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

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT04539262
Collaborator
(none)
156
Enrollment
28
Locations
8
Arms
6.2
Actual Duration (Months)
5.6
Patients Per Site
0.9
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
  • Drug: Remdesivir (RDV)
  • Drug: Placebo
 Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
156 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official 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
Actual Study Start Date :
Sep 14, 2020
Actual Primary Completion Date :
Feb 26, 2021
Actual Study Completion Date :
Mar 22, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Remdesivir (RDV), Part A

Participants will receive inhaled RDV 31 mg administered daily for 5 days.

Drug: Remdesivir (RDV)
Administered as an aerosolized solution
Other Names:
  • GS-5734™

    		•
    Experimental: RDV + Placebo, Part A

    Participants will receive inhaled RDV 31 mg administered daily for 3 days followed by placebo to match RDV daily for 2 days.

    Drug: Remdesivir (RDV)
    Administered as an aerosolized solution
    Other Names:
  • GS-5734™

    • Drug: Placebo
    Administered as an aerosolized solution
    Placebo Comparator: Placebo, Part A

    Participants will receive placebo to match inhaled RDV in Part A daily for 5 days.

    Drug: Placebo
    Administered as an aerosolized solution
    Experimental: RDV, Part B

    Participants will receive inhaled RDV 62 mg administered daily for up to 5 days.

    Drug: Remdesivir (RDV)
    Administered as an aerosolized solution
    Other Names:
  • GS-5734™

    		•
    Experimental: RDV + Placebo, Part B

    Participants will receive inhaled RDV 62 mg administered daily for up to 3 days followed by placebo to match RDV daily for 2 days.

    Drug: Remdesivir (RDV)
    Administered as an aerosolized solution
    Other Names:
  • GS-5734™

    • Drug: Placebo
    Administered as an aerosolized solution
    Placebo Comparator: Placebo, Part B

    Participants will receive placebo to match inhaled RDV in Part B daily for 5 days.

    Drug: Placebo
    Administered as an aerosolized solution
    Experimental: RDV, Part C

    Participants will receive inhaled RDV 39 mg administered daily for 5 days.

    Drug: Remdesivir (RDV)
    Administered as an aerosolized solution
    Other Names:
  • GS-5734™

    		•
    Placebo Comparator: Placebo, Part C

    Participants will receive placebo to match inhaled RDV in Part C daily for 5 days.

    Drug: Placebo
    Administered as an aerosolized solution

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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.

    3. 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 Outcome Measures

    1. 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.

    2. 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.

    3. Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation [First dose date up to 5 days plus 30 days]

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    11. 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.

    12. 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.

    13. 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.

    14. 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.

    15. 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.

    16. 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.

    17. 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.

    18. 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.

    19. Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5 [Baseline, Day 5]

    20. Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5 [Baseline, Day 5]

    21. Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5 [Baseline, Day 5]

    22. Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7 [Baseline, Day 7]

    23. Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7 [Baseline, Day 7]

    24. Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7 [Baseline, Day 7]

    25. Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B [Baseline, Day 14]

    26. Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B [Baseline, Day 14]

    27. Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B [Baseline, Day 14]

    28. 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.

    29. 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.

    30. 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.

    31. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. 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/Exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Institute for Liver Health Mesa Arizona United States 85210
    2 The Institute for Liver Health Tucson Arizona United States 85712
    3 Franco Felizarta, MD Bakersfield California United States 93301
    4 Aurora FDRC Inc. Costa Mesa California United States 92627
    5 Elevated Health Huntington Beach California United States 92648
    6 Cedars-Sinai Medical Center Los Angeles California United States 90048
    7 Western Clinical Research Placentia California United States 92870
    8 UC Davis Health/Medical Center Sacramento California United States 95817
    9 Bradenton Research Center, Inc. Bradenton Florida United States 34205
    10 Integrity Clinical Research, LLC Doral Florida United States 33166
    11 Holy Cross Hospital Fort Lauderdale Florida United States 33308
    12 Evolution Clinical Trials, Inc. Hialeah Gardens Florida United States 33016
    13 Research in Miami, Inc. Hialeah Florida United States 33013
    14 Optimus U Corporation Miami Florida United States 33125
    15 L & C Professional Medical Research Institute Miami Florida United States 33144
    16 Westchester Research Center at Westchester General Hospital Miami Florida United States 33155
    17 MedBio Trials Miami Florida United States 33180
    18 Nuovida Research Center, Corp Miami Florida United States 33186
    19 IMIC Inc Palmetto Bay Florida United States 33157
    20 Triple O Research Institute, PA West Palm Beach Florida United States 33401
    21 Family Care Research Boise Idaho United States 83704
    22 CTU Covid Research Center New Orleans Louisiana United States 70112
    23 STAT Research Vandalia Ohio United States 45066
    24 Inquest Clinical Research Baytown Texas United States 77521
    25 DFW Clinical Research Dallas Texas United States 75234
    26 Baylor Research Institute Dallas Texas United States 75246
    27 PCP for Life-Tidwell Houston Texas United States 77093
    28 Providence Regional Medical Center Everett Everett Washington United States 98201

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT04539262
    Other Study ID Numbers:
    • GS-US-553-9020
    First Posted:
    Sep 4, 2020
    Last Update Posted:
    Mar 3, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    COVID-19
    Remdesivir

    Study Results

    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 Detail 168 participants were screened.
    Arm/Group Title Remdesivir (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
    Arm/Group Description Participants received inhaled remdesivir (RDV) 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Period Title: Overall Study
    STARTED 12 13 12 12 12 13 62 20
    COMPLETED 12 12 11 11 12 13 61 20
    NOT COMPLETED 0 1 1 1 0 0 1 0

    Baseline Characteristics

    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days. Total of all reporting groups
    Overall Participants 12 12 12 12 12 13 61 20 154
    Age, Customized (Count of Participants)
    < 60 years
    10
    83.3%
    11
    91.7%
    9
    75%
    12
    100%
    10
    83.3%
    12
    92.3%
    55
    90.2%
    15
    75%
    134
    87%
    ≥ 60 years
    2
    16.7%
    1
    8.3%
    3
    25%
    0
    0%
    2
    16.7%
    1
    7.7%
    6
    9.8%
    5
    25%
    20
    13%
    Sex: Female, Male (Count of Participants)
    Female
    8
    66.7%
    5
    41.7%
    4
    33.3%
    7
    58.3%
    5
    41.7%
    6
    46.2%
    34
    55.7%
    8
    40%
    77
    50%
    Male
    4
    33.3%
    7
    58.3%
    8
    66.7%
    5
    41.7%
    7
    58.3%
    7
    53.8%
    27
    44.3%
    12
    60%
    77
    50%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    6
    50%
    3
    25%
    3
    25%
    2
    16.7%
    6
    50%
    4
    30.8%
    40
    65.6%
    14
    70%
    78
    50.6%
    Not Hispanic or Latino
    6
    50%
    9
    75%
    9
    75%
    10
    83.3%
    4
    33.3%
    9
    69.2%
    21
    34.4%
    6
    30%
    74
    48.1%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    16.7%
    0
    0%
    0
    0%
    0
    0%
    2
    1.3%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    0
    0%
    1
    8.3%
    1
    8.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    1.3%
    Black
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    1
    7.7%
    12
    19.7%
    2
    10%
    16
    10.4%
    White
    11
    91.7%
    9
    75%
    10
    83.3%
    11
    91.7%
    10
    83.3%
    12
    92.3%
    47
    77%
    16
    80%
    126
    81.8%
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.6%
    1
    5%
    2
    1.3%
    Not Permitted
    1
    8.3%
    2
    16.7%
    1
    8.3%
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    0
    0%
    5
    3.2%
    Other
    0
    0%
    0
    0%
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    1
    1.6%
    1
    5%
    3
    1.9%
    SARS-CoV-2 Viral load - Nasopharyngeal (log10 copies/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log10 copies/mL]
    7.29
    (1.901)
    6.56
    (1.065)
    6.81
    (1.065)
    5.23
    (1.980)
    6.41
    (1.883)
    7.09
    (1.288)
    5.69
    (2.004)
    5.76
    (1.839)
    6.14
    (1.859)
    SARS-CoV-2 Viral load - Oropharyngeal (log10 copies/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log10 copies/mL]
    5.69
    (0.959)
    4.74
    (1.225)
    5.57
    (1.275)
    4.40
    (1.772)
    5.16
    (1.356)
    4.79
    (1.377)
    4.38
    (1.610)
    3.94
    (1.203)
    4.64
    (1.505)
    SARS-CoV-2 Viral load - Saliva (log10 copies/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log10 copies/mL]
    5.56
    (1.682)
    5.19
    (1.312)
    4.77
    (1.218)
    5.15
    (2.048)
    4.77
    (1.281)
    5.60
    (1.074)
    4.93
    (1.785)
    4.57
    (1.559)
    5.00
    (1.613)

    Outcome Measures

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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 11 11 11 8 10 13 44 16
    Mean (Standard Deviation) [log10 copies/mL]
    -2.04
    (0.999)
    -1.51
    (0.812)
    -1.24
    (0.961)
    -1.21
    (1.108)
    -1.42
    (0.975)
    -1.40
    (0.796)
    -1.91
    (1.186)
    -1.93
    (1.284)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection RDV, Part A, Placebo, Part A
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1117
    Comments Least square (LS) Mean, Standard Error (SE), 95% CI and p-value were from Analysis of covariance (ANCOVA) with baseline viral load as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Least Square Mean Difference by Day 7
    Estimated Value -0.66
    Confidence Interval (2-Sided) 95%
    -1.49 to 0.16
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.40
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection RDV + Placebo, Part A, Placebo, Part A
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3793
    Comments LS Mean (SE), 95% CI, and p-value were from ANCOVA with baseline viral load as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value -0.35
    Confidence Interval (2-Sided) 95%
    -1.16 to 0.46
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.40
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection RDV, Part B, Placebo, Part B
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5248
    Comments LS Mean (SE), 95% CI, and p-value were from ANCOVA with baseline viral load as a covariate
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value -0.24
    Confidence Interval (2-Sided) 95%
    -1.00 to 0.52
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.37
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection RDV + Placebo, Part B, Placebo, Part B
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4610
    Comments
    Method ANCOVA
    Comments LS Mean (SE), 95% CI, and p-value were from ANCOVA with baseline viral load as a covariate
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value -0.25
    Confidence Interval (2-Sided) 95%
    -0.94 to 0.44
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.34
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection RDV, Part C, Placebo, Part C
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5006
    Comments LS Mean (SE), 95% CI and p-value were from ANCOVA with baseline viral load as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value 0.20
    Confidence Interval (2-Sided) 95%
    -0.40 to 0.81
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.30
    Estimation Comments
    2. Primary Outcome
    Title Time-weighted Average Change From Baseline in Oropharyngeal SARS-CoV-2 Viral Load Through Day 7
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 11 11 11 9 9 11 41 12
    Mean (Standard Deviation) [log10 copies/mL]
    -1.10
    (0.856)
    -0.55
    (0.868)
    -1.39
    (1.036)
    -1.14
    (1.133)
    -0.85
    (1.164)
    -0.70
    (0.902)
    -0.83
    (1.073)
    -0.46
    (1.152)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection RDV, Part A, Placebo, Part A
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3417
    Comments LS Mean (SE), 95% CI, and p-value were from ANCOVA with baseline viral load as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value 0.33
    Confidence Interval (2-Sided) 95%
    -0.37 to 1.02
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.34
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection RDV + Placebo, Part A, Placebo, Part A
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1803
    Comments LS Mean (SE), 95% CI, and p-value were from ANCOVA with baseline viral load as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value 0.49
    Confidence Interval (2-Sided) 95%
    -0.24 to 1.21
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.35
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection RDV, Part B, Placebo, Part B
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1233
    Comments LS Mean (SE), 95% CI, and p-value were from ANCOVA with baseline viral load as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value -0.55
    Confidence Interval (2-Sided) 95%
    -1.27 to 0.16
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.35
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection RDV + Placebo, Part B, Placebo, Part B
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8203
    Comments LS Mean (SE), 95% CI, and p-value were from ANCOVA with baseline viral load as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value 0.08
    Confidence Interval (2-Sided) 95%
    -0.64 to 0.80
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.35
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection RDV, Part C, Placebo, Part C
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6458
    Comments LS Mean (SE), 95% CI, and p-value were from ANCOVA with baseline viral load as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value -0.12
    Confidence Interval (2-Sided) 95%
    -0.65 to 0.41
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.26
    Estimation Comments
    3. Primary Outcome
    Title Time-weighted Average Change From Baseline in Saliva SARS-CoV-2 Viral Load Through Day 7
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 10 10 8 9 9 12 44 16
    Mean (Standard Deviation) [log10 copies/mL]
    -0.80
    (0.469)
    -1.27
    (0.877)
    -0.49
    (1.148)
    -1.09
    (1.497)
    -0.61
    (0.676)
    -0.93
    (0.678)
    -1.25
    (0.977)
    -1.01
    (1.096)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection RDV, Part A, Placebo, Part A
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5951
    Comments LS Mean (SE), 95% CI, and p-value were from ANCOVA with baseline viral load as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value -0.22
    Confidence Interval (2-Sided) 95%
    -1.05 to 0.61
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.40
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection RDV + Placebo, Part A, Placebo, Part A
    Comments
    Type of Statistical Test Superiority
    Comments LS Mean (SE), 95% CI, and p-value were from ANCOVA with baseline viral load as a covariate.
    Statistical Test of Hypothesis p-Value 0.0872
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value -0.71
    Confidence Interval (2-Sided) 95%
    -1.54 to 0.11
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.40
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection RDV, Part B, Placebo, Part B
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6031
    Comments LS Mean (SE), 95% CI, and p-value were from ANCOVA with baseline viral load as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value -0.19
    Confidence Interval (2-Sided) 95%
    -0.94 to 0.56
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.36
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection RDV + Placebo, Part B, Placebo, Part B
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.7578
    Comments LS Mean (SE), 95% CI, and p-value were from ANCOVA with baseline viral load as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value 0.12
    Confidence Interval (2-Sided) 95%
    -0.64 to 0.87
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.37
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection RDV, Part C, Placebo, Part C
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8846
    Comments LS Mean (SE), 95% CI, and p-value were from ANCOVA with baseline viral load as a covariate.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean Difference by Day 7
    Estimated Value 0.04
    Confidence Interval (2-Sided) 95%
    -0.48 to 0.56
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.26
    Estimation Comments
    4. Secondary Outcome
    Title Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    The Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 12 12 12 12 12 13 61 20
    Number [percentage of participants]
    58.3
    485.8%
    58.3
    485.8%
    41.7
    347.5%
    33.3
    277.5%
    58.3
    485.8%
    38.5
    296.2%
    42.6
    69.8%
    25.0
    125%
    5. Secondary Outcome
    Title Percentage of Participants With Treatment-Emergent Laboratory Abnormalities as Per Severity Grade
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Safety Analysis Set with available data were analyzed.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 12 12 11 11 12 13 61 20
    Number [percentage of participants]
    58.3
    485.8%
    91.7
    764.2%
    63.6
    530%
    63.6
    530%
    83.3
    694.2%
    61.5
    473.1%
    68.9
    113%
    75.0
    375%
    6. Secondary Outcome
    Title Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation
    Description
    Time Frame First dose date up to 5 days plus 30 days

    Outcome Measure Data

    Analysis Population Description
    Participants in the Safety Analysis Set were analyzed.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 12 12 12 12 12 13 61 20
    Number [percentage of participants]
    0
    0%
    0
    0%
    8.3
    69.2%
    0
    0%
    0
    0%
    0
    0%
    1.6
    2.6%
    0
    0%
    7. Secondary Outcome
    Title Number of Participants With All-Cause Medically Attended Visits (MAVs) or Death by Day 28
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 12 12 12 12 12 13 61 20
    Count of Participants [Participants]
    1
    8.3%
    1
    8.3%
    1
    8.3%
    0
    0%
    1
    8.3%
    1
    7.7%
    0
    0%
    0
    0%
    8. Secondary Outcome
    Title Number of Participants With COVID-19 Related MAVs or Death by Day 28
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 12 12 12 12 12 13 61 20
    Count of Participants [Participants]
    0
    0%
    1
    8.3%
    1
    8.3%
    0
    0%
    0
    0%
    1
    7.7%
    0
    0%
    0
    0%
    9. Secondary Outcome
    Title Number of Participants With Hospitalization by Day 28
    Description The composite of all-cause hospitalization was estimated using Kaplan-Meier methods by treatment group.
    Time Frame Day 1 up to Day 28

    Outcome Measure Data

    Analysis Population Description
    Participants in the Full Analysis Set were analyzed.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 12 12 12 12 12 13 61 20
    Count of Participants [Participants]
    0
    0%
    1
    8.3%
    1
    8.3%
    0
    0%
    1
    8.3%
    1
    7.7%
    0
    0%
    0
    0%
    10. Secondary Outcome
    Title Pharmacokinetic (PK) Parameter: AUC0-24h of Remdesivir (RDV) and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
    Description 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.

    Outcome Measure Data

    Analysis Population Description
    As only 1 participant was evaluated, results for PK parameters were not reported for the protection of personal data and to avoid re-identification.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 0 0 0 0 0 0
    11. Secondary Outcome
    Title PK Parameter: AUClast of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
    Description 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.
    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.

    Outcome Measure Data

    Analysis Population Description
    As only 1 participant was evaluated, results for PK parameters were not reported for the protection of personal data and to avoid re-identification.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 0 0 0 0 0 0
    12. Secondary Outcome
    Title PK Parameter: CLss/F of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
    Description 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.
    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.

    Outcome Measure Data

    Analysis Population Description
    As only 1 participant was evaluated, results for PK parameters were not reported for the protection of personal data and to avoid re-identification.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 0 0 0 0 0 0
    13. Secondary Outcome
    Title PK Parameter: t1/2 of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
    Description 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.
    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.

    Outcome Measure Data

    Analysis Population Description
    As only 1 participant was evaluated, results for PK parameters were not reported for the protection of personal data and to avoid re-identification.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 0 0 0 0 0 0
    14. Secondary Outcome
    Title PK Parameter: Vz/F of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
    Description 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.
    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.

    Outcome Measure Data

    Analysis Population Description
    As only 1 participant was evaluated, results for PK parameters were not reported for the protection of personal data and to avoid re-identification.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 0 0 0 0 0 0
    15. Secondary Outcome
    Title PK Parameter: Cmax of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
    Description 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.
    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.

    Outcome Measure Data

    Analysis Population Description
    As only 1 participant was evaluated, results for PK parameters were not reported for the protection of personal data and to avoid re-identification.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 0 0 0 0 0 0
    16. Secondary Outcome
    Title PK Parameter: Tmax of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
    Description 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.
    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.

    Outcome Measure Data

    Analysis Population Description
    As only 1 participant was evaluated, results for PK parameters were not reported for the protection of personal data and to avoid re-identification.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered as an aerosolized solution by inhalation through facemask daily for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 0 0 0 0 0 0
    17. Secondary Outcome
    Title PK Parameter: Clast of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
    Description 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.
    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.

    Outcome Measure Data

    Analysis Population Description
    As only 1 participant was evaluated, results for PK parameters were not reported for the protection of personal data and to avoid re-identification.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 0 0 0 0 0 0
    18. Secondary Outcome
    Title PK Parameter: Tlast of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
    Description 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.
    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.

    Outcome Measure Data

    Analysis Population Description
    As only 1 participant was evaluated, results for PK parameters were not reported for the protection of personal data and to avoid re-identification.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 0 0 0 0 0 0
    19. Secondary Outcome
    Title PK Parameter: AUCtau of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
    Description 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.
    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.

    Outcome Measure Data

    Analysis Population Description
    As only 1 participant was evaluated, results for PK parameters were not reported for the protection of personal data and to avoid re-identification.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 0 0 0 0 0 0
    20. Secondary Outcome
    Title PK Parameter: λz of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
    Description 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.
    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.

    Outcome Measure Data

    Analysis Population Description
    As only 1 participant was evaluated, results for PK parameters were not reported for the protection of personal data and to avoid re-identification.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 0 0 0 0 0 0
    21. Secondary Outcome
    Title PK Parameter: Ctau of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
    Description 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.
    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.

    Outcome Measure Data

    Analysis Population Description
    As only 1 participant was evaluated, results for PK parameters were not reported for the protection of personal data and to avoid re-identification.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 0 0 0 0 0 0
    22. Secondary Outcome
    Title Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5
    Description
    Time Frame Baseline, Day 5

    Outcome Measure Data

    Analysis Population Description
    Participants in the Nasopharyngeal mFAS with available data were analyzed.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 11 11 11 8 9 12 40 12
    Mean (Standard Deviation) [log10 copies/mL]
    -2.44
    (1.240)
    -1.67
    (0.992)
    -1.78
    (1.357)
    -1.53
    (1.063)
    -1.68
    (1.475)
    -2.09
    (1.052)
    -2.01
    (1.402)
    -2.06
    (1.321)
    23. Secondary Outcome
    Title Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5
    Description
    Time Frame Baseline, Day 5

    Outcome Measure Data

    Analysis Population Description
    Participants in the Oropharyngeal mFAS with available data were analyzed.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 11 10 11 8 9 9 40 12
    Mean (Standard Deviation) [log10 copies/mL]
    -1.24
    (0.957)
    -0.88
    (0.839)
    -1.26
    (1.418)
    -1.29
    (1.457)
    -1.13
    (1.394)
    -1.10
    (0.988)
    -0.92
    (1.213)
    -0.66
    (1.581)
    24. Secondary Outcome
    Title Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5
    Description
    Time Frame Baseline, Day 5

    Outcome Measure Data

    Analysis Population Description
    Participants in the Saliva mFAS with available data were analyzed.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 10 8 8 8 7 10 42 14
    Mean (Standard Deviation) [log10 copies/mL]
    -0.99
    (0.562)
    -1.26
    (1.288)
    -0.77
    (1.449)
    -1.60
    (1.443)
    -0.31
    (0.708)
    -0.92
    (1.040)
    -1.36
    (1.056)
    -1.15
    (0.962)
    25. Secondary Outcome
    Title Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7
    Description
    Time Frame Baseline, Day 7

    Outcome Measure Data

    Analysis Population Description
    Participants in the Nasopharyngeal mFAS with available data were analyzed.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 11 9 11 8 10 10 39 15
    Mean (Standard Deviation) [log10 copies/mL]
    -3.05
    (1.225)
    -2.12
    (1.051)
    -2.09
    (1.331)
    -1.80
    (1.389)
    -2.30
    (1.257)
    -2.34
    (1.873)
    -2.64
    (1.299)
    -2.62
    (1.555)
    26. Secondary Outcome
    Title Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7
    Description
    Time Frame Baseline, Day 7

    Outcome Measure Data

    Analysis Population Description
    Participants in the Oropharyngeal mFAS with available data were analyzed.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 11 9 10 8 9 9 36 10
    Mean (Standard Deviation) [log10copies/mL]
    -1.76
    (1.113)
    -0.40
    (1.049)
    -1.98
    (0.971)
    -1.73
    (1.513)
    -1.08
    (1.160)
    -1.27
    (0.845)
    -1.07
    (1.122)
    -0.62
    (1.606)
    27. Secondary Outcome
    Title Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7
    Description
    Time Frame Baseline, Day 7

    Outcome Measure Data

    Analysis Population Description
    Participants in the Saliva mFAS with available data were analyzed.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 10 8 7 8 9 8 38 15
    Mean (Standard Deviation) [log10 copies/mL]
    -1.28
    (1.102)
    -1.24
    (2.108)
    -0.62
    (1.406)
    -1.91
    (1.667)
    -0.99
    (0.943)
    -1.53
    (1.553)
    -1.69
    (1.302)
    -1.31
    (1.752)
    28. Secondary Outcome
    Title Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B
    Description
    Time Frame Baseline, Day 14

    Outcome Measure Data

    Analysis Population Description
    Participants in the Nasopharyngeal mFAS with available were analyzed.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 11 10 8 6 9 11
    Mean (Standard Deviation) [log10 copies/mL]
    -4.11
    (1.304)
    -2.96
    (1.475)
    -3.31
    (1.198)
    -2.82
    (1.888)
    -2.86
    (1.837)
    -3.41
    (1.442)
    29. Secondary Outcome
    Title Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B
    Description
    Time Frame Baseline, Day 14

    Outcome Measure Data

    Analysis Population Description
    Participants in the Oropharyngeal mFAS with available were analyzed.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 10 10 11 6 7 8
    Mean (Standard Deviation) [log10 copies/mL]
    -2.46
    (0.908)
    -1.47
    (0.841)
    -2.36
    (0.951)
    -1.46
    (1.194)
    -1.95
    (1.283)
    -2.05
    (1.092)
    30. Secondary Outcome
    Title Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B
    Description
    Time Frame Baseline, Day 14

    Outcome Measure Data

    Analysis Population Description
    Participants in the Saliva mFAS with available were analyzed.
    Arm/Group Title RDV, Part A RDV + Placebo, Part A Placebo, Part A RDV, Part B RDV + Placebo, Part B Placebo, Part B
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days.
    Measure Participants 9 8 6 6 8 3
    Mean (Standard Deviation) [log10 copies/mL]
    -2.58
    (1.413)
    -2.27
    (1.136)
    -1.78
    (0.618)
    -2.30
    (1.505)
    -2.11
    (1.171)
    -3.53
    (1.253)
    31. Secondary Outcome
    Title Time to Negative Nasopharyngeal SARS-CoV-2 Polymerase Chain Reaction (PCR)
    Description 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 Frame Baseline up to Day 17

    Outcome Measure Data

    Analysis Population Description
    Participants in the Nasopharyngeal mFAS with available data were analyzed.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 11 11 11 8 10 13 46 16
    Median (95% Confidence Interval) [days]
    NA
    17.0
    NA
    16.0
    NA
    NA
    NA
    NA
    32. Secondary Outcome
    Title Time to Negative Oropharyngeal SARS-CoV-2 Polymerase Chain Reaction (PCR)
    Description 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 Frame Baseline up to Day 17

    Outcome Measure Data

    Analysis Population Description
    Participants in the Oropharyngeal mFAS with available data were analyzed.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 11 11 11 9 9 11 41 12
    Median (95% Confidence Interval) [days]
    14.0
    15.0
    13.0
    5.0
    NA
    14.0
    NA
    NA
    33. Secondary Outcome
    Title Time to Negative Saliva SARS-CoV-2 Polymerase Chain Reaction (PCR)
    Description 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 Frame Baseline up to Day 17

    Outcome Measure Data

    Analysis Population Description
    Participants in the Saliva mFAS with available data were analyzed.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 11 10 8 10 9 12 45 16
    Median (95% Confidence Interval) [days]
    NA
    17.0
    NA
    16.0
    14.0
    NA
    NA
    16.0
    34. Secondary Outcome
    Title 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
    Description 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.
    Time Frame First dose date up to Day 14

    Outcome Measure Data

    Analysis Population Description
    Participants in FAS with available data were analyzed.
    Arm/Group Title RDV, Part C Placebo, Part C
    Arm/Group Description Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    Measure Participants 39 9
    Median (95% Confidence Interval) [days]
    NA
    NA

    Adverse Events

    Time Frame Adverse Events: First dose date up to 5 days plus 30 days All-Cause Mortality: Randomization date up to 35 days
    Adverse Event Reporting Description Adverse Events: The Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study treatment. All-Cause Mortality: All Randomized Analysis Set included all participants who were randomized in the study.
    Arm/Group Title 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
    Arm/Group Description Participants received inhaled RDV 31 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part A daily for 5 days. Participants received inhaled RDV 62 mg administered daily as an aerosolized solution by inhalation through facemask for 5 days. 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. Participants received placebo to match inhaled RDV in Part B daily for 5 days. Participants received inhaled RDV 39 mg administered daily as an aerosolized solution by inhalation through mouth piece for 5 days. Participants received placebo to match inhaled RDV in Part C daily for 5 days.
    All Cause Mortality
    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
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/12 (0%) 0/13 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/62 (0%) 0/20 (0%)
    Serious Adverse Events
    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
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/12 (0%) 1/12 (8.3%) 2/12 (16.7%) 0/12 (0%) 1/12 (8.3%) 1/13 (7.7%) 0/61 (0%) 0/20 (0%)
    Cardiac disorders
    Acute myocardial infarction 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    General disorders
    Incarcerated hernia 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Infections and infestations
    Covid-19 pneumonia 0/12 (0%) 1/12 (8.3%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/61 (0%) 0/20 (0%)
    Other (Not Including Serious) Adverse Events
    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
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/12 (58.3%) 7/12 (58.3%) 5/12 (41.7%) 4/12 (33.3%) 6/12 (50%) 5/13 (38.5%) 24/61 (39.3%) 5/20 (25%)
    Blood and lymphatic system disorders
    Leukocytosis 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Neutropenia 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Neutrophilia 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/61 (0%) 0/20 (0%)
    Ear and labyrinth disorders
    Tinnitus 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Eye disorders
    Lacrimation increased 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/61 (1.6%) 2/20 (10%)
    Photophobia 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/61 (1.6%) 1/20 (5%)
    Gastrointestinal disorders
    Abdominal distension 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Abdominal pain upper 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 3/61 (4.9%) 0/20 (0%)
    Diarrhoea 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 1/20 (5%)
    Dyspepsia 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Nausea 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 5/61 (8.2%) 0/20 (0%)
    Toothache 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Vomiting 0/12 (0%) 2/12 (16.7%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    General disorders
    Chest discomfort 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/61 (1.6%) 0/20 (0%)
    Non-cardiac chest pain 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Infections and infestations
    Otitis media viral 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Sinusitis 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Investigations
    Alanine aminotransferase increased 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 1/12 (8.3%) 1/13 (7.7%) 2/61 (3.3%) 0/20 (0%)
    Aspartate aminotransferase increased 0/12 (0%) 0/12 (0%) 2/12 (16.7%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/61 (1.6%) 0/20 (0%)
    Blood creatine phosphokinase increased 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Blood glucose increased 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/61 (1.6%) 0/20 (0%)
    Blood phosphorus decreased 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Blood potassium increased 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Gamma-glutamyltransferase increased 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 1/61 (1.6%) 0/20 (0%)
    Hepatic enzyme abnormal 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Hepatic enzyme increased 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 1/61 (1.6%) 0/20 (0%)
    Lipase increased 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/61 (0%) 0/20 (0%)
    Lymphocyte count increased 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Neutrophil count decreased 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Platelet count decreased 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Platelet count increased 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/61 (0%) 0/20 (0%)
    Transaminases increased 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    White blood cell count decreased 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    White blood cell count increased 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/61 (0%) 0/20 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/61 (1.6%) 1/20 (5%)
    Haemochromatosis 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/61 (1.6%) 1/20 (5%)
    Costochondritis 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Muscle twitching 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Musculoskeletal chest pain 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Myalgia 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/61 (0%) 0/20 (0%)
    Nervous system disorders
    Ageusia 1/12 (8.3%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/61 (1.6%) 0/20 (0%)
    Anosmia 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 1/61 (1.6%) 0/20 (0%)
    Dizziness 3/12 (25%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 5/61 (8.2%) 1/20 (5%)
    Dysgeusia 1/12 (8.3%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 3/61 (4.9%) 0/20 (0%)
    Head discomfort 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Headache 1/12 (8.3%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 3/61 (4.9%) 0/20 (0%)
    Hypoaesthesia 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Psychiatric disorders
    Anxiety 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Depression 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/61 (0%) 0/20 (0%)
    Reproductive system and breast disorders
    Menorrhagia 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Menstruation irregular 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 1/12 (8.3%) 1/12 (8.3%) 0/13 (0%) 6/61 (9.8%) 1/20 (5%)
    Epistaxis 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/61 (0%) 0/20 (0%)
    Hiccups 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/13 (7.7%) 0/61 (0%) 0/20 (0%)
    Nasal congestion 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 5/61 (8.2%) 0/20 (0%)
    Oropharyngeal pain 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 2/61 (3.3%) 0/20 (0%)
    Productive cough 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 1/12 (8.3%) 0/13 (0%) 4/61 (6.6%) 1/20 (5%)
    Rhinorrhoea 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 2/61 (3.3%) 1/20 (5%)
    Sneezing 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 2/61 (3.3%) 2/20 (10%)
    Vascular disorders
    Hypertension 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)
    Orthostatic hypotension 0/12 (0%) 1/12 (8.3%) 0/12 (0%) 0/12 (0%) 0/12 (0%) 0/13 (0%) 0/61 (0%) 0/20 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other 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

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT04539262
    Other Study ID Numbers:
    • GS-US-553-9020
    First Posted:
    Sep 4, 2020
    Last Update Posted:
    Mar 3, 2022
    Last Verified:
    Feb 1, 2022