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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04539262
Recruitment Status : Recruiting
First Posted : September 4, 2020
Last Update Posted : November 19, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

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
COVID-19 Drug: Remdesivir (RDV) Drug: Placebo Phase 1 Phase 2

Detailed Description:

This study will have multiple parts: Part A, Part B (optional), 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 282 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 : September 14, 2020
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Remdesivir (RDV), Part A
Participants will receive 31 mg inhaled RDV daily for 5 days
Drug: Remdesivir (RDV)
Administered as an aerosolized solution
Other Name: GS-5734™

Experimental: RDV + Placebo, Part A
Participants will receive 31 mg inhaled RDV for 3 days followed by placebo through Day 5
Drug: Remdesivir (RDV)
Administered as an aerosolized solution
Other Name: GS-5734™

Drug: Placebo
Administered as an aerosolized solution

Placebo Comparator: Placebo, Part A
Participants will receive placebo daily for 5 days
Drug: Placebo
Administered as an aerosolized solution

Experimental: RDV, Part B (Optional)
Participants will receive 62 mg inhaled RDV daily for up to 5 days
Drug: Remdesivir (RDV)
Administered as an aerosolized solution
Other Name: GS-5734™

Experimental: RDV + Placebo, Part B (Optional)
Participants will receive 62 mg inhaled RDV for up to 3 days followed by placebo through Day 5
Drug: Remdesivir (RDV)
Administered as an aerosolized solution
Other Name: GS-5734™

Drug: Placebo
Administered as an aerosolized solution

Placebo Comparator: Placebo, Part B (Optional)
Participants will receive placebo daily for 5 days
Drug: Placebo
Administered as an aerosolized solution

Experimental: RDV+ Placebo, Part C

Up to two regimens from Part A and/or Part B will be evaluated in Part C. Either one RDV-containing regimen + placebo, or two RDV-containing regimens + placebo will be selected.

Participants will receive up to 2 of the following 4 treatments:

31 mg inhaled RDV daily for 5 days, 31 mg inhaled RDV daily for 3 days followed by placebo daily for 2 days, or 62 mg inhaled RDV daily for up to 5 days, or 62 mg inhaled RDV daily for up to 3 days followed by placebo for 2 days

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

Drug: Placebo
Administered as an aerosolized solution

Placebo Comparator: Placebo, Part C
Participants will receive placebo daily for 5 days
Drug: Placebo
Administered as an aerosolized solution




Primary Outcome Measures :
  1. Time-weighted Average Change From Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7 [ Time Frame: Baseline, Day 7 ]
    Time-weighted Average Change in SARS-CoV-2 viral load is defined as area under the concentration versus time curve (AUC) of viral load change divided by time between baseline through Day 7


Secondary Outcome Measures :
  1. Proportion of Participants Experiencing any Treatment-Emergent Adverse Events [ Time Frame: First dose date up to 5 days plus 30 days ]
  2. Proportion of Participants Experiencing any Treatment-Emergent Graded Laboratory Abnormalities [ Time Frame: First dose date up to 5 days plus 30 days ]
  3. Proportion of Participants Experiencing any Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation [ Time Frame: First dose date up to 5 days plus 30 days ]
  4. Proportion of Participants Progressing From Early Stage Coronavirus Disease 2019 (COVID-19) to Hospitalization or Death by Day 14 [ Time Frame: Day 14 ]
  5. Pharmacokinetic (PK) Parameter: AUC0-24h of Remdesivir (RDV) and its Metabolites (GS-441524 and GS-704277) [ 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. ]

    AUC0-24h is 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.


  6. PK Parameter: AUClast of RDV and its Metabolites (GS-441524 and GS-704277) [ 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. ]

    AUClast is 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.


  7. PK Parameter: CLss/F of RDV and its Metabolites (GS-441524 and GS-704277) [ 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. ]

    CLss/F is 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.


  8. PK Parameter: t1/2 of RDV and its Metabolites (GS-441524 and GS-704277) [ 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. ]

    t1/2 is 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.


  9. PK Parameter: Vz/F of RDV and its Metabolites (GS-441524 and GS-704277) [ 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. ]

    Vz/F is 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.


  10. PK Parameter: Cmax of RDV and its Metabolites (GS-441524 and GS-704277) [ 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. ]

    Cmax is 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.


  11. PK Parameter: Tmax of RDV and its Metabolites (GS-441524 and GS-704277) [ 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. ]

    Tmax is 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.


  12. PK Parameter: Clast of RDV and its Metabolites (GS-441524 and GS-704277) [ 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. ]

    Clast is 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.


  13. PK Parameter: Tlast of RDV and its Metabolites (GS-441524 and GS-704277) [ 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. ]

    Tlast is 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.


  14. PK Parameter: AUCtau of RDV and its Metabolites (GS-441524 and GS-704277) [ 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. ]

    AUCtau is defined as concentration of drug over time (the area under the concentration verses 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.


  15. PK Parameter: λz of RDV and its Metabolites (GS-441524 and GS-704277) [ 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. ]

    λz is 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.


  16. PK Parameter: Ctau of RDV and its Metabolites (GS-441524 and GS-704277) [ 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. ]

    Ctau is 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.


  17. Change in SARS-CoV-2 Viral Load From Baseline to Day 4 [ Time Frame: Baseline, Day 4 ]
  18. Change in SARS-CoV-2 Viral Load From Baseline to Day 7 [ Time Frame: Baseline, Day 7 ]
  19. Change in SARS-CoV-2 Viral Load From Baseline to Day 14 [ Time Frame: Baseline, Day 14 ]
  20. Time to Negative SARS-CoV-2 Polymerase Chain Reaction (PCR) [ Time Frame: First dose date up to 14 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection first confirmed by polymerase chain reaction (PCR) ≤ 4 days prior to randomization
  • Presence of ≥ 1 symptom(s) consistent with coronavirus disease 2019 (COVID-19) for ≤ 7 days prior to randomization (fever, cough, fatigue, shortness of breath, sore throat, headache, myalgia/arthralgia)
  • 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 treatment for COVID-19
  • Prior or current hospitalization for COVID-19 or need for hospitalization
  • Concurrent or planned treatment with other agents with actual or possible direct antiviral activity against SARS-CoV-2 including intravenous (IV) remdesivir (RDV)
  • 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04539262


Contacts
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Contact: Gilead Clinical Study Information Center 1-833-445-3230 (GILEAD-0) GileadClinicalTrials@gilead.com

Locations
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United States, Arizona
The Institute for Liver Health Recruiting
Mesa, Arizona, United States, 85210
The Institute for Liver Health Recruiting
Tucson, Arizona, United States, 85712
United States, California
Saint Josephs Clinical Research Recruiting
Anaheim, California, United States, 92804
Franco Felizarta, MD Recruiting
Bakersfield, California, United States, 93301
Aurora FDRC Inc. Recruiting
Costa Mesa, California, United States, 92627
Elevated Health Recruiting
Huntington Beach, California, United States, 92648
Western Clinical Research Recruiting
Placentia, California, United States, 92870
United States, Florida
Bradenton Research Center, Inc. Recruiting
Bradenton, Florida, United States, 34205
Westchester Research Center at Westchester General Hospital Recruiting
Miami, Florida, United States, 33155
IMIC Inc Recruiting
Palmetto Bay, Florida, United States, 33157
Triple O Research Institute, PA Recruiting
West Palm Beach, Florida, United States, 33401
United States, Idaho
Family Care Research Recruiting
Boise, Idaho, United States, 83704
United States, Louisiana
CTU Covid Research Center Recruiting
New Orleans, Louisiana, United States, 70112
United States, Ohio
STAT Research Recruiting
Vandalia, Ohio, United States, 45066
United States, Texas
Baylor Research Institute Recruiting
Dallas, Texas, United States, 75246
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT04539262    
Other Study ID Numbers: GS-US-553-9020
First Posted: September 4, 2020    Key Record Dates
Last Update Posted: November 19, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Aspiration
Respiration Disorders
Respiratory Tract Diseases
Pathologic Processes