Clinical trial NCT04539262: Study in Participants With Early Stage Coronavirus Disease 2019 (COVID-19) to Evaluate the Safety, Efficacy, and Pharmacokinetics of Remdesivir Administered by Inhalation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: COVID-19
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2020-09-04
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

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

Eligibility criteria: Key Inclusion Criteria:

* Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
* SARS-CoV-2 infection first confirmed by polymerase chain reaction (PCR) (Parts A and B) or by nucleic acid testing or direct antigen testing (Part C) with sample collected ≤ 4 days prior to randomization
* COVID-19 symptom onset ≤ 7 days prior to randomization
* Oxygen saturation as measured by pulse oximetry (SpO2) \> 94% on room air

Key Exclusion Criteria:

* Ongoing or prior participation in any other clinical trial of an experimental vaccine or treatment for COVID-19
* Prior or current hospitalization for COVID-19 or need for hospitalization
* Treatment of COVID-19 with other agents with actual or possible direct antiviral activity against SARS-CoV-2 including intravenous (IV) RDV or administration of any SARS-CoV-2 (or COVID-19) vaccine

  * Participants chronically administered chloroquine or hydroxychloroquine for any reason are to be excluded
* Requiring oxygen supplementation
* Positive pregnancy test
* Breastfeeding female
* Known hypersensitivity to the study treatment, its metabolites, or formulation excipient
* Pre-existing pulmonary conditions such as chronic obstructive pulmonary disease or asthma (Parts A and B only)

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Time-weighted Average Change From Baseline in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7
timeFrame: Baseline, Day 7
measure: Time-weighted Average Change From Baseline in Oropharyngeal SARS-CoV-2 Viral Load Through Day 7
timeFrame: Baseline, Day 7
measure: Time-weighted Average Change From Baseline in Saliva SARS-CoV-2 Viral Load Through Day 7
timeFrame: Baseline, Day 7
Secondary outcomes:
measure: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
timeFrame: First dose date up to 5 days plus 30 days
measure: Percentage of Participants With Treatment-Emergent Laboratory Abnormalities as Per Severity Grade
timeFrame: First dose date up to 5 days plus 30 days
measure: Percentage of Participants With Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation
timeFrame: First dose date up to 5 days plus 30 days
measure: Number of Participants With All-Cause Medically Attended Visits (MAVs) or Death by Day 28
timeFrame: Randomization up to Day 28
measure: Number of Participants With COVID-19 Related MAVs or Death by Day 28
timeFrame: Randomization up to Day 28
measure: Number of Participants With Hospitalization by Day 28
timeFrame: Day 1 up to Day 28
measure: Pharmacokinetic (PK) Parameter: AUC0-24h of Remdesivir (RDV) and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
timeFrame: 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.
measure: PK Parameter: AUClast of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
timeFrame: 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.
measure: PK Parameter: CLss/F of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
timeFrame: 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.
measure: PK Parameter: t1/2 of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
timeFrame: 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.
measure: PK Parameter: Vz/F of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
timeFrame: 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.
measure: PK Parameter: Cmax of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
timeFrame: 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.
measure: PK Parameter: Tmax of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
timeFrame: 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.
measure: PK Parameter: Clast of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
timeFrame: 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.
measure: PK Parameter: Tlast of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
timeFrame: 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.
measure: PK Parameter: AUCtau of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
timeFrame: 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.
measure: PK Parameter: λz of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
timeFrame: 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.
measure: PK Parameter: Ctau of RDV and Its Metabolites (GS-441524 and GS-704277) in Parts A and B
timeFrame: 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.
measure: Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5
timeFrame: Baseline, Day 5
measure: Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 5
timeFrame: Baseline, Day 5
measure: Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 5
timeFrame: Baseline, Day 5
measure: Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7
timeFrame: Baseline, Day 7
measure: Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 7
timeFrame: Baseline, Day 7
measure: Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 7
timeFrame: Baseline, Day 7
measure: Change in Nasopharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B
timeFrame: Baseline, Day 14
measure: Change in Oropharyngeal SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B
timeFrame: Baseline, Day 14
measure: Change in Saliva SARS-CoV-2 Viral Load From Baseline to Day 14 in Parts A and B
timeFrame: Baseline, Day 14
measure: Time to Negative Nasopharyngeal SARS-CoV-2 Polymerase Chain Reaction (PCR)
timeFrame: Baseline up to Day 17
measure: Time to Negative Oropharyngeal SARS-CoV-2 Polymerase Chain Reaction (PCR)
timeFrame: Baseline up to Day 17
measure: Time to Negative Saliva SARS-CoV-2 Polymerase Chain Reaction (PCR)
timeFrame: Baseline up to Day 17
measure: 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
timeFrame: First dose date up to Day 14
Other outcomes:
Locations:
city: Mesa
country: United States
facility: The Institute for Liver Health
state: Arizona
city: Tucson
country: United States
facility: The Institute for Liver Health
state: Arizona
city: Bakersfield
country: United States
facility: Franco Felizarta, MD
state: California
city: Costa Mesa
country: United States
facility: Aurora FDRC Inc.
state: California
city: Huntington Beach
country: United States
facility: Elevated Health
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Placentia
country: United States
facility: Western Clinical Research
state: California
city: Sacramento
country: United States
facility: UC Davis Health/Medical Center
state: California
city: Bradenton
country: United States
facility: Bradenton Research Center, Inc.
state: Florida
city: Doral
country: United States
facility: Integrity Clinical Research, LLC
state: Florida
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Hialeah Gardens
country: United States
facility: Evolution Clinical Trials, Inc.
state: Florida
city: Hialeah
country: United States
facility: Research in Miami, Inc.
state: Florida
city: Miami
country: United States
facility: Optimus U Corporation
state: Florida
city: Miami
country: United States
facility: L & C Professional Medical Research Institute
state: Florida
city: Miami
country: United States
facility: Westchester Research Center at Westchester General Hospital
state: Florida
city: Miami
country: United States
facility: MedBio Trials
state: Florida
city: Miami
country: United States
facility: Nuovida Research Center, Corp
state: Florida
city: Palmetto Bay
country: United States
facility: IMIC Inc
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, PA
state: Florida
city: Boise
country: United States
facility: Family Care Research
state: Idaho
city: New Orleans
country: United States
facility: CTU Covid Research Center
state: Louisiana
city: Vandalia
country: United States
facility: STAT Research
state: Ohio
city: Baytown
country: United States
facility: Inquest Clinical Research
state: Texas
city: Dallas
country: United States
facility: DFW Clinical Research
state: Texas
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Houston
country: United States
facility: PCP for Life-Tidwell
state: Texas
city: Everett
country: United States
facility: Providence Regional Medical Center Everett
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: