Clinical trial NCT04539262
Conditions: COVID-19
Sponsor: Gilead Sciences
Start date: 2020-09-14; Completion date: 2021-03-22
Enrollment: 156 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to characterize the impact of inhaled remdesivir (RDV) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in participants with early stage coronavirus disease 2019 (COVID-19).

Detailed description:
This study will have multiple parts: Part A, Part B, and Part C. Part B will be conducted if supported by evaluation in healthy volunteers in another Phase 1a Gilead study (GS-US-553-9018). Participants in Part C will be enrolled after review of preliminary safety and available efficacy data from Parts A and B through at least Day 7.

GS-US-553-9018 is a Phase 1a randomized, blinded, placebo-controlled, single- and multiple-dose study in healthy volunteers to evaluate the safety, tolerability, and pharmacokinetics of remdesivir administered by inhalation.

Arms: arm 1: Participants will receive inhaled RDV 31 mg administered daily for 5 days. arm 2: Participants will receive inhaled RDV 31 mg administered daily for 3 days followed by placebo to match RDV daily for 2 days. arm 3: Participants will receive placebo to match inhaled RDV in Part A daily for 5 days. arm 4: Participants will receive inhaled RDV 62 mg administered daily for up to 5 days. arm 5: Participants will receive inhaled RDV 62 mg administered daily for up to 3 days followed by placebo to match RDV daily for 2 days. arm 6: Participants will receive placebo to match inhaled RDV in Part B daily for 5 days. arm 7: Participants will receive inhaled RDV 39 mg administered daily for 5 days. arm 8: Participants will receive placebo to match inhaled RDV in Part C daily for 5 days.
Interventions: intervention 1: Remdesivir (RDV) intervention 2: Placebo
Intervention descriptions: intervention 1: Administered as an aerosolized solution intervention 2: Administered as an aerosolized solution

Protocol documents:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL
Study Title:
A Phase 1b/2a Study in Participants with Early Stage COVID-19 to 
Evaluate the Safety, Efficacy, and Pharmacokinetics of Remdesivir
Administered by Inhalation
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
150732
Not Applicable
NCT04539262
Indication:
COVID-19
Protocol ID:
GS-US-553-9020
Contact Information:
The medical monitor name and contact information will be 
provided on the Key Study Team Contact List.
Protocol 
Version/Date:
Original:
31 July 2020
Amendment 1:
26 August 2020
Amendment 2: 
14 December 2020
Amendment 3:
13 January 2021
This study will be conducted under US Food & Drug Administration investigational new drug 
(IND) regulations (21 Code of Federal Regulations Part 312); however, sites located in the 
European Economic Area and Switzerland are not included under the IND and are considered 
non-IND sites.
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable 
Institutional Review Board or Independent Ethics Committee. The information is only to be 
used by you in connection with authorized clinical studies of the investigational drug 
described in the protocol. You will not disclose any of the information to others without 
written authorization from Gilead Sciences, Inc., except to the extent necessary to obtain 
informed consent from those persons to whom the drug may be administered.
(rJ GILEAiJ 


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TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................................. 2 
PROTOCOL SYNOPSIS .............................................................................................................................................. 5 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................... 13 
I. 
INTRODUCTION .............................................................................................................................................. 16 
1.1. 
Background ............................................................................................................................................ 16 
1.2. 
Remdesivir (ROY; GS-5734) for Inhaled Administration ..................................................................... 16 
1.2.1. 
General Information ............................................................................................................. 16 
1.2.2. 
Additional Clinical Studies of Remdesivir ........................................................................... 17 
1.2.3. 
Rationale for This Study ....................................................................................................... 18 
1.3. 
Rationale for the Dose Selection ............................................................................................................ 19 
1.4. 
Risk/Benefit Assessment for the Study .................................................................................................. 20 
1.5. 
Compliance ............................................................................................................................................ 2 1 
2. 
OBJECTIYES ..................................................................................................................................................... 22 
3. 
STUDY DESIGN ................................................................................................................................................ 23 
3.1. 
3.2. 
3.3. 
3.4. 
3.5. 
3.6. 
3.7. 
3.8. 
3.9. 
Endpoints ............................................................................................................................................... 23 
Study Design .......................................................................................................................................... 24 
Study Treatments ................................................................................................................................... 24 
Safety Review Team .............................................................................................................................. 26 
Duration ofTreatment ............................................................................................................................ 27 
Discontinuation Criteria ......................................................................................................................... 27 
End of Study ........................................................................................................................................... 27 
Poststudy Care ........................................................................................................................................ 27 
Source Data ............................................................................................................................................ 28 
4. 
SUBJECT POPULATION .................................................................................................................................. 29 
4.1. 
Number of Subjects and Subject Selection ............................................................................................ 29 
4.1.1. 
Subject Replacement ............................................................................................................ 29 
4.2. 
Inclusion Criteria .................................................................................................................................... 29 
4.3. 
Exclusion Criteria ................................................................................................................................... 29 
5. 
INYESTIGATIONAL MEDICINAL PRODUCTS ........................................................................................... 3 1 
5.1. 
Randomization, Blinding, and Treatment Codes Access ....................................................................... 3 1 
5.1.1. 
Randomization ..................................................................................................................... 3 1 
5.1.2. 
Blinding ................................................................................................................................ 3 1 
5.1.3. 
Procedures for Breaking Treatment Codes ........................................................................... 32 
5.2. 
Description and Handling of Remdesivir ............................................................................................... 32 
5.2.1. 
Formulation .......................................................................................................................... 32 
5.2.2. 
Packaging and Labeling ....................................................................................................... 33 
5.2.3. 
Storage and Handling ........................................................................................................... 33 
5.3. 
Dosage and Administration of Remdesivir ............................................................................................ 34 
5.4. 
Dispensing, Accountability, and Disposal or Return of Study Treatment .............................................. 34 
5.5. 
Prior and Concomitant Medications ....................................................................................................... 35 
6. 
STUDY PROCEDURES .................................................................................................................................... 36 
6.1. 
Subject Enrollment and Treatment Assignment ..................................................................................... 36 
6.2. 
Pretreatment Assessments ...................................................................................................................... 36 
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6.2.1.
Study Parts A, B, and C: Screening Visit.............................................................................36
6.2.2.
Study Parts A and B: Baseline/Day 1 Assessments..............................................................37
6.3.
Study Parts A and B: Daily Study Assessments (Days 2-5)...................................................................38
6.4.
Study Parts A and B: Follow-Up Assessments (Days 7 and 14)............................................................39
6.5.
Study Parts A and B: Day 28 Follow-Up Assessment (± 5 days) ..........................................................40
6.6.
Study Part C: Baseline/Day 1, Days 3, 5, and 7 Assessments................................................................40
6.7.
Study Part C: Days 2 and 4 Assessments...............................................................................................41
6.8.
Study Part C: Follow-Up Assessments (Days 14 and 28)......................................................................41
6.9.
Chest X-Ray...........................................................................................................................................42
6.10.
FEV1.......................................................................................................................................................42
6.11.
Clinical Laboratory Assessments ...........................................................................................................42
6.12.
Pharmacokinetic Assessments................................................................................................................43
6.13.
Assessments for Early Discontinuation from Study...............................................................................43
6.13.1.
Criteria for Discontinuation of Study Treatment..................................................................43
6.14.
End of Study...........................................................................................................................................44
6.15.
Poststudy Care........................................................................................................................................44
6.16.
Sample Storage.......................................................................................................................................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.
Study Treatments and Gilead Concomitant Therapy Special Situations 
Reports .................................................................................................................................46
7.2.
Assessment of Adverse Events and Serious Adverse Events.................................................................47
7.2.1.
Assessment of Causality for Study Treatments and Procedures...........................................47
7.2.2.
Assessment of Severity ........................................................................................................47
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events.......................................................................................................................................48
7.3.1.
Requirements for Collection Prior to Study Treatment Initiation ........................................48
7.3.2.
Adverse Events.....................................................................................................................48
7.3.3.
Serious Adverse Events........................................................................................................48
7.3.4.
Study Treatment Special Situations Reports ........................................................................48
7.3.5.
Concomitant Therapy Reports..............................................................................................49
7.4.
Reporting Process for Serious Adverse Events and Special Situation Reports......................................49
7.4.1.
Serious Adverse Event Reporting Process ...........................................................................49
7.4.2.
Special Situations Reporting Process ...................................................................................50
7.5.
Gilead Reporting Requirements.............................................................................................................51
7.6.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or 
Serious Adverse Events..........................................................................................................................52
7.7.
Toxicity Management ............................................................................................................................52
8.
STATISTICAL CONSIDERATIONS................................................................................................................54
8.1.
Analysis Objectives and Endpoints........................................................................................................54
8.1.1.
Analysis Objectives..............................................................................................................54
8.1.2.
Primary Endpoint .................................................................................................................54
8.1.3.
Secondary Endpoint .............................................................................................................54
8.2.
Planned Analyses ...................................................................................................................................55
8.2.1.
Interim Analysis ...................................................................................................................55
8.2.2.
Final Analysis.......................................................................................................................56
8.3.
Analysis Conventions.............................................................................................................................56
8.3.1.
Analysis Sets ........................................................................................................................56
8.3.2.
Data Handling Conventions .................................................................................................56
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8.4.
Demographic and Baseline Characteristics Analysis .............................................................................57
8.5.
Efficacy Analysis ...................................................................................................................................57
8.5.1.
Primary Analysis..................................................................................................................57
8.5.2.
Secondary Analyses .............................................................................................................57
8.6.
Safety Analysis.......................................................................................................................................57
8.6.1.
Extent of Exposure...............................................................................................................57
8.6.2.
Adverse Events.....................................................................................................................57
8.6.3.
Laboratory Evaluations ........................................................................................................58
8.7.
Adjustments for Multiplicity..................................................................................................................58
8.8.
Pharmacokinetic Analysis......................................................................................................................58
8.9.
Sample Size............................................................................................................................................58
9.
RESPONSIBILITIES..........................................................................................................................................59
9.1.
Investigator Responsibilities ..................................................................................................................59
9.1.1.
Good Clinical Practice..........................................................................................................59
9.1.2.
Financial Disclosure.............................................................................................................59
9.1.3.
Institutional Review Board/Independent Ethics Committee Review and 
Approval...............................................................................................................................59
9.1.4.
Informed Consent.................................................................................................................59
9.1.5.
Confidentiality......................................................................................................................60
9.1.6.
Study Files and Retention of Records ..................................................................................60
9.1.7.
Case Report Forms...............................................................................................................62
9.1.8.
Investigator Inspections........................................................................................................62
9.1.9.
Protocol Compliance............................................................................................................62
9.2.
Sponsor Responsibilities ........................................................................................................................62
9.2.1.
Protocol Modifications.........................................................................................................62
9.2.2.
Study Report and Publications .............................................................................................63
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................63
9.3.1.
Payment Reporting...............................................................................................................63
9.3.2.
Access to Information for Monitoring..................................................................................63
9.3.3.
Access to Information for Auditing or Inspections ..............................................................64
9.3.4.
Study Discontinuation..........................................................................................................64
10.
REFERENCES ...................................................................................................................................................65
11.
APPENDICES ....................................................................................................................................................66
Appendix 1.
Investigator Signature Page....................................................................................................67
Appendix 2.
Pandemic Risk Assessment and Mitigation Plan....................................................................68
Appendix 3.
Study Procedures Tables ........................................................................................................71
Appendix 4.
Management of Clinical and Laboratory Adverse Events......................................................75
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................76


Remdesivir (RDV; GS-5734T") 
Protocol GS-US-553-9020 
Gilead Sciences, Inc. 
Study Title: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Study Centers 
Planned: 
Objectives: 
CONFIDENTIAL 
PROTOCOL SYNOPSIS 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404 
FINAL 
Amendment3 
A Phase 1b/2a Study in Participants with Early Stage COVID-19 to 
Evaluate the Safety, Efficacy, and Phannacokinetics of Remdesivir 
Administered by Inhalation 
150732 
Not Applicable 
NCT04539262 
Up to approximately 50 centers globally 
The primary objective of this study is: 
• 
To characterize the impact of inhaled remdesivir (RDV) on severe 
acute respiratory syndrome (SARS)-coronavirus (CoV)-2 viral 
load in participants with early stage corona virus disease 2019 
(COVID-19) 
The secondary objectives of this study are: 
• 
To evaluate the safety and tolerability of inhaled Remdesivir for 
Injection fonnulation in participants with early stage COVID-19 
• 
To evaluate the phannacokinetics (PK) of inhaled Remdesivir for 
Injection fonnulation and its metabolites in participants with early 
stage COVID-19 in Parts A and B 
• 
To characterize and evaluate disease progression from baseline 
• 
To characterize the efficacy, safety, and tolerability of Remdesivir 
for Inhalation Solution fonnulation administered with a 
mouthpiece in Part C of the study 
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Study Design:
This is a Phase 1b/2a randomized, blinded, placebo-controlled, 
multicenter study of RDV therapy for outpatients with early stage 
COVID-19 evaluating inhaled RDV (treatment arm) or 
placebo-to-match (PTM) (placebo arm).
The study will feature multiple parts: Part A, Part B, and Part C.
The goal of the study is to evaluate the safety, efficacy, and PK of 
inhaled RDV in participants with early stage COVID-19. Parts A and 
B of the study will evaluate 2 different nominal dosing regimens 
(31 mg in Part A and 62 mg in Part B [Remdesivir for Injection 
formulation]) for up to 5 days of daily dosing. Safety and efficacy of 
an inhaled RDV formulation with reduced sulfobutylether 
β-cyclodextrin sodium (SBECD) content (Remdesivir for Inhalation 
Solution formulation) will be evaluated in Part C of the study. The 
RDV formulation used within each Study Part is as follows:
Study 
Part
Formulation
Volume/Nominal 
Dose (mg)
Duration of 
Nebulization 
(minutes)
Part A
Remdesivir for Injection 
formulation via nebulization
31 mga
17 minutes
Part B
Remdesivir for Injection 
formulation via nebulization
62 mga
34 minutes
Part C
Remdesivir for Inhalation 
Solution formulation via 
nebulization
39 mgb
19 minutes 
a
Sealed Facemask: Nominal dose of 31 mg and 62 mg to achieve a deposited dose of 5 mg
and 10 mg, respectively: Overall delivery efficiency  16.1%.
b
Mouthpiece: Nominal dose of 39 mg to achieve a deposited dose of 10 mg: Overall 
delivery efficiency  25.6%.
The term “inhaled remdesivir” refers to both the Remdesivir for 
Injection formulation and Remdesivir for Inhalation Solution
formulation when administered via nebulization using the LC Sprint. 
Part A: In Part A, approximately 36 participants who meet all 
eligibility criteria will be randomized in a 1:1:1 ratio into one of the 
following 3 treatment groups:
Treatment Group 1: 31 mg inhaled Remdesivir for Injection 
formulation daily for 5 days
Treatment Group 2: 31 mg inhaled Remdesivir for Injection 
formulation daily for 3 days followed by PTM daily for 2 days
Treatment Group 3: PTM daily for 5 days


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Part B: In Part B, if supported by evaluation in healthy volunteers in 
the Phase 1a study, an additional 36 total participants may be 
randomized in a 1:1:1 ratio into one of the following 3 treatment 
groups:
Treatment Group 4: 62 mg inhaled Remdesivir for Injection 
formulation daily for up to 5 days
Treatment Group 5: 62 mg inhaled Remdesivir for Injection 
formulation daily for up to 3 days followed by PTM daily through 
Day 5
Treatment Group 6: PTM daily for 5 days
Part C: Part C of the study will include an expanded safety and 
efficacy assessment of an additional 80 participants. Participants in 
Part C will be enrolled after review of preliminary safety data from 
Parts A and B through at least Day 7. Approximately 80 participants 
will be randomized in a 3:1 ratio into one of the following 2 treatment 
groups: 
Treatment Group 7: 39 mg Remdesivir for Inhalation Solution 
formulation once daily for 5 days by mouthpiece
Treatment Group 8: PTM daily for 5 days by mouthpiece
Number of 
Participants 
Planned:
Part A and Part B: Approximately 36 participants will be enrolled in 
each part.
Part C: Approximately 80 participants will be enrolled.
Target Population:
Parts A and B: Participants ≥18 years of age with polymerase chain 
reaction (PCR)-confirmed early stage COVID-19
Part C: Participants ≥18 years of age with early stage COVID-19
confirmed by nucleic acid testing or direct antigen testing
Duration of 
Treatment:
RDV and/or PTM will be administered for 5 days.
Diagnosis and 
Main Eligibility 
Criteria:
Eligible participants will be at least 18 years of age who meet the 
following eligibility criteria:
Key Inclusion Criteria:

Willing and able to provide written informed consent, or with a 
legal representative who can provide informed consent

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection first confirmed by PCR (Parts A and B) or by nucleic 
acid testing or direct antigen testing (Part C) with sample collected 
≤ 4 days prior to randomization


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
COVID-19 symptom onset ≤ 7 days prior to randomization

Oxygen saturation as measured by pulse oximetry (SpO2) > 94% 
on room air
Key Exclusion Criteria:

Ongoing or prior participation in any other clinical trial of an 
experimental vaccine or treatment for COVID-19

Prior or current hospitalization for COVID-19 or need for 
hospitalization

Treatment of COVID-19 with other agents with actual or possible 
direct antiviral activity against SARS-CoV-2 including IV RDV or 
administration of any SARS-CoV-2 (or COVID-19) vaccine
Patients chronically administered chloroquine or 
hydroxychloroquine for any reason are to be excluded

Requiring oxygen supplementation

Positive pregnancy test

Breastfeeding female

Known hypersensitivity to the study treatment, its metabolites, or 
formulation excipient

Pre-existing pulmonary conditions such as chronic obstructive 
pulmonary disease or asthma (Parts A and B only)
Study Procedures/
Frequency:
At screening, after the participant has provided informed consent, 
assessments will include but are not limited to the following: 
demographic and baseline characteristics, medical history, and 
concomitant medications will be documented. Body weight and height 
will be measured. A urine pregnancy test will be performed for women 
of childbearing potential. Vital signs including heart rate, temperature, 
blood pressure, and SpO2 will be recorded. A complete physical 
examination will be performed.
Study Parts A and B:
On Days 1 through 5, assessments will include a symptom-directed 
physical examination. A 12-lead electrocardiogram (ECG) will be 
performed at Day 1. Vital signs will be measured predose and 
postdose. Concomitant medications and adverse events (AEs) will be 
documented. Laboratory samples will be obtained for safety 
assessments (Days 1, 3, 5) and PK assessments (Days 1, 3, 5).
Nasopharyngeal, oropharyngeal swab samples and saliva samples for 
SARS-CoV-2 testing and possible viral resistance testing will be 
performed on Days 1 through 5. A chest x-ray will be performed at
Day 1 to identify any pulmonary infiltrates. Forced expiratory volume 


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in the first second of expiration (FEV1) will be performed daily during 
treatment days and will be performed both predose and 10 minutes 
postdose. Repeat FEV1 should be performed at 30 minutes postdose if 
there is > 15% reduction in FEV1 at 10 minutes postdose compared 
with the same day predose FEV1. FEV1 assessment may also be 
performed if there is a clinical concern of bronchospasm. Inhaled 
Remdesivir for Injection formulation or PTM will be administered at 
Days 1 through 5. If Day 1 assessments are performed on the same day 
as the screening assessments, procedures need not be repeated.
Participants will complete the adapted InFLUenza Patient-Reported 
Outcome (FLU-PRO©) questionnaire daily (Days 1-14).
On Days 7 and 14, assessments will include a symptom-directed 
physical examination. Vital signs will be measured, concomitant 
medications and AEs will be documented. Laboratory samples will be 
obtained for safety assessments, single PK assessment (Day 7), and 
nasopharyngeal and oropharyngeal swab samples and saliva samples 
for SARS-CoV-2 testing and possible viral resistance testing.
On Day 28, assessments will include review of AEs and concomitant 
medications. The Day 28 follow-up assessments may be completed by 
telephone.
If supported by review of at least 7-day safety data from participants in 
Parts A and B, then the Remdesivir for Inhalation Solution formulation 
will be evaluated in Part C.
Pharmacokinetic Assessments:
Sparse plasma PK assessments will be conducted in all participants at 
selected sites in Parts A and B. Sparse plasma PK samples will be 
collected at Day 1 (end of nebulization, 
 
) and Day 3 (predose and end of nebulization).
Up to 6 participants/group in Part A and Part B will have intensive PK 
assessments. Intensive PK samples will be collected at Day 1 and an 
additional collection, either at Day 3 or Day 5, at the following time 
points relative to the end of nebulization: 0 (predose), 0.25, 0.5, 0.75, 
1, 1.5, 2, 4, and 24 hours post end of nebulization. An additional single 
PK sample will be collected on Day 7 visit for subjects who participate 
in the intensive PK assessments.
Study Part C:
Remdesivir for Inhalation Solution formulation or PTM will be 
administered Days 1 through 5 with telehealth support as needed.
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On Days 1, 3, 5, and 7, assessments will include a symptom-directed 
physical examination. Nasopharyngeal, oropharyngeal swab samples 
and saliva samples for SARS-CoV-2 testing and possible viral 
resistance testing will be collected predose with the assistance of home 
nursing on Days 1, 3, 5, and 7. Vital signs will be performed predose 
on Days 1, 3, and 5 and on Day 7. Concomitant medications and AEs 
will be documented. Laboratory samples will be obtained for safety 
assessments predose on Days 1, 3, 5, and 7. Plasma samples will be 
obtained for PK assessments predose on Days 3 and 5 and Day 7 
(anytime sample) in all participants.
Participants will complete the adapted FLU-PRO© questionnaire daily 
(Days 1-14).
FEV1 will be performed daily during treatment days and will be 
performed both predose and 10 minutes postdose. Repeat FEV1 should 
be performed at 30 minutes postdose if there is > 15% reduction in 
FEV1 at 10 minutes postdose compared with the same day predose 
FEV1. FEV1 assessment may also be performed if there is a clinical 
concern of bronchospasm.
On Days 14 and 28, assessments will include review of AEs and 
concomitant medications. The Day 14 and 28 follow-up assessments 
may be completed by telephone.
Test Product, Dose, 
and Mode of 
Administration:
In Part A and Part B, the Remdesivir for Injection formulation 
delivered by inhalation, will be used. In Part C, the Remdesivir for 
Inhalation Solution formulation will be used.
Part A: 31 mg (nominal dose) Remdesivir for Injection administered 
via inhalation once daily at approximately the same time each day
Part B: 62 mg (nominal dose) Remdesivir for Injection administered 
via inhalation once daily at approximately the same time each day
Part C: 39 mg (nominal dose) by mouthpiece of Remdesivir for 
Inhalation Solution formulation administered via inhalation once daily 
at approximately the same time each day
Reference Therapy, 
Dose, and Mode of 
Administration:
Placebo administered via inhalation once daily at approximately the 
same time each day
Criteria for 
Evaluation:
Safety:
Proportion of participants with treatment-emergent AEs and laboratory
abnormalities.


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Efficacy: 
Change in SARS-CoV-2 viral load will be measured. A FLU-PRO© 
questio1maire will be utilized to report COVID-19 symptom severity 
and duration. Disease progression from baseline will be assessed by 
duration and change in severity of COVID-19 clinical symptoms and 
need for medically attended visits (MA Vs). 
Pharmacokinetics: 
For Parts A and B, the plasma concentrations of inhaled RDV and its 
metabolites will be measured, as appropriate. The following plasma 
PK parameters will be calculated for each analyte (RDV, GS-441524 
and GS-704277), as applicable: AUCo 24h AUC1au AUC1as1 CLsslF t,12, 
Statistical Methods: 
No statistical sample size/power calculation was perfonned as the 
sample size of up to approximately 152 participants is deemed feasible 
and sufficient to provide a descriptive assessment of viral kinetics, 
safety and tolerability, PK and disease progression in this study. 
CONFIDENTIAL 
Antiviral activity evaluation will be based on time weighted average 
change in SARS-CoV-2 viral load (defined as the AUC of viral load 
change divided by time between baseline to Day 7) and will be 
summarized by treatment group and each RDV group compared with 
placebo. 
Safety: 
Adverse event data will be listed by participant. Adverse events 
leading to study treatment discontinuation, treatment-emergent AEs, 
and serious AEs will be summarized by treatment, system organ class, 
and preferred tenn using the Medical Dictionary for Regulatory 
Activities (MedDRA). 
Listings of individual participants laboratory results and change from 
predose values for selected laboratory values will be summarized by 
treatment. 
Incidence of treatment-emergent laboratory abnonnalities will be 
smmnarized by treatment. 
Vital signs and ECG data will be smmnarized by treatment. 
FEY, values will be smmnarized by treatment. 
Listings of individual participants progression of COVID-19 
symptoms as reported by adapted FLU-PRO© questio1maire will be 
smmnarized by treatment. 
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PK: 
FINAL 
Amendment3 
For Parts A and B, plasma PK parameters for inhaled RDV and its 
metabolites will be summarized by treatment group using descriptive 
statistics (including mean, geometric mean, median, minimmn, 
maximum, and sample size). Concentrations of inhaled RDV and its 
metabolites in lasma over time will be smmnarized. 
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents. 
CONFIDENTIAL 
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Remdesivir (RDV; GS-5734™)
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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
λz
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
%AUCexp
percentage of AUC extrapolated between AUClast and AUCinf
AE
adverse event
ALT
alanine aminotransferase 
ARDS
acute respiratory distress syndrome
AST
aspartate aminotransferase 
ATP
adenosine triphosphate
AUC
area under the concentration versus time curve
AUCinf
area under the concentration versus time curve extrapolated to infinite time, calculated as 
AUClast + (Clast/λz)
AUClast
area under the concentration versus time curve from time zero to the last quantifiable 
concentration
AUCtau
area under the concentration versus time curve over the dosing interval
CI
confidence interval
CLss/F
apparent oral clearance at steady state after administration of the drug:
CLss/F = Dose/AUCtau, where “Dose” is the dose of the drug
Clast
last observed quantifiable concentration of the drug
CLcr
creatinine clearance
Cmax
maximum observed concentration of drug
COPD
chronic obstructive pulmonary disease
COVID-19
coronavirus disease 2019
CoV
coronavirus
CRF
case report form
Ctau
observed drug concentration at the end of the dosing interval
DAIDS
Division of AIDS
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
EudraCT
European Clinical Trials Database
EU
European Union
EUA
Emergency Use Authorization
FDA
Food and Drug Administration
FEV1
forced expiratory volume in the first second of expiration
FLU-PRO©
InFLUenza Patient-Reported Outcome
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
Gilead
Gilead Sciences, Inc.
GLPS
Global Patient Safety


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IB
investigator’s brochure
ICF
informed consent form
ICH
International Council on Harmonisation (of Technical Requirements for Registration of 
Pharmaceuticals for Human Use)
IEC
independent ethics committee
IND
investigational new drug 
IRB
institutional review board
IUD
intrauterine device
IV
intravenous
IXRS
interactive voice/web response system
LLOQ
lower limit of quantitation
MAV
medically attended visit
MedDRA
Medical Dictionary for Regulatory Activities
MERS
Middle East respiratory syndrome
NOAEL
no observed adverse effect level
PCR
polymerase chain reaction
PI
principal investigator
PK
pharmacokinetic(s)
PT
preferred term
PTM
placebo-to-match
PVE
Pharmacovigilance and Epidemiology
RDV
remdesivir (GS-5734™)
RNA
ribonucleic acid
RT-qPCR
quantitative reverse transcriptase polymerase chain reaction
SAE
serious adverse event 
SARS
severe acute respiratory syndrome
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SBECD
sulfobutylether β-cyclodextrin sodium
SDV
source data verification
SpO2
oxygen saturation as measured by pulse oximetry
SOC
standard of care
SOP
standard operating procedure
SRT
safety review team
SSR
special situation report
SUSAR
suspected unexpected serious adverse reaction
TEAE
treatment-emergent adverse event
Tlast
time (observed time point) of Clast
Tmax
the time (observed time point) of Cmax
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 (λz)


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ULN
upper limit of normal
US
United States
Vz/F
apparent volume of distribution of the drug


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1.
INTRODUCTION
1.1.
Background
Coronaviruses (CoVs) are positive-sense, single-stranded, enveloped RNA viruses, many of 
which are commonly found in humans and cause mild symptoms. However, over the past 
2 decades, emerging pathogenic CoVs that can cause life-threatening disease in humans and 
animals have been identified, namely severe acute respiratory syndrome coronavirus 
(SARS-CoV;{de Wit 2016, Ksiazek 2003}), Middle Eastern respiratory syndrome coronavirus 
(MERS-CoV; {Assiri 2013, Choi 2016, Who Mers-Cov Research Group 2013}), and severe 
acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus 
disease 2019 (COVID-19; {Zhu 2020}). Coronaviruses are known to have high mutation and 
recombination rates, which may allow them to cross species barriers and adapt to new hosts {Lau 
2015}. Bats are reservoir hosts for many types of CoVs and are thought to have spread emerging 
CoVs to new species. Cross-species transmission to animals and subsequent zoonotic 
transmission has resulted in disease in humans {de Wit 2016}.
SARS-CoV-2, a single-stranded RNA virus, is identified as the cause of an outbreak of 
respiratory illness that was first detected in Wuhan, China in December 2019. The virus has now 
spread globally, resulting in a global pandemic and causing severe respiratory illness throughout 
the world. Severe cases progress to pneumonia and multi-organ failure, which can lead to death. 
Gilead Sciences, Inc. (Gilead) has been working closely with global health authorities to respond 
to the ongoing pandemic and to evaluate the utility of intravenous (IV) remdesivir (RDV; 
GS-5734™) as a treatment option for COVID-19. Supported by Phase 3 clinical studies, IV
RDV has been approved for treatment of COVID-19 in Japan, the European Union (EU), the 
United States (US), and other countries.
1.2.
Remdesivir (RDV; GS-5734) for Inhaled Administration
Remdesivir is being developed by Gilead and is formulated for IV administration and for 
administration via nebulization.
1.2.1.
General Information
Remdesivir is an adenosine nucleotide prodrug that distributes into cells where it is metabolized
to form the pharmacologically active nucleoside triphosphate metabolite. Metabolism of
remdesivir to remdesivir triphosphate has been demonstrated in multiple cell types. Remdesivir
triphosphate acts as an analog of adenosine triphosphate (ATP) and competes with the natural
ATP substrate for incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent
RNA polymerase, which results in inhibition of viral replication.
For further information on RDV, refer to the investigator’s brochure (IB) for RDV. 


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1.2.2.
Additional Clinical Studies of Remdesivir
1.2.2.1.
GS-US-553-9018 Inhaled Remdesivir Phase 1a Study
Study GS-US-553-9018 is an ongoing randomized, blinded, placebo-controlled, single- and 
multiple-dose study with staggered dose escalation and adaptive dose selection evaluating 
inhaled RDV. In each cohort, 10 healthy male and nonpregnant, nonlactating, female volunteers, 
aged 18 through 45, inclusive are randomized 4:1 to receive inhaled RDV or placebo-to-match
(PTM). Participants received single doses of 12.5 mg, 31 mg, and 62 mg of Remdesivir for 
Injection formulation via nebulization in Cohorts 1, 2, and 4 respectively or multiple doses of 
31 mg or 62 mg each day for 5 days in Cohorts 3 and 5. Cohorts 1 through 5 received 
Remdesivir for Injection formulation via nebulization, and Cohort 6 received Remdesivir for 
Inhalation Solution formulation. Safety data as of 10 September 2020 included all participants in 
Cohorts 1 through 5. All AEs were mild or moderate. There were no deaths, serious adverse 
events (SAEs), pregnancies, or study drug discontinuations.
Preliminary plasma PK data in healthy participants are available following administration of 
inhaled Remdesivir for Injection formulation as single nominal doses of 12.5 mg to 62 mg (2 mg 
to 10 mg deposited), and as multiple nominal doses of 31 mg (5 mg deposited) and 62 mg 
(10 mg deposited) for 5 days. Following single nominal dose administration of 12.5 mg, 31 mg,
and 62 mg inhaled Remdesivir for Injection formulation, maximal concentrations of RDV and 
GS-704277 were achieved at the end of nebulization or within 30 minutes after the end of 
nebulization; plasma concentrations declined rapidly thereafter and were undetectable (below the 
limit of quantitation) at 2 hours and 4 hours postdose for RDV and GS-704277, respectively. 
GS-441524 concentrations peaked at 3 to 4 hours postdose and remained detectable up to 
48 hours postdose in most participants. Approximately dose proportional increases in the 
exposures of RDV and the metabolites were observed following 12.5 mg, 31 mg and 62 mg 
single dose administration. Following multiple dose administration, no accumulation was noted 
for RDV and GS-704277, consistent with the short half-lives. Accumulation ratios of GS-441524 
ranging from 1.2 to 1.6 were observed on Day 5 consistent with its longer half-life ranging from 
11.2 hours (31 mg single dose) to 28.6 hours (62 mg multiple doses, Day 5).
Overall, the observed steady-state plasma exposures at the 31 mg and 62 mg nominal dose were 
substantially below those observed with the 100 mg IV clinical dose at steady-state (IV 
exposures were approximately 101 and 70-fold higher for RDV, 11 and 6.5-fold higher for 
GS-704277, and 16 and 8.5-fold higher for GS-441524 compared with the 31 mg, and 62 mg
nominal dose of inhaled Remdesivir for Injection formulation, respectively). These results were 
similar to those observed in the nonclinical inhaled Remdesivir for Injection formulation study in 
African green monkeys. Comparison of the preliminary human and nonclinical African green 
monkey PK data indicate that it is reasonable to expect that the 31 mg and 62 mg human nominal 
inhaled doses (5 mg and 10 mg deposited) may produce similar, or exceeding GS-443902 
(triphosphate) levels in respiratory tissues as the 100 mg human IV dose.


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1.2.3.
Rationale for This Study
The evaluation of inhaled RDV as a treatment for COVID-19 is supported by clinical data from 
studies of IV RDV in patients with COVID-19, inhaled administration of RDV in healthy 
volunteers, and nonclinical characterization of inhaled administration in PK, toxicology, and 
efficacy studies.
Remdesivir for treatment of COVID-19 administered by IV infusion is now approved in Japan, 
the EU, US, and numerous countries globally. Emerging data suggest that upper airway disease 
precedes lower airway and lung disease in individuals infected with SARS-CoV-2 {Wolfel 
2020}. Delivery of RDV by inhalation could enable antiviral activity in the respiratory tract 
while achieving lower systemic drug exposures, potentially offering an option in 
non-hospitalized patients, and enabling use of RDV in patients who are not currently eligible for 
IV administration of RDV. Inhalation is a less invasive route of administration which will 
support outpatient administration. Furthermore, drug supply may be more efficiently utilized as 
there is potentially less total active pharmaceutical ingredient needed for each dose by inhalation 
versus IV administration. The current lyophilized clinical formulation of IV RDV, Remdesivir
for Injection, 100 mg, is suitable for nebulization. Additionally, a new formulation with a 
reduced content of sulfobutylether β-cyclodextrin sodium (SBECD), Remdesivir for Inhalation 
Solution, 40 mg, is being evaluated in a Phase 1a study. 
Data from nonclinical studies evaluating inhalation of RDV indicate minimal respiratory tract 
findings in a single dose PK study in African green monkeys, and a 7-day rat repeat-dose toxicity 
study. These studies demonstrate the localized delivery of RDV and formation of the active 
triphosphate, GS-443902, in respiratory tissues with lower systemic exposure to RDV and 
metabolites.
This study will evaluate the potential for a short course of nebulized RDV to prevent progression 
of COVID-19 in participants with early infection. The doses selected are anticipated to result in 
similar levels of triphosphate in the lung as that which results from IV administration.
Remdesivir by IV administration has a favorable safety and efficacy profile. Enrollment of this 
study in multiple parts will allow an initial assessment of safety and antiviral kinetics of 
nebulized RDV in early stage COVID-19 patients in Parts A and B of the study. Part C of the 
study will allow for evaluation of safety and efficacy of an inhaled RDV formulation with 
reduced SBECD content (Remdesivir for Inhalation Solution formulation via a mouthpiece). The 
use of a mouthpiece allows more drug to be administered over a shorter time period compared to 
a facemask and is more suitable for self/at-home administration.


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1.3.
Rationale for the Dose Selection
Remdesivir has been approved for the treatment of COVID-19 in Japan, the EU, and the US at 
an initial dose of 200 mg IV followed by 100 mg IV for the next 4 or 9 days. This protocol 
proposes investigation of a new route of administration through the respiratory tract to deliver 
drug directly to the primary site of infection while reducing overall systemic exposure.
Safety, tolerability, and PK of RDV administered via inhalation are being evaluated in an 
ongoing Phase 1a study in healthy participants (GS-US-553-9018). Two different RDV 
formulations, Remdesivir for Injection formulation and Remdesivir for Inhalation Solution 
formulation, were evaluated in this study at the nominal doses up to 62 mg (estimated 10 mg 
deposited dose, administered using LC® Sprint (PARI Respiratory Equipment, Inc.) equipped 
with sealed facemask and an exhaust filter, 16.1% to 17% device efficiency) once daily for 
5 days. Safety and preliminary PK data are available for the Remdesivir for Injection 
formulation, and PK and safety results for Remdesivir for Inhalation Solution formulation are 
forthcoming. An amendment to protocol GS-US-553-9018 is ongoing to generate additional 
safety and PK data for LC Sprint equipped with mouthpiece, and Remdesivir for Inhalation 
Solution formulation. This additional cohort is planned to run in parallel to Part C of the 
GS-US-553-9020 study, and together will inform on the Phase 3 dose selection for inhaled RDV. 
Both formulations were well tolerated in the healthy volunteer study up to 62 mg nominal dose 
(10 mg deposited). Preliminary data are discussed in Section 1.2.2.1. 
Based on these results, 31 mg and 62 mg doses are proposed for evaluation in Parts A and B of 
the current study, respectively. Briefly, a nominal dose of 31 mg Remdesivir for Injection 
formulation (estimated 5 mg deposited dose; utilizing 16.1% device efficiency) for 3 or 5 days is 
proposed for evaluation in Part A. This dose is predicted to achieve similar concentrations of the 
active GS-443902 in respiratory tissues as those expected following a 100 mg human IV dose. A 
higher nominal dose of 62 mg (estimated 10 mg deposited dose; utilizing 16.1% device 
efficiency), which may provide increased efficacy when administered to patients, is proposed for 
Part B. In both Parts, RDV will be administered using LC Sprint equipped with sealed facemask 
and an exhaust filter. 
Part C: 
Remdesivir for Inhalation Solution formulation and a new device configuration of LC Sprint 
utilizing a mouthpiece for drug delivery will be evaluated in Part C. This new formulation 
contains reduced levels of an excipient, SBECD (7.5% after reconstitution, as compared to 15% 
for Remdesivir for Injection formulation), which may offer improved safety when RDV is 
administered via inhalation. Both the new formulation and the new device configuration are 
being evaluated in healthy participants: Cohort 6 (60 mg Remdesivir for Inhalation Solution 
formulation or placebo, for 5 days, inhaled via sealed facemask) and Cohort 7 (39 mg 
Remdesivir for Inhalation Solution formulation or placebo, single dose, inhaled via mouthpiece). 
In alignment with the doses evaluated in the healthy volunteers study, the nominal dose in Part C 
is projected to be 39 mg (estimated 10 mg deposited dose; utilizing 25.6% mouthpiece 
configuration efficiency).


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The proposed doses for evaluation in Part A, B, and C are anticipated to be safe and efficacious, 
based on the cumulative clinical and nonclinical information available to date (Section 1.2.2.1
and inhalation IB). Estimated dose margins based on mg/g lung weight at the lowest and highest 
nominal doses evaluated in this study are 5.2- and 2.6-fold, respectively (inhalation IB).
Duration of 3 to 5 days of dosing will be evaluated in this study. The 5-day dosing duration is the 
recommended IV remdesivir duration for treatment of COVID-19 requiring hospitalization and 
not requiring invasive mechanical ventilation and/or extracorporeal membrane oxygenation
{VEKLURY 2020}. Shorter treatment duration of IV RDV for 3 days is currently being 
evaluated in an outpatient study (GS-US-540-9012) in COVID-19 patients at risk for disease 
progression.
1.4.
Risk/Benefit Assessment for the Study
Potential risks of a participant’s study involvement include unknown adverse events (AEs) due 
to inhaled RDV. Strategies to mitigate these risks include close monitoring of participant’s
clinical status and laboratory testing. Parameters for discontinuation of the study treatment due to 
AEs will be well defined and closely followed.
Transient, Grade ≤2, treatment-emergent elevations in alanine aminotransferase (ALT) and 
aspartate aminotransferase (AST) were observed with daily IV RDV administration in Phase 1 
studies in healthy volunteers. Transaminases increased is a listed adverse drug reaction to RDV. 
However, due to the reduced systemic exposure to RDV compared to the IV regimen, it is 
anticipated that there will be a lower effect on ALT and AST. Nonetheless, liver function testing 
will be closely monitored during the study.
Remdesivir contains SBECD, an approved excipient. In nonclinical species, SBECD 
administration has been associated with kidney vacuolation and hypertrophy. However, 
nonclinical inhalation toxicology studies and available inhaled clinical data with SBECD support 
its use in the RDV clinical formulation.
Participants may or may not clinically benefit from participation in the study. If efficacious, 
benefits might include shorter duration or lower severity of COVID-19 symptoms or reduced 
progression to severe disease. They may also benefit from increased observations and 
evaluations by health care professionals. Data from this study may support further evaluation of 
inhaled RDV in patients with COVID-19.
During a pandemic, additional potential risks to participants may include adequate study 
treatment availability, interruptions to the 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.
Considering the above, the benefit-risk balance for this study is considered positive.


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1.5.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.


Remdesivir (RDV; GS-5734T") 
Protocol GS-US-553-9020 
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2. 
OBJECTIVES 
The primary objective of this study is: 
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• 
To characterize the impact of inhaled RDV on SARS-CoV-2 viral load in participants with 
early stage COVID-19 
The secondary objectives of this study are: 
• 
To evaluate the safety and tolerability of inhaled Remdesivir for Injection fonnulation in 
participants with early stage COVID-19 
• 
To evaluate the PK of inhaled Remdesivir for Injection fonnulation and its metabolites in 
participants with early stage COVID-19 in Parts A and B 
• 
To characterize and evaluate disease progression from baseline 
• 
To characterize the efficacy, safety, and tolerability of Remdesivir for Inhalation Solution 
fonnulation administered with a mouthpiece in Part C of the study 
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3. 
STUDY DESIGN 
3.1. 
Endpoints 
The primary endpoint of this study is: 
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• 
Time weighted average change in SARS-CoV-2 viral load which is defined as AUC of viral 
load change divided by time between baseline through Day 7 
The secondary endpoints of this study are: 
• 
Proportion of participants with treatment-emergent AEs (TEAEs) and laboratory 
abnonnali ties 
• 
Proportion of participants with TEAEs leading to study treatment discontinuation 
• 
Composite of all-cause medically attended visits (MA Vs) (medical visits attended in person 
by the participant and a health care professional) or death by Day 28 
• 
Composite of COVID-19 related MA Vs (medical visits attended in person by the participant 
and a health care professional) or death by Day 28 
• 
Proportion of participants hospitalized by Day 28 
• 
Characterization of the plasma concentrations of inhaled RDV and its metabolites including 
AUCo 24h, AUC1as1, CLss!F, t112, V vF, Cmax, Tmax, C1as1, T1as1, AUC1au, ')....L., and C1au (Parts A and B 
only) 
• 
Change in SARS-CoV-2 viral load from baseline to Day 5 
• 
Change in SARS-CoV-2 viral load from baseline to Day 7 
• 
Change in SARS-CoV-2 viral load from baseline to Day 14 (Parts A and B only) 
• 
Time to negative SARS-CoV-2 polymerase chain reaction (PCR) 
• 
Time to alleviation (mild or absent) of baseline COVID-19 symptoms as reported on the 
COVID-19 adapted InFLUenza Patient-Reported Outcome (FLU-PRO~ questionnaire 
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3.2. 
Study Design 
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This study is a randomized, blinded, placebo-controlled, multicenter study of inhaled RDV in 
participants with early stage COVID-19 infection. In Parts A and B of the study, eligible 
participants will be randomized in equal proportions to 1 of 3 treatment groups. 
Part C of this study is a randomized, blinded, placebo-controlled, multicenter study of 
Remdesivir for Inhalation Solution fonnulation in participants with early stage COVID-19 
infection. Eligible participants will be randomized in a 3: 1 ratio to 1 of 2 treatment groups to 
receive Remdesivir for Inhalation Solution fonnulation or PTM administered by mouthpiece. 
The tenn "inhaled remdesivir" refers to both the Remdesivir for Injection fonnulation and 
Remdesivir for Inhalation Solution fonnulation when administered via nebulization using the LC 
Sprint. 
3.3. 
Study Treatments 
The study will feature multiple parts: Part A, Part B, and Part C. The pla1med nominal doses are 
provided below by treatment group. 
In Part A, approximately 36 participants who meet all eligibility criteria will be randomized in a 
1: 1: 1 ratio into one of the following 3 treatment groups: 
Treatment Group 1: 31 mg inhaled Remdesivir for Injection fonnulation daily for 5 days 
Treatment Group 2: 31 mg inhaled Remdesivir for Injection fonnulation daily for 3 days 
followed by PTM daily for 2 days 
Treatment Group 3: PTM daily for 5 days 
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Part A
In Part B, if supported by Phase 1a data in healthy volunteers, an additional 36 participants who 
meet all eligibility criteria may be randomized in a 1:1:1 ratio into one of the following treatment 
groups:
Treatment Group 4: 62 mg inhaled Remdesivir for Injection formulation daily for up to 5 days
Treatment Group 5: 62 mg inhaled Remdesivir for Injection formulation daily for up to 3 days 
followed by PTM through Day 5
Treatment Group 6: PTM daily for 5 days
Part B
In Parts A and B, at in-clinic screening, after the participant has provided informed consent, 
assessments will include but are not limited to the following: demographic and baseline 
characteristics, medical history, and concomitant medications will be documented. Body weight 
and height will be measured. A urine pregnancy test will be performed for women of 
childbearing potential. Vital signs including heart rate, temperature, blood pressure, and SpO2
will be recorded. A complete physical examination will be performed.
Participants with PCR-confirmed COVID-19 who enroll in the study will return to clinic daily on 
Days 1 through 5 for study treatment administration and clinical assessments. Participants will 
return to clinic on Days 7 and 14 for follow-up clinical assessment and undergo a Day 28 
follow-up which may be completed by telephone.
n = 36 
Randomized 
1: 1: 1 
n = 36 
Randomized 
1:1:1 
n = 12 
I 
n = 12 
I 
n = 12 
I 
n = 12 
I 
n = 12 
I 
n = 12 
I 
Inhaled Remdesivir for Injection formulation daily 
for 5 days, 31 mg nominal dose 
Inhaled Remdesivir for Injection formulation daily 
for 3 days, 31 mg nominal dose 
PTM daily for 5 days 
Inhaled Remdesivir for Injection formulation daily 
for up to 5 days, 62 mg nominal dose 
Inhaled Remdesivir for Injection formulation daily 
for up to 3 days, 62 mg nominal dose 
PTM daily for 5 days 


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Part C
Part C of the study will include an expanded safety and efficacy assessment of an additional 
80 participants. Participants in Part C will be enrolled after review of preliminary safety data 
from Parts A and B through at least Day 7. Approximately 80 participants will be randomized 
3:1 to 1 of 2 treatment groups:
Treatment Group 7: 39 mg Remdesivir for Inhalation Solution formulation once daily for 
5 days by mouthpiece
Treatment Group 8: PTM daily for 5 days by mouthpiece
At screening, after the participant has provided informed consent, assessments will include but 
are not limited to the following: demographic and baseline characteristics, medical history, and 
concomitant medications will be documented. Body weight and height will be measured. A urine 
pregnancy test will be performed for women of childbearing potential. Vital signs including heart 
rate, temperature, blood pressure, and SpO2 will be recorded. A complete physical examination 
will be performed.
In Part C, participants with nucleic acid testing or direct antigen testing-confirmed COVID-19 
who enroll in the study will be administered Remdesivir for Inhalation Solution formulation or 
PTM on Days 1 through 5. Clinical assessments may be conducted at home with the assistance 
of home nursing on Days 1, 3, 5, and 7. Participants will undergo Days 14 and 28 telephone 
contact follow-ups.
3.4.
Safety Review Team
A safety review team (SRT) will be established to assess safety and make decisions on dose 
selection and duration before initiating Part C.
The SRT will include the Gilead medical monitor. Other members of the SRT may include 
representatives from Global Patient Safety (GLPS) (formerly known as Pharmacovigilance and 
Epidemiology [PVE]), Clinical Operations, Biostatistics, and/or Clinical Pharmacology. 
Additional members may be invited to participate if additional expertise is needed. The medical 
monitor serves as the chair of the SRT. An SRT charter (or similar document) will be agreed 
upon by all SRT members prior to the first SRT meeting.
n = 80 
Randomized 
3:1 
n = 60 
n = 20 
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Remdesivir for Inhalation Solution formulation daily 
for 5 days by mouthpiece, 39 mg nominal dose 
PTM daily for 5 days by mouthpiece 


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The data reviewed at the SRT meetings to make optimal dosing and duration decisions will be 
defined in the SRT charter, including safety and nonclinical toxicity data. The quality control 
checks performed on the data reviewed and used for making optimal dosing and duration
decisions will also be described in the SRT charter.
Source data verification may not be performed prior to the meetings. Alternative data quality 
control checks that are performed on data used to make optimal dosing and duration decisions 
are described in the SRT charter.
3.5.
Duration of Treatment
In Parts A and B, participants will receive study treatment with inhaled Remdesivir for Injection 
formulation or PTM for 5 days. The duration of nebulization for Remdesivir for Injection is 
approximately 17 minutes for a nominal dose of 31 mg Remdesivir for Injection formulation
RDV and approximately 34 minutes for a nominal dose of 62 mg inhaled Remdesivir for 
Injection formulation.
In Part C, participants will receive study treatment with Remdesivir for Inhalation Solution or 
PTM for 5 days via a mouthpiece. The duration of nebulization for Remdesivir for Inhalation 
Solution is approximately 19 minutes for a nominal dose of 39 mg Remdesivir for Inhalation 
Solution formulation through a mouthpiece.
3.6.
Discontinuation Criteria
Study treatment dosing in an individual subject will be placed on hold and may be discontinued 
following a review of all available clinical data by the medical monitor and discussion with the 
investigator, if any of the following occurs:

Any SAE or ≥ Grade 3 AE suspected to be related to RDV

Any elevations in ALT ≥5 upper limit of normal (ULN); or ALT ≥3 ULN and total 
bilirubin ≥2 ULN, confirmed by immediate repeat testing

FEV1 decline of > 15% at 30 minutes postdose compared with same day predose FEV1
Discontinuation of study medication is not a seriousness criterion.
Subjects, who discontinue the study medication, should be encouraged to remain in the study and 
attend study visits as described in Section 6 (Study Procedures).
3.7.
End of Study
The end of this study will be the last subject’s last observation (or visit).
3.8.
Poststudy Care
The long-term care of the participant will remain the responsibility of their primary treating 
physician. Remdesivir is being supplied with curative intent. There is no provision for poststudy 
availability.


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The source data for this study will be obtained from electronic data capture (EDC), central 
laboratory, local laboratory, and specialty laboratory (for PK data). 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
In Part A and Part B, approximately 36 participants will be enrolled in each part. Approximately 
80 participants will be enrolled in Part C. Participants in Part C may receive study treatment in a 
home setting.
4.1.1.
Subject Replacement
Subjects who discontinue prior to the end of study will not be replaced.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study:
1) Willing and able to provide written informed consent, or with a legal representative who can 
provide informed consent
2) Aged ≥ 18 years
3) SARS-CoV-2 infection first confirmed by PCR (Parts A and B) or by nucleic acid testing or 
direct antigen testing (Part C) with sample collected ≤ 4 days prior to randomization
4) COVID-19 symptom onset ≤ 7 days prior to randomization
5) SpO2 > 94% on room air
6) Participants of childbearing potential who engage in heterosexual intercourse must agree to 
use protocol specified method(s) of contraception as described in Appendix 5
4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
1) Ongoing or prior participation in any other clinical trial of an experimental vaccine or 
treatment for COVID-19
2) Prior or current hospitalization for COVID-19 or need for hospitalization


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3) Treatment of COVID-19 with other agents with actual or possible direct antiviral activity 
against SARS-CoV-2 including IV RDV or administration of any SARS-CoV-2 (or 
COVID-19) vaccine
a) Patients chronically administered chloroquine or hydroxychloroquine for any reason are 
to be excluded 
4) Requiring oxygen supplementation
5) Positive pregnancy test (Appendix 5)
6) Breastfeeding female
7) Known hypersensitivity to the study treatment, its metabolites, or formulation excipient
8) Pre-existing pulmonary conditions such as chronic obstructive pulmonary disease or asthma 
(Parts A and B only)


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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding, and Treatment Codes Access
5.1.1.
Randomization
In Part A, approximately 36 participants who meet eligibility criteria will be randomized in a 
1:1:1 ratio to receive either of two inhaled 31 mg RDV regimens or PTM starting on Day 1 using 
an interactive voice/web response system (IXRS) and assigned a subject number. In Part B, an 
additional 36 participants who meet eligibility criteria will be randomized in a 1:1:1 ratio to 
receive either of two inhaled 62 mg RDV regimens or PTM starting on Day 1 using an IXRS and 
assigned a subject number.
In Part C, approximately 80 participants will be randomized 3:1 to 1 of 2 treatment groups to 
receive either: Remdesivir for Inhalation Solution formulation (nominal dose of 39 mg to 
achieve 10 mg deposited dose) administered by mouthpiece or PTM administered by mouthpiece
starting on Day 1 using an IXRS and assigned a subject number.
5.1.2.
Blinding
The study will be sponsor unblinded. During the randomized phase, Gilead personnel and site 
pharmacist will be unblinded while the investigational site(s) and subjects participating in the 
study will remain blinded. To mitigate the risks of inadvertently releasing the treatment 
information, certain Gilead staff will only be provided with the unblinded information when 
there is a need to access such information for data analysis to support internal dose 
determination. Should Gilead staff receive unblinding information, they will maintain the 
confidentiality of the unblinded information, and will not communicate the information to 
blinded sites, or subjects as specified in Gilead standard operating procedures (SOPs).
During the randomized phase, subjects and all study site 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 treatment will be dispensed by an unblinded
pharmacist to the subjects. Monitors, who will oversee activities relating to study drug, such as 
drug storage, drug accountability, and verifying randomization schedules as documented in the 
Study Monitoring Plan, will remain unblinded. Other non-Gilead personnel who are responsible 
for ensuring data integrity or participant safety may be unblinded as well. 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 Packaging & Labeling or Clinical Supply Management who have an 
Unblinded Inventory Manager role in the IXRS system for purposes of study treatment inventory 
management will remain unblinded. Individuals in Clinical Virology responsible for the selection 
of samples for sequencing and/or interpretation of sequencing data will remain unblinded. 
Individuals in GLPS responsible for safety signal detection, 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. External (ie, contract research 
organizations) Biostatisticians and Programmers may be unblinded for data monitoring purposes.


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Regulatory Quality and Compliance personnel in Research and Development may also be 
unblinded for purposes of supporting Quality Assurance activities and/or Regulatory Agency 
inspections.
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 subject, the investigator may obtain treatment assignment for that subject. 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 subject 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 and therefore, if a 
subject’s treatment assignment is disclosed to the investigator, the subject will have study 
treatment discontinued. All subjects will be followed until study completion unless consent to do 
so is specifically withdrawn by the subject.
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 remdesivir that is to be reconstituted with 19 mL of 
sterile water for injection prior to administration by inhalation through a nebulizer. Following 
reconstitution, each vial contains a 5 mg/mL remdesivir concentrated solution with sufficient 
volume to allow withdrawal of 20 mL (100 mg of remdesivir). Remdesivir for Injection, 100 mg, 
is supplied as a sterile product in a single-use, 30 mL, Type 1 clear glass vial. 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 supplied Placebo-to-Match Remdesivir for Injection, 100 mg, (PTM Remdesivir for 
Injection, 100 mg) is identical in physical appearance to the active formulation and contains the 
same inactive ingredients.
Remdesivir for Inhalation Solution, 40 mg, is a preservative-free, white to off-white or yellow, 
lyophilized solid containing RDV that is to be reconstituted with 8.4 mL of sterile water for 
injection prior to administration by inhalation through a nebulizer. Following reconstitution, each 
vial contains a 5 mg/mL RDV solution with sufficient volume to allow withdrawal of 8 mL 
(40 mg of RDV). Remdesivir for Inhalation Solution, 40 mg, is supplied as a sterile product in a 
single-use, 20 mL, Type I clear glass vial. In addition to the active ingredient, Remdesivir for 
Inhalation Solution, 40 mg, contains the following inactive ingredients: SBECD, water for 


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injection, hydrochloric acid, and sodium hydroxide. Hydrochloric acid and sodium hydroxide are 
used to adjust the formulation to a pH of 3.0 to 4.0.
The supplied Placebo-to-Match Remdesivir for Inhalation Solution, 40 mg, (PTM Remdesivir 
for Inhalation Solution, 40 mg) is identical in physical appearance to the active formulation and 
contains the same inactive ingredients.
Detailed information regarding study treatment administration and reconstitution instructions are 
included in a pharmacy manual provided to the investigator.
5.2.2.
Packaging and Labeling
Remdesivir for Injection, 100 mg, and placebo are provided in 30 mL glass vials enclosed with 
rubber stopper and aluminum seal with a polypropylene flip-off cap. Following reconstitution, 
each single-use vial contains sufficient volume to allow withdrawal of 20 mL (100 mg RDV or 
placebo).
Remdesivir for Inhalation Solution, 40 mg, and placebo are provided in 20 mL glass vials 
enclosed with rubber stopper and aluminum seal with a polypropylene flip-off cap. Following 
reconstitution, each single-use vial contains sufficient volume to allow withdrawal of 8 mL 
(40 mg RDV or placebo).
Remdesivir for Injection, 100 mg, Remdesivir for Inhalation Solution, 40 mg, and their matching 
placebo vials to be distributed to study centers and shall be labeled to meet applicable 
requirements of the US FDA and/or local regulations.
Sufficient quantities of Remdesivir for Injection, 100 mg, Remdesivir for Inhalation Solution, 
40 mg, and their matching placebo vials will be shipped to the investigator or qualified designee 
from Gilead Sciences Clinical Supplies Management (or its designee).
5.2.3.
Storage and Handling
Remdesivir for Injection, 100 mg, and PTM Remdesivir for Injection, 100 mg, vials should be 
stored below 30 °C prior to use. Remdesivir for Injection and placebo vials are recommended to 
be reconstituted and diluted within the same day as administration. Remdesivir for Injection and 
placebo vials do not contain any preservatives and are intended for single-use. Any unused 
Remdesivir for Injection and placebo material should be discarded.
The total storage time of reconstituted solution containing Remdesivir for Injection or placebo 
should not exceed 4 hours at room temperature (20 °C to 25 °C) or 24 hours at refrigerated 
temperature (2 °C to 8 °C). Any unused Remdesivir for Injection and placebo material should be 
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Remdesivir for Inhalation Solution, 40 mg, and PTM Remdesivir for Inhalation Solution, 40 mg, 
vials should be stored below 30 °C prior to use. Remdesivir for Inhalation Solution and placebo 
vials are recommended to be reconstituted and diluted within the same day as administration, if 
feasible. Remdesivir for Inhalation Solution and placebo vials do not contain any preservatives 
and are intended for single-use. Any unused Remdesivir for Inhalation Solution and placebo 
material should be discarded.
The total storage time of reconstituted solution containing Remdesivir for Inhalation Solution or 
placebo should not exceed 4 hours at room temperature (20 °C to 25 °C) or 7 days at refrigerated 
temperature (2 °C to 8 °C). Any unused Remdesivir for Inhalation Solution and placebo material 
should be discarded.
5.3.
Dosage and Administration of Remdesivir
Remdesivir for Injection, 100 mg, and Remdesivir for Inhalation Solution, 40 mg, will be 
provided by Gilead. Remdesivir for Injection will be administered in Parts A and B of the study 
and Remdesivir for Inhalation Solution will be administered in Part C of the study. 
All study treatments will be administered at approximately the same time each day.
In Parts A and B, RDV or PTM will be administered as an aerosolized solution by inhalation 
through a sealed facemask coupled with a nebulizer with a single inlet/outlet and exhaust filter.
The duration of nebulization is approximately 17 minutes for a nominal dose of 31 mg inhaled 
Remdesivir for Injection. The duration of nebulization is approximately 34 minutes for a nominal 
dose of 62 mg inhaled Remdesivir for Injection.
In Part C, RDV or PTM will be administered as an aerosolized solution by inhalation through a 
mouthpiece coupled with a nebulizer with a single inlet/outlet. The duration of nebulization is 
approximately 19 minutes for a nominal dose of 39 mg Remdesivir for Inhalation Solution.
Detailed information regarding study treatment administration and reconstitution instructions can 
be found in the pharmacy manual.
5.4.
Dispensing, Accountability, and Disposal or Return of Study Treatment
The investigator (or designee, eg, study center pharmacist) will acknowledge receipt of the study 
treatment (after reviewing the shipment’s content and condition) from Gilead (or designee). The 
investigator will maintain an accurate inventory of all study drugs. For Parts A and B, each dose 
of the study treatments administered at the study center will be administered by qualified study 
center staff. The dose of study treatments administered to subjects in the clinic under the 
supervision of staff will be accurately recorded on the Study Drug Accountability form provided 
by Gilead (or on equivalent documentation maintained by the study center), which indicates the 
date and quantity of each dosage formulation dispensed to individual subjects. For Part C, each 
dose of study treatment may be administered at home or in-clinic. During study drug 
dispensation, the dose of study treatment will be accurately recorded on the Study Drug 
Accountability form provided by Gilead (or on equivalent documentation maintained by the 


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study center), which indicates the date and quantity of each dosage formulation dispensed to 
individual subjects. If study drug is administered at the home setting, a home health service 
provider will be available to provide supervision either in-person or via telehealth. All 
information and documentation related to home administration of study drug will be provided to 
the investigator by the home health provider, wherever applicable, in a timely manner.
Gilead recommends that used and unused study treatment should be destroyed at the site. If the 
site has an appropriate SOP for drug destruction as determined by Gilead, the site may destroy 
used (empty or partially empty) and unused study treatment supplies in accordance with that 
site’s approved SOP. A copy of the site’s approved SOP will be obtained for the electronic Trial 
Master File. If study drug is destroyed onsite, the investigator must maintain accurate records for 
all study treatments destroyed. Records must show the identification and quantity of each unit 
destroyed, the method of destruction, and the person who disposed of the study treatment. Upon 
study completion, copies of the study treatment accountability records must be filed at the site. 
Another copy will be returned to Gilead.
If the site does not have an appropriate SOP for drug destruction, used and unused study 
treatment supplies are to be sent to the designated disposal facility for destruction. The study 
monitor will provide instructions for return.
The study monitor will review study treatment supplies and associated records at periodic 
intervals.
For both disposal options listed above, the study monitor must first perform drug accountability 
during a remote monitoring visit.
5.5.
Prior and Concomitant Medications
Due to antagonism observed in vitro with RDV, use of chronically administered chloroquine or 
hydroxychloroquine for any reason is exclusionary. 
Concomitant treatment with other agents with actual or possible direct antiviral activity against
SARS-CoV-2 (including IV RDV) is prohibited.
Medications will be assessed from screening to the Day 28 Follow-up visit.


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6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 3 and described in the text that follows.
The investigator must document any deviation from the protocol procedures and notify Gilead or 
contract research organization.
6.1.
Subject Enrollment and Treatment Assignment
Entry into screening does not guarantee enrollment into the study. In order to manage the total 
study enrollment, Gilead, at its sole discretion, may suspend screening and/or enrollment at any 
site or study-wide at any time. In Part C of the study, study visits may be performed in-clinic or
at the participant’s home via home health and/or telehealth, virtually or remotely, as permitted by 
local and institutional regulations.
6.2.
Pretreatment Assessments
6.2.1.
Study Parts A, B, and C: Screening Visit
Subjects will be screened in-clinic within 2 days before randomization to determine eligibility 
for participation in the study. The following will be performed and documented at screening:

Obtain written informed consent, or with a legal representative who can provide informed 
consent
After the informed consent the following assessments are performed to determine eligibility 
requirements as specified in the inclusion and exclusion criteria:

Obtain medical history including the following information (eg, date of first symptoms, 
overall symptoms, exposure source, demographics, baseline characteristics), allergies, and 
medical history

Review concomitant medications

Complete physical examination (urogenital/reproductive/anorectal exams will be performed 
only if clinically indicated) including vital signs (heart rate, temperature, blood pressure, and 
SpO2), body weight, and height

Urine pregnancy test (females of childbearing potential only)

Childbearing female participants who are not postmenopausal (see Appendix 5) who do not 
wish to follow protocol-defined contraception will need a serum follicle-stimulating hormone 
(FSH) test (FSH test is required for women who are < 54 years old and have stopped 
menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure)


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
Documentation of SARS-CoV-2 infection first confirmed by PCR (Parts A and B) or by 
nucleic acid testing or direct antigen testing (Part C) with sample collected ≤4 days prior to 
randomization

Record any SAEs and all AEs related to protocol-mandated procedures occurring after 
signing of the consent form
In Study Parts A and B, study subjects who qualify should be immediately randomized. 
Randomization and dosing should occur on the same day if possible.
From the time of obtaining informed consent through the first administration of study treatment, 
record all SAEs, as well as any AEs related to protocol-mandated procedures on the AEs
electronic case report form (eCRF). All other untoward medical occurrences observed during the 
screening period, including exacerbation or changes in medical history are to be considered 
medical history. See Section 7 Adverse Events and Toxicity Management for additional details.
6.2.2.
Study Parts A and B: Baseline/Day 1 Assessments
The following evaluations are to be completed at the Day 1 visit in-clinic. The investigator must 
have confirmed eligibility before proceeding with randomization. If the screening and Day 1 
visits occur on the same day, no procedures need to be repeated. Participants must complete the 
following assessments before being administered study treatment, unless otherwise stated:

Complete symptom-directed physical examination including vital signs (heart rate, 
temperature, blood pressure, SpO2)

Perform 12-lead electrocardiogram (ECG)

Perform FEV1 (predose and 10 minutes postdose)
Repeat of FEV1 should be performed 30 minutes postdose if there is > 15% reduction in 
FEV1 at 10 minutes postdose compared with the same day predose FEV1. FEV1
assessment may also be performed if there is a clinical concern of bronchospasm

Perform chest x-ray

Complete daily adapted FLU-PRO© questionnaire

Safety laboratory samples will be collected for the following analyses:
Hematology
Coagulation
Chemistry


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• 
Obtain nasopharyngeal and oropharyngeal swabs, and saliva samples for SARS-CoV-2 
quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) testing and possible 
viral resistance testing 
• --na PK assessment: end of nebulization 
I 
I 
• 
Review AEs and concomitant medications 
• 
Inhaled Remdesivir for Injection fonnulation administration: 
6.3. 
Inhaled Remdesivir for Injection fonnulation will be administered to participants at the 
site under close supervision. 
Healthcare professionals administering inhaled Remdesivir for Injection fonnulation 
should have the appropriate medication available for immediate use in case of 
hypersensitivity. The participant should be treated according to the standard of care 
(SOC) for management of hypersensitivity reaction. After dose administration, 
monitoring should be done as follows: 
Approximately 30 minutes post dose administration, participants should be observed, 
and vital signs should be perfonned prior to discharge 
Study Parts A and B: Daily Study Assessments (Days 2-5) 
The following evaluations are to be completed daily and prior to study treatment administration 
from Days 2-5 in-clinic, unless otherwise stated: 
• 
Complete symptom-directed physical examination including vital signs (heart rate, 
temperature, blood pressure, SpO2) 
• 
Complete daily adapted FLU-PRO© questio1maire 
• 
Safety laboratory samples (Days 3 and 5) 
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
Obtain nasopharyngeal, oropharyngeal swabs, and saliva samples for SARS-CoV-2 
RT-qPCR testing and possible viral resistance testing

Perform FEV1 (predose and 10 minutes postdose)
Repeat of FEV1 should be performed 30 minutes postdose if there is > 15% reduction in 
FEV1 at 10 minutes postdose compared with the same day predose FEV1. FEV1
assessment may also be performed if there is a clinical concern of bronchospasm

Sparse plasma PK assessment: predose and end of nebulization (Day 3)

Review AEs and concomitant medications

Inhaled Remdesivir for Injection formulation administration:
Inhaled Remdesivir for Injection formulation will be administered to participants at the 
site under close supervision. Healthcare professionals administering inhaled Remdesivir 
for Injection formulation should have the appropriate medication available for immediate 
use in case of hypersensitivity. The participant should be treated according to the SOC
for management of hypersensitivity reaction. After dose administration, monitoring 
should be done as follows:
Approximately 30 minutes post dose administration, participants should be observed, and 
vital signs should be performed prior to discharge
6.4.
Study Parts A and B: Follow-Up Assessments (Days 7 and 14)
The following evaluations are to be completed on Days 7 and 14 (± 3 days) in-clinic:

Complete symptom-directed physical examination including vital signs (heart rate, 
temperature, blood pressure, SpO2)

Complete daily adapted FLU-PRO© questionnaire

Safety laboratory samples

Obtain nasopharyngeal, oropharyngeal swabs, and saliva samples for SARS-CoV-2 
RT-qPCR testing and possible viral resistance testing

Single PK assessment (Day 7)

Review AEs and concomitant medications
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6.5.
Study Parts A and B: Day 28 Follow-Up Assessment (± 5 days)
The following evaluations are to be completed on Day 28 and may be completed by telephone:

Review AEs and concomitant medications
6.6.
Study Part C: Baseline/Day 1, Days 3, 5, and 7 Assessments
The investigator must have confirmed eligibility before proceeding with randomization. If the 
screening and Day 1 visits occur on the same day, no procedures need to be repeated. Whenever 
possible, Day 1 dosing should occur on the same day as screening. The following evaluations are 
to be completed at Days 1, 3, 5, and 7. They may be completed at home with the assistance of 
home nursing. Participants must complete the following assessments before being administered 
study treatment, unless otherwise stated:

Complete symptom-directed physical examination including vital signs (heart rate, 
temperature, blood pressure, SpO2)

Complete daily adapted FLU-PRO© questionnaire

On Days 1 through 5, perform FEV1 (predose and 10 minutes postdose)
Repeat of FEV1 should be performed 30 minutes postdose if there is > 15% reduction in 
FEV1 at 10 minutes postdose compared with the same day predose FEV1. FEV1
assessment may also be performed if there is a clinical concern of bronchospasm

Obtain nasopharyngeal and oropharyngeal swabs, and saliva samples for SARS-CoV-2 
RT-qPCR testing and possible viral resistance testing

PK assessments
Days 3 and 5: Sparse plasma PK assessment at predose
Day 7: Single anytime plasma PK assessment

Safety laboratory samples (Days 1, 3, 5, and 7)

Review AEs and concomitant medications

Remdesivir for Inhalation Solution formulation administration (Days 1-5):
Remdesivir for Inhalation Solution formulation may be administered at home to 
participants with in-person or telehealth support
For participants with pre-existing pulmonary conditions (ie, chronic obstructive 
pulmonary disease [COPD] or asthma) enrolled in Part C of the study, prescribed inhalers 
may not be used ≤ 30 minutes prior to Remdesivir for Inhalation Solution formulation 
administration


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Healthcare professionals overseeing Remdesivir for Inhalation Solution formulation 
therapy remotely will observe the patient for any signs of adverse event. If any adverse 
event is observed and cannot be managed remotely appropriate urgent care measures will 
be implemented. 
■
Approximately 30 minutes after dose administration, participants should be observed
remotely prior to telehealth support session concluding
6.7.
Study Part C: Days 2 and 4 Assessments
The following evaluations are to be completed daily and prior to study treatment administration 
on Days 2 and 4. They may be completed at home with telehealth support, unless otherwise 
stated:

Complete daily adapted FLU-PRO© questionnaire

Perform FEV1 (predose and 10 minutes postdose)
Repeat of FEV1 should be performed 30 minutes postdose if there is > 15% reduction in 
FEV1 at 10 minutes postdose compared with the same day predose FEV1. FEV1
assessment may also be performed if there is a clinical concern of bronchospasm

Review AEs and concomitant medications

Remdesivir for Inhalation Solution formulation administration:
Remdesivir for Inhalation Solution formulation may be administered at home to 
participants with in-person or telehealth support
For participants with pre-existing pulmonary conditions (ie, COPD or asthma) enrolled in
Part C of the study, prescribed inhalers may not be used ≤30 minutes prior Remdesivir 
for Inhalation Solution formulation administration
Healthcare professionals overseeing Remdesivir for Inhalation Solution formulation 
therapy remotely will observe the patient for any signs of adverse event. If any adverse 
event is observed and cannot be managed remotely appropriate urgent care measures will 
be implemented. 
■
Approximately 30 minutes after dose administration, participants should be observed
remotely prior to telehealth support session concluding
6.8.
Study Part C: Follow-Up Assessments (Days 14 and 28)
The following evaluations are to be completed on Day 14 (± 3 days) and Day 28 (± 5 days) and 
may be completed by telephone:

Complete daily adapted FLU-PRO© questionnaire (Day 14 only)

Review AEs and concomitant medications


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6.9.
Chest X-Ray
In Study Parts A and B, a chest x-ray will be performed at Day 1. If screening visit and Day 1 are 
the same day, chest x-ray does not need to be repeated if completed as SOC < 2 days before 
screening. 
6.10.
FEV1
FEV1 will be performed daily during treatment days and will be performed both predose and 
10 minutes postdose. Repeat FEV1 should be performed at 30 minutes postdose if there is 
> 15% reduction in FEV1 at 10 minutes postdose compared with the same day pre-dose FEV1.
FEV1 assessment may also be performed if there is a clinical concern of bronchospasm.
All subjects with >15% reduction in FEV1 compared with same day predose FEV1 should be
monitored until FEV1 normalizes.
FEV1 assessments will be performed as per the current American Thoracic Society 
Standardization.
6.11.
Clinical Laboratory Assessments
Clinical laboratory assessments will be performed throughout the study as outlined below and in
Appendix 3.
The following clinical laboratory assessments will be performed at screening and analyzed 
locally at sites:

Urine pregnancy test (females of childbearing potential only)

FSH testing (screening only): females who are < 54 years old and have ceased menstruating 
for ≥ 12 months but do not have documentation of ovarian hormonal failure only and do not 
wish to follow protocol-defined contraception
The following clinical laboratory assessments will be performed at the applicable visits and sent 
to a central laboratory for analysis:

Chemistry: alkaline phosphatase, AST, ALT, gamma-glutamyl transferase, total bilirubin, 
direct and indirect bilirubin, total protein, albumin, lactate dehydrogenase, creatine 
phosphokinase, bicarbonate, blood urea nitrogen, calcium, chloride, creatinine, glucose, 
lipase, magnesium, phosphorus, potassium, sodium, uric acid 

Hematology: hematocrit, hemoglobin, platelet count, red blood cell count, white blood cell
count with differential (absolute and percentage), including lymphocytes, monocytes, 
neutrophils, eosinophils, basophils, and mean corpuscular volume

Coagulation panel: prothrombin time, partial thromboplastin time, and international 
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
Virology assessments: nasopharyngeal and oropharyngeal swab samples and saliva samples 
will be used to assess SARS-CoV-2 viral load by RT-qPCR. Once viral load testing is 
complete, the remnant samples may be used to evaluate the emergence of viral resistance by 
SARS-CoV-2 sequencing and/or phenotypic testing

Estimated glomerular filtration rate will be determined according to:
Cockcroft-Gault formula for creatinine clearance for participants ≥ 18 years of age
Creatinine clearance will be estimated based on screening body weight
Men: 
(140 age in years) × (wt in kg)
 creatinine clearance (CLcr) (mL/min)
72 × (serum creatinine in mg/dL)
Women: (140 age in years) × (wt in kg) × 0.85  CLcr (mL/min)
72 × (serum creatinine in mg/dL)
6.12.
Pharmacokinetic Assessments
Sparse plasma PK assessments will be conducted in all participants in Parts A, B, and C. In 
Study Parts A and B, sparse plasma PK samples will be collected at Day 1 (end of nebulization, 
) and Day 3 (predose and end of nebulization). In 
Study Part C, sparse plasma PK samples will be collected at Days 3 and 5 (predose) and a single 
anytime PK sample will be collected on Day 7.
Up to 6 participants/group in Part A and Part B will have intensive PK assessments. Intensive PK
samples will be collected at Day 1 and an additional collection, either at Day 3 or Day 5, at the 
following time points relative to the end of nebulization: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 
and 24 hours post end of nebulization. An additional single PK sample will be collected on 
Day 7 visit for subjects who participate in the intensive PK assessments.
6.13.
Assessments for Early Discontinuation from Study
If a participant discontinues study dosing (for example, as a result of an AE), every attempt 
should be made to keep the participant in the study and continue to perform the required 
study-related follow-up and procedures (see Section 6.13.1, 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.
6.13.1.
Criteria for Discontinuation of Study Treatment
Study treatment may be discontinued in the following instances:

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree. Following resolution of intercurrent illness, the subject 
may resume study dosing if supported by both investigator and Gilead medical monitor
CCI


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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 subject's best 
interest 
• 
Lack of efficacy 
• 
Subject request to discontinue for any reason 
• 
Subject noncompliance 
• 
Pregnancy during the study; refer to Appendix 5 
• 
Discontinuation of the study at the request of Gilead, a regulatory agency, or an institutional 
review board (IRB) or independent ethics c01mnittee (IEC) 
• 
Any SAE or~ Grade 3 AE suspected to be related to RDY 
• 
FEY I decline of > 15% at 30 minutes postdose compared with same day predose FEY 1 
• 
Meeting toxicity management criteria necessitating discontinuation, refer to Section 7.7. 
6.14. 
End of Study 
The end of the study will occur at the last participant's last observation ( or visit). 
6.15. 
Poststudy Care 
The long-tenn care of the participant will remain the responsibility of their primary treating 
physician. Remdesivir is being supplied with curative intent. There is no provision for poststudy 
availability. 
6.16. 
Sample Storage 
The stored biological samples may be used by Gilead or its research partner for future testing to 
provide additional data to answer questions that relate to the main study. At the end of this study, 
these samples may be retained in storage by Gilead for a period up to 15 years. If subjects 
provide additional specific consent, residual PK samples may be destroyed no later than 15 years 
after the end of the study or per country requirements. 
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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events and Serious Adverse Events
7.1.1.
Adverse Events
An AE is any untoward medical occurrence in a clinical study subject administered a study 
treatment, 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 a study treatment, whether or not the AE is considered related to the study 
treatment. 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 study treatment 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 subject was at risk of death at the time of the event; it does not 
refer to an event that hypothetically might have caused death if it were more severe.)

In-patient hospitalization or prolongation of existing hospitalization


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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: Such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse.
7.1.3.
Study Treatments 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 of falsified medicine, and 
pregnancy regardless of an associated AE.
Medication error is any unintentional error in the prescribing, dispensing, preparation for 
administration or administration of a study treatment 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 a study treatment by a 
subject.
Misuse is defined as any intentional and inappropriate use of a study treatment 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 a study 
treatment given per administration or cumulatively which is above the maximum recommended 
dose as per protocol or in the product labeling (as it applies to the daily dose of the subject in 
question). In cases of a discrepancy in drug accountability, overdose will be established only 
when it is clear that the subject has taken the excess dose(s). Overdose cannot be established 
when the subject cannot account for the discrepancy, except in cases in which the investigator 
has reason to suspect that the subject has taken the additional dose(s).
Occupational exposure is defined as exposure to a study treatment as a result of one’s 
professional or nonprofessional occupation.
Drug interaction is defined as any drug/drug, drug/food, or drug/device interaction.


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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 study treatment.
Counterfeit or falsified medicine: Any study treatment 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 Study Treatments and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to study 
treatment using clinical judgment and the following considerations:

No: Evidence exists that the AE has an etiology other than the study treatment. For SAEs, an 
alternative causality must be provided (eg, preexisting condition, underlying disease, 
intercurrent illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the study 
treatment.
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of AE reporting.
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the AE has an etiology other than the study procedure.

Yes: The AE occurred as a result of protocol procedures (eg, venipuncture).
7.2.2.
Assessment of Severity
The severity of AEs will be graded using the Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017. For each episode, 
the highest grade attained should be reported as defined in the grading scale. The DAIDS scale is 
available at the following location:
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf


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7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events
7.3.1.
Requirements for Collection Prior to Study Treatment Initiation
After informed consent, but prior to initiation of study treatment, 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 treatment, collect all AEs, regardless of cause or relationship, 
including the protocol-required posttreatment follow-up period 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 subject 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 PVE) 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 study treatment, regardless of causality, should also be reported.
Investigators are not obligated to actively seek SAEs after the protocol-defined follow-up period;
however, if the investigator learns of any SAEs that occur after the protocol-defined follow-up 
period has concluded and the event is deemed relevant to the use of study treatment, 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.
Study Treatment Special Situations Reports
All study treatment SSRs that occur from study treatment 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 study 
treatment), that occurs after the subject first consents to participate in the study (ie, signing the 
informed consent) and throughout the duration of the study, including the posttreatment 
follow-up visit, must be reported to Gilead GLPS utilizing the paper SSR (Section 7.4.2.1).
7.3.5.2.
Non-Gilead Concomitant Therapy Report
Special situations involving non-Gilead concomitant medications does 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 subject identification, 
maintaining the traceability of a document to the subject identifiers.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF and the SAE narrative section of the Safety Report 
Form eCRF.
7.4.1.1.
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
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 GLPS.
7.4.2.
Special Situations Reporting Process
7.4.2.1.
Paper Special Situations Reporting Process for Study Treatment

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 study treatment initiation throughout the duration of the 
study, including the protocol required post treatment follow-up period.
Gilead GLPS 
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 study 
treatment 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
Gilead GLPS Email
 
or
Fax: 

Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.

Special situations involving non-Gilead concomitant medications do not need to be reported
on the SSR form; however, special situations that result in AEs due to a non-Gilead 
concomitant medication, must be reported as an AE.
PPD
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7.4.2.3.
Pregnancy Reporting Process

The investigator should report pregnancies in female study subjects and/or female partners of 
male subjects that are identified after initiation of study treatment and throughout the study, 
including the post study treatment 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 
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 post 
study must be reported to the Gilead GLPS.

The subject 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 5 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 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 study treatment. 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 study treatment 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 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.
All AEs, SAEs, and clinically significant laboratory abnormalities will be followed until 
resolution or until stability of the abnormality is demonstrated.
7.7.
Toxicity Management
Nebulized RDV will be administered to participants under close supervision.
Inhaled Remdesivir for Injection formulation will be administered to participants at the clinical 
site (Parts A and B). Healthcare professionals administering inhaled Remdesivir for Injection 
formulation should have the appropriate medication available for immediate use in case of 
hypersensitivity. The participant should be treated according to the SOC for management of 
hypersensitivity reaction. After dose administration, monitoring should be done as follows:

Approximately 30 minutes after dose administration, participants should be observed, and 
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Remdesivir for Inhalation Solution formulation may be administered to participants in the
participant’s home with in-person or telehealth support (Part C only). Healthcare professionals 
overseeing Remdesivir for Inhalation Solution formulation therapy remotely will observe the 
patient for any signs of adverse event. If any adverse event is observed and cannot be managed 
remotely, appropriate urgent care measures will be implemented. 

Approximately 30 minutes after dose administration, participants should be observed
remotely prior to telehealth support session concluding
For participants with pre-existing pulmonary conditions (ie, COPD or asthma) enrolled in Part C 
of the study, prescribed inhalers may not be used ≤ 30 minutes prior to Remdesivir for Inhalation 
Solution formulation administration.
The participant should be treated according to the SOC for management of hypersensitivity or 
bronchospasm according to site or home health protocol. The medical monitor should be notified 
prior to study treatment discontinuation when medically feasible. Study treatment dosing in an 
individual participant will be placed on hold and may be permanently discontinued, following 
review of all available clinical data by the Medical Monitor and discussion with the investigator, 
in the following conditions:

Development of ALT levels ≥ 5 × ULN

Development of ALT levels ≥ 3 × ULN and bilirubin ≥ 2 × ULN

Acute anaphylactic reaction to RDV

Estimated creatinine clearance < 30 mL/min based on the Cockcroft-Gault formula

Any SAEs and Grade 3 and 4 abnormal laboratory results assessed as related to study 
treatment
For clinical queries, please contact the medical monitor. Study treatment dosing may be resumed 
if it was held due to laboratory abnormality and is now within acceptable range, if the 
abnormality was not attributed to study treatment.
Please refer to Appendix 4 for further details on the management of clinical and laboratory AEs.


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8.1. 
8.1.1. 
STATISTICAL CONSIDERATIONS 
Analysis Objectives and Endpoints 
Analysis Objectives 
The primary objective of this study is: 
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To characterize the impact of inhaled RDV on SARS-CoV-2 viral load in participants with 
early stage COVID-19 
The secondary objectives of this study are: 
• 
To evaluate the safety and tolerability of inhaled Remdesivir for Injection fonn ulation in 
participants with early stage COVID-19 
• 
To evaluate the PK of inhaled Remdesivir for Injection fonnulation and its metabolites in 
participants with early stage COVID-19 in Parts A and B 
• 
To characterize and evaluate disease progression from baseline 
• 
To characterize the efficacy, safety, and tolerability of Remdesivir for Inhalation Solution 
fonnulation administered with a mouthpiece in Part C of the study 
I 
I 
8.1.2. 
Primary Endpoint 
• 
Time-weighted average change in SARS-CoV-2 viral load which is defined as AUC of viral 
load change divided by time between baseline through Day 7 
8.1.3. 
Secondary Endpoint 
The secondary endpoints of this study are: 
• 
Proportion of participants with TEAEs and laboratory abnonnalities 
• 
Proportion of participants with TEAEs leading to study treatment discontinuation 
• 
Composite of all-cause MA Vs (medical visits attended in person by the participant and a 
health care professional) or death by Day 28 
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Composite of COVID-19 related MA Vs (medical visits attended in person by the participant 
and a health care professional) or death by Day 28 
• 
Proportion of participants hospitalized by Day 28 
• 
Characterization of the plasma concentrations of inhaled RDV and its metabolites including 
AUCo 24h, AUC1as1, CLss!F, t112, V vF, Cmax, Tmax, C1as1, T1as1, AUC1au, ')....L., and C1au (Parts A and B 
only) 
• 
Change in SARS-CoV-2 viral load from baseline to Day 5 
• 
Change in SARS-CoV-2 viral load from baseline to Day 7 
• 
Change in SARS-CoV-2 viral load from baseline to Day 14 (Parts A and B only) 
• 
Time to negative SARS-CoV-2 PCR 
• 
Time to alleviation (mild or absent) of baseline COVID-19 symptoms as reported on the 
COVID-19 adapted FLU-PRO© questionnaire 
-
I 
I 
I 
I 
I 
I 
8.2. 
8.2.1. 
Planned Analyses 
Interim Analysis 
Prior to the final analysis, interim analyses may be conducted and the analyses may be submitted 
to regulatory agencies to seek guidance for the overall clinical development program. 
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8.2.2.
Final Analysis
The unblinded final analysis will be performed at the end of study, after all subjects have 
completed the study, outstanding data queries have been resolved or adjudicated as unresolvable, 
and the data have been cleaned and finalized.
8.3.
Analysis Conventions
8.3.1.
Analysis Sets
8.3.1.1.
Efficacy
The primary analysis set for efficacy analysis is defined as the Full Analysis Set, which will 
include all participants who (1) are randomized into the study and (2) have received at least 
1 dose of study treatment. Participants will be grouped according to the treatment to which they 
were randomized.
8.3.1.2.
Safety
The primary analysis set for safety analyses is defined as Safety Analysis Set, which will include 
all participants who (1) are randomized into the study and (2) have received at least 1 dose of 
study treatment. Participants will be grouped according to the treatment which they received.
8.3.1.3.
Pharmacokinetics
Each PK Analysis Set will include all randomized subjects who received at least 1 dose of study 
treatment and had at least 1 nonmissing PK concentration datum reported by the PK laboratory 
for each respective analyte.
8.3.2.
Data Handling Conventions
Natural logarithm transformation for PK parameters will be applied for PK analysis.
For summary statistics, PK concentration values below the limit of quantitation will be treated as 
zero at predose and one-half of the lower limit of quantitation (LLOQ) for postdose time points.
Laboratory data that are continuous in nature but are less than the LLOQ or above the upper limit 
of quantitation, will be imputed to the value of the lower or upper limit plus or minus 
1 significant digit, respectively (e.g., if the result of a continuous laboratory test is < 20, a value 
of 19 will be assigned).
Missing data can have an impact upon the interpretation of the trial data. In general, values for 
missing data will not be imputed. However, a missing pretreatment laboratory result would be 
treated as normal (i.e., no toxicity grade) for the laboratory abnormality summary.
All available data for participants that do not complete the study will be included in data listings.


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8.4.
Demographic and Baseline Characteristics Analysis
Demographic and baseline measurements will be summarized using standard descriptive 
methods.
Demographic summaries will include sex, race/ethnicity, and age.
8.5.
Efficacy Analysis
8.5.1.
Primary Analysis
SARS-CoV-2 viral load will be summarized by treatment using descriptive statistics in Part A 
and Part B. For Part C, time weighted average change in SARS-CoV-2 viral load will be 
compared between the RDV and placebo groups using analysis of covariance with baseline viral 
load included in the model as a covariate.
8.5.2.
Secondary Analyses
The proportion of participants all-cause MAV (medical visits attended in person by the 
participant and a health care professional) or death by Day 28 will be estimated using 
Kaplan-Meier methods by treatment group in Part C. The proportion of participants COVID-19 
related MAVs or death by Day 28 will be estimated using Kaplan-Meier methods by treatment 
group in Part C. The proportion of hospitalization by Day 28 will be summarized by treatment 
group. Kaplan Meier product limit method will be used to estimate time to negative 
SARS-CoV-2 PCR and time to alleviation (mild or absent) of baseline COVID-19 symptoms by 
treatment group.
8.6.
Safety Analysis
All safety data collected on or after the randomization date through Day 28 will be summarized 
by treatment group (according to the study treatment received). Data for the pretreatment will be 
included in data listings.
8.6.1.
Extent of Exposure
A subject’s extent of exposure to study treatment data will be generated from the study treatment
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 (PT), 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 TEAE will be 
defined as any AE that begins on or after the date of first dose of study treatment up to the date 
of last dose of study treatment plus 30 days.


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Summaries (number and percentage of subjects) of TEAEs (by system organ class and PT) 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 post baseline up to the end date of the study, 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.
Laboratory abnormalities that occur before the first dose of study treatment or after the subject 
has been discontinued from treatment for more than 30 days will be included in a data listing.
8.7.
Adjustments for Multiplicity
No adjustments for multiple comparison are planned.
8.8.
Pharmacokinetic Analysis
For Parts A and B, plasma concentrations and PK parameters (if applicable) for inhaled RDV 
and its metabolites will be listed and summarized using descriptive statistics by treatment group 
(including mean, geometric mean, median, minimum, maximum, and sample size). 
Concentrations of inhaled RDV and its metabolites in plasma over time will be summarized. For 
Part C, plasma concentration of GS-441524 will be listed and summarized using descriptive 
statistics by nominal time.
8.9.
Sample Size
The sample size in this study is determined based on practical considerations and past experience 
with similar types of studies. No sample size/power calculation was performed. A sample size up 
to approximately 152 participants (72 participants for Part A and Part B; 80 participants for 
Part C) should provide a suitable assessment of the descriptive efficacy, and safety profile in this 
population.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with International Council
on Harmonisation (of Technical Requirements for Registration of Pharmaceuticals for Human 
Use) (ICH) E6(R2) addendum to its guideline for GCP and applicable laws and regulations.
9.1.2.
Financial Disclosure
The investigator and subinvestigators will provide prompt and accurate documentation of their 
financial interest or arrangements with Gilead, or proprietary interests in the investigational drug 
during the course of a clinical study. This documentation must be provided prior to the 
investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.3.
Institutional Review Board/Independent Ethics Committee Review and 
Approval
The investigator (or Gilead as appropriate according to local regulations) will submit this 
protocol, ICF, and any accompanying material to be provided to the subject (such as 
advertisements, subject information sheets, or descriptions of the study used to obtain informed 
consent) to an IRB/IEC. The investigator will not begin any study subject activities until 
approval from the IRB/IEC has been documented and provided as a letter to the investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/IEC any modifications made to the protocol or any accompanying material to be 
provided to the subject after initial IRB/IEC approval, with the exception of those necessary to 
reduce immediate risk to study participants.
9.1.4.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study before undertaking any study-related procedures. The investigator 
must use the most current IRB- or IEC-approved consent form for documenting written informed 
consent. Each informed consent (or assent as applicable) will be appropriately signed and dated 
by the subject or the subject’s legally authorized representative and the person conducting the 
consent discussion, and also by an impartial witness (if required by IRB or IEC or local 
requirements).


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9.1.5. 
Confidentiality 
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The investigator must assure that subjects' anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only an identification code and any other 
unique identifier(s) as allowed by local law (such as year of birth) will be recorded on any fonn 
or biological sample submitted to Gilead, IRB or IEC or laboratory. Laboratory specimens must 
be labeled in such a way as to protect subject identity while allowing the results to be recorded to 
the proper subject. Refer to specific laboratory instructions or in accordance with local 
regulations. NOTE: The investigator must keep a screening log with details for all subjects 
screened and enrolled in the study, in accordance with the site procedures and regulations. 
Subject data will be processed in accordance with all applicable regulations. 
The investigator agrees that all infonnation received from Gilead, including but not limited to the 
IB, this protocol, eCRF, the study treatment, and any other study infonnation, remain the sole 
and exclusive property of Gilead during the conduct of the study and thereafter. This infonnation 
is not to be disclosed to any third party ( except employees or agents directly involved in the 
conduct of the study or as required by law) without prior written consent from Gilead. The 
investigator further agrees to take all reasonable precautions to prevent the disclosure by any 
employee or agent of the study site to any third party or otherwise into the public domain. 
9.1.6. 
Study Files and Retention of Records 
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully docmnented and the study data to be subsequently verified. These docmnents should 
be classified into at least the following 2 categories: (1) investigator's study file, and (2) subject 
clinical source documents. 
The investigator's study file will contain the protocol/amendments, paper or electronic 
completed subject case report fonns (CRFs), IRB or IEC and govenunental approval with 
correspondence, infonned consent, drug records, staff curriculmn vitae and authorization fonns, 
and other appropriate documents and correspondence. 
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The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification

Documentation that subject meets eligibility criteria, ie, medical history, physical 
examination, and confirmation of diagnosis (to support inclusion and exclusion criteria)

Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number)

Study discussed and date of informed consent

Dates of all visits

Documentation that protocol-specific procedures were performed

Results of efficacy parameters, as required by the protocol

Start and end date (including dose regimen) of study treatment, including dates of dispensing 
and return

Record of all AEs and other safety parameters (start and end date, and including causality 
and severity), and documentation that adequate medical care has been provided for any AE

Concomitant medication (including start and end date, dose if relevant; dose changes)

Date of study completion and reason for ED, if it occurs
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, the US, Europe, or Japan) and until there are no pending or planned marketing 
applications in an ICH region; or, if no application is filed or if the application is not approved 
for such indication, until 2 years after the investigation is discontinued and regulatory authorities 
have been notified. Investigators may be required to retain documents longer if specified by 
regulatory requirements, by local regulations, or by an agreement with Gilead. The investigator 
must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.


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


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


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


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10.
REFERENCES
Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A, et al. 
Epidemiological, Demographic, and Clinical Characteristics of 47 Cases of 
Middle East Respiratory Syndrome Coronavirus Disease From Saudi Arabia: A 
Descriptive Study. Lancet Infect Dis 2013;13 (9):752-61.
Choi WS, Kang CI, Kim Y, Choi JP, Joh JS, Shin HS, et al. Clinical Presentation and Outcomes 
of Middle East Respiratory Syndrome in the Republic of Korea. Infect Chemother 
2016;48 (2):118-26.
de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: Recent Insights Into 
Emerging Coronaviruses. Nature Review 2016;14:523-34.
Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, et al. A Novel Coronavirus 
Associated with Severe Acute Respiratory Syndrome. N Engl J Med 2003;348 
(20):1953-66.
Lau SK, Chan JF. Coronaviruses: Emerging and Re-Emerging Pathogens in Humans and 
Animals. Virology journal 2015;12:1-3.
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:
Who Mers-Cov Research Group. State of Knowledge and Data Gaps of Middle East Respiratory 
Syndrome Coronavirus (MERS-CoV) in Humans. PLoS currents 2013;5.
Wolfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Muller MA, et al. Virological 
Assessment of Hospitalized Patients with COVID-2019 [Abstract] [Accepted]. 
Nature 2020.
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with 
Pneumonia in China, 2019. N Engl J Med 2020.


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11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Pandemic Risk Assessment and Mitigation Plan
Appendix 3.
Study Procedures Tables
Appendix 4.
Management of Clinical and Laboratory Adverse Events
Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements


Rerndesivir (RDV; GS-5734"") 
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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404 
STUDY ACKNOWLEDGMENT 
FINAL 
Amendment3 
A Phase lb/2a Study in Participants with Early Stage COVID-19 to Evaluate the Safety, 
Efficacy, and Pharmacokinetics of Remdesivir Administered by Inhalation 
GS-US-553-9020, Amendment 3, 13 January 2021 
This protocol bas been approved by Gilead Sciences, Inc. The following signature documents 
this approval. 
PPD 
IPPD 
V 
I 
Date 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personuel 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 subjects being unable to attend 
study visits have been identified for this study.
These risks can be summarized as follows:
1) Study drug supplies to subjects and sites:
a) Subjects may be unable to return to the site for a number of visits to get the study drug, or 
the site may be unable to accept any subject visits. Without study drugs, the subject 
would not be able to stay on the study drug as planned per protocol.
Mitigation plan: Study drug supplies may be provided to the subject from the site without 
a clinic visit, once it is confirmed that the subject may safely continue on study drug as 
determined by the principal investigator (PI). A virtual study visit, via phone or video 
conferencing, must be performed prior to remote study drug resupply. At the earliest 
opportunity, the site will schedule in-person subject visits and return to the protocol’s 
regular schedule of assessments. A qualified courier may be utilized to ship the study 
drug from sites to study subjects if permitted by local ethics committee/institutional 
review boards (IRB)/Regulatory Authority as applicable and with sponsor’s approval.
b) Shipments of study drug could be delayed because of transportation issues. Without study 
drug subject would not be able to stay on the study drug as planned per protocol.
Mitigation plan: The sites’ study drug inventory should be closely monitored. Site staff 
should notify the sponsor or delegate if they foresee shortage in study drug inventory or if 
there is any interruption in local shipping service. The sponsor will continue to monitor 
inventory at the study drug depot and study sites. Manual shipments will be triggered as 
necessary.
2) Subject safety monitoring and follow-up:
a) Subjects may be unable or unwilling to come to the study site for their scheduled study 
visits as required per protocol.
Mitigation plan: For subjects 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 subject within 
target visit window date whenever possible. During the virtual study visit, the following 
information at minimum will be reviewed:
i)
Confirm if subject has experienced any adverse events (AEs)/serious adverse events 
(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 subjects study drug supply is sufficient to last until the next 
planned visit date. If study drug resupply is needed it will be provided as described 
above in (1).
v) If applicable, remind subject to maintain current dosing and to keep all dispensed 
study drug kits for return at the next on-site visit.
b) Subjects 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 subject safety until 
the subject 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.
c) Subjects may be unable or unwilling to attend the study visit to sign an updated informed 
consent form (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 subject 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.


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b) Monitors may be unable to carry out source data review or source data verification 
(SDV), or study drug accountability or assess protocol and GCP compliance. 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 subjects 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 subjects 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 subjects 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 RDV in study subjects remains unchanged.


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Appendix 3.
Study Procedures Tables
Appendix Table 1.
Study Parts A and B: Study Procedures Table
Schedule of Assessments
Screening
TREATMENT PERIOD
FOLLOW-UP PERIOD
Day 1a
Day 2
Day 3
Day 4
Day 5
Day 7
Day 14
(± 3 days)
Day 28b 
(± 5 days)
Obtain Informed Consent
X
Inclusion/Exclusion Criteria
X
Medical History 
X
Documentation of SARS-CoV-2
X
ECGc
X
Complete or Symptom-Directed Physical 
Examination
X
X
X
X
X
X
X
X
Body Weight
X
Height
X
Vital Signs (Heart Rate, Temperature, Blood 
Pressure, SpO2)
X
X
X
X
X
X
X
X
Completion of Daily Adapted FLU-PRO©
Questionnaired
X
X
X
X
X
X
X
Chest X-Raye
X
FEV1
X
X
X
X
X
Safety Laboratory Assessments (Hematology, 
Chemistry, Coagulation)
X
X
X
X
X
Pregnancy Test (Urine)
X
Serum FSH Testf
X
Nasopharyngeal and Oropharyngeal Swabs 
and Saliva Samples for 
SARS-CoV-2 RT-qPCR Testing and Possible 
Viral Resistance Testing
X
X
X
X
X
X
X
Sparse Plasma PK Assessmentsg
X
X


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TREATMENT PERIOD 
FOLLOW-UP PERIOD 
Schedule of Assessments 
Screening 
Day 1• 
Day 2 
Day 3 
Day 4 
Day s 
Day 7 
Day 14 
(± 3 days) 
Day 28b 
(± 5 days) 
---------------------------------------
Inhaled Remdesivir for Injection Formulation 
X 
X 
X 
X 
X 
or PTM Administrationi 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG = electrocardiogram; FEY 1 = forced expiratory volume in the first second of expiration; FLU-PRO° = lnFLUenza Patient-Reported Outcome; 
FSH = follicle-stimulating hormone; PCR = polymerase chain reaction; PK = pharmacokinetic(s); RT-qPCR = quantitative reverse transcriptase polymerase 
chain reaction; RDV = (remdesivir, GS 5734-rM); SARS-CoY-2 = severe acute respiratory syndrome coronavirus 2; SpO2 = oxygen saturation as measured by 
pulse oximetry 
a 
b 
C 
d 
e 
f 
I 
If the screening and Day I visits occur on the same day, no procedures need to be repeated. 
Day 28 assessments may be completed by telephone. 
ECG will not be re.quired at screening. However, ECG should be perfom1ed prior to dosing on Day I. If subject randomizes and doses on the same day as screening, then 
ECG will be done at screening. 
Adapted FLU PRO° questionnaire is to be completed daily (Days I 14). 
Chest x ray will be perfom1ed at Day I. If screening visit and Day I are the same day, chest x ray does not need to be repeated if completed as SOC < 2 days before 
screening. 
Semm FSH test: Childbearing female participants who are not postmenopausal (see Appendix 5 who do not wish to follow protocol defined contraception will need a semm 
FSH test (FSH test is re.quired for women who are < 54 years old and have sto 
ed menstmating for 2: 12 months but do not have documentation of ovarian hom10nal failure) 
S arse lasma PK will be collected at Da I end ofnebulization 
and Da 3 
redose and end ofnebulization . 
Inhaled Remdes1vir for Injection fomrnlation will be administered to participants at the site under close supervision. Healthcare professionals administering inhaled 
Remdesivir for Injection fomrnlation should have the appropriate medication available for immediate use in case of hypersensitivity. The participant should be treated 
according to the SOC for management of hypersensitivity reaction. After dose administration, monitoring should be done as follows: Approximately 30 minutes post dose 
administration, participants should be observed, and vital signs should be perfom1ed prior to discharge. 
CONFIDENTIAL 
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Appendix Table 2.
Study Part C: Study Procedures Table
Schedule of Assessments
Screeninga
TREATMENT PERIOD
FOLLOW-UP PERIOD
Day 1b
Day 2
Day 3
Day 4
Day 5
Day 7
Day 14c
(± 3 days)
Day 28c
(± 5 days)
Obtain Informed Consent
X
Inclusion/Exclusion Criteria
X
Medical History 
X
Documentation of SARS-CoV-2d
X
Complete or Symptom-Directed Physical 
Examination
X
X
X
X
X
Body Weight
X
Height
X
Vital Signs (Heart Rate, Temperature, Blood 
Pressure, SpO2)
X
X
X
X
X
Completion of Daily Adapted FLU-PRO©
Questionnairee
X
X
X
X
X
X
X
FEV1
X
X
X
X
X
Safety Laboratory Assessments (Hematology, 
Chemistry, Coagulation)
X
X
X
X
Pregnancy Test (Urine)
X
Serum FSH Testf
X
Nasopharyngeal and Oropharyngeal Swabs and 
Saliva Samples for 
SARS-CoV-2 RT-qPCR Testing and Possible 
Viral Resistance Testing
X
X
X
X
Sparse/Single Plasma PK Assessmentsg
X
X
X


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Schedule of Assessments
Screeninga
TREATMENT PERIOD
FOLLOW-UP PERIOD
Day 1b
Day 2
Day 3
Day 4
Day 5
Day 7
Day 14c
(± 3 days)
Day 28c
(± 5 days)
Remdesivir for Inhalation Solution Formulation or 
PTM Administrationh
X
X
X
X
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
COPD  chronic obstructive pulmonary disease; ECG  electrocardiogram; FEV1
forced expiratory volume in the first second of expiration; FLU PRO©
 InFLUenza 
Patient Reported Outcome; FSH  follicle stimulating hormone; PCR
polymerase chain reaction; PK  pharmacokinetic(s); RT qPCR  quantitative reverse transcriptase 
polymerase chain reaction; RDV  (remdesivir, GS 5734™); SARS CoV 2  severe acute respiratory syndrome coronavirus 2; SpO2
 oxygen saturation as measured by pulse 
oximetry
a
Study visits, with the exception of the screening visit, may be performed in clinic or at the participant’s home via home health and/or telehealth, virtually or remotely, as 
permitted by local and institutional regulations.
b
If the screening and Day 1 visits occur on the same day, no procedures need to be repeated.
c
Days 14 and 28 assessments may be completed by telephone.
d
Documentation of SARS CoV 2 infection first confirmed by nucleic acid testing or direct antigen testing with sample collected ≤ 4 days prior to randomization  
e
Adapted FLU PRO© questionnaire is to be completed daily (Days 1 14).
f
Serum FSH test: Childbearing female participants who are not postmenopausal (see Appendix 5) who do not wish to follow protocol defined contraception will need a serum 
FSH test (FSH test is required for women who are < 54 years old and have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure)
g
Sparse plasma PK will be collected at Days 3 and 5 (predose). A single anytime PK sample will be collected on Day 7 visit.
h
Remdesivir for Inhalation Solution formulation may be administered to participants in the participant’s home with in person or telehealth support. For participants with 
pre existing pulmonary conditions (ie, COPD or asthma) enrolled in Part C of the study, prescribed inhalers may not be used ≤30 minutes prior to Remdesivir for Inhalation 
Solution formulation administration. Healthcare professionals overseeing Remdesivir for Inhalation Solution formulation therapy remotely will observe the patient for any 
signs of adverse event. If any adverse event is observed and cannot be managed remotely, appropriate urgent care measures will be implemented. Approximately 30 minutes 
after dose administration, participants should be observed remotely prior to telehealth support session concluding.


Remdesivir (RDV; GS-5734T") 
Protocol GS-US-553-9020 
Gilead Sciences, Inc. 
FINAL 
Amendment3 
Appendix 4. 
Management of Clinical and Laboratory Adverse Events 
Grade 1 
Grade 2 
1: 
e 
on of 
May continue on th 
study at the discreti 
the invest gator 
" 
lfcoofirmed urrelated 
to the study drug. Oosing 
may contirue at the 
discretion of the 
ilvestigator 
CONFIDENTIAL 
Grade 3 
+ 
Repeat lab to coofinn 
tocicity grade 
' 
If confirmed and related 
to study drug, subject 
should be discontinued 
from thesrudy crug 
Page 75 
Grade 4 
-
If coofirmed and related to 
study drug, tl-e 
iwestigational prod.Jct 
should be discootinued and 
suqect managed according 
-, 
to bcal practice. Suq ect 
should be fol owed as 
clilically indi:ated lJlti the 
laboratory abnonnality 
returns to baseline, or is 
otherwise exp ailed 
13 January 2021 


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Appendix 5.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
1) Definitions
a. Definition of Childbearing Potential
For the purposes of this study, a female born participant is considered of childbearing potential 
until becoming postmenopausal, unless permanently sterile or with 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 of any age with amenorrhea of > 12 months may also be considered 
postmenopausal if their follicle-stimulating hormone (FSH) level is in the postmenopausal range 
and they are not using hormonal contraception or hormonal replacement therapy.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female participant of any age.
b. Definition of Male Fertility
For the purposes of this study, a male born participant is considered of fertile after the initiation 
of puberty unless permanently sterile by bilateral orchidectomy or with medical documentation.
2) Contraception Requirements for Female Participants
a. Study Drug Effects on Pregnancy and Hormonal Contraception
In nonclinical reproductive toxicity studies, RDV demonstrated no adverse effect on embryofetal 
development when administered to pregnant animals. Embryonic toxicity was seen when RDV 
was initiated in female animals prior to mating and conception, but only a at a systemically toxic 
dose. RDV has not yet been studied in pregnant women. Before enrolling participants into 
studies with RDV, women of childbearing potential must have pregnancy testing performed at 
screening.
Available data indicate that RDV potentially causes an interaction with hormonal contraception, 
but the effect is considered to be of limited clinical significance. Hormonal methods must be 
used together with a barrier method.
Refer to the latest version of the IB for additional information.


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b. Contraception Requirements for Female Participants of Childbearing Potential
The inclusion of female participants of childbearing potential requires using at least an 
acceptable effective contraceptive measure. They must have a negative urine pregnancy test at 
screening prior to enrollment. In the event of a delayed menstrual period (over 1 month between 
menstruations), a pregnancy test must be performed to rule out pregnancy. This is applicable also 
for women of childbearing potential with infrequent or irregular periods. They must also agree to 
one of the following until Day 28:

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 one of the following methods of birth control listed below:
Non-hormonal intrauterine device (IUD)
Hormonal IUD (must be used with a barrier method)
Tubal sterilization
Essure® micro-insert system (provided confirmation of success 3 months after procedure)
Vasectomy in the male partner (provided that the partner is the sole sexual partner and 
had confirmation of surgical success 3 months after procedure)
Or

Barrier methods
Female barriers: Diaphragm with spermicide, cervical cap with spermicide, or sponge 
with spermicide
Male barriers: Male condom (with or without spermicide)
Or

Hormonal methods are restricted to drugs associated with the inhibition of ovulation. Each 
method must be used with a barrier method, preferably male condom. Hormonally-based 
contraceptives permitted for use in this protocol are as follows:
Oral contraceptives (either combined or progesterone only)
Injectable progesterone


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Subdermal contraceptive implant
Transdermal contraceptive patch
Contraceptive vaginal ring
Female participants must also refrain from egg donation and in vitro fertilization during 
treatment and until the last investigational product dose.
3)
Contraception Requirements for Male Participants
During the study, male participants with female partners of childbearing potential should use 
condoms until Day 28 when engaging in intercourse of reproductive potential.
4)
Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, 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
Participants will be instructed to notify the investigator and discontinue investigational product 
immediately, if they become pregnant at any time during the study. Participants whose partner 
has become pregnant or suspects she is pregnant during the study must report the information to 
the investigator. Instructions for reporting pregnancy, partner pregnancy, and pregnancy outcome 
are outlined in Section 7.4.2.3.

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A Phase 1b/2a Study in Participants with Early Stage 
COVID-19 to Evaluate the Safety, Efficacy, and 
Pharmacokinetics of Remdesivir Administered by Inhalation
Name of Test Drug:
Remdesivir 
Study Number:
GS-US-553-9020
Protocol Version (Date):
Amendment 3: 
13 January 2021
Analysis Type:
Final Analysis
Analysis Plan Version:
1.0
Analysis Plan Date:
04 June 2021
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION
PPD
GILEAU 


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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................................................2
LIST OF ABBREVIATIONS.........................................................................................................................................4
PHARMACOKINETIC ABBREVIATIONS.................................................................................................................6
1.
INTRODUCTION..................................................................................................................................................7
1.1.
Study Objectives........................................................................................................................................7
1.2.
Study Endpoints.........................................................................................................................................7
1.3.
Study Design .............................................................................................................................................9
1.4.
Sample Size and Power ...........................................................................................................................11
2.
TYPE OF PLANNED ANALYSIS......................................................................................................................12
2.1.
Interim Analyses......................................................................................................................................12
2.2.
Final Analysis..........................................................................................................................................12
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES.............................................................................13
3.1.
Analysis Sets ...........................................................................................................................................13
3.1.1.
All Randomized Analysis Set................................................................................................13
3.1.2.
Full Analysis Set....................................................................................................................13
3.1.3.
Modified Full Analysis Set....................................................................................................13
3.1.4.
Safety Analysis Set................................................................................................................14
3.1.5.
Pharmacokinetic Analysis Set ...............................................................................................14
3.2.
Participant Grouping ...............................................................................................................................14
3.3.
Strata and Covariates...............................................................................................................................14
3.4.
Examination of Participant Subgroups....................................................................................................15
3.5.
Multiple Comparisons .............................................................................................................................15
3.6.
Missing Data and Outliers.......................................................................................................................15
3.6.1.
Missing Data..........................................................................................................................15
3.6.2.
Outliers ..................................................................................................................................15
3.7.
Data Handling Conventions and Transformations ..................................................................................15
3.8.
Analysis Visit Windows..........................................................................................................................17
3.8.1.
Definition of Study Day ........................................................................................................17
3.8.2.
Analysis Visit Windows........................................................................................................18
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window .................................................................................................................................20
4.
PARTICIPANT DISPOSITION ..........................................................................................................................22
4.1.
Participant Enrollment and Disposition...................................................................................................22
4.2.
Extent of Study Drug Exposure...............................................................................................................22
4.3.
Protocol Deviations .................................................................................................................................23
5.
BASELINE CHARACTERISTICS .....................................................................................................................24
5.1.
Demographics and Baseline Characteristics ...........................................................................................24
5.2.
Other Baseline Characteristics ................................................................................................................24
5.3.
Additional Baseline Characteristics ........................................................................................................25
5.4.
Medical History.......................................................................................................................................25
6.
EFFICACY ANALYSES.....................................................................................................................................26
6.1.
Primary Efficacy Endpoint......................................................................................................................26
6.1.1.
Definition of the Primary Efficacy Endpoint ........................................................................26
6.1.2.
Statistical Hypothesis for the Primary Efficacy Endpoint.....................................................26
6.1.3.
Analysis of the Primary Efficacy Endpoint...........................................................................27


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6.2. 
Secondruy Efficacy Endpoints ................................................................................................................ 27 
. 
. 
7. 
SAFETY ANALYSES ......................................................................................................................................... 31 
7.1. 
Adverse Events and Deaths ..................................................................................................................... 31 
7.1. 1. 
Adverse Event Dictionaty .................................................................................................... .31 
7.1.2. 
Adverse Event Severity ......................................................................................................... 31 
7.1.3. 
Relationship of Adverse Events to Study Dmg ..................................................................... 31 
7.1.4. 
Relationship of Adverse Events to Study Procedme ............................................................. 32 
7.1.5. 
Serious Adverse Events ......................................................................................................... 32 
7.1.6. 
Treattnent-Emergent Adverse Events .................................................................................... 32 
7 .1.6.1. 
Definition of Treattnent-Emergent Adverse Events ........................................ 32 
7.1.6.2. 
Incotnplete Dates ............................................................................................. 32 
7.1.7. 
Smnmaries of Adverse Events and Deaths ............................................................................ 33 
7.2. 
Laboratoty Evaluations ........................................................................................................................... 34 
7.2.1. 
Smnmaries of Numeric Labora.t01y Results .......................................................................... 34 
7.2.2. 
Graded Laboratoty Values .................................................................................................... 35 
7 .2.2.1. 
Treattnent-Emergent Laborat01y Abnonnalities ............................................. 35 
7.2.2.2. 
Smnmaries of Laborat01y Abnonnalities ........................................................ 35 
7.3. 
Vital Signs, SpO2, and FEV1 ................................................................................................................... 36 
7.4. 
Prior and Concomitant Medications ........................................................................................................ 36 
7.5. 
Electrocru·diogratn Results ....................................................................................................................... 37 
7.6. 
Other Safety Measmes ............................................................................................................................ 37 
7 .7. 
Changes from Protocol-Specified Safety Analyses ................................................................................. 37 
8. 
PHARMA CO KINETIC ANALYSES .................................................................................................................. 38 
9. 
REFERENCES ..................................................................................................................................................... 39 
10. SOFTWARE ........................................................................................................................................................ .40 
11. SAP REVISION .................................................................................................................................................. .41 
12. APPENDICES ..................................................................................................................................................... .42 
Appendix 1. 
Appendix 2. 
Table 3-1. 
Table 3-2. 
Table 3-3. 
Table 3-4. 
Table 3-5. 
Table 3-6. 
CONFIDENTIAL 
Schedule of Assessments ........................................................................................................ .43 
Programming Specifications ................................................................................................... .4 7 
LIST OF IN-TEXT TABLES 
Analysis Visit Windows for Vita.I Signs, and SpO2 in Patts A and B ..................................... 18 
Analysis Visit Windows for Vita.I Signs and SpO2 in Part C .................................................. 18 
Analysis Visit Windows for SARS-Co V-2 Viral Load in Patts A and B ............................... 19 
Analysis Visit Windows for SARS-Co V-2 Viral Load in Patt C ............................................ 19 
Analysis Visit Windows for Hematology, Coagulation, and Chemistiy Laboratoty 
Tests in Patts A and B ............................................................................................................. 19 
Analysis Visit Windows for Hematology, Coagulation, and Chemistiy Laboratoty 
Tests in Patt C .......................................................................................................................... 20 
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LIST OF ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
AUC
area-under-the-curve
BLQ
below the limit of quantitation
BMI
body mass index
CI
confidence interval
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
DOB
date of birth
FAS
Full Analysis Set
FEV1
forced expiratory volume in the first second of expiration
FLU-PRO©
InFLUenza Patient-Reported Outcome
Hb
Hemoglobin
HLT
high-level term
HLGT
high-level group term
ICH
International Conference on Harmonization (of Technical Requirements for Registration of 
Pharmaceuticals for Human Use)
IXRS
interactive voice or web response system
LLT
lower-level term
LOQ
limit of quantitation
MAVs
medically attended visits
MedDRA
Medical Dictionary for Regulatory Activities
mFAS
Modified full analysis set
PCR
polymerase chain reaction
PK
pharmacokinetics
PT
preferred term
PTM
Placebo to match
Q1, Q3
first quartile, third quartile
RDV
remdesivir (GS-5734™)
RNA 
ribonucleic acid
RT-qPCR 
quantitative reverse transcriptase polymerase chain reaction
SAE
serious adverse event
SAP
statistical analysis plan


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SARS
severe acute respiratory syndrome
SE
standard error
SD
standard deviation
SOC
system organ class
SpO2
oxygen saturation
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
WHO
World Health Organization


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PHARMACOKINETIC ABBREVIATIONS
AUClast
area under the concentration versus time curve from time zero to the last quantifiable 
concentration
AUCtau
area under the concentration versus time curve over the dosing interval
Clast
last observed quantifiable concentration of the drug 
Cmax
maximum observed concentration of drug 
Ctau
observed drug concentration at the end of the dosing interval
CLss/F
apparent oral clearance after administration of the drug:
at steady state: CLss/F = Dose/AUCtau , where “Dose” is the dose of the drug
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)
Tlast
time (observed time point) of Clast
Tmax
time (observed time point) of Cmax
z
terminal elimination rate constant, estimated by linear regression of the terminal elimination 
phase of the concentration of drug versus time curve
Vz/F
apparent volume of distribution of the drug


Remdesivir (RDV; GS-5734'™) 
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Version 1.0 
L 
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 repo1t (CSR) 
for Study GS-US-553-9020. This SAP is based on the study Protocol Amendment 3 dated 
13 Januaiy 2021 and the electronic case repo1t f01m (eCRF). The SAP will be finalized before 
database finalization. Any changes made to the SAP after the finalization will be documented in 
the CSR. 
1.1. 
Study Objectives 
The prima1y objective of this study is: 
• 
To chai·acterize the impact of inhaled RDV on SARS-Co V-2 viral load in participants with 
eai·ly stage COVID-19 
The secondaiy objectives of this study are as follows: 
• 
To evaluate the safety and tolerability of inhaled Remdesivir for Injection fo1mulation in 
pait icipants with eai·ly stage COVID-19 
• 
To evaluate the PK of inhaled Remdesivir for Injection fo1mulation and its metabolites in 
pait icipants with eai·ly stage COVID-19 in Paits A and B 
• 
To chai·acterize and evaluate disease progression from baseline 
• 
To chai·acterize the efficacy, safety, and tolerability of Remdesivir for Inhalation Solution 
fo1mulation administered with a mouthpiece in Pait C of the study 
I 
I 
1.2. 
Study Endpoints 
The primaiy endpoint of this study is: 
• 
Time weighted average change in SARS-CoV-2 viral load which is defined as AUC of viral 
load change divided by time between baseline through Day 7 
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Remdesivir (RDV; GS-5734'™) 
GS-US-553-9020 Statistical Analysis Plan - Final Analysis 
The secondaiy endpoints of this study are: 
• 
Propo1t ion of pa1t icipants with treatment-emergent AEs (TEAEs) and laborato1y 
abnonnalities 
• 
Proportion of paiticipants with TEAEs leading to study treatment discontinuation 
Version 1.0 
• 
Composite of all-cause medically attended visits (MA Vs) (medical visits attended in person 
by the paiticipant and a health care professional) or death by Day 28 
• 
Composite of COVID-19 related medically attended visits (MA Vs) (medical visits attended 
in person by the paiticipant and a health cai·e professional) or death by Day 28 
• 
Propo1t ion of pa1t icipants hospitalized by Day 28 
• 
Chai·acterization of the plasma concentrations of inhaled RDV and its metabolites including 
AUCo-24h, AUC1ast, CLssJF, t112, VzJF, Cmax, Tmax, C1ast, T1ast, AUCtau, Az, and Ctau (Parts A and B 
only) 
• 
Change in SARS-CoV-2 viral load from baseline to Day 5 
• 
Change in SARS-Co V-2 viral load from baseline to Day 7 
• 
Change in SARS-CoV-2 viral load from baseline to Day 14 (Paits A and B only) 
• 
Time to negative SARS-CoV-2 polymerase chain reaction (PCR) 
• 
Time to alleviation (mild or absent) of baseline COVID-19 symptoms as repo1ted on the 
COVID-19 adapted InFLUenza Patient-Reported Outcome (FLU-PRO'°) questionnaire 
I 
I 
I 
I 
I 
I 
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1.3.
Study Design
This is a randomized, blinded, placebo-controlled, multicenter study to evaluate the safety, 
efficacy, and PK of inhaled RDV in participants with early stage COVID-19. The study will be 
conducted in 3 parts (Parts A, B, and C).
Parts A and B
In Part A, approximately 36 eligible participants will be randomized in a 1:1:1 ratio to receive 
1 of the following 3 study treatments administered via facemask:
Treatment Group 1: 31 mg inhaled Remdesivir for Injection formulation daily for 5 days
Treatment Group 2: 31 mg inhaled Remdesivir for Injection formulation daily for 3 days 
followed by PTM daily for 2 days
Treatment Group 3: PTM daily for 5 days
Part A
In Part B, if supported by Phase 1a data in healthy volunteers, an additional 36 eligible 
participants may be randomized in a 1:1:1 ratio to receive 1 of the following 3 study treatments 
administered via facemask:
Treatment Group 4: 62 mg inhaled Remdesivir for Injection formulation daily for up to 5 days
Treatment Group 5: 62 mg inhaled Remdesivir for Injection formulation daily for up to 3 days 
followed by PTM through Day 5
Treatment Group 6: PTM daily for 5 days
n = 12 
n = 36 
Randomized 
n = 12 
1:1:1 
n = 12 
I 
I 
I 
Inhaled Remdesivir for Injection formulation daily 
for 5 days, 31 mg nominal dose 
Inhaled Remdesivir for Injection formulation daily 
for 3 days, 31 mg nominal dose 
PTM daily for 5 days 


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Part B
In Parts A and B, at in-clinic screening, after the participant has provided informed consent, 
assessments will include but are not limited to the following: demographic and baseline 
characteristics, medical history, and concomitant medications will be documented. Body weight 
and height will be measured. A urine pregnancy test will be performed for women of 
childbearing potential. Vital signs including heart rate, temperature, blood pressure, respiration 
rate and SpO2 will be recorded. A complete physical examination will be performed.
Participants with PCR-confirmed COVID-19 who enroll in the study will return to clinic daily on 
Days 1 through 5 for study treatment administration and clinical assessments. Participants will 
return to clinic on Days 7 and 14 for follow-up clinical assessment and undergo a Day 28 
follow-up which may be completed by telephone.
Part C
Part C of the study will include an expanded safety and efficacy assessment of an additional 
80 participants. Participants in Part C will be enrolled after review of preliminary safety data 
from Parts A and B through at least Day 7. Approximately 80 eligible participants will be 
randomized in a 3:1 ratio to receive 1 of the following 2 study treatments administered via 
mouthpiece:
Treatment Group 7: 39 mg Remdesivir for Inhalation Solution formulation once daily for 
5 days
Treatment Group 8: PTM daily for 5 days
n = 36 
Randomized 
1:1:1 
n = 80 
Randomized 
3:1 
n = 12 
n = 12 
n = 12 
n = 60 
n = 20 
I 
I 
I 
I 
I 
Inhaled Remdesivir for Injection formulation daily 
for up to 5 days, 62 mg nominal dose 
Inhaled Remdesivir for Injection formulation daily 
for up to 3 days, 62 mg nominal dose 
PTM daily for 5 days 
Remdesivir for Inhalation Solution formulation daily 
for 5 days by mouthpiece, 39 mg nominal dose 
PTM daily for 5 days by mouthpiece 


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At screening, after the participant has provided informed consent, assessments will include but 
are not limited to the following: demographic and baseline characteristics, medical history, and 
concomitant medications will be documented. Body weight and height will be measured. A urine 
pregnancy test will be performed for women of childbearing potential. Vital signs including heart 
rate, temperature, blood pressure, respiration rate and SpO2 will be recorded. A complete 
physical examination will be performed.
In Part C, participants with nucleic acid testing, direct antigen testing, or PCR-confirmed 
COVID-19 who enroll in the study will be administered Remdesivir for Inhalation Solution 
formulation or PTM on Days 1 through 5. Clinical assessments may be conducted at home with 
the assistance of home nursing on Days 1, 3, 5, and 7. Participants will undergo Days 14 and 28 
telephone contact follow-ups.
Additional details regarding study assessment can be found in Appendix 1.
1.4.
Sample Size and Power
The sample size in this study is determined based on practical considerations and past experience 
with similar types of studies. No sample size or power calculation was performed. A sample size 
up to approximately 152 participants (72 participants for Part A and Part B; 80 participants for 
Part C) should provide a suitable assessment of the descriptive efficacy, PK, and safety profiles 
in this population.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Interim Analyses
No interim analysis is planned.
2.2.
Final Analysis
The unblinded final analysis will be performed after all participants have completed the study, 
outstanding data queries have been resolved or adjudicated as unresolvable, and the data have 
been cleaned and finalized.


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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 study part and participant identification (ID) number in ascending order, visit date, 
and time (if applicable), unless otherwise specified. Data collected on log forms, such as AEs, 
will be presented in chronological order within the participant. The treatment group to which 
participants were randomized will be used in the listings. Age, sex at birth, race, and ethnicity 
will be included in the listings, as space permits.
3.1.
Analysis Sets
Analysis sets define the participants to be included in an analysis. Analysis sets and their 
definitions are provided in this section. 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 included will be summarized in 
the disposition table by treatment group as described in Section 4.
A listing of reasons for exclusion from analysis sets will be provided by participant.
3.1.1.
All Randomized Analysis Set
The all Randomized Analysis Set includes all participants who are randomized into the study.
3.1.2.
Full Analysis Set
The Full Analysis Set (FAS) includes all participants who (1) are randomized into the study, and 
(2) have received at least 1 dose of study treatment. Participants will be grouped according to the 
treatment to which they were randomized. This is the primary analysis set for MAVs and 
FLU-PRO questionnaire analyses.
3.1.3.
Modified Full Analysis Set
The modified Full Analysis Set (mFAS) includes all participants who (1) are randomized into the 
study, (2) have received at least 1 dose of study treatment, and (3) have positive SARS-CoV-2 
viral load at baseline (result of ‘No SARS-CoV-2 detected’ is considered as negative). The 
mFAS is defined separately for SARS-CoV-2 viral load from nasopharyngeal swab sample 
(Nasopharyngeal mFAS), oropharyngeal swab samples (Oropharyngeal mFAS), and saliva 
samples (Saliva mFAS). Participants will be grouped according to the treatment to which they 
were randomized. The mFAS is the primary analysis set for SARS-CoV-2 viral load analyses.


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3.1.4.
Safety Analysis Set
The primary analysis set for safety analyses is defined as the Safety Analysis Set, which includes 
all participants who (1) are randomized into the study and (2) have received at least 1 dose of 
study treatment. Participants will be grouped according to the actual treatment received. 
3.1.5.
Pharmacokinetic Analysis Set
The PK Analysis Set is defined separately for each analyte and includes all participants who 
(1) are randomized into the study, (2) have received at least 1 dose of RDV, (3) have at least 1 
nonmissing postdose PK concentration datum reported by the PK laboratory. Participants will be 
grouped according to the actual treatment received. 
3.2.
Participant Grouping
For analyses based on the All Randomized Analysis Set, FAS, or mFAS, participants will be 
grouped according to the treatment to which they were randomized. For analyses based on the 
Safety Analysis Set, participants will be grouped according to the actual treatment received. The 
actual treatment received will differ from the randomized treatment only when their actual 
treatment differs from randomized treatment for the entire treatment duration. For the PK 
Analysis Set, participants will be grouped according to the actual treatment received.
The analysis of time-weighted average change from baseline through day 7 (DAVG7) in 
SARS-CoV-2 viral load based on the mFAS, and time to COVID-19-related MAVs or all-cause 
death by Day 28 based on the FAS may also be grouped according to the following:

5 RDV treatments (31 mg for 3 days vs. 31 mg for 5 days vs. 62 mg for 3 days vs. 62 mg for 
5 days vs. 39 mg for 5 days) vs. pooled PTM (Parts A, B, and C)

Pooled all RDV treatments (31 mg for 3 days, 31 mg for 5 days, 62 mg for 3 days, 62 mg for 
5 days, and 39 mg for 5 days) vs. pooled PTM (Parts A, B, and C)

Pooled 31 mg RDV (31 mg for 3 days and 31 mg for 5 days) vs. pooled 62 mg RDV (62 mg 
for 3 days and 62 mg for 5 days) vs. 39 mg RDV for 5 days vs. pooled PTM (Parts A, B, and 
C) 
3.3.
Strata and Covariates
For the primary efficacy endpoint, the baseline value of the SARS-CoV-2 viral load will be 
included as a covariate in the efficacy analysis model.
This study does not use a stratified randomization schedule when enrolling participants.


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3.4.
Examination of Participant Subgroups
The primary efficacy endpoint will be examined using the following subgroups:

Age: < 60 years and  60 years

Sex at birth: male and female

Race: (a) Asian, (b) Black, (c)White, and (d) other (all races other than Asian, Black and 
White including Not Permitted)

Baseline SARS-CoV-2 viral load (log10 copies/ml): < median and  median
If there is an imbalance between treatment groups in the presumed prognostic baseline 
characteristics that are not prespecified, subgroupings based on these imbalanced baseline 
characteristics may also be explored for analysis of efficacy endpoints.
3.5.
Multiple Comparisons
No prespecified multiplicity adjustments are planned for confidence intervals or statistical tests.
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 (i.e., no 
toxicity grade) for the laboratory abnormality summary. The handling of missing or incomplete 
dates for AE onset is described in Section 7.1.6.2, and for prior and concomitant medications in 
Section 7.4.
3.6.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be done to evaluate the impact of outliers on efficacy or safety 
outcomes, unless specified otherwise. All data will be included in the analyses.
3.7.
Data Handling Conventions and Transformations
In general, age collected at Day 1 (in years) will be used for analyses and presented in listings. If 
age at Day 1 is not available for a participant, then age derived based on date of birth and the 
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.


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Laboratory data that are continuous in nature but are less than the lower limit of quantitation 
(LOQ) or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “ x” (where x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate summary statistics. An exception to this rule is any value reported as < 1 or < 0.1, 
etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used to 
calculate summary statistics.

A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.

The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).
SARS-CoV-2 viral load results that are below LOQ but have a positive signal will be reported as 
“< 2228cp/mL SARS-CoV-2 detected” (nasopharyngeal/oropharyngeal swabs) or “<1390cp/mL 
SARS-CoV-2 detected” (saliva) and those that are below LOD and negative will be reported as 
“No SARS-CoV-2 detected”. The data will be imputed as follows:

A value of 1114 copies/ml (1/2 of the LOQ of 2228 copies/ml) will be used to calculate 
descriptive statistics if the datum is reported as “< 2228cp/mL SARS-CoV-2 detected” from 
nasopharyngeal/oropharyngeal swab sample. 

A value of 746.5 copies/ml (1/2 of the LOD of 1493 copies/ml) will be used to calculate 
descriptive statistics if the datum is reported as “No SARS-CoV-2 detected” from 
nasopharyngeal/oropharyngeal swab sample.

A value of 695 copies/ml (1/2 of the LOQ of 1390 copies/ml) will be used to calculate 
descriptive statistics if the datum is reported as “< 1390cp/mL SARS-CoV-2 detected” from 
saliva sample. 

A value of 501 copies/ml (1/2 of the LOD of 1002 copies/ml) will be used to calculate 
descriptive statistics if the datum is reported as “No SARS-CoV-2 detected” from saliva 
sample.
Any SARS-CoV-2 viral load samples collected on or after the participants are receiving 
additional COVID-19 treatments (see Appendix 2) will be excluded from the viral load analysis.
Patients with negative viral load at baseline are not included in the viral load analysis.
Base 10 logarithm transformation will be used for analyzing SARS-CoV-2 viral load.
Sparse PK concentration values that are below the limit of quantitation (BLQ) will be presented 
as “BLQ” in the data listing. 


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Natural logarithm transformation will be used for analyzing concentrations. Concentration values 
that are BLQ will be presented as “BLQ” in the concentration data listing.  For intensive PK 
concentration, values that are BLQ will be treated as 0 at predose time points, and one-half the 
value of the LOQ at postdose time points for summary purpose. For predose or postdose 
timepoint of sparse PK and single anytime PK, values that are BLQ will be treated as one-half 
the value of the LLOQ for summary purpose. 
The following conventions will be used for the presentation of summary and order statistics: 

If at least 1 subject has a concentration value of BLQ for the time point, the minimum value 
will be displayed as “BLQ.”

If more than 25% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum and Q1 values will be displayed as “BLQ.” 

If more than 50% of the subjects 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 subjects 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 subjects have concentration data values of BLQ for a given time point, all order 
statistics (minimum, Q1, median, Q3, and maximum) and summary statistics will be 
displayed as “BLQ.”
3.8.
Analysis Visit Windows
3.8.1.
Definition of Study Day
Study Day 1 is defined as the first dosing date of study drug.
Study Days are calculated relative to Study Day 1 and derived as follows:

For postdose study days: Assessment Date – First Dosing Date + 1

For days prior to the first dose: Assessment Date – First Dosing Date 
Therefore, Study Day 1/ First Dose Date is the day of first dose of study drug administration, as 
recorded on the Study Drug Administration eCRF form.
Last Dose Date is defined as the maximum, nonmissing, nonzero dose end date of treatment 
recorded on the Study Drug Administration eCRF form with “Study Drug Permanently 
Withdrawn” box checked for participants who prematurely discontinued or completed study drug 
according to the Study Drug Completion eCRF.


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Last Study Date is the latest of the study drug start dates and end dates, the clinic visit dates, 
FLU-PRO questionnaire collection date, and the laboratory visit dates, including the 28-day 
follow-up visit date, and the death date (if applicable, only for participants who prematurely 
discontinued study according to the Study Completion eCRF).
Baseline value is defined as the last value obtained on or prior to the first dose date (and time, 
if available) unless otherwise specified (see Section 3.8.3).
3.8.2.
Analysis Visit Windows
Participant visits might not occur on protocol-specified days. Therefore, for the purpose of 
analysis, observations will be assigned to analysis windows.
The analysis windows for vital signs and SpO2 are provided in Table 3-1 (Parts A and B) and 
Table 3-2 (Part C).
Table 3-1.
Analysis Visit Windows for Vital Signs, and SpO2 in Parts A and B
Visit Window Study Day
Nominal Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1
(none) 
1 (pre dose)*
Day 1
1
1 (post dose)
1
Day 2
2
2
2
Day 3
3
3
3
Day 4
4
4
4
Day 5
5
5
6
Day 7
7
7
9
Day 14
14
10
21
Post Day 14
28
22
(None)
* 
For Baseline, the upper limit includes values collected at or prior to the first dose date/time.
Table 3-2.
Analysis Visit Windows for Vital Signs and SpO2 in Part C
Visit Window Study Day
Nominal Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1
(none)
1 (pre dose)*
Day 1
1
1 (post dose)
1
Day 3
3
2
4
Day 5
5
5
6
Day 7
7
7
13
Post Day 7
14
14
(None)
* 
For Baseline, the upper limit includes values collected at or prior to the first dose date/time.
The analysis windows for SARS-CoV-2 viral load are provided in Table 3-3 (Parts A and B) and 
Table 3-4 (Part C).


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Table 3-3.
Analysis Visit Windows for SARS-CoV-2 Viral Load in Parts A and B
Visit Window Study Day
Nominal Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1
(none)
1 (pre dose)*
Day 2
2
1 (post dose)
2
Day 3
3
3
3
Day 4
4
4
4
Day 5
5
5
6
Day 7
7
7
9
Day 14
14
10
21
Post Day 14
28
22
(None)
* 
For Baseline, the upper limit includes values collected at or prior to the first dose date/time.
Table 3-4.
Analysis Visit Windows for SARS-CoV-2 Viral Load in Part C
Visit Window Study Day
Nominal Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1
(none)
1 (pre dose)*
Day 3
3
1 (post dose)
4
Day 5
5
5
6
Day 7
7
7
9
Post Day 7
14
10
(None)
* 
For Baseline, the upper limit includes values collected at or prior to the first dose date/time.
The analysis windows for hematology, coagulation, and chemistry laboratory tests are provided 
in Table 3-5 (Parts A and B) and Table 3-6 (Part C).
Table 3-5.
Analysis Visit Windows for Hematology, Coagulation, and Chemistry 
Laboratory Tests in Parts A and B
Visit Window Study Day
Nominal Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1
(none)
1 (pre dose)*
Day 3
3
1 (post dose)
4
Day 5
5
5
6
Day 7
7
7
9
Day 14
14
10
21
Post Day 14**
28
22
(None)
* 
For Baseline, the upper limit includes values collected at or prior to the first dose date/time
**
Post Day 14 laboratory values will be considered for treatment-emergent laboratory presentations only.


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Table 3-6.
Analysis Visit Windows for Hematology, Coagulation, and Chemistry 
Laboratory Tests in Part C
Visit Window Study Day
Nominal Visit
Nominal Study Day
Lower Limit
Upper Limit
Baseline
1
(none)
1 (pre dose) *
Day 3
3
1 (post dose)
4
Day 5
5
5
6
Day 7
7
5
13
Post Day 7**
14
14
(None)
* 
For Baseline, the upper limit includes values collected at or prior to the first dose date/time.
**
Post Day 7 laboratory values will be considered for treatment-emergent laboratory presentations only.
FEV1 will be performed daily during treatment days; therefore, windows are not assigned and 
results will be summarized for each study day. Participants will complete the adapted FLU-PRO 
Questionnaire daily from Day 1 through Day 14; therefore, windows are not assigned and results 
will be summarized for each study day. 
3.8.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window
Depending on the statistical analysis method, single values may be required for each analysis 
window or study day. For example, change from baseline by visit usually requires a single value, 
whereas a time-to-event analysis would not require 1 value per analysis window or study day.
If multiple valid, nonmissing measurements exist in an analysis window or study day, records will 
be chosen based on the following rules if a single value is needed:

For baseline, the last nonmissing value on or prior to the first dosing date (and time, if 
available) of study drug will be selected, unless specified differently. If there are multiple 
records with the same time or no time recorded on the same day, the baseline value will be 
the average of the measurements for continuous data, or the measurement with the lowest 
severity for categorical data.
For FLU-PRO data, if there are multiple records on Day 1, the baseline value will be 
selected as follows:
■
The record closest to the dosing day will be selected. 
■
If there are more than 1 records on the selected day with different times, the least 
severe score will be selected as baseline. If there are multiple records with same 
severity, the measurement with the lowest severity at later time will be selected. 

For postbaseline values (other than PCR negative confirmation and PCR for DAVG):
The record closest to the nominal day for that visit will be selected with the exception of 
viral load in which the latest record will be selected.


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If there are 2 records that are equidistant from the nominal day, the later day will be 
selected.
If there is more than 1 record on the selected day, values will be selected for analysis as 
follows:
■
For viral load, if there is more than 1 record on the selected day, the latest value will 
be selected. If there are multiple records with the same time or no time recorded on 
the same day, the geometric mean value (copies/mL) will be taken. 
■
For FLU-PRO questionnaire response, the worst severity will be taken if there is 
more than 1 record on the selected day. If the severity is the same, the latest record 
will be selected.
■
For other parameters, if there is more than 1 record on the selected day, the average 
will be taken for continuous data and the worst severity will be taken for categorical 
data, unless otherwise specified.

For postbaseline values of PCR negative confirmation (separately by sample types):
Use all available data to derive negative confirmation except if there are multiple records 
on the same day, worst value will be used for negative confirmation for that day
The record closest to the nominal day for that visit will be selected.
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.

For postbaseline values PCR for DAVG calculation:
All values from different days within an analysis window will be used for DAVG 
calculation.
If there is more than 1 record on a study day, the latest value will be selected. If there are 
multiple records with the same time or no time recorded on the same day, the geometric 
mean value (copies/mL) will be taken.


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4.
PARTICIPANT DISPOSITION
4.1.
Participant Enrollment and Disposition
A summary of participant enrollment will be provided by treatment group and overall for each 
investigator site by study part using the Safety Analysis Set. The summary will present the 
number and percentage of participants enrolled. For each column, the denominator for the 
percentage calculation will be the total number of participants analyzed for that column.
A summary of participant disposition will be provided by treatment group and overall by study 
part for all screened participants. This summary will present the number of participants screened, 
screen failure participants who were not enrolled, participants who met all eligibility criteria but 
were not randomized, participants randomized, participants randomized but never treated, and 
participants in each of the categories listed below:

Safety Analysis Set

Full Analysis Set

Modified Full Analysis Set for each sample type

PK Analysis Set for each analyte
In addition, the number and percentage of the participants in the following categories will be 
summarized: 

Completed randomized treatment as recorded on the Study Drug Completion form

Prematurely discontinuing study drug prior to completion of dosing with summary of reasons 
for discontinuing study drug as recorded on the Study Drug Completion form

Completed study

Prematurely discontinuing study
The denominator for the percentages of participants in each category will be the number of 
participants in the Safety Analysis Set. 
No inferential statistics will be generated. A data listing of reasons for premature study 
drug/study discontinuation will be provided.
4.2.
Extent of Study Drug Exposure
Number of doses received will be summarized as continuous and categorical variables by 
treatment groups including placebo group for the Safety Analysis Set.  Exposure data will be 
listed.


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4.3.
Protocol Deviations 
A listing will be provided for those participants who did not meet at least 1 eligibility (inclusion 
or exclusion) criterion. The listing will present the eligibility criterion (or criteria if more than 1 
deviation) that participants did not meet and related comments, if collected.
Protocol deviations occurring after participants entered the study are documented during routine 
monitoring. The number and percentage of participants with important protocol deviations and 
the total number of important protocol deviations by deviation reason (e.g., nonadherence to 
study drug, violation of select inclusion/exclusion criteria) will be summarized by treatment 
group for the FAS. A by-participant listing will be provided for those participants with important 
protocol deviation.


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Baseline Characteristics
Participant demographic variables (i.e., age, sex at birth, race, and ethnicity) and baseline 
characteristics (body weight [in kg], height [in cm], body mass index [BMI; in kg/m2]) will be 
summarized by part and treatment group and overall using descriptive statistics (n, mean, SD, 
median, Q1, Q3, minimum, and maximum) for continuous variables and using number and 
percentage of participants for categorical variables. The summary of demographic and baseline 
characteristics data will be provided for the Safety Analysis Set.
In addition, age groups (< 60 vs ≥ 60 years), and race groups (Asian, Black, White, and other) 
will be summarized by treatment group and overall.
For categorical data, the Cochran-Mantel-Haenszel (CMH) test (ie, general association statistic 
for nominal data and row mean scores for ordinal data [age group]) will be used. For continuous 
data, the Kruskal-Wallis test will be used to compare the 3 treatment groups, and the Wilcoxon 
rank sum test will be used to compare the 2 treatment groups.
A by-participant demographic listing will be provided by study part and participant ID number in 
ascending order.
5.2.
Other Baseline Characteristics
The following baseline disease characteristics will be summarized by treatment group and 
overall for each part using descriptive statistics: 

Duration of symptoms prior to first dose of study drug

Duration from SARS-CoV-2 PCR/NAAT/antigen testing confirmation to first dose of study 
drug

Baseline alanine aminotransferase (ALT)

Baseline aspartate aminotransferase (AST)

Baseline respiration rate

Baseline SARS-CoV-2 viral Load (as a continuous variable, and a categorical variable with 
categories of < median and ≥ median) for each sample type collected
The summary of these baseline characteristics will be provided for the Safety Analysis Set. For 
categorical data, the Cochran-Mantel-Haenszel (CMH) test (i.e. general association) will be used. 
For continuous data, the Kruskal-Wallis test will be used to compare the 3 treatment groups, and 
the Wilcoxon rank sum test will be used to compare the 2 treatment groups.


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A by-participant listing of other baseline characteristics will be provided by study part and 
participant ID number in ascending order.
5.3.
Additional Baseline Characteristics 
Symptoms for each domain will be summarized as categories 0-4 from FLU-PRO for 
participants in Part C. The Cochran-Mantel-Haenszel (CMH) test (i.e. row mean scores for 
ordinal data) will be used to compare the 2 treatment groups. 
5.4.
Medical History
Any medical condition or clinically significant laboratory abnormality with an onset date before 
the consent form is signed and not related to a protocol-associated procedure is considered to be 
preexisting and should be documented as medical history. General medical history data will be 
collected at screening. It will be coded using the MedDRA Version 23.1. A summary table will 
present the percentages of participants reporting each medical history preferred term, sorted first 
in alphabetical order by system organ class (SOC) and then by preferred term (PT) in descending 
order of total frequency within SOC.
A by-participant listing of medical history will be provided by participant ID number in 
ascending order.


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6.
EFFICACY ANALYSES
6.1.
Primary Efficacy Endpoint
The viral load assay for the primary analysis is: 2019-nCoV Real-Time RT-PCR Viral Load 
assay (v2). The assay is based on CDC’s qualitative 2019-nCoV EUA Assay using primers 
targeting SARS-CoV-2 nucleocapsid (N) gene. 
6.1.1.
Definition of the Primary Efficacy Endpoint
The primary endpoint of the study is time-weighted average change from baseline to Study 
Day 7 (DAVG7) in SARS-CoV-2 viral load (log10 copies/mL). The DAVG7 in SARS-CoV-2 
viral load is defined as the time-weighted average between the first postbaseline value through 
the last available value up to Study Day 7 minus the baseline value in SARS-CoV-2 viral load. 
DAVG7 is calculated using the trapezoidal rule and the area-under-the-curve (AUC) concept as 
follows:
𝐷𝐴𝑉𝐺7 =
𝐴𝑈𝐶𝑡1―𝑡7
(𝑡7 ― 𝑡1) ― 𝑌0
The AUC between 𝑡1 and 𝑡𝑛 in a time (i.e., study day) versus SARS-CoV-2 viral load plot is 
calculated as follows: 
𝐴𝑈𝐶𝑡1―𝑡𝑛=
𝑖=1 𝑡𝑜 (𝑛―1)
1
2 (𝑌𝑖+ 𝑌𝑖+1) × (𝑡𝑖+1 ― 𝑡𝑖)
Where 𝑌𝑖 is the SARS-CoV-2 viral load at time 𝑡𝑖,  𝑡1 is the first postbaseline time, and 𝑌0 is the 
baseline SARS-CoV-2 viral load. 
For participant with SARS-CoV-2 viral load data only available up to Day 𝑥 (𝑥< 7), the 
DAVG7 is defined as 
𝐷𝐴𝑉𝐺7 =
𝐴𝑈𝐶𝑡1―𝑡𝑥
(𝑡𝑥― 𝑡1) ― 𝑌0
If there is no post-baseline data, then the participant will be excluded from the analysis. If there 
is one post-baseline data value 𝑌𝑖, 𝐷𝐴𝑉𝐺7 = 𝑌𝑖― 𝑌0.
6.1.2.
Statistical Hypothesis for the Primary Efficacy Endpoint
Null hypothesis: The RDV groups are not different from the PTM groups in virologic response 
with respect to DAVG7 in SARS-CoV-2 viral load.
Alternative hypothesis: The RDV groups are different from the PTM groups in virologic 
response with respect to DAVG7 in SARS-CoV-2 viral load.
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6.1.3.
Analysis of the Primary Efficacy Endpoint
DAVG7 in SARS-CoV-2 viral load will be summarized by treatment group using descriptive 
statistics in Parts A, B and C. For Part C, DAVG7 in SARS-CoV-2 viral load will be compared 
between the RDV and PTM groups using analysis of covariance (ANCOVA) with baseline viral 
load included in the model as a covariate. Due to small sample sized in Parts A and B, no 
comparison test will be applied.
The following summary tables will be provided by treatment group:

DAVG7 in SARS-CoV-2 viral load based on nasopharyngeal swab samples

DAVG7 in SARS-CoV-2 viral load based on oropharyngeal swab samples

DAVG7 in SARS-CoV-2 viral load based on saliva samples 
After checking that the Part A, Part B, and Part C data are poolable with regard to demographic 
and baseline characteristics, DAVG7 in SARS-CoV-2 viral load will be analyzed by the pooled 
groups outlined in Section 3.2 and comparison will be done using ANCOVA with baseline viral 
load as the covariate.
The mFAS will be the primary analysis set for evaluation of DAVG7 in SARS-CoV-2 viral load. 
A by-participant listing for DAVG7 in SARS-CoV-2 viral load will be provided. Descriptive 
statistics will be provided for DAVG7 in SARS-CoV-2 viral load by treatment group for each of 
the subgroups defined in Section 3.4. 
6.2.
Secondary Efficacy Endpoints 
Secondary efficacy endpoints are listed in Section 1.2. 
6.2.1.
Analysis of Secondary Efficacy Endpoints
The FAS will be the primary analysis set for hospitalizations, MAVs and FLU-PRO 
questionnaire analyses. The mFAS will be the primary analysis set for SARS-CoV-2 viral load 
analyses. 
Composite Endpoint of All-Cause MAVs or All-Cause Death by Day 28
The proportion of participants with all-cause MAVs or all-cause death by Study Day 28 will be 
estimated using Kaplan-Meier methods by treatment group and compared among 3 treatment 
groups in Part A and Part B and between the 2 treatment groups in Part C using a log-rank test.
If participants have no event by Study Day 28, participants will be censored at date of earlier of 
Study Day 28 and last study day. If a participant has a MAV first and then dies, then date of the 
MAV and status will be used for this participant.


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Composite Endpoint of COVID-19 Related MAVs or All-Cause Death by Day 28
The proportion of participants with COVIS-19 related MAVs or all-cause death will be analyzed 
using the same method as used for composite endpoint of all MAVs or all-cause death by day 28.
In additional, a summary by pooled RDV and Pooled PTM may be provided and compared using 
CMH method including Part as strata in the model. 
Proportion of participants hospitalized by Day 28
The proportion of participants with all-cause hospitalization (ICU, non-ICU, or unknown ward 
from Hospitalization/MAVs CRF) by Study Day 28 will be estimated using the Kaplan-Meier 
method and compared among treatment groups using a log-rank test. The time to all-cause 
hospitalization is defined using the first hospitalization date by Study Day 28, depending on 
which happens first. If participants have no event by Study Day 28, participants will be censored 
at date of earlier of Study Day 28 and last study day/death. 
Time to Negative SARS-CoV-2 PCR
Negative SARS-CoV-2 PCR based on RT-PCR viral load is defined as: 
(1) the results reported as ‘No SARS-CoV-2 detected’, AND 
(2) two consecutive negative results, or negative at last available sample for participants 
who completed or discontinued from study. 
The time to negative SARS-CoV-2 PCR is defined (in days) as the number of days to first 
confirmed negative:  
First date of two consecutive dates achieving negative result – First dose date +1. 
Participants without negative SARS-CoV-2 PCR will be censored at last non-missing SARS-
CoV-2 viral load date. The Kaplan-Meier product limit method will be used to estimate time to 
negative SARS-CoV-2 PCR and p-values will be calculated using a log-rank test. 
Time to Alleviation of Baseline COVID-19 Symptoms (Part C)
Using the COVID-19-adpated FLU-PRO Plus, the alleviation (mild or absent) of baseline 
COVID-19 symptoms, i.e. overall alleviation of all symptoms scored 1 or higher at baseline for 
each participant,  is defined as: 
(1) symptoms scored as 2 or higher at baseline are scored as 0 or 1 at post-baseline, 
AND symptoms scored as 1 at baseline are scored as 0 at post-baseline, AND 
(2) for two consecutive days. 
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First date of the two consecutive dates achieving alleviation - First dose date + 1. 
If a pa1t icipant has baseline COVID-19 symptoms and not achieved symptom alleviation at last 
FLU-PRO assessment or early discontinuation of study, the paiticipant will be censored at the 
date of last FLU-PRO assessment. The Kaplan-Meier product limit method will be used to 
estimate and log-rank test will be used to compai·e time to alleviation (mild or absent) of baseline 
COVID-19 symptoms by treatment group. The hazard ratio and its 95% CI from Cox model will 
be provided. 
Change in SARS-Co V-2 Viral Load from Baseline 
Change in SARS-Co V-2 viral load from baseline at each postbaseline analysis window will be 
provided for each of nasophaiyngeal swab samples, oropha1yngeal swab samples and saliva 
samples. Descriptive statistics will be provided by treatment group for each nasophaiyngeal, 
orophaiyngeal and saliva test as follows: (1) Baseline values, (2) Values at each postbaseline 
analysis window, (3) Change from baseline at each postbaseline analysis window. 
Following by-paiticipant listing will be provided by study pait, paiticipant ID number and time 
point in chronological order: 
• 
Hospitalizations/MA Vs 
• 
SARS-Co V-2 viral load (log10 copies/mL) 
• 
COVID-19-adapted FLU-PRO'° questionnaire 
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7.
SAFETY ANALYSES
Safety data will be summarized for the participants in the safety analysis set. All safety data 
collected on or after the date that study drug was first dispensed through 30 days after last dose 
will be summarized by treatment group for the Safety Analysis Set, unless specified otherwise. 
Safety endpoints listed in Section 1.2 include: 

Proportion of participants with treatment-emergent AEs (TEAEs) and laboratory 
abnormalities

Proportion of participants with TEAEs leading to study treatment discontinuation
All safety data will be included in data listings.
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the current version of 
MedDRA. System organ class (SOC), high-level group term (HLGT), high-level term (HLT), 
preferred term (PT), and lower-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
The severity of AEs will be graded using the Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events, Version 2.1 dated July 2017. For each episode, 
the highest grade attained should be reported as defined in the grading scale. The DAIDS scale is 
available at the following location:
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf
Adverse events are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 
(severe), Grade 4 (life threatening) or Grade 5 (death) 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
Study drug-related AEs are those for which the investigator selected “Related” on the AE CRF to 
the question of “Related to Study Treatment.” Events for which the investigator did not record 
relationship to study drug will be considered related to study drug for summary purposes. 
However, by-participant data listings will show the relationship as missing.


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7.1.4.
Relationship of Adverse Events to Study Procedure
Study procedure-related AEs are those for which the investigator selected “Yes” on the AE CRF 
to the question of “Related to Study Procedures.” Events for which the investigator did not 
record relationship to study procedure will be considered as missing. No summary table for 
relationship of AE to study procedure will be presented.  
7.1.5.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definition 
of SAE specified in the study protocol. SAE captured and stored in the clinical database will be 
reconciled with the SAE database from the Gilead Global Patient Safety (GLPS) before data 
finalization.
7.1.6.
Treatment-Emergent Adverse Events 
7.1.6.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the study drug start date and no later than 30 days 
after permanent discontinuation of study drug

Any AEs leading to premature discontinuation of study drug.
7.1.6.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The AE onset 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 to be treatment emergent. In 
addition, an AE with the onset date missing and incomplete stop date with the same or later 
month and year (or year alone if month is not recorded) as the first dosing date of study drug will 
be considered treatment emergent.


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


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
Study-Drug-Related SAEs 

Deaths

AEs leading to premature discontinuation of study drug
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set and will include data collected up to the last dose of study drug plus 30 days. 
The analysis will be based on values reported in conventional units. When values are below the 
LOQ, they will be listed as such, and the closest imputed value will be used for the purpose of 
calculating summary statistics as specified in Section 3.7. 
A by-participant listing for laboratory test results will be provided by study part and participant 
ID number and visit in chronological order for hematology, coagulation, and serum chemistry 
separately. Values falling outside of the relevant reference range and/or having a severity grade 
of 1 or higher on the DAIDS Grading Scale will be flagged in the data listings, as appropriate.
No formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for each laboratory test specified in the 
study protocol as follows:

Baseline values 

Values at each postbaseline analysis window

Change from baseline at each postbaseline analysis window

Percentage change from baseline to each postbaseline analysis window (if specified)
A baseline laboratory value will be defined as the last 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. For glucose, only assessments under fasting status 
will be summarized. 
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3.


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7.2.2.
Graded Laboratory Values
The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Event, Version 2.1 
(July 2017) will be used to assign toxicity grades (0 to 4) to laboratory results for analysis. 
Grade 0, which is not included in the DAIDS table, will be used to 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. 
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. 
Treatment-emergent laboratory abnormalities will be summarized for fasting glucose or 
nonfasting glucose if their baseline values are observed. Maximum postbaseline grade will be 
summarized for both fasting glucose and nonfasting glucose with or without baseline assessment.
Abnormalities in coagulation parameters will be graded for international normalized ratio (INR) 
and aPTT.
For INR,  prothrombin time (PT) and aPTT, protocol specified toxicity grading scale depends on 
the upper limit of normal range (ULN). While the ULN of INR and aPTT depends on whether 
the participant is taking anticoagulant medication or not (ie, Not taking oral anticoagulant: 0.8 - 
1.2; Taking oral anticoagulant: 2.0 – 3.0), this information is not collected by the reference 
laboratory. As a result, INR and aPTT will be graded by assuming the participant is not taking an 
oral anticoagulant, which is a conservative approach that may lead to over-reporting of 
abnormalities for INR and aPTT.
7.2.2.2.
Summaries of Laboratory Abnormalities
The following summaries (number and percentage of participants) for treatment-emergent 
laboratory abnormalities will be provided by study part, 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 after last dosing date.


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A by-participant listing of all treatment-emergent laboratory analyses and treatment-emergent 
Grade 3 or 4 laboratory abnormalities will be provided by study part and participant ID number 
and visit in chronological order. 
7.3.
Vital Signs, SpO2, and FEV1
Descriptive statistics will be provided by treatment group for vital signs (heart rate,  blood 
pressure, and respiration rate), SpO2, and FEV1 as follows:

Baseline value

Values at each postbaseline time point

Change from baseline at each postbaseline time point
Two types of baseline will be defined for vital signs. An overall baseline value will be defined as 
the last available value collected on or prior to the date/time of first dose of study drug. Day 1 
pre-dose baseline is defined the same as the overall baseline. A pre-dose baseline per day for 
each of dosing days 2-5 will use the “Predose” record on that day as baseline. Change from 
baseline to a postbaseline visit will be defined as the postbaseline value minus the respective 
baseline value. 
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.8.3. No formal statistical testing is planned.
Additionally, for FEV1, the number and percentage of participants with > 15% reduction in 
FEV1 at 10 minutes postdose compared with the same day predose FEV1 will be summarized by 
study day through day 5.
Temperature will not be summarized due to different methods of measuring temperature.
A by-participant listing of body weight, BMI, vital signs (heart rate, temperature, blood pressure, 
and respiration rate), SpO2, and FEV1 will be provided by study part, participant ID number and 
visit in chronological order. 
7.4.
Prior and Concomitant Medications
Medications collected at screening and during the study will be coded using the current version 
of the Gilead-modified World Health Organization (WHO) Drug dictionary.
Concomitant medications are defined as medications taken while a participant took study drug. 
Use of concomitant medications will be summarized by preferred name using the number and 
percentage of participants for each study part and treatment group. A participant reporting the 
same medication more than once will be counted only once when calculating the number and 
percentage of participants who received that medication. The summary will be ordered by 
preferred term in descending overall frequency. For drugs with the same frequency, sorting will 
be done alphabetically.


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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.
All prior and concomitant medications (other than per-protocol study drug) will be provided in a 
listing sorted by study part and participant ID number and administration date in chronological 
order.
7.5.
Electrocardiogram Results
ECG was performed at baseline only. A listing for ECG assessment results will be provided by 
study part and participant ID number. 
7.6.
Other Safety Measures
A data listing will be provided for participants experiencing pregnancy during the study.
Although not necessarily related to safety, a listing of all comments received during the study on 
the comments form will be provided by study part, participant ID number, and form for which 
the comment applied. 
7.7.
Changes from Protocol-Specified Safety Analyses
There are no deviations from the protocol-specified safety analyses.


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PHARMACOKINETIC ANALYSES 
lasma PK will be collected at Day 1 ( end of nebulization 
and Da 3 
redose and end of nebulization . 
Descnptive statistics n, mean, SD, 
coefficient of variation [%CV], minimum, median, maximum, Ql, Q3, geometric mean, and its 
95% CI) will be presented for plasma concentration and parameter data. For concentrntion values 
BLQ, the number of pa1ticipants with values of BLQ will be presented. 
In study Pait C, sparse plasma PK will be collected at Days 3 and 5 (predose). A single anytime 
PK sample will be collected on Day 7. 
The following tables will be provided for Remdesivir GS-704277 and GS-441524 by visit day 
and nominal timepoint in Paits A and B. 
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9.
REFERENCES


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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.
Schedule of Assessments
Appendix Table 1.
Study Parts A and B: Study Procedures Table
Appendix Table 2.
Study Part C: Study Procedures Table
Appendix 2.
Programming Specifications


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Appendix 1.
Schedule of Assessments
Appendix Table 1.
Study Parts A and B: Study Procedures Table
TREATMENT PERIOD
FOLLOW-UP PERIOD
Schedule of Assessments
Screening
Day 1a
Day 2
Day 3
Day 4
Day 5
Day 7
Day 14
(± 3 days)
Day 28b 
(± 5 days)
Obtain Informed Consent
X
Inclusion/Exclusion Criteria
X
Medical History 
X
Documentation of SARS-CoV-2
X
ECGc
X
Complete or Symptom-Directed Physical 
Examination
X
X
X
X
X
X
X
X
Body Weight
X
Height
X
Vital Signs (Heart Rate, Temperature, Blood 
Pressure), SpO2
X
X
X
X
X
X
X
X
Completion of Daily Adapted FLU-PRO© 
Questionnaired
X
X
X
X
X
X
X
Chest X-Raye
X
FEV1
X
X
X
X
X
Safety Laboratory Assessments (Hematology, 
Chemistry, Coagulation)
X
X
X
X
X
Pregnancy Test (Urine)
X
Serum FSH Testf
X
Nasopharyngeal and Oropharyngeal Swabs 
and Saliva Samples for 
SARS-CoV-2 RT-qPCR Testing and Possible 
Viral Resistance Testing
X
X
X
X
X
X
X
Sparse Plasma PK Assessmentsg
X
X
CCI


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TREATMENT PERIOD 
FOLLOW-UP PERIOD 
Inhaled Remdesivir for Injection Formulation 
or PTM Administ:rationi 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG = electrocardiogram; FEV1 = forced expirat01y volume in the first second of expiration; FLU-PRO©= InFLUenza Patient-Repo1ted Outcome; 
FSH = follicle-stimulating ho1mone; PCR = polymerase chain reaction; PK = pha1macokinetic(s); RT-qPCR = quantitative reverse transcriptase polymerase 
chain reaction; RDV = (remdesivir, GS 5734'™); SARS-CoV-2 = severe acute respiratory syndrome coronavims 2; SpO2 = oxygen saturation as measured by 
pulse oximetty 
a 
b 
C 
d 
e 
f 
I 
If the screening and Day 1 visits occur on the same day, no procedtu·es need to be repeated. 
Day 28 assessments may be completed by telephone. 
ECG w-ill not be requit·ed at screening. However, ECG should be performed prior to dosing on Day 1. If subject randomizes and doses on the same day as screening, then 
ECG w-ill be done at screening. 
Adapted FLU-PRO© questionnait·e is to be completed daily (Days 1-14). 
Chest x-ray will be pe1fo1med at Day 1. If screening visit and Day 1 aie the same day, chest x-ray does not need to be repeated if completed as SOC < 2 days before 
screening. 
Serum FSH test: Childbeaiing female participants who aie not postmenopausal (see Protocol Appendix 5 who do not wish to follow protocol defined contraception will need 
a semm FSH test (FSH test is required for women who aie < 54 years old and have stopped menstmating for c:: 12 months but do not have documentation of ovarian hormonal 
faihu·e) 
S arse lasma PK will be collected at Da 1 end of nebulization, 
1a e 
em es,vir for Injection fo,mulation will be administered to participants at the site tu1der close supervision. Healthcaie professionals administering inhaled 
Remdesivit· for Injection formulation should have the appropriate medication available for inimediate use in case of hypersensitivity. The participant should be treated 
according to the SOC for management of hypersensitivity reaction. After dose administration, monito,-ing should be done as follows: Approxituately 30 minutes post dose 
administration, pa,t icipants should be observed, and vital signs should be pe1fo1med prior to dischaige. 
CONFIDENTIAL 
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Appendix Table 2.
Study Part C: Study Procedures Table
TREATMENT PERIOD
FOLLOW-UP PERIOD
Schedule of Assessments
Screeninga
Day 1b
Day 2
Day 3
Day 4
Day 5
Day 7
Day 14c
(± 3 days)
Day 28c 
(± 5 days)
Obtain Informed Consent
X
Inclusion/Exclusion Criteria
X
Medical History 
X
Documentation of SARS-CoV-2d
X
Complete or Symptom-Directed Physical 
Examination
X
X
X
X
X
Body Weight
X
Height
X
Vital Signs (Heart Rate, Temperature, Blood 
Pressure), SpO2
X
X
X
X
X
Completion of Daily Adapted FLU-PRO© 
Questionnairee
X
X
X
X
X
X
X
FEV1
X
X
X
X
X
Safety Laboratory Assessments (Hematology, 
Chemistry, Coagulation)
X
X
X
X
Pregnancy Test (Urine)
X
Serum FSH Testf
X
Nasopharyngeal and Oropharyngeal Swabs and 
Saliva Samples for 
SARS-CoV-2 RT-qPCR Testing and Possible 
Viral Resistance Testing
X
X
X
X


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TREATMENT PERIOD
FOLLOW-UP PERIOD
Schedule of Assessments
Screeninga
Day 1b
Day 2
Day 3
Day 4
Day 5
Day 7
Day 14c
(± 3 days)
Day 28c 
(± 5 days)
Sparse/Single Plasma PK Assessmentsg
X
X
X
Remdesivir for Inhalation Solution Formulation or 
PTM Administrationh
X
X
X
X
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
COPD = chronic obstructive pulmonary disease; ECG = electrocardiogram; FEV1 = forced expiratory volume in the first second of expiration; FLU-PRO© = InFLUenza 
Patient-Reported Outcome; FSH = follicle-stimulating hormone; PCR =polymerase chain reaction; PK = pharmacokinetic(s); RT-qPCR = quantitative reverse transcriptase 
polymerase chain reaction; RDV = (remdesivir, GS 5734™); SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SpO2 = oxygen saturation as measured by pulse 
oximetry
a
Study visits, with the exception of the screening visit, may be performed in-clinic or at the participant’s home via home health and/or telehealth, virtually or remotely, as 
permitted by local and institutional regulations.
b
If the screening and Day 1 visits occur on the same day, no procedures need to be repeated.
c
Days 14 and 28 assessments may be completed by telephone.
d
Documentation of SARS-CoV-2 infection first confirmed by nucleic acid testing or direct antigen testing with sample collected ≤ 4 days prior to randomization  
e
Adapted FLU-PRO© questionnaire is to be completed daily (Days 1-14).
f
Serum FSH test: Childbearing female participants who are not postmenopausal (see Protocol Appendix 5) who do not wish to follow protocol defined contraception will need 
a serum FSH test (FSH test is required for women who are < 54 years old and have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal 
failure)
g
Sparse plasma PK will be collected at Days 3 and 5 (predose). A single anytime PK sample will be collected on Day 7 visit.
h
Remdesivir for Inhalation Solution formulation may be administered to participants in the participant’s home with in-person or telehealth support. For participants with 
pre-existing pulmonary conditions (ie, COPD or asthma) enrolled in Part C of the study, prescribed inhalers may not be used ≤ 30 minutes prior to Remdesivir for Inhalation 
Solution formulation administration. Healthcare professionals overseeing Remdesivir for Inhalation Solution formulation therapy remotely will observe the participant for any 
signs of adverse event. If any adverse event is observed and cannot be managed remotely, appropriate urgent care measures will be implemented. Approximately 30 minutes 
after dose administration, participants should be observed remotely prior to telehealth support session concluding.


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Appendix 2.
Programming Specifications
1) If the age from the Day 1 eCRF is not available, age will be calculated as follows:
Only year is provided for the date of birth (DOB). Use July 1 for the month and day.
a) AGE (years) is calculated from the number of days between the DOB and Study Day 1,
b) Use the SAS INTCK function to determine the number of “1st-of-month days” 
(eg, January 1st, February 1st, March 1st) between DOB and Day 1 (inclusive),
c) Divide the result in (b) by 12,
AGE = the integer of the result in (c),
Age for laboratory test reference range will be based on the age at the sample collection 
date.
2) All screened participants refer to all participants who are screened (ie, with non-missing 
screening date) and have a screening number. For summaries the same participant is counted 
only once.
3) Screen failure participants are the participants who were screened and answered “No” for any 
inclusion criteria or “Yes” for any exclusion criteria regardless of which version of protocol 
the participant was consented to.
4) Participants in the randomized analysis set are defined as participants randomized into the 
study. IXRSRAND is the source to determine whether the 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.
8) For demographics tables, “Not Permitted”, “Unknown”, or missing categories will be 
excluded from percentage for detailed race categories summary (i.e. race categories collected 
on eCRF). For combined Race category (e.g. Asian, White, Black, Other), “Not Permitted” is 
included in “Other” and “Other” will be include in the count of percentage. 


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9) TEAE
Events with Missing Onset Day and/or Month
An event is considered treatment emergent if all of the following 3 criteria are met:
i.
The month and year (or year) of onset date is the same as or after the month and year 
(or year) of the first dose of study drug, and
ii.
The month and year (or year) of the onset date is the same as or before the month and 
year (or year) of the 30th day after the date of the last dose of study drug, and
iii.
End date is as follows: 
The (complete) end date is on or after the first dose date, or
The month and year (or year) of end date is the same or after the month and year 
(or year) of the first dose of study drug, or
End date is completely missing 
Events with Completely Missing Onset Date
An AE with a completely missing onset date is defined as TEAE if end date meets any of the 
3 criteria specified above.
10) The precision in reporting numerical values should be as follows:
Raw measurements will be reported the same as the data captured electronically or on the 
eCRF for all.
Standard deviation and standard error will be reported to one more significant decimal place 
than the raw measurement.
Mean, median, minimum, Q1, Q3, and maximum will be reported to the same number of 
decimal places of the raw measurements. 
Exceptions may be considered; for example, if more than 4 significant digits are provided for 
the measurement.
Precision for derived parameters will be kept as 8 decimals and in listings 2 decimals will be 
kept.
Precision for derived parameters as follows:
Parameters
Decimal Places
log 10 of SARS-CoV-2 viral load
2
Time-weighted average change in 
SARS-CoV-2 viral load
2
BMI
2


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11) Last dose date is not expected to be missing. However, if last dose date is missing, it will be 
imputed using the maximum of non-missing, non-zero dose, study drug start and stop dates.
12) Incomplete death dates will be imputed as the maximum of the study drug start dates (lasfdt), 
study drug end dates (lasldt), clinic visit dates (lvis28dt), laboratory visit dates (llab28dt), 
including the 28-day follow-up visit date plus 1, ie dthdt = 
max(lasfdt,lasldt,lvis28dt,llab28dt) + 1.
13) Censoring rules
Time to hospitalization: If a participant prematurely discontinues from the study prior to 
Day 28 or the hospitalization status is missing, the participant is censored at last study date 
or day 28 whichever is earlier.
Time to negative SARS-CoV-2 viral load, participants are censored at the last assessment 
day and participants are required to have at least one postbaseline assessment to be included 
in the analysis.
Time to alleviation of baseline COVID-19 symptoms: 
■
For overall baseline symptom alleviation, participants are censored at the last 
assessment day that at least one of the baseline symptoms were assessed. 
■
For baseline symptom alleviation for each domain, participants are censored at the 
last assessment day that at least one of the baseline symptoms within that domain 
were assessed.
14) For 95% CI of KM%, log-log transformation method is adopted.
15) Hazard ratio for time to alleviation
The following SAS code will be used to compute hazard ratio (HR) and its 95% CI:
proc phreg;
class trt01pn;
model days*censor(0) = trt01pn / rl;
run;


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16)  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)
Neutrophils
Decrease
Neutrophils (Decreased)
Platelets
Decrease
Platelets (Decreased)
Hematology
WBC
Decrease
WBC (Decreased)
Albumin
Decrease
Albumin (Decreased)
Alkaline Phosphatase
Increase
Alkaline Phosphatase (Increased)
ALT
Increase
ALT (Increased)
AST
Increase
AST (Increased)
Bicarbonate
Decrease
Bicarbonate (Decreased)
Corrected Calcium
Increase
Corrected Calcium (Hypercalcemia)
Corrected Calcium
Decrease
Corrected Calcium (Hypocalcemia)
Creatine Kinase (CK)
Increase
Creatine Kinase (Increased)
Creatinine
Increase
Creatinine (Increased)
Creatinine Clearance 
Decrease
Creatinine Clearance (Decreased)
Direct Bilirubin
Increase
Direct Bilirubin (Hyperbilirubinemia)
Lipase
Increase
Lipase (Increased)
Magnesium
Decrease
Magnesium (Hypomagnesemia)
Phosphate
Decrease
Phosphate (Hypophosphatemia)
Serum Glucose (Fasting)
Increase
Serum Glucose (Fasting, Hyperglycemia)
Serum Glucose (Nonfasting)
Increase
Serum Glucose (Nonfasting, Hyperglycemia)
Serum Glucose
Decrease
Serum Glucose (Hypoglycemia)
Serum Potassium
Increase
Serum Potassium (Hyperkalemia)
Serum Potassium
Decrease
Serum Potassium (Hypokalemia)
Serum Sodium
Increase
Serum Sodium (Hypernatremia)
Serum Sodium
Decrease
Serum Sodium (Hyponatremia)
Total Bilirubin
Increase
Total Bilirubin (Hyperbilirubinemia)
Uric Acid
Increase
Uric Acid (Hyperuricemia)
Prothrombin Intl. 
Normalized Ratio (INR)
Increase
Prothrombin Intl. Normalized Ratio (Increased)
Activated partial 
thromboplastin time (aPTT)
Increase
Activated partial thromboplastin time (Increased)
Chemistry
Prothrombin Time (PT) 
Increase 
N/A


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17) The first Part B participant was screened on Oct 29, 2020 and the first Part C participant was 
screened on Jan 24, 2021. Screen failure participants of each study part is derived from 
scrndt, 
if part='' then do;
   if .< scrndt <29Oct2020 then part='Part A';
      else if scrndt >= 29Oct2020 & scrndt <24Jan2021 then part='Part B'; 
      else part=’Part C’;
end;
18) SARS-CoV-2 viral load from nasopharyngeal and oropharyngeal swabs and saliva samples 
were to be collected. SARS-CoV-2 viral load in nasopharyngeal and oropharyngeal swabs 
and saliva samples will be analyzed separately.
a) For numeric SARS-CoV2 summary (e.g, mean viral load, change from baseline 
etc.), “Inconclusive” SARs-CoV2 result is set to missing. 
b) For categorical SARS-CoV2 summary, 3 categories will be included, i.e. Positive, 
Inconclusive, and Negative.
i)
Positive  =  any numeric result or “<LLOQ SARS-CoV2 detected” -  LLOQ could 
vary by sample type
ii) Negative = “No SARS-CoV2 detected”
iii) Inconclusive  = “Inconclusive” 
c) For Negative SARS-CoV2 confirmation, “Inconclusive” SARs-CoV2 result will not be 
considered as missing thus a “Negative” followed by a “Inconclusive” is NOT confirmed. 
d) 2 negative results from the same day do not equal confirmation.
e) If last PCR sample is negative for participants completed the study or for participant 
withdrawn early from the study, then one negative PCR of last sample is considered as 
confirmed negative.
f)
Categorical SARS-CoV2 and SARS-CoV2 negative summary will be separated out by 
sample type.  There will be no combined positive or negative category using 2 or more 
sample types.
19) SAS code for ANCOVA analysis of DAVG:
ods output ParameterEstimates=out1 LSMeans=out2 LSMeanCL=out3 
LSMeanDiffCL=out4; 
proc glm data=dat1 plots=none;
  class trt01pn;
  model DAVG = trt01pn base / solution;
  lsmeans trt01pn / stderr cl pdiff;
run;
ods output close; quit;


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


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Domain 
Items 
Scoring 
Minimum Data Requirement 
Sense*
Loss Smell
Loss Taste
Arithmetic mean of 2 items 
within Sense domain
Daily score for 1 of 2 items must 
be present to calculate domain 
score
Total 
All above 34 items 
Arithmetic mean of all 
34 items within FLU-PRO 
In the presence of missing data, the 
above conditions for the calculation 
of all domain scores must be met in 
order to calculate the FLU-PRO 
total score. 
*
Newly added for COVID-19.
22) Symptom alleviation and time to baseline symptom alleviation
1. Baseline symptoms: Baseline symptoms are the symptoms at day 1 and score ≥1.
■
Item 1 to 34 of the FLUPRO are symptoms.  Global assessments (last 6 items in the 
questionnaire) are not symptoms.
■
Each subject's baseline symptoms including number of symptoms likely are different. 
■
For alleviation of baseline symptoms, only need to follow the symptoms presented 
(≥1) at day 1
○
If a participant has 5 baseline symptoms, only the 5 symptoms will be followed to 
derive alleviation.
○
If a symptom (e.g. coughing) is not one of the baseline symptoms and has a score 
>1 post baseline, the symptom will not be considered to derive the subject's 
baseline symptom alleviation. 
○
If participant has no symptom ≥1 at baseline, alleviation status for the participant 
is missing for all visit. 
○
If Day 1 symptoms ≥1 symptoms from Day 2 and later are all missing, the 
alleviation status for the symptom is missing for all visits.
2. Alleviation of a symptom: 
■
Symptom scored as 2 or higher at baseline are scored as 0 or 1 at postbaseline
■
Symptom scored as 1 at baseline are scored as 0 at postbaseline
■
for two consecutive days - need to be confirmed with 2 visits
○
one missing day between two visits (that meets the alleviation definition) is 
allowed, but 2 or more days of missing is not considered reach alleviation
○
for Day 14 (or last assessment on Day x), if the symptom meets definition of 
alleviation, and day 13 (or Day x -1) also meets the definition of alleviation, then 
it is considered as confirmed. One missing day is allowed for the confirmation of 
Day 14 or last assessment, i.e if day 13 (or Day x-1 ) is missing and Day 12 
(or Day x-2) meets the definition of alleviation, then it is considered as confirmed. 


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Examples:
Day 
Alleviation 
for a 
symptom 
on day 
Example
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1
2
2
2
1
1
1
0
0
0
0
0
0
0
0
4
baseline 2 or higher needs to be 1 or 
0
2
2
2
2
0
1
1
0
0
0
0
0
0
0
0
4
baseline 2 or higher needs to be 1 or 
0
3
2
2
2
0
2
1
1
0
0
0
0
0
0
0
6
day 4 is not confirmed
4
3
2
2
1
1
1
0
2
1
1
0
0
0
0
4
still on day 4 if worsen after 
confirmation
5
1
1
1
0
0
0
1
0
1
1
0
0
0
0
4
Worsening on day7
6
1
1
1
1
0
0
0
0
0
0
0
0
0
0
5
baseline 1 needs to be 0
7
2
2
2
1
.
1
0
0
0
0
0
0
0
0
4
allow one missing 
8
2
2
2
1
.
.
1
1
.
0
0
0
0
0
7
day 4 is not confirmed if there are 
two or more days’ response 
missing, re-start the check for 
confirmation
9
2
2
2
2
2
2
2
2
4
2
2
2
2
1
14
censor
10
2
2
2
2
2
2
2
2
2
2
2
2
1
.
13
censor
11
2
2
2
2
2
2
2
2
2
2
2
2
1
1
13
Confirmed on day 13 and 14
12
2
2
2
2
2
2
2
2
1
.
.
.
.
.
9
censor
13
2
2
2
2
2
2
2
2
1
1
.
.
.
.
9
Confirmed on day 9 and 10
Yellow –Confirmed alleviation, Tan – Not confirmed, Blue - Worsening 


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3. Alleviation of baseline symptoms for a participant
The alleviation status for a participant at each visit is 
■
Yes, if all confirmed baseline symptom alleviation status are Yes.
■
if > 25% of symptoms are missing, then alleviation status is No, else ignore missing.
■
No, if any baseline symptom alleviation status is No.
4. Tim to alleviation of baseline symptoms
First day of participant level alleviation status equals Yes.  If a participant has not 
achieved symptom alleviation at last FLUPRO assessment, the participant will be 
censored at the date of last FLUPRO assessment. For symptom alleviation of a domain, 
the last assessment date is only among those baseline symptoms within the domain. 
23) Covid-19 medications include: Chloroquine, Hydroxychloroquine, IV remdesivir, 
Bamlanivimab, Casirivimab/Imdevimab, Molnupiravir, Lopinavir-ritonavir, and Ribavirin.
Additional medication may be included during final review of Concomitant medications 
prior to data finalization and documented in a separate programming specification.
24) Glucose  
Fasting is not required per protocol for collecting Glucose sample, mixed fasting Glucose and 
non-fasting Glucose results are presented in the dataset.  Lab abnormality for Glucose will be 
summarized as follows:
if fasting glucose is collected at baseline, max TE lab toxicity grade is selected for 
post-baseline fasting glucose, max post-baseline toxicity grade (i.e. not TE toxicity grade) 
is selected for the post-baseline glucose regardless fasting status.
if non-fasting glucose is collected at baseline, TE lab toxicity grade is selected for 
post-baseline non-fasting glucose, max post-baseline toxicity grade is selected for the 
post-baseline glucose regardless fasting status.
Max TE lab toxicity grade for fasting glucose and non-fasting glucose, max post-baseline 
toxicity grade for fasting glucose and non-fasting glucose will be summarized separately 
in the lab abnormality table.
In the any TE lab toxicity section of the lab abnormality table, max post-baseline toxicity 
grade will be included. 


GS-US-553-9020-SAP-v1.0
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
07-Jun-2021
15:06:42
Clinical Research eSigned 07-Jun-2021
19:02:43
PPD
PPD