COVID-19
Conditions
Brief summary
The goal of this clinical study is to test how well the study drug, obeldesivir (GS-5245), works and how safe it is in treating coronavirus disease 2019 (COVID-19) in participants that have a higher risk of getting a serious illness.
Interventions
DRUGObeldesivir
Tablets administered orally without regard to food.
Placebo tablets administered orally without regard to food.
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Willing and able to provide written informed consent. * Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by PCR or an approved alternative assay (eg. Rapid Antigen Test) ≤ 5 days before randomization. Serologic tests will not be accepted. * Initial onset of COVID-19 signs/symptoms ≤ 5 days before randomization. * Not currently hospitalized or requiring hospitalization. * Presence of ≥ 1 risk factor (if unvaccinated) or ≥ 2 risk factors (if vaccinated at any point) for progression to severe disease. Key
Exclusion criteria
* Anticipated use of COVID-19 therapies during the current COVID-19 illness. * Received any direct acting antiviral drug against SARS-CoV-2 for the treatment of COVID-19 \< 28 days or \< 5 half-lives, whichever is longer, before randomization. * Anticipated need for hospitalization \< 48 hours after randomization. * New oxygen requirement \< 24 hours before randomization. * Decompensated cirrhosis (Child-Pugh class B or C) or acute liver injury/failure. * Undergoing dialysis, or history of moderate to severe renal impairment. * Pregnant or breastfeeding (nursing). * Unwilling to use protocol-mandated birth control. * Received an approved, authorized or investigational COVID-19 vaccine (including booster dose) \<120 days before randomization. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Coronavirus Disease 2019 (COVID-19) Related Hospitalization or All-Cause Death by Day 29 | Up to Day 29 | COVID-19-related hospitalization was defined as ≥ 24 hours of acute care for a reason related to COVID-19, in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with COVID-19. This included specialized acute medical care units within an assisted living facility or nursing home. This did not include hospitalization for the purposes of public health and/or clinical trial execution. The date and duration of hospital admission, and primary reason for hospitalization (including if the hospitalization was related to COVID-19) were recorded. Percentages were rounded off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Laboratory Abnormalities | First dose date up to 5 Days plus 30 Days | Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days. Percentages were rounded off. |
| Percentage of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation | First dose date up to 5 Days plus 30 Days | A treatment emergent AE is defined as an AE that occurs or worsens in severity on or after the date of the first dose of study drug but no later than 30 days after the permanent discontinuation of study drug or an AE leading to discontinuation of study drug. A SAE is defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction. Percentages were rounded off. |
| Percentage of Participants With All-Cause Hospitalization by Day 29 | Up to Day 29 | All-cause hospitalization was defined as ≥ 24 hours of acute care, in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with COVID-19. This includes specialized acute medical care units within an assisted living facility or nursing home. This does not include hospitalization for the purposes of public health and/or clinical study execution. The date and duration of hospital admission, and primary reason for hospitalization (including if the hospitalization is related to COVID-19) were recorded. Percentages were rounded off. |
| Percentage of Participants With COVID-19-Related Medically Attended Visits (MAVs) or All-Cause Death by Day 29 | Up to Day 29 | Medically attended visits were defined as interactions with health care professionals other than study staff or designees including hospitalization; in-person emergency, urgent, or primary care visits; or any other in-person visit attended by the participant and a health care professional. The nature and cause of the visit were identified. KM estimates were used in the outcome measure analysis. Percentages were rounded off. |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) | First dose date up to 5 Days plus 30 Days | TEAEs were defined as 1 or both of the following: 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. Any AEs leading to premature discontinuation of study drug. Percentages were rounded off. |
| Percentage of Participants With All-cause Death by Day 29 | Up to Day 29 | Percentages were rounded off. |
| Time to COVID-19 Symptom Alleviation by Day 15 | Up to Day 15 | Time to COVID-19 symptom alleviation was calculated as symptom alleviation date/time minus the first dose date/time. Symptom alleviation was evaluated for the 15 targeted symptoms using symptoms of infection with coronavirus-19 (SIC) questionnaire. The SIC questionnaire assessed all targeted symptoms, alleviation was defined as the SIC rating of 0, or at least 3 points decrease in rating from baseline, or an answer No to the question for at least 48 consecutive hours. |
| Change From Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Nasal Swab Viral Load at Day 5 | Day 5 | The mixed model for repeated measures (MMRM) was used for analysis. |
| Plasma Concentrations of GS-441524 (Metabolite of Obeldesivir) | Day 1, 0.75 and 2 hours postdose and Day 5 predose and 0.75 hours postdose | — |
| Percentage of Participants With COVID-19-Related MAVs by Day 29 | Up to Day 29 | Medically attended visits were defined as interactions with health care professionals other than study staff or designees including hospitalization; in-person emergency, urgent, or primary care visits; or any other in-person visit attended by the participant and a health care professional. The nature and cause of the visit were identified. KM estimates were used in the outcome measure analysis. Percentages were rounded off. |
Countries
Brazil, Bulgaria, Canada, France, Hungary, Italy, Japan, Mexico, Poland, Portugal, Romania, Singapore, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom
Participant flow
Recruitment details
Participants were enrolled at study sites in the South America, Europe, North America, Africa and Asia.
Pre-assignment details
515 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Obeldesivir Participants received obeldesivir 350 mg orally twice daily for 5 days. | 233 |
| Placebo Participants received placebo-to-match obeldesivir orally twice daily for 5 days. | 235 |
| Total | 468 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Investigator's discretion | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Randomized but never treated | 0 | 3 |
| Overall Study | Withdrew consent | 6 | 2 |
Baseline characteristics
| Characteristic | Obeldesivir | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 14.9 | 55 years STANDARD_DEVIATION 15.8 | 53 years STANDARD_DEVIATION 16.6 |
| Age, Customized Adults (18 - 64 Years) | 159 Participants | 332 Participants | 173 Participants |
| Age, Customized Geriatrics (65 - 84 Years) | 71 Participants | 130 Participants | 59 Participants |
| Age, Customized Geriatrics (85 Years and Over) | 3 Participants | 6 Participants | 3 Participants |
| Baseline Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Nasal Swab Viral Load | 6.15 log10 copies/mL STANDARD_DEVIATION 1.629 | 6.15 log10 copies/mL STANDARD_DEVIATION 1.624 | 6.15 log10 copies/mL STANDARD_DEVIATION 1.622 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 79 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 197 Participants | 389 Participants | 192 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 21 Participants | 40 Participants | 19 Participants |
| Race/Ethnicity, Customized Asian | 24 Participants | 56 Participants | 32 Participants |
| Race/Ethnicity, Customized Black or African American | 9 Participants | 19 Participants | 10 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Other or More Than One Race | 1 Participants | 5 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 178 Participants | 346 Participants | 168 Participants |
| Region of Enrollment Brazil | 3 Participants | 8 Participants | 5 Participants |
| Region of Enrollment Bulgaria | 97 Participants | 196 Participants | 99 Participants |
| Region of Enrollment Canada | 7 Participants | 18 Participants | 11 Participants |
| Region of Enrollment France | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Hungary | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Italy | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Japan | 2 Participants | 5 Participants | 3 Participants |
| Region of Enrollment Mexico | 24 Participants | 48 Participants | 24 Participants |
| Region of Enrollment Poland | 12 Participants | 19 Participants | 7 Participants |
| Region of Enrollment Portugal | 4 Participants | 9 Participants | 5 Participants |
| Region of Enrollment Romania | 29 Participants | 53 Participants | 24 Participants |
| Region of Enrollment Singapore | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment South Africa | 15 Participants | 31 Participants | 16 Participants |
| Region of Enrollment South Korea | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment Spain | 11 Participants | 23 Participants | 12 Participants |
| Region of Enrollment Taiwan | 17 Participants | 40 Participants | 23 Participants |
| Region of Enrollment Turkey | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United Kingdom | 8 Participants | 8 Participants | 0 Participants |
| Sex: Female, Male Female | 147 Participants | 264 Participants | 117 Participants |
| Sex: Female, Male Male | 86 Participants | 204 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 234 | 1 / 234 |
| other Total, other adverse events | 0 / 234 | 0 / 231 |
| serious Total, serious adverse events | 2 / 234 | 2 / 231 |
Outcome results
Primary
Percentage of Participants With Coronavirus Disease 2019 (COVID-19) Related Hospitalization or All-Cause Death by Day 29
COVID-19-related hospitalization was defined as ≥ 24 hours of acute care for a reason related to COVID-19, in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with COVID-19. This included specialized acute medical care units within an assisted living facility or nursing home. This did not include hospitalization for the purposes of public health and/or clinical trial execution. The date and duration of hospital admission, and primary reason for hospitalization (including if the hospitalization was related to COVID-19) were recorded. Percentages were rounded off.
Time frame: Up to Day 29
Population: The Full Analysis Positive Set included all randomized participants who received at least 1 dose of study drug and were SARS-CoV-2 positive at baseline as confirmed by cepheid's xpert xpress coronavirus-2/flu/respiratory syncytial virus plus test or SARS-CoV-2 reverse transcriptase quantitative polymerase chain reaction test from the central laboratory.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obeldesivir | Percentage of Participants With Coronavirus Disease 2019 (COVID-19) Related Hospitalization or All-Cause Death by Day 29 | 0 percentage of participants |
| Placebo | Percentage of Participants With Coronavirus Disease 2019 (COVID-19) Related Hospitalization or All-Cause Death by Day 29 | 0.5 percentage of participants |
p-value: 0.3161Log Rank
Secondary
Change From Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Nasal Swab Viral Load at Day 5
The mixed model for repeated measures (MMRM) was used for analysis.
Time frame: Day 5
Population: Virology Analysis Set included all randomized participants who received at least 1 dose of study drug and had baseline SARS-CoV-2 viral load greater than or equal to lower limit of quantitation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Obeldesivir | Change From Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Nasal Swab Viral Load at Day 5 | -2.80 log10 copies/mL | Standard Error 0.092 |
| Placebo | Change From Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Nasal Swab Viral Load at Day 5 | -2.22 log10 copies/mL | Standard Error 0.092 |
p-value: <0.000195% CI: [-0.83, -0.33]MMRM
Secondary
Percentage of Participants Experiencing Laboratory Abnormalities
Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days. Percentages were rounded off.
Time frame: First dose date up to 5 Days plus 30 Days
Population: Participants from the Safety Analysis Set who had available post baseline data were analyzed. One participant randomized to placebo arm received obeldesivir and was counted in obeldesivir group for the analysis of this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Obeldesivir | Percentage of Participants Experiencing Laboratory Abnormalities | Any grade | 56.1 percentage of participants |
| Obeldesivir | Percentage of Participants Experiencing Laboratory Abnormalities | Grade 3 or 4 | 6.5 percentage of participants |
| Placebo | Percentage of Participants Experiencing Laboratory Abnormalities | Any grade | 61.7 percentage of participants |
| Placebo | Percentage of Participants Experiencing Laboratory Abnormalities | Grade 3 or 4 | 4.8 percentage of participants |
Secondary
Percentage of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation
A treatment emergent AE is defined as an AE that occurs or worsens in severity on or after the date of the first dose of study drug but no later than 30 days after the permanent discontinuation of study drug or an AE leading to discontinuation of study drug. A SAE is defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction. Percentages were rounded off.
Time frame: First dose date up to 5 Days plus 30 Days
Population: Participants in the Safety Analysis Set were analyzed. One participant randomized to placebo arm received obeldesivir and was counted in obeldesivir group for the analysis of this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Obeldesivir | Percentage of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation | AEs Leading to Study Drug Discontinuation | 1.7 percentage of participants |
| Obeldesivir | Percentage of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation | SAEs Leading to Study Drug Discontinuation | 0.9 percentage of participants |
| Placebo | Percentage of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation | AEs Leading to Study Drug Discontinuation | 0.9 percentage of participants |
| Placebo | Percentage of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation | SAEs Leading to Study Drug Discontinuation | 0.9 percentage of participants |
Secondary
Percentage of Participants With All-cause Death by Day 29
Percentages were rounded off.
Time frame: Up to Day 29
Population: Participants in the Full Analysis Positive Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obeldesivir | Percentage of Participants With All-cause Death by Day 29 | 0 percentage of participants |
| Placebo | Percentage of Participants With All-cause Death by Day 29 | 0.5 percentage of participants |
p-value: 0.3161Log Rank
Secondary
Percentage of Participants With All-Cause Hospitalization by Day 29
All-cause hospitalization was defined as ≥ 24 hours of acute care, in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with COVID-19. This includes specialized acute medical care units within an assisted living facility or nursing home. This does not include hospitalization for the purposes of public health and/or clinical study execution. The date and duration of hospital admission, and primary reason for hospitalization (including if the hospitalization is related to COVID-19) were recorded. Percentages were rounded off.
Time frame: Up to Day 29
Population: Participants in the Full Analysis Positive Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obeldesivir | Percentage of Participants With All-Cause Hospitalization by Day 29 | 0.5 percentage of participants |
| Placebo | Percentage of Participants With All-Cause Hospitalization by Day 29 | 0 percentage of participants |
p-value: 0.3219Log Rank
Secondary
Percentage of Participants With COVID-19-Related MAVs by Day 29
Medically attended visits were defined as interactions with health care professionals other than study staff or designees including hospitalization; in-person emergency, urgent, or primary care visits; or any other in-person visit attended by the participant and a health care professional. The nature and cause of the visit were identified. KM estimates were used in the outcome measure analysis. Percentages were rounded off.
Time frame: Up to Day 29
Population: Participants in the Full Analysis Positive Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obeldesivir | Percentage of Participants With COVID-19-Related MAVs by Day 29 | 1 percentage of participants |
| Placebo | Percentage of Participants With COVID-19-Related MAVs by Day 29 | 0.5 percentage of participants |
p-value: 0.31995% CI: [0.311, 28.74]Log Rank
Secondary
Percentage of Participants With COVID-19-Related Medically Attended Visits (MAVs) or All-Cause Death by Day 29
Medically attended visits were defined as interactions with health care professionals other than study staff or designees including hospitalization; in-person emergency, urgent, or primary care visits; or any other in-person visit attended by the participant and a health care professional. The nature and cause of the visit were identified. KM estimates were used in the outcome measure analysis. Percentages were rounded off.
Time frame: Up to Day 29
Population: Participants in the Full Analysis Positive Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obeldesivir | Percentage of Participants With COVID-19-Related Medically Attended Visits (MAVs) or All-Cause Death by Day 29 | 1.0 percentage of participants |
| Placebo | Percentage of Participants With COVID-19-Related Medically Attended Visits (MAVs) or All-Cause Death by Day 29 | 1.0 percentage of participants |
p-value: 0.656895% CI: [0.25, 8.952]Log Rank
Secondary
Percentage of Participants With Treatment-Emergent Adverse Events (TEAE)
TEAEs were defined as 1 or both of the following: 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. Any AEs leading to premature discontinuation of study drug. Percentages were rounded off.
Time frame: First dose date up to 5 Days plus 30 Days
Population: The Safety Analysis Set included all participants who received at least 1 dose of study drug. One participant randomized to placebo arm received obeldesivir and was counted in obeldesivir group for the analysis of this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obeldesivir | Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) | 22.2 percentage of participants |
| Placebo | Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) | 20.8 percentage of participants |
Secondary
Plasma Concentrations of GS-441524 (Metabolite of Obeldesivir)
Time frame: Day 1, 0.75 and 2 hours postdose and Day 5 predose and 0.75 hours postdose
Population: Pharmacokinetic Analysis Set included all randomized participants who received at least 1 dose of study drug and had at least 1 non missing concentration value reported by the PK laboratory with available data were analyzed .
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeldesivir | Plasma Concentrations of GS-441524 (Metabolite of Obeldesivir) | Day 1, 0.75 hours postdose | 2330.42 ng/mL | Standard Deviation 1709.56 |
| Obeldesivir | Plasma Concentrations of GS-441524 (Metabolite of Obeldesivir) | Day 1, 2 hours postdose | 2535.84 ng/mL | Standard Deviation 1370.131 |
| Obeldesivir | Plasma Concentrations of GS-441524 (Metabolite of Obeldesivir) | Day 5, Predose | 1116.81 ng/mL | Standard Deviation 1101.371 |
| Obeldesivir | Plasma Concentrations of GS-441524 (Metabolite of Obeldesivir) | Day 5, 0.75 hours postdose | 3089.09 ng/mL | Standard Deviation 1839.992 |
Secondary
Time to COVID-19 Symptom Alleviation by Day 15
Time to COVID-19 symptom alleviation was calculated as symptom alleviation date/time minus the first dose date/time. Symptom alleviation was evaluated for the 15 targeted symptoms using symptoms of infection with coronavirus-19 (SIC) questionnaire. The SIC questionnaire assessed all targeted symptoms, alleviation was defined as the SIC rating of 0, or at least 3 points decrease in rating from baseline, or an answer No to the question for at least 48 consecutive hours.
Time frame: Up to Day 15
Population: Participants in the Full Analysis Positive Set with Covid19 symptoms who completed Symptoms of Infection With Coronavirus-19 at baseline were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Obeldesivir | Time to COVID-19 Symptom Alleviation by Day 15 | 7.3 Days |
| Placebo | Time to COVID-19 Symptom Alleviation by Day 15 | 9.3 Days |
p-value: 0.085995% CI: [0.961, 2.112]Log Rank