Study in Participants With Early Stage Coronavirus Disease 2019 (COVID-19) to Evaluate the Safety, Efficacy, and Pharmacokinetics of Remdesivir Administered by Inhalation

A Phase 1b/2a Study in Participants With Early Stage COVID-19 to Evaluate the Safety, Efficacy, and Pharmacokinetics of Remdesivir Administered by Inhalation

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04539262

Enrollment

156

Registered

2020-09-04

Start date

2020-09-14

Completion date

2021-03-22

Last updated

2022-03-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COVID-19

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.

Interventions

DRUGRemdesivir (RDV)

Administered as an aerosolized solution

DRUGPlacebo

Administered as an aerosolized solution

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: * Willing and able to provide written informed consent, or with a legal representative who can provide informed consent * SARS-CoV-2 infection first confirmed by polymerase chain reaction (PCR) (Parts A and B) or by nucleic acid testing or direct antigen testing (Part C) with sample collected ≤ 4 days prior to randomization * 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 intravenous (IV) RDV or administration of any SARS-CoV-2 (or COVID-19) vaccine * Participants 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) Note: Other protocol defined Inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Time-weighted Average Change From Baseline in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7	Baseline, Day 7	Time-weighted average change in SARS-CoV-2 viral load was defined as area under the concentration versus time curve (AUC) of viral load change divided by time between baseline through Day 7.
Time-weighted Average Change From Baseline in Oropharyngeal SARS-CoV-2 Viral Load Through Day 7	Baseline, Day 7	Time-weighted average change in SARS-CoV-2 viral load was defined as AUC of viral load change divided by time between baseline through Day 7.
Time-weighted Average Change From Baseline in Saliva SARS-CoV-2 Viral Load Through Day 7	Baseline, Day 7	Time-weighted average change in SARS-CoV-2 viral load was defined as AUC of viral load change divided by time between baseline through Day 7.

Secondary

Measure	Time frame	Description
Number of Participants With All-Cause Medically Attended Visits (MAVs) or Death by Day 28	Randomization up to Day 28	The composite outcome of all-cause MAVs (medical visits attended in person by the participant and a health care professional) or all-cause death by Study Day 28 were estimated using Kaplan-Meier methods by treatment group.
Number of Participants With COVID-19 Related MAVs or Death by Day 28	Randomization up to Day 28	The composite outcome of COVID-19 related MAVs (medical visits attended in person by the participant and a health care professional) or all-cause death by Study Day 28 were estimated using Kaplan-Meier methods by treatment group.
Number of Participants With Hospitalization by Day 28	Day 1 up to Day 28	The composite of all-cause hospitalization was estimated using Kaplan-Meier methods by treatment group.
Pharmacokinetic (PK) Parameter: AUC0-24h of Remdesivir (RDV) and Its Metabolites (GS-441524 and GS-704277) in Parts A and B	Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.	AUC0-24h was defined as the concentration of drug over time between time 0 to time 24 hours. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.
PK Parameter: AUClast of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B	Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.	AUClast was defined as the concentration of drug from time zero to the last observable concentration.Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.
PK Parameter: CLss/F of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B	Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.	CLss/F was defined as apparent oral clearance at steady state after administration of the drug. CLss/F = Dose/AUCtau, where Dose is the dose of the drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.
PK Parameter: t1/2 of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B	Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.	t1/2 was defined as the estimate of the terminal elimination half-life of the drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.
PK Parameter: Vz/F of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B	Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.	Vz/F was defined as the apparent volume of distribution of the drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.
PK Parameter: Cmax of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B	Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.	Cmax was defined as the maximum observed concentration of drug.Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.
PK Parameter: Tmax of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B	Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.	Tmax was defined as the time (observed time point) of Cmax. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.
PK Parameter: Clast of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B	Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.	Clast was defined as the last observable concentration of drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.
PK Parameter: Tlast of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B	Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.	Tlast was defined as the time (observed time point) of Clast. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.
PK Parameter: AUCtau of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B	Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.	AUCtau is defined as concentration of drug over time (the area under the concentration versus time curve over the dosing interval). Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.
PK Parameter: λz of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B	Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.	λz was defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.
Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	First dose date up to 5 days plus 30 days	An adverse event (AE) was any untoward medical occurrence in a participant administered a study drug, which did not necessarily have a causal relationship with the treatment. AE was therefore any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. TEAEs: AE with an onset date on or after the study drug start date and no later than 30 days after study drug stop date; or any AE leading to study drug discontinuation.
Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	Baseline, Day 5	—
Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	Baseline, Day 5	—
Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5	Baseline, Day 5	—
Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	Baseline, Day 7	—
Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	Baseline, Day 7	—
Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7	Baseline, Day 7	—
Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	Baseline, Day 14	—
Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	Baseline, Day 14	—
Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	Baseline, Day 14	—
Time to Negative Nasopharyngeal SARS-CoV-2 Polymerase Chain Reaction (PCR)	Baseline up to Day 17	The time to negative nasopharyngeal SARS-CoV-2 PCR was defined as the number of days to first confirmed negative (first date of two consecutive dates achieving negative result) using nasopharyngeal sample. Time to negative nasopharyngeal SARS-CoV-2 PCR was calculated using Kaplan-Meier estimates.
Time to Negative Oropharyngeal SARS-CoV-2 Polymerase Chain Reaction (PCR)	Baseline up to Day 17	The time to negative oropharyngeal SARS-CoV-2 PCR was defined as the number of days to first confirmed negative (first date of two consecutive dates achieving negative result) using an oropharyngeal sample. Time to negative oropharyngeal SARS-CoV-2 PCR was calculated using Kaplan-Meier estimates.
Time to Negative Saliva SARS-CoV-2 Polymerase Chain Reaction (PCR)	Baseline up to Day 17	The time to saliva SARS-CoV-2 PCR was defined as the number of days to first confirmed negative (first date of two consecutive dates achieving negative result) using saliva sample. Time to negative saliva SARS-CoV-2 PCR was calculated using Kaplan-Meier estimates.
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 in Part C	First dose date up to Day 14	The InFLUenza Patient-Reported Outcome (FLU-PRO©) is a 32-item patient-reported outcome questionnaire that assesses the severity of symptoms of influenza and influenza-like illness across six body systems. An additional two items can be added to assess changes in taste or smell, if the instrument is used to quantify symptoms in studies of COVID-19. Each domain scores ranges from 0 (symptom-free) to 4 (very severe symptoms). Higher scores on this scale represent higher disease severity. Alleviation is defined as symptom scores as 2 or higher at baseline are scored as 0 (absent) or 1 (mild) at post-baseline, and symptoms scored as 1 at baseline are scored as 0 at post-baseline, and for two consecutive days. Time to alleviation was calculated using Kaplan-Meier estimates.
PK Parameter: Ctau of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B	Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.	Ctau was defined as the observed drug concentration at the end of the dosing interval. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.
Percentage of Participants With Treatment-Emergent Laboratory Abnormalities as Per Severity Grade	First dose date up to 5 days plus 30 days	Treatment-emergent laboratory abnormalities were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 July 2017. Laboratory abnormalities were graded as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening). Percentage of participants with any severity grade were reported.
Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation	First dose date up to 5 days plus 30 days	—

Countries

United States

Participant flow

Recruitment details

Participants were enrolled at study sites in the United States. The first participant was screened on 14 September 2020. The last study visit occurred on 22 March 2021.

Pre-assignment details

168 participants were screened.

Participants by arm

Arm	Count
RDV, Part A Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days.	12
RDV + Placebo, Part A Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 3 days followed by placebo to match RDV daily for 2 days.	12
Placebo, Part A Participants received placebo to match inhaled RDV in Part A daily for 5 days.	12
RDV, Part B Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days.	12
RDV + Placebo, Part B Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 3 days followed by placebo to match RDV daily for 2 days.	12
Placebo, Part B Participants received placebo to match inhaled RDV in Part B daily for 5 days.	13
RDV, Part C Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days.	61
Placebo, Part C Participants received placebo to match inhaled RDV in Part C daily for 5 days.	20
Total	154

Withdrawals & dropouts

Period	Reason	FG001	FG002	FG003	FG006
Overall Study	Adverse Event	0	1	0	0
Overall Study	Randomized, Not treated	1	0	0	1
Overall Study	Withdrew Consent	0	0	1	0

Baseline characteristics

Characteristic	RDV, Part A	RDV + Placebo, Part A	Placebo, Part A	RDV, Part B	RDV + Placebo, Part B	Placebo, Part B	RDV, Part C	Placebo, Part C	Total
Age, Customized < 60 years	10 Participants	11 Participants	9 Participants	12 Participants	10 Participants	12 Participants	55 Participants	15 Participants	134 Participants
Age, Customized ≥ 60 years	2 Participants	1 Participants	3 Participants	0 Participants	2 Participants	1 Participants	6 Participants	5 Participants	20 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants	3 Participants	3 Participants	2 Participants	6 Participants	4 Participants	40 Participants	14 Participants	78 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants	9 Participants	9 Participants	10 Participants	4 Participants	9 Participants	21 Participants	6 Participants	74 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Race/Ethnicity, Customized Race American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	2 Participants
Race/Ethnicity, Customized Race Asian	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants
Race/Ethnicity, Customized Race Black	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	12 Participants	2 Participants	16 Participants
Race/Ethnicity, Customized Race Not Permitted	1 Participants	2 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	5 Participants
Race/Ethnicity, Customized Race Other	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	3 Participants
Race/Ethnicity, Customized Race White	11 Participants	9 Participants	10 Participants	11 Participants	10 Participants	12 Participants	47 Participants	16 Participants	126 Participants
SARS-CoV-2 Viral load - Nasopharyngeal	7.29 log10 copies/mL STANDARD_DEVIATION 1.901	6.56 log10 copies/mL STANDARD_DEVIATION 1.065	6.81 log10 copies/mL STANDARD_DEVIATION 1.065	5.23 log10 copies/mL STANDARD_DEVIATION 1.98	6.41 log10 copies/mL STANDARD_DEVIATION 1.883	7.09 log10 copies/mL STANDARD_DEVIATION 1.288	5.69 log10 copies/mL STANDARD_DEVIATION 2.004	5.76 log10 copies/mL STANDARD_DEVIATION 1.839	6.14 log10 copies/mL STANDARD_DEVIATION 1.859
SARS-CoV-2 Viral load - Oropharyngeal	5.69 log10 copies/mL STANDARD_DEVIATION 0.959	4.74 log10 copies/mL STANDARD_DEVIATION 1.225	5.57 log10 copies/mL STANDARD_DEVIATION 1.275	4.40 log10 copies/mL STANDARD_DEVIATION 1.772	5.16 log10 copies/mL STANDARD_DEVIATION 1.356	4.79 log10 copies/mL STANDARD_DEVIATION 1.377	4.38 log10 copies/mL STANDARD_DEVIATION 1.61	3.94 log10 copies/mL STANDARD_DEVIATION 1.203	4.64 log10 copies/mL STANDARD_DEVIATION 1.505
SARS-CoV-2 Viral load - Saliva	5.56 log10 copies/mL STANDARD_DEVIATION 1.682	5.19 log10 copies/mL STANDARD_DEVIATION 1.312	4.77 log10 copies/mL STANDARD_DEVIATION 1.218	5.15 log10 copies/mL STANDARD_DEVIATION 2.048	4.77 log10 copies/mL STANDARD_DEVIATION 1.281	5.60 log10 copies/mL STANDARD_DEVIATION 1.074	4.93 log10 copies/mL STANDARD_DEVIATION 1.785	4.57 log10 copies/mL STANDARD_DEVIATION 1.559	5.00 log10 copies/mL STANDARD_DEVIATION 1.613
Sex: Female, Male Female	8 Participants	5 Participants	4 Participants	7 Participants	5 Participants	6 Participants	34 Participants	8 Participants	77 Participants
Sex: Female, Male Male	4 Participants	7 Participants	8 Participants	5 Participants	7 Participants	7 Participants	27 Participants	12 Participants	77 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	0 / 12	0 / 13	0 / 12	0 / 12	0 / 12	0 / 13	0 / 62	0 / 20
other Total, other adverse events	7 / 12	7 / 12	5 / 12	4 / 12	6 / 12	5 / 13	24 / 61	5 / 20
serious Total, serious adverse events	0 / 12	1 / 12	2 / 12	0 / 12	1 / 12	1 / 13	0 / 61	0 / 20

Outcome results

Primary

Time-weighted Average Change From Baseline in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7

Time-weighted average change in SARS-CoV-2 viral load was defined as area under the concentration versus time curve (AUC) of viral load change divided by time between baseline through Day 7.

Time frame: Baseline, Day 7

Population: Participants in the Nasopharyngeal Modified Full Analysis Set (mFAS) (all participants who were randomized into the study, had received at least 1 dose of study treatment and had positive SARS-CoV-2 viral load using nasopharyngeal swab sample at baseline \[the result of 'No SARS-CoV-2 detected' was considered as negative\]) with available data were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
RDV, Part A	Time-weighted Average Change From Baseline in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7	-2.04 log10 copies/mL	Standard Deviation 0.999
RDV + Placebo, Part A	Time-weighted Average Change From Baseline in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7	-1.51 log10 copies/mL	Standard Deviation 0.812
Placebo, Part A	Time-weighted Average Change From Baseline in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7	-1.24 log10 copies/mL	Standard Deviation 0.961
RDV, Part B	Time-weighted Average Change From Baseline in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7	-1.21 log10 copies/mL	Standard Deviation 1.108
RDV + Placebo, Part B	Time-weighted Average Change From Baseline in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7	-1.42 log10 copies/mL	Standard Deviation 0.975
Placebo, Part B	Time-weighted Average Change From Baseline in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7	-1.40 log10 copies/mL	Standard Deviation 0.796
RDV, Part C	Time-weighted Average Change From Baseline in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7	-1.91 log10 copies/mL	Standard Deviation 1.186
Placebo, Part C	Time-weighted Average Change From Baseline in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7	-1.93 log10 copies/mL	Standard Deviation 1.284

p-value: 0.111795% CI: [-1.49, 0.16]ANCOVA

p-value: 0.379395% CI: [-1.16, 0.46]ANCOVA

p-value: 0.524895% CI: [-1, 0.52]ANCOVA

p-value: 0.46195% CI: [-0.94, 0.44]ANCOVA

p-value: 0.500695% CI: [-0.4, 0.81]ANCOVA

Primary

Time-weighted Average Change From Baseline in Oropharyngeal SARS-CoV-2 Viral Load Through Day 7

Time-weighted average change in SARS-CoV-2 viral load was defined as AUC of viral load change divided by time between baseline through Day 7.

Time frame: Baseline, Day 7

Population: Participants in the Oropharyngeal mFAS (all participants who were randomized into the study, had received at least 1 dose of study treatment and had positive SARS-CoV-2 viral load using oropharyngeal swab sample at baseline \[the result of 'No SARS-CoV-2 detected' was considered as negative\]) with available data were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
RDV, Part A	Time-weighted Average Change From Baseline in Oropharyngeal SARS-CoV-2 Viral Load Through Day 7	-1.10 log10 copies/mL	Standard Deviation 0.856
RDV + Placebo, Part A	Time-weighted Average Change From Baseline in Oropharyngeal SARS-CoV-2 Viral Load Through Day 7	-0.55 log10 copies/mL	Standard Deviation 0.868
Placebo, Part A	Time-weighted Average Change From Baseline in Oropharyngeal SARS-CoV-2 Viral Load Through Day 7	-1.39 log10 copies/mL	Standard Deviation 1.036
RDV, Part B	Time-weighted Average Change From Baseline in Oropharyngeal SARS-CoV-2 Viral Load Through Day 7	-1.14 log10 copies/mL	Standard Deviation 1.133
RDV + Placebo, Part B	Time-weighted Average Change From Baseline in Oropharyngeal SARS-CoV-2 Viral Load Through Day 7	-0.85 log10 copies/mL	Standard Deviation 1.164
Placebo, Part B	Time-weighted Average Change From Baseline in Oropharyngeal SARS-CoV-2 Viral Load Through Day 7	-0.70 log10 copies/mL	Standard Deviation 0.902
RDV, Part C	Time-weighted Average Change From Baseline in Oropharyngeal SARS-CoV-2 Viral Load Through Day 7	-0.83 log10 copies/mL	Standard Deviation 1.073
Placebo, Part C	Time-weighted Average Change From Baseline in Oropharyngeal SARS-CoV-2 Viral Load Through Day 7	-0.46 log10 copies/mL	Standard Deviation 1.152

p-value: 0.341795% CI: [-0.37, 1.02]ANCOVA

p-value: 0.180395% CI: [-0.24, 1.21]ANCOVA

p-value: 0.123395% CI: [-1.27, 0.16]ANCOVA

p-value: 0.820395% CI: [-0.64, 0.8]ANCOVA

p-value: 0.645895% CI: [-0.65, 0.41]ANCOVA

Primary

Time-weighted Average Change From Baseline in Saliva SARS-CoV-2 Viral Load Through Day 7

Time-weighted average change in SARS-CoV-2 viral load was defined as AUC of viral load change divided by time between baseline through Day 7.

Time frame: Baseline, Day 7

Population: Participants in the saliva mFAS (all participants who were randomized into the study, had received at least 1 dose of study treatment and had positive SARS-CoV-2 viral load using saliva swab sample at baseline \[the result of 'No SARS-CoV-2 detected' was considered as negative\]) with available data were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
RDV, Part A	Time-weighted Average Change From Baseline in Saliva SARS-CoV-2 Viral Load Through Day 7	-0.80 log10 copies/mL	Standard Deviation 0.469
RDV + Placebo, Part A	Time-weighted Average Change From Baseline in Saliva SARS-CoV-2 Viral Load Through Day 7	-1.27 log10 copies/mL	Standard Deviation 0.877
Placebo, Part A	Time-weighted Average Change From Baseline in Saliva SARS-CoV-2 Viral Load Through Day 7	-0.49 log10 copies/mL	Standard Deviation 1.148
RDV, Part B	Time-weighted Average Change From Baseline in Saliva SARS-CoV-2 Viral Load Through Day 7	-1.09 log10 copies/mL	Standard Deviation 1.497
RDV + Placebo, Part B	Time-weighted Average Change From Baseline in Saliva SARS-CoV-2 Viral Load Through Day 7	-0.61 log10 copies/mL	Standard Deviation 0.676
Placebo, Part B	Time-weighted Average Change From Baseline in Saliva SARS-CoV-2 Viral Load Through Day 7	-0.93 log10 copies/mL	Standard Deviation 0.678
RDV, Part C	Time-weighted Average Change From Baseline in Saliva SARS-CoV-2 Viral Load Through Day 7	-1.25 log10 copies/mL	Standard Deviation 0.977
Placebo, Part C	Time-weighted Average Change From Baseline in Saliva SARS-CoV-2 Viral Load Through Day 7	-1.01 log10 copies/mL	Standard Deviation 1.096

p-value: 0.595195% CI: [-1.05, 0.61]ANCOVA

p-value: 0.087295% CI: [-1.54, 0.11]ANCOVA

p-value: 0.603195% CI: [-0.94, 0.56]ANCOVA

p-value: 0.757895% CI: [-0.64, 0.87]ANCOVA

p-value: 0.884695% CI: [-0.48, 0.56]ANCOVA

Secondary

Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B

Time frame: Baseline, Day 14

Population: Participants in the Nasopharyngeal mFAS with available were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
RDV, Part A	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-4.11 log10 copies/mL	Standard Deviation 1.304
RDV + Placebo, Part A	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-2.96 log10 copies/mL	Standard Deviation 1.475
Placebo, Part A	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-3.31 log10 copies/mL	Standard Deviation 1.198
RDV, Part B	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-2.82 log10 copies/mL	Standard Deviation 1.888
RDV + Placebo, Part B	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-2.86 log10 copies/mL	Standard Deviation 1.837
Placebo, Part B	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-3.41 log10 copies/mL	Standard Deviation 1.442

Secondary

Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5

Time frame: Baseline, Day 5

Population: Participants in the Nasopharyngeal mFAS with available data were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
RDV, Part A	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-2.44 log10 copies/mL	Standard Deviation 1.24
RDV + Placebo, Part A	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-1.67 log10 copies/mL	Standard Deviation 0.992
Placebo, Part A	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-1.78 log10 copies/mL	Standard Deviation 1.357
RDV, Part B	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-1.53 log10 copies/mL	Standard Deviation 1.063
RDV + Placebo, Part B	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-1.68 log10 copies/mL	Standard Deviation 1.475
Placebo, Part B	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-2.09 log10 copies/mL	Standard Deviation 1.052
RDV, Part C	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-2.01 log10 copies/mL	Standard Deviation 1.402
Placebo, Part C	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-2.06 log10 copies/mL	Standard Deviation 1.321

Secondary

Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7

Time frame: Baseline, Day 7

Population: Participants in the Nasopharyngeal mFAS with available data were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
RDV, Part A	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-3.05 log10 copies/mL	Standard Deviation 1.225
RDV + Placebo, Part A	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-2.12 log10 copies/mL	Standard Deviation 1.051
Placebo, Part A	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-2.09 log10 copies/mL	Standard Deviation 1.331
RDV, Part B	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-1.80 log10 copies/mL	Standard Deviation 1.389
RDV + Placebo, Part B	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-2.30 log10 copies/mL	Standard Deviation 1.257
Placebo, Part B	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-2.34 log10 copies/mL	Standard Deviation 1.873
RDV, Part C	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-2.64 log10 copies/mL	Standard Deviation 1.299
Placebo, Part C	Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-2.62 log10 copies/mL	Standard Deviation 1.555

Secondary

Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B

Time frame: Baseline, Day 14

Population: Participants in the Oropharyngeal mFAS with available were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
RDV, Part A	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-2.46 log10 copies/mL	Standard Deviation 0.908
RDV + Placebo, Part A	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-1.47 log10 copies/mL	Standard Deviation 0.841
Placebo, Part A	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-2.36 log10 copies/mL	Standard Deviation 0.951
RDV, Part B	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-1.46 log10 copies/mL	Standard Deviation 1.194
RDV + Placebo, Part B	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-1.95 log10 copies/mL	Standard Deviation 1.283
Placebo, Part B	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-2.05 log10 copies/mL	Standard Deviation 1.092

Secondary

Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5

Time frame: Baseline, Day 5

Population: Participants in the Oropharyngeal mFAS with available data were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
RDV, Part A	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-1.24 log10 copies/mL	Standard Deviation 0.957
RDV + Placebo, Part A	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-0.88 log10 copies/mL	Standard Deviation 0.839
Placebo, Part A	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-1.26 log10 copies/mL	Standard Deviation 1.418
RDV, Part B	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-1.29 log10 copies/mL	Standard Deviation 1.457
RDV + Placebo, Part B	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-1.13 log10 copies/mL	Standard Deviation 1.394
Placebo, Part B	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-1.10 log10 copies/mL	Standard Deviation 0.988
RDV, Part C	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-0.92 log10 copies/mL	Standard Deviation 1.213
Placebo, Part C	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5	-0.66 log10 copies/mL	Standard Deviation 1.581

Secondary

Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7

Time frame: Baseline, Day 7

Population: Participants in the Oropharyngeal mFAS with available data were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
RDV, Part A	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-1.76 log10copies/mL	Standard Deviation 1.113
RDV + Placebo, Part A	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-0.40 log10copies/mL	Standard Deviation 1.049
Placebo, Part A	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-1.98 log10copies/mL	Standard Deviation 0.971
RDV, Part B	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-1.73 log10copies/mL	Standard Deviation 1.513
RDV + Placebo, Part B	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-1.08 log10copies/mL	Standard Deviation 1.16
Placebo, Part B	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-1.27 log10copies/mL	Standard Deviation 0.845
RDV, Part C	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-1.07 log10copies/mL	Standard Deviation 1.122
Placebo, Part C	Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7	-0.62 log10copies/mL	Standard Deviation 1.606

Secondary

Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B

Time frame: Baseline, Day 14

Population: Participants in the Saliva mFAS with available were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
RDV, Part A	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-2.58 log10 copies/mL	Standard Deviation 1.413
RDV + Placebo, Part A	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-2.27 log10 copies/mL	Standard Deviation 1.136
Placebo, Part A	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-1.78 log10 copies/mL	Standard Deviation 0.618
RDV, Part B	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-2.30 log10 copies/mL	Standard Deviation 1.505
RDV + Placebo, Part B	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-2.11 log10 copies/mL	Standard Deviation 1.171
Placebo, Part B	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B	-3.53 log10 copies/mL	Standard Deviation 1.253

Secondary

Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5

Time frame: Baseline, Day 5

Population: Participants in the Saliva mFAS with available data were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
RDV, Part A	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5	-0.99 log10 copies/mL	Standard Deviation 0.562
RDV + Placebo, Part A	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5	-1.26 log10 copies/mL	Standard Deviation 1.288
Placebo, Part A	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5	-0.77 log10 copies/mL	Standard Deviation 1.449
RDV, Part B	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5	-1.60 log10 copies/mL	Standard Deviation 1.443
RDV + Placebo, Part B	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5	-0.31 log10 copies/mL	Standard Deviation 0.708
Placebo, Part B	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5	-0.92 log10 copies/mL	Standard Deviation 1.04
RDV, Part C	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5	-1.36 log10 copies/mL	Standard Deviation 1.056
Placebo, Part C	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5	-1.15 log10 copies/mL	Standard Deviation 0.962

Secondary

Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7

Time frame: Baseline, Day 7

Population: Participants in the Saliva mFAS with available data were analyzed.

Arm	Measure	Value (MEAN)	Dispersion
RDV, Part A	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7	-1.28 log10 copies/mL	Standard Deviation 1.102
RDV + Placebo, Part A	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7	-1.24 log10 copies/mL	Standard Deviation 2.108
Placebo, Part A	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7	-0.62 log10 copies/mL	Standard Deviation 1.406
RDV, Part B	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7	-1.91 log10 copies/mL	Standard Deviation 1.667
RDV + Placebo, Part B	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7	-0.99 log10 copies/mL	Standard Deviation 0.943
Placebo, Part B	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7	-1.53 log10 copies/mL	Standard Deviation 1.553
RDV, Part C	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7	-1.69 log10 copies/mL	Standard Deviation 1.302
Placebo, Part C	Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7	-1.31 log10 copies/mL	Standard Deviation 1.752

Secondary

Number of Participants With All-Cause Medically Attended Visits (MAVs) or Death by Day 28

The composite outcome of all-cause MAVs (medical visits attended in person by the participant and a health care professional) or all-cause death by Study Day 28 were estimated using Kaplan-Meier methods by treatment group.

Time frame: Randomization up to Day 28

Population: Participants in the Full Analysis Set (all participants who were randomized into the study, and had received at least 1 dose of study treatment) were analyzed.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
RDV, Part A	Number of Participants With All-Cause Medically Attended Visits (MAVs) or Death by Day 28	1 Participants
RDV + Placebo, Part A	Number of Participants With All-Cause Medically Attended Visits (MAVs) or Death by Day 28	1 Participants
Placebo, Part A	Number of Participants With All-Cause Medically Attended Visits (MAVs) or Death by Day 28	1 Participants
RDV, Part B	Number of Participants With All-Cause Medically Attended Visits (MAVs) or Death by Day 28	0 Participants
RDV + Placebo, Part B	Number of Participants With All-Cause Medically Attended Visits (MAVs) or Death by Day 28	1 Participants
Placebo, Part B	Number of Participants With All-Cause Medically Attended Visits (MAVs) or Death by Day 28	1 Participants
RDV, Part C	Number of Participants With All-Cause Medically Attended Visits (MAVs) or Death by Day 28	0 Participants
Placebo, Part C	Number of Participants With All-Cause Medically Attended Visits (MAVs) or Death by Day 28	0 Participants

Secondary

Number of Participants With COVID-19 Related MAVs or Death by Day 28

The composite outcome of COVID-19 related MAVs (medical visits attended in person by the participant and a health care professional) or all-cause death by Study Day 28 were estimated using Kaplan-Meier methods by treatment group.

Time frame: Randomization up to Day 28

Population: Participants in the Full Analysis Set were analyzed.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
RDV, Part A	Number of Participants With COVID-19 Related MAVs or Death by Day 28	0 Participants
RDV + Placebo, Part A	Number of Participants With COVID-19 Related MAVs or Death by Day 28	1 Participants
Placebo, Part A	Number of Participants With COVID-19 Related MAVs or Death by Day 28	1 Participants
RDV, Part B	Number of Participants With COVID-19 Related MAVs or Death by Day 28	0 Participants
RDV + Placebo, Part B	Number of Participants With COVID-19 Related MAVs or Death by Day 28	0 Participants
Placebo, Part B	Number of Participants With COVID-19 Related MAVs or Death by Day 28	1 Participants
RDV, Part C	Number of Participants With COVID-19 Related MAVs or Death by Day 28	0 Participants
Placebo, Part C	Number of Participants With COVID-19 Related MAVs or Death by Day 28	0 Participants

Secondary

Number of Participants With Hospitalization by Day 28

The composite of all-cause hospitalization was estimated using Kaplan-Meier methods by treatment group.

Time frame: Day 1 up to Day 28

Population: Participants in the Full Analysis Set were analyzed.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
RDV, Part A	Number of Participants With Hospitalization by Day 28	0 Participants
RDV + Placebo, Part A	Number of Participants With Hospitalization by Day 28	1 Participants
Placebo, Part A	Number of Participants With Hospitalization by Day 28	1 Participants
RDV, Part B	Number of Participants With Hospitalization by Day 28	0 Participants
RDV + Placebo, Part B	Number of Participants With Hospitalization by Day 28	1 Participants
Placebo, Part B	Number of Participants With Hospitalization by Day 28	1 Participants
RDV, Part C	Number of Participants With Hospitalization by Day 28	0 Participants
Placebo, Part C	Number of Participants With Hospitalization by Day 28	0 Participants

Secondary

Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)

An adverse event (AE) was any untoward medical occurrence in a participant administered a study drug, which did not necessarily have a causal relationship with the treatment. AE was therefore any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. TEAEs: AE with an onset date on or after the study drug start date and no later than 30 days after study drug stop date; or any AE leading to study drug discontinuation.

Time frame: First dose date up to 5 days plus 30 days

Population: The Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment.

Arm	Measure	Value (NUMBER)
RDV, Part A	Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	58.3 percentage of participants
RDV + Placebo, Part A	Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	58.3 percentage of participants
Placebo, Part A	Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	41.7 percentage of participants
RDV, Part B	Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	33.3 percentage of participants
RDV + Placebo, Part B	Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	58.3 percentage of participants
Placebo, Part B	Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	38.5 percentage of participants
RDV, Part C	Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	42.6 percentage of participants
Placebo, Part C	Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	25.0 percentage of participants

Secondary

Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation

Time frame: First dose date up to 5 days plus 30 days

Population: Participants in the Safety Analysis Set were analyzed.

Arm	Measure	Value (NUMBER)
RDV, Part A	Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation	0 percentage of participants
RDV + Placebo, Part A	Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation	0 percentage of participants
Placebo, Part A	Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation	8.3 percentage of participants
RDV, Part B	Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation	0 percentage of participants
RDV + Placebo, Part B	Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation	0 percentage of participants
Placebo, Part B	Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation	0 percentage of participants
RDV, Part C	Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation	1.6 percentage of participants
Placebo, Part C	Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation	0 percentage of participants

Secondary

Percentage of Participants With Treatment-Emergent Laboratory Abnormalities as Per Severity Grade

Treatment-emergent laboratory abnormalities were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 July 2017. Laboratory abnormalities were graded as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening). Percentage of participants with any severity grade were reported.

Time frame: First dose date up to 5 days plus 30 days

Population: Participants in the Safety Analysis Set with available data were analyzed.

Arm	Measure	Value (NUMBER)
RDV, Part A	Percentage of Participants With Treatment-Emergent Laboratory Abnormalities as Per Severity Grade	58.3 percentage of participants
RDV + Placebo, Part A	Percentage of Participants With Treatment-Emergent Laboratory Abnormalities as Per Severity Grade	91.7 percentage of participants
Placebo, Part A	Percentage of Participants With Treatment-Emergent Laboratory Abnormalities as Per Severity Grade	63.6 percentage of participants
RDV, Part B	Percentage of Participants With Treatment-Emergent Laboratory Abnormalities as Per Severity Grade	63.6 percentage of participants
RDV + Placebo, Part B	Percentage of Participants With Treatment-Emergent Laboratory Abnormalities as Per Severity Grade	83.3 percentage of participants
Placebo, Part B	Percentage of Participants With Treatment-Emergent Laboratory Abnormalities as Per Severity Grade	61.5 percentage of participants
RDV, Part C	Percentage of Participants With Treatment-Emergent Laboratory Abnormalities as Per Severity Grade	68.9 percentage of participants
Placebo, Part C	Percentage of Participants With Treatment-Emergent Laboratory Abnormalities as Per Severity Grade	75.0 percentage of participants

Secondary

Pharmacokinetic (PK) Parameter: AUC0-24h of Remdesivir (RDV) and Its Metabolites (GS-441524 and GS-704277) in Parts A and B

AUC0-24h was defined as the concentration of drug over time between time 0 to time 24 hours. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

Time frame: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.