Study to Evaluate the Efficacy and Safety of Remdesivir (GS-5734™) Treatment of Coronavirus Disease 2019 (COVID-19) in an Outpatient Setting

• ClinicalTrials.gov Identifier: NCT04501952
• Recruitment Status: Terminated
• First Posted: August 6, 2020
• Results First Posted: November 16, 2021
• Last Update Posted: November 16, 2021
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: August 5, 2020
• First Posted Date: August 6, 2020
• Results First Submitted Date: November 4, 2021
• Results First Posted Date: November 16, 2021
• Last Update Posted Date: November 16, 2021
• Actual Study Start Date: September 18, 2020
• Actual Primary Completion Date: May 6, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 4, 2021)

• Percentage of Participants With Coronavirus Disease 2019 (COVID-19) Related Hospitalization (Defined as at Least 24 Hours of Acute Care) or All-Cause Death by Day 28 [ Time Frame: Randomization up to Day 28 ]
  The composite outcome of COVID-19 related hospitalization (defined as at least 24 hours of acute care) or all-cause death by Day 28 was derived by combining the available all-cause death and COVID-19 related hospitalization reported by the site. The first COVID-19 related hospitalization was used for the percentage of COVID-19 related hospitalization or all-cause death. The percentage of the composite outcome was from the Kaplan-Meier estimate.
• Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: First dose date up to last dose date (maximum: 3 days) plus 30 days ]
  TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and/or any AEs leading to premature discontinuation of study drug.

Original Primary Outcome Measures (submitted: August 5, 2020)

• Composite Endpoint Measuring Proportion of Participants Hospitalized or Death From Any Cause by Day 14. [ Time Frame: From date of randomization up to Day 14 ]
• Proportion of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: From date of randomization up to 3 days plus 30 days ]

Current Secondary Outcome Measures (submitted: November 4, 2021)

• Percentage of Participants With COVID-19 Related Medical Visits Attended in Person by the Participant and a Health Care Professional (MAVs) or All-Cause Death by Day 28 [ Time Frame: Randomization up to Day 28 ]
  The composite outcome of COVID-19 related MAVs or all-cause death by Day 28 was derived by combining the available all-cause death and COVID-19 related MAVs reported by the site. The percentage of the composite outcome was from the Kaplan-Meier estimate.
• Percentage of Participants Who Died by Day 28 [ Time Frame: Randomization up to Day 28 ]
• Percentage of Participants With COVID-19 Related Hospitalization at Day 28 [ Time Frame: Randomization up to Day 28 ]
  COVID-19 related hospitalization is defined as at least 24 hours of acute care derived by COVID-19 related hospitalization reported by the site. The percentage of the outcome and the corresponding 95% confidence interval were from Kaplan-Meier estimate.
• Percentage of Participants With COVID-19 Related Hospitalization or All-Cause Death by Day 14 [ Time Frame: Randomization up to Day 14 ]
  The composite outcome of COVID-19 related hospitalization (defined as at least 24 hours of acute care) or all-cause death by Day 14 was derived by combining the available all-cause death and COVID-19 related hospitalization reported by the site. The first COVID-19 related hospitalization was used for the percentage of COVID-19 related hospitalization or all-cause death. The percentage of the composite outcome was from the Kaplan-Meier estimate.
• Percentage of Participants With COVID-19 Related MAVs or All-Cause Death by Day 14 [ Time Frame: Randomization up to Day 14 ]
  The composite outcome of COVID-19 related MAVs or all-cause death by Day 14 was derived by combining the available all-cause death and COVID-19 related MAVs reported by the site. The percentage of the composite outcome was from the Kaplan-Meier estimate.
• Time-Weighted Average Change in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Viral Load From Baseline to Day 7 [ Time Frame: Baseline up to Day 7 ]
  The time-weighted average change from baseline to study Day 7 (DAVG7) in SARS-CoV-2 viral load is defined as the time-weighted average between the first postbaseline value through the last available value up to Day 7 minus the baseline value in SARS-CoV-2 viral load (log10 copies/mL). DAVG7 is calculated using the trapezoidal rule and the area under the curve (AUC). For participants with data through days prior to Day 7, the time-weighted average change used data up to last available timepoint. If there was no postbaseline data, the participant was excluded from the analysis.
• Time to Alleviation (Mild or Absent) of Baseline COVID-19 Symptoms as Reported on the COVID-19-adapted Influenza Patient-Reported Outcome Plus Questionnaire (FLU-PRO Plus) [ Time Frame: First Dose Date up to Day 14 ]
  The COVID-19-adapted FLU-PRO Plus is a questionnaire that assesses the severity of symptoms in participants with COVID-19 across six body systems: nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic. Each domain scores range from 0 (symptom free) to 4 (very severe symptoms). A higher score indicates increased symptom severity. Alleviation is defined as symptom scores of 0 (absent) or 1 (mild). Time to alleviation of baseline COVID-19 symptoms is defined (in days) as: First Date of the two consecutive dates achieving alleviation - First dose Date + 1. If a participant had not achieved symptom alleviation at last FLU-PRO Plus assessment or early discontinuation of study, the participant was censored at last FLU-PRO Plus assessment date.
• Percentage of Participants With Worsening After Alleviation of Baseline COVID-19 Symptoms as Reported on the COVID-19-adapted FLU-PRO Plus Questionnaire [ Time Frame: First dose date up to Day 28 ]
  The worsening after alleviation of baseline COVID-19 symptoms is defined as for a participant who has achieved alleviation of baseline COVID-19 symptoms, if symptom scored as 2 or higher at baseline is scored as 2 or higher postbaseline after achieved alleviation, or symptoms scored as 1 at baseline are scored as 1 or higher postbaseline after achieved alleviation. The COVID-19-adapted FLU-PRO Plus was used. It is a questionnaire that assesses the severity of symptoms in participants with COVID-19 across six body systems: nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic. Each domain scores range from 0 (symptom free) to 4 (very severe symptoms). A higher score indicates increased symptom severity. Alleviation is defined as symptom scores of 0 (absent) or 1 (mild).
• Percentage of Participants Who Required Oxygen Supplementation by Day 28 [ Time Frame: Randomization up to Day 28 ]

Original Secondary Outcome Measures (submitted: August 5, 2020)

• All-cause Mortality at Day 28 [ Time Frame: Day 28 ]
• Rate of Hospitalization by Day 28 [ Time Frame: Day 28 ]
• Time-weighted Average Change in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) Viral Load from Baseline to Day 7 [ Time Frame: Baseline; Day 7 ]
• Time to Resolution of COVID-19-Related Symptoms [ Time Frame: First Dose Date Up to Day 28 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Efficacy and Safety of Remdesivir (GS-5734™) Treatment of Coronavirus Disease 2019 (COVID-19) in an Outpatient Setting
• Official Title: A Phase 3 Randomized, Double-Blind Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Remdesivir (GS-5734™) Treatment of COVID-19 in an Outpatient Setting
• Brief Summary: The primary objectives of this study are to evaluate the efficacy of remdesivir (RDV) in reducing the rate of of coronavirus disease 2019 (COVID-19) related hospitalization or all-cause death in non-hospitalized participants with early stage COVID-19 and to evaluate the safety of RDV administered in an outpatient setting.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• Drug: RDV
  Administered as an intravenous infusion
  Other Names:

  • GS-5734™
  • Veklury®
• Drug: Placebo to Match RDV
  Administered as an intravenous infusion

Study Arms

• Experimental: Remdesivir (RDV)
  Participants will receive a single dose of intravenous (IV) RDV 200 mg on Day 1 followed by IV RDV 100 mg on Days 2 and 3.
  Intervention: Drug: RDV
• Placebo Comparator: Placebo
  Participants will receive IV placebo to match (PTM) RDV on Days 1 to 3.
  Intervention: Drug: Placebo to Match RDV

• Publications *: Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, Oguchi G, Ryan P, Nielsen BU, Brown M, Hidalgo A, Sachdeva Y, Mittal S, Osiyemi O, Skarbinski J, Juneja K, Hyland RH, Osinusi A, Chen S, Camus G, Abdelghany M, Davies S, Behenna-Renton N, Duff F, Marty FM, Katz MJ, Ginde AA, Brown SM, Schiffer JT, Hill JA; GS-US-540-9012 (PINETREE) Investigators. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. N Engl J Med. 2022 Jan 27;386(4):305-315. doi: 10.1056/NEJMoa2116846. Epub 2021 Dec 22.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 4, 2021): 584
• Original Estimated Enrollment (submitted: August 5, 2020): 1230
• Actual Study Completion Date: May 6, 2021
• Actual Primary Completion Date: May 6, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Willing and able to provide written informed consent, (individuals ≥ 18 years of age) or assent (individuals ≥ 12 and < 18 years of age) prior to performing study procedures. Individuals age ≥ 18 years may be enrolled with the consent of a legal representative where permitted according to local law and approved nationally and by the relevant institutional review board (IRB) or independent ethics committee (IEC). For individuals ≥ 12 and < 18 years of age, a parent or legal guardian must be willing and able to provide written informed consent prior to performing study procedures

• Either:

  • Age ≥ 18 years (at all sites) or aged ≥ 12 and < 18 years of age weighing ≥ 40 kg (where permitted according to local law and approved nationally and by the relevant IRB or IEC with at least 1 pre-existing risk factor for progression to hospitalization (chronic lung disease, hypertension, cardiovascular or cerebrovascular disease, diabetes, obesity (body mass index ≥ 30), immunocompromised, chronic mild or moderate kidney disease, chronic liver disease, current cancer, or sickle cell disease)
  • Or aged ≥ 60 years
• Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 infection confirmed by molecular diagnosis (nucleic acid (polymerase chain reaction (PCR) or antigen testing) ≤ 4 days prior to screening
• Presence of ≥ 1 symptom(s) consistent with COVID-19 for ≤ 7 days prior to randomization
• Not currently requiring hospitalization (hospitalization defined as ≥ 24 hours of acute care)

Key Exclusion Criteria:

• Participation in any other clinical trial of an experimental treatment and prevention for COVID-19
• Prior hospitalization for COVID-19
• Treatment with other agents with actual or possible direct antiviral activity against SARS-CoV-2 or administration of any SARS-CoV-2 (or COVID-19) vaccine
• Requiring oxygen supplementation

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, Spain, United Kingdom, United States
• Removed Location Countries: Portugal

Administrative Information

• NCT Number: NCT04501952
• Other Study ID Numbers: GS-US-540-9012; 2020-003510-12 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: November 2021