
model aval*cnsr(1) = trt /risklimits = wald;
ods output  ParameterEstimates=Est1 ModelANOVA = pvout1;
run;
24) log-rank test
Log-rank test between treatment groups: 
proc lifetest;
time aval*cnsr(1);
strata trt;
run;
The binary indicator variable (cnsr) with a value of 0 indicates the time to the event of interest is 
complete or 1 indicates the time to the event is censored.
25) Stratified log-rank test
Log-rank test between treatment groups: 
proc lifetest;
time aval*cnsr(1);
strata strat1 strat2 strat3/group=trt;
run;
The binary indicator variable (cnsr) with a value of 0 indicates the time to the event of 
interest is complete or 1 indicates the time to the event is censored. 


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26) Competing risk analysis
The following SAS code will be used to generate the cause-specific hazard ratio and 95% 
confidence intervals for the competing risk analysis:
proc phreg;
class trt strat1 strat2 strat3;
model aval* cnsr (1, 2) = trt strat1 strat2 strat3 / rl;
hazardratio “Cause-specific hazard” trt;
run;
where cnsr  = 0 if the participant had the event; cnsr = 2 if the participant died prior to having 
the event, and cnsr  =1 if the participant did not have the event and did not die. 
SAS codes to obtain a cumulative incidence function plot and dataset for further processing 
for time to first event table: 
proc lifetest outcif=outcif plots=cif;
strata trt;
time aval* cnsr (1) / failcode = 0;*Note: this produces data for the event of interest only;
run;
SAS code to obtain support tables: 
proc univariate;
 by trt cnsr;
 var aval;
 output pctlpre=P_ min=min max=max pctlpts= 10, 25, 50, 75, 90;
run;
27) SAS code for stratified 2-sided Wilcoxon Rank sum test (stratified on baseline result)
proc freq;
   table base*trt*aval/cmh2 scores=modridit;
run;
where BASE is the baseline value.
28) SAS code for ANCOVA:
ods output ParameterEstimates=out1 LSMeans=out2 LSMeanCL=out3 
LSMeanDiffCL=out4; 
proc glm data=dat1 plots=none;
  class trt;
  model DAVG = trt base / solution;
  lsmeans trt / stderr cl pdiff;
  run;
ods output close; quit;


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GS-US-540-5912 Statistical Analysis Plan - Final Analysis 
29) SAS code for CMH test and estimates with strntification factors adjustment: 
proc freq data=dat 1; 
tables strntl *strat2*strat3*tii*Y/ list cmh; 
ods output cmh=cmhpval CommonRelRisks=risk; 
nm; 
Version 1.0 
30) Renal and hepatic adverse events include prefened tenns from search te1m list 'Acute Renal 
Failure (SMQ)' and search te1m list 'Acute and non-infectious liver events' Med.DRA 25.0. 
31) Vital signs, and SCr collected after Day 29, PCR collected after day 44 will be assigned to 
"Post Day 29". 
33) For coagulation laborato1y tests, both local and Covance lab records are collected in the data. 
In a visit where both Covance and local lab records are collected, Covance records will be 
picked over local lab records. 
34) Reference ranges are based on Covance laborato1y reference ranges. 
35) COVID-19 medications include the following dmgs: 
Drug name 
Chloroquine 
Hydroxychloroquine 
Lopinavir/ritonavir 
Ribavirin 
Remdesivir 
Bamlanivimab/ etesevimab 
Casirivimab/Imdevimab 
Molnupiravir 
Monoclonal antibodies 
Convalescent plasma 
Sotrovimab 
Ni1matrelvir 
Paxlovid 
Regdanivimab 
Tixagevimab/ cilgavimab 
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22 July 2022 


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with preferred term codes (WHODrug BMAR2022): 
Prohibited PREF 
Codes
Prohibited PREF 
Codes
Prohibited PREF 
Codes
Prohibited PREF 
Codes
Prohibited PREF 
Codes
15665101001
14055301001
13983301001
13980301001
14248901001
15585401001
14068301001
14000901001
15847201001
08968801001
00001001001
15250901001
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08030701001
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11725301001
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13999801001
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01555201001
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14039101001
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11725402001
01555206001
13981201001
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13117801001
01555205001
14004701001
08342601001
14346101001
13118301001
01555203001
14005201001
01555210001
07222101001
13118401001
12336402001
14031101001
14397901001
01555213001


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Prohibited PREF 
Codes
Prohibited PREF 
Codes
Prohibited PREF 
Codes
Prohibited PREF 
Codes
Prohibited PREF 
Codes
13183901001
14396302001
14001401001
14030401001
07244601001
13480201001
14396401001
07841501001
14585201001
06331801001
13480202001
14396501001
09304401001
14155601001
07209901001
14001301001
14396502001
09304402001
13979801001
15464401001
14001302001
14397801001
01445608001
15350501001
15429001001
14001303001
13975801001
12759302001
01445601001
01759101001
15363001001
14849201001
14033001001
01445604001
14359501001
15363002001
13776401001
12759301001
01445609001
15267901001
15616901001
14398601001
14148601001
01445605001
 
00072601001
14398701001
14148501001
01445606001
 
00072602001
15290001001
15603201001
01445607001
 
00072603001
15868501001
13982501001
01445602001
 
11725301001
13157101001
12734302001
01445603001
 
11725302001
14404701001
12759102001
15960101001
 
12881901001
14399701001
12689502001
12771001001
 
14693401001
14399801001
13111502001
13947001001
 
15440701001
15378701001
14040601001
07251001001
 
15469801001
14847801001
12734301001
07339901001
 
15470001001
12336401001
12759101001
09018701001
 
15326101001
14848001001
14152701001
09018702001
 
15892101001
14396301001
14165501001
14213701001
 
15748501001
13826001001
14053001001
14031901001
 
15892101001
14400001001
13109601001
13981601001
 
15400501001
14400002001
12689501001
14165301001
 
14269001001
13840901001
13111501001
14055901001
 
00816701001
15900001001
14228101001
14055902001
 
06821701001
13696801001
14151501001
15334201001
 
12751901001
14982301001
14279401001
15583201001
 
12751902001
15578501001
14182701001
08745601001
 
13389401001
14400101001
14031501001
14741401001
 
13485001001
14400102001
14048101001
15325601001
 
13633501001
14955501001
13111401001
01555208001
 
13709401001
14400201001
14279402001
08290701001
 


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Prohibited PREF 
Codes
Prohibited PREF 
Codes
Prohibited PREF 
Codes
Prohibited PREF 
Codes
Prohibited PREF 
Codes
13769601001
14400202001
14216301001
14194301001
 
13769901001
15502802001
13110601001
15269501001
 
13770201001
15502801001
13111503001
14410101001
 
13770901001
14400301001
13981901001
14183101001
 
13771401001
14400302001
13982601001
14039401001
 
13772801001
15868401001
13110701001
13980401001
 
15464401001
01402505001
13110702001
01555209001
 
01612901001
01612906001
14000501001
15500901001
 
01612904001
01555204001
14030001001
15261201001
 
01612903001
14193001001
14023901001
07872901001
 
01612907001
14054001001
14034301001
15520801001
 
01612911001
14054801001
15927901001
15539901001
 
01612902001
14181501001
13980101001
15578201001
 
01612909001
12759202001
14032301001
15628001001
 
01612910001
14666301001
14032501001
15536601001
 
01612905001
14000401001
15388901001
07252301001
 
01612908001
12759201001
14407901001
01601501001
 
14022001001
14032001001
14997401001
14972001001
 
14156901001
14032401001
14151801001
13978201001
 
14149701001
15632601001
13979301001
15586901001
 
36) Hypersensitivity including Infusion-Related Reaction includes MedDRA Terms 
(MedDRA 25.0) listed in the following table:
MedDRA Term Name
MedDRA Term Name
MedDRA Term Name
MedDRA Term Name
Acquired C1 inhibitor 
deficiency
Cross sensitivity 
reaction
Injection site urticaria
Skin necrosis
Acute generalised 
exanthematous pustulosis
Cutaneous vasculitis
Injection site vasculitis
Skin reaction
Administration related 
reaction
Dennie-Morgan fold
Instillation site 
hypersensitivity
Skin test positive
Administration site 
dermatitis
Dermal filler reaction
Instillation site rash
Solar urticaria
Administration site eczema
Dermatitis
Instillation site urticaria
Solvent sensitivity


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MedDRA Term Name
MedDRA Term Name
MedDRA Term Name
MedDRA Term Name
Administration site 
hypersensitivity
Dermatitis acneiform
Interstitial granulomatous 
dermatitis
Stevens-Johnson 
syndrome
Administration site rash
Dermatitis allergic
Intestinal angioedema
Stoma site 
hypersensitivity
Administration site recall 
reaction
Dermatitis atopic
Iodine allergy
Stoma site rash
Administration site 
urticaria
Dermatitis bullous
Kounis syndrome
Stridor
Administration site 
vasculitis
Dermatitis contact
Laryngeal oedema
Swelling face
Allergic bronchitis
Dermatitis exfoliative
Laryngitis allergic
Swelling of eyelid
Allergic colitis
Dermatitis exfoliative 
generalised
Laryngospasm
Swollen tongue
Allergic cough
Dermatitis herpetiformis
Laryngotracheal oedema
Symmetrical drug-related 
intertriginous and flexural 
exanthema
Allergic cystitis
Dermatitis infected
Limbal swelling
Throat tightness
Allergic eosinophilia
Dermatitis psoriasiform
Lip oedema
Tongue oedema
Allergic gastroenteritis
Device allergy
Lip swelling
Toxic epidermal 
necrolysis
Allergic hepatitis
Dialysis membrane 
reaction
Mast cell activation 
syndrome
Toxic skin eruption
Allergic keratitis
Distributive shock
Mast cell degranulation 
present
Tracheal oedema
Allergic lymphangitis
Documented 
hypersensitivity to 
administered product
Medical device site 
dermatitis
Type I hypersensitivity
Allergic oedema
Drug eruption
Medical device site 
eczema
Type II hypersensitivity
Allergic otitis externa
Drug hypersensitivity
Medical device site 
hypersensitivity
Type III immune complex 
mediated reaction
Allergic otitis media
Drug provocation test
Medical device site rash
Type IV hypersensitivity 
reaction
Allergic pharyngitis
Drug reaction with 
eosinophilia and 
systemic symptoms
Medical device site recall 
reaction
Urticaria
Allergic reaction to 
excipient
Eczema
Medical device site 
urticaria
Urticaria cholinergic
Allergic respiratory 
disease
Eczema infantile
Mouth swelling
Urticaria chronic


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MedDRA Term Name
MedDRA Term Name
MedDRA Term Name
MedDRA Term Name
Allergic respiratory 
symptom
Eczema nummular
Mucocutaneous rash
Urticaria contact
Allergic sinusitis
Eczema vaccinatum
Multiple allergies
Urticaria papular
Allergic stomatitis
Eczema vesicular
Nephritis allergic
Urticaria physical
Allergic transfusion 
reaction
Eczema weeping
Nikolsky's sign
Urticaria pigmentosa
Allergy alert test positive
Encephalitis allergic
Nodular rash
Urticaria vesiculosa
Allergy test positive
Encephalopathy allergic
Nutritional supplement 
allergy
Urticarial dermatitis
Allergy to 
immunoglobulin therapy
Eosinophilic 
granulomatosis with 
polyangiitis
Oculomucocutaneous 
syndrome
Urticarial vasculitis
Allergy to surgical sutures
Epidermal necrosis
Oculorespiratory 
syndrome
Vaccination site 
dermatitis
Allergy to vaccine
Epidermolysis
Oedema mouth
Vaccination site eczema
Anal eczema
Epidermolysis bullosa
Oral allergy syndrome
Vaccination site 
exfoliation
Anaphylactic reaction
Epiglottic oedema
Orbital swelling
Vaccination site 
hypersensitivity
Anaphylactic shock
Erythema multiforme
Oropharyngeal blistering
Vaccination site rash
Anaphylactic transfusion 
reaction
Erythema nodosum
Oropharyngeal oedema
Vaccination site recall 
reaction
Anaphylactoid reaction
Exfoliative rash
Oropharyngeal spasm
Vaccination site urticaria
Anaphylactoid shock
Eye allergy
Oropharyngeal swelling
Vaccination site vasculitis
Anaphylaxis treatment
Eye oedema
Palatal oedema
Vaccination site vesicles
Angioedema
Eye swelling
Palatal swelling
Vaginal ulceration
Anti-neutrophil 
cytoplasmic antibody 
positive vasculitis
Eyelid oedema
Palisaded neutrophilic 
granulomatous dermatitis
Vancomycin infusion 
reaction
Antiallergic therapy
Face oedema
Palpable purpura
Vascular access site 
dermatitis
Antiendomysial antibody 
positive
Fixed eruption
Pathergy reaction
Vascular access site 
eczema
Application site dermatitis
Flushing
Perioral dermatitis
Vasculitic rash
Application site eczema
Generalised bullous 
fixed drug eruption
Periorbital dermatitis
Vasodilatation
Application site 
hypersensitivity
Giant papillary 
conjunctivitis
Periorbital oedema
Vernal 
keratoconjunctivitis
Application site rash
Gingival oedema
Periorbital swelling
Vessel puncture site rash


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MedDRA Term Name
MedDRA Term Name
MedDRA Term Name
MedDRA Term Name
Application site recall 
reaction
Gingival swelling
Pharyngeal oedema
Vessel puncture site 
vesicles
Application site urticaria
Gleich's syndrome
Pharyngeal swelling
Vulval eczema
Application site vasculitis
Haemorrhagic urticaria
Polymers allergy
Vulval ulceration
Arthritis allergic
Hand dermatitis
Post procedural fever
Vulvovaginal rash
Aspirin-exacerbated 
respiratory disease
Heart rate decreased
Procedural shock
Vulvovaginal ulceration
Atopic cough
Henoch-Schonlein 
purpura
Pruritus allergic
Vulvovaginitis allergic
Atopy
Henoch-Schonlein 
purpura nephritis
Pseudoallergic reaction
Blepharitis allergic
Heparin-induced 
thrombocytopenia
Radioallergosorbent test 
positive
Blood immunoglobulin E 
abnormal
Hyperhidrosis
Rash
Blood immunoglobulin E 
increased
Hypersensitivity
Rash erythematous
Blood pressure decreased
Hypersensitivity 
myocarditis
Rash follicular
Blood pressure diastolic 
decreased
Hypersensitivity 
pneumonitis
Rash macular
Blood pressure diastolic 
increased
Hypersensitivity 
vasculitis
Rash maculo-papular
Blood pressure increased
Hypertension
Rash maculovesicular
Blood pressure systolic 
decreased
Hypotension
Rash morbilliform
Blood pressure systolic 
increased
Idiopathic urticaria
Rash neonatal
Bone cement allergy
Immediate post-injection 
reaction
Rash papulosquamous
Bradyarrhythmia
Immune 
thrombocytopenia
Rash pruritic
Bradycardia
Immune tolerance 
induction
Rash pustular
Bromoderma
Implant site dermatitis
Rash rubelliform
Bronchial obstruction
Implant site 
hypersensitivity
Rash scarlatiniform
Bronchospasm
Implant site rash
Rash vesicular
Bullous haemorrhagic 
dermatosis
Implant site urticaria
Reaction to azo-dyes


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MedDRA Term Name
MedDRA Term Name
MedDRA Term Name
MedDRA Term Name
Catheter site dermatitis
Incision site dermatitis
Reaction to colouring
Catheter site eczema
Incision site rash
Reaction to excipient
Catheter site 
hypersensitivity
Infusion related 
hypersensitivity reaction
Reaction to flavouring
Catheter site rash
Infusion related reaction
Reaction to food additive
Catheter site urticaria
Infusion site dermatitis
Reaction to preservatives
Catheter site vasculitis
Infusion site eczema
Reaction to sweetener
Chronic eosinophilic 
rhinosinusitis
Infusion site 
hypersensitivity
Rhinitis allergic
Chronic hyperplastic 
eosinophilic sinusitis
Infusion site rash
Scleral oedema
Circulatory collapse
Infusion site recall 
reaction
Scleritis allergic
Circumoral oedema
Infusion site urticaria
Scrotal dermatitis
Circumoral swelling
Infusion site vasculitis
Scrotal oedema
Conjunctival oedema
Injection related reaction
Serum sickness
Conjunctivitis allergic
Injection site dermatitis
Serum sickness-like 
reaction
Contact stomatitis
Injection site eczema
Shock
Contrast media allergy
Injection site 
hypersensitivity
Shock symptom
Contrast media reaction
Injection site rash
Sinus bradycardia
Corneal oedema
Injection site recall 
reaction
SJS-TEN overlap
37) COVID-19 vaccines include the following preferred term codes (WHODrug BMAR2022):
Prohibited PREF Codes
Prohibited PREF Codes
Prohibited PREF Codes
00002001001
15268629001
15268666001
06201402001
15268630001
15268667001
06439204001
15268631001
15268668001
06559301001
15268632001
15268669001
06559307001
15268633001
15268670001
13195801001
15268634001
15268671001
13949502001
15268635001
15268672001
13950013001
15268636001
15268673001


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Prohibited PREF Codes
Prohibited PREF Codes
Prohibited PREF Codes
14953401001
15268637001
15268674001
14953501001
15268638001
15268675001
15092101001
15268639001
15268676001
15268601001
15268640001
15268677001
15268602001
15268641001
15268678001
15268603001
15268642001
15268679001
15268604001
15268643001
15268680001
15268605001
15268644001
15268681001
15268607001
15268645001
15268682001
15268609001
15268646001
15268683001
15268610001
15268647001
15268684001
15268611001
15268648001
15268685001
15268612001
15268649001
15268686001
15268613001
15268650001
15268687001
15268614001
15268651001
15268688001
15268615001
15268652001
15268689001
15268616001
15268653001
15268690001
15268617001
15268654001
15268691001
15268618001
15268655001
15268692001
15268619001
15268656001
15268693001
15268620001
15268657001
90031301001
15268621001
15268658001
15268622001
15268659001
 
15268623001
15268660001
 
15268624001
15268661001
 
15268625001
15268662001
 
15268626001
15268663001
 
15268627001
15268664001
 
15268628001
15268665001
 


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38) Antithrombotic medications include the following drugs:
Drug name
Direct factor Xa inhibitors
Direct thrombin inhibitors
Low molecular weight heparins (LMWH) and heparinoids
Other heparins
Other antithrombotic drugs
Platelet aggregation inhibitors, excluding heparin
Thrombolytic drugs
Vitamin K antagonists
Heparins
with preferred term codes (WHODrug BMAR2022): 
Prohibited 
PREF Codes
Prohibited 
PREF Codes
Prohibited 
PREF Codes
Prohibited 
PREF Codes
Prohibited 
PREF Codes
Prohibited 
PREF Codes
Prohibited 
PREF Codes
06259501001
13765501001
12384902001
12353501001
13595102001
11890502001
12800601001
06324201001
13765502001
13825101001
12353502001
11902101001
12829002001
11012901001
06324202001
13766301001
13825102001
12354601001
11902102001
12779502001
13576201001
06297801001
15159701001
13824801001
12354201001
12382602001
12779503001
11885501001
06297802001
15159702001
12385301001
12354202001
12382402001
12779602001
13576701001
06297803001
12430501001
12385501001
12353602001
12382601001
11485302001
90045701001
01551201001
12430502001
12384901001
12353601001
12382401001
11756602001
13185301001
01551202001
11096401001
13824501001
13623001001
12382403001
12150301001
12189002001
05705201001
11096402001
11549402001
12150502001
13749001001
11923801001
12189003001
01369401001
11902001001
11549401001
12150503001
13707401001
12151101001
12189001001
01369402001
11902002001
10534502001
12150501001
13707402001
11902401001
13599601001
01506801001
13600801001
10534501001
11610504001
11890503001
11641801001
13599602001
01506802001
12150602001
12268601001
11610502001
12406404001
13629501001
11442802001
01633201001
12150601001
12268602001
11610002001
12406403001
12150201001
11442801001
01633202001
01384201001
12269902001
11610203001
12382702001
11492701001
12180302001
01633203001
01384202001
12283302001
11610202001
11578403001
13313701001
12646902001
01288601001
11097102001
11177702001
14527702001
11578402001
12151401001
12646901001
01346001001
11678602001
12283301001
12406402001
11096101001
10907301001
00889601001
01384201001
11678601001
12269901001
12456903001
11096102001
11052701001
00889603001
01384202001
11097101001
11177701001
12456902001
12416702001
12286502001
00889602001
07368201001
13431901001
14427201001
12156601001
12416701001
12286501001
11866102001
07368202001
11623502001
14421501001
12156602001
00027701001
13572501001
11866101001
01708301001
11623501001
14488101001
11699802001
00027702001
12150701001
00723702001


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Prohibited 
PREF Codes
Prohibited 
PREF Codes
Prohibited 
PREF Codes
Prohibited 
PREF Codes
Prohibited 
PREF Codes
Prohibited 
PREF Codes
Prohibited 
PREF Codes
01708302001
13629801001
14488102001
11699803001
90006801001
12408701001
12344202001
01353901001
12181303001
01691801001
12186802001
00027705001
12406401001
11643102001
01353902001
12181302001
11699701001
11699602001
00027711001
12457201001
11012902001
06297801001
12181301001
11699702001
11699801001
00027710001
12456901001
13576202001
06297802001
07368201001
12475602001
12186801001
00027704001
12690401001
11885502001
06297803001
07368202001
12475601001
11699601001
00027708001
10999501001
01437701001
01707901001
12472001001
11375501001
14440702001
00027712001
12150901001
01437702001
01707902001
12472002001
11375502001
14440701001
00027707001
12382701001
07957701001
07957501001
11645802001
15876401001
01708201001
12150302001
12151201001
07957702001
07957502001
11645801001
15260602001
01708202001
11923802001
15778101001
00552101001
10679802001
10995602001
15260601001
12231802001
12151102001
12748001001
00552102001
13575901001
10995601001
12424001001
12231801001
11902402001
12517101001
11196102001
13575902001
12747502001
12424002001
11095802001
11641802001
11890501001
11657802001
10679801001
12747501001
10685602001
11095801001
13629502001
12829001001
11173402001
12601302001
12471001001
10685601001
11610503001
12150202001
14455101001
11196101001
12150802001
12471002001
01708301001
13472301001
11492702001
12779501001
11657801001
12150801001
11645702001
01708302001
13472302001
12151402001
12779601001
11173401001
12669701001
11645701001
01353901001
11718202001
10907302001
11485301001
13178201001
12669702001
11729402001
01353902001
11718201001
10907303001
15876301001
05509001001
11681801001
11729401001
07957801001
11610501001
11052702001
15878201001
05509002001
11681802001
12385504001
07957802001
11610001001
12150702001
11756601001
08069601001
12601301001
12385602001
07368001001
11610201001
12408702001
00723701001
08069602001
12430802001
12385601001
12190302001
14527701001
12457202001
13599501001
07579101001
13802202001
12385002001
12190301001
12382902001
12690402001
13720001001
07579102001
12431002001
12385001001
11514301001
12382302001
10999502001
13313601001
08336301001
12431001001
12479901001
11514302001
11885902001
12150902001
12180301001
01486301001
12430801001
12479902001
11732402001
12382301001
12151202001
12188202001
01063701001
13802201001
12385502001
11732301001
12382901001
12748002001
12188201001
00027709001
13802203001
12385503001
11732302001
11885901001
12748003001
12344201001
06563401001
15767701001
12385302001
11732401001
13595301001
12517103001
11643101001
06563402001
15767702001
12384903001
12354602001
13595101001
12517102001
11578401001
01707901001
00075201001
00007401001
00014801001
00014803001
00014804001
01707902001
00723901001
00062601001
00014805001
00014802001
00393001001
39) Figures:
For figures, for a time point where n (sample size) is <= 5, data will not be displayed at that time 
point in the figure, but all data will be included in the corresponding table summary.


GS-US-540-5912-SAP-Final Analysis
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
26-Jul-2022
17:28:10
Clinical Research eSigned
27-Jul-2022
14:25:46
PPD
PPD-