Study of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalized Patients

Oxygen-free recovery at Day 29 is defined as being alive, discharged, and not receiving supplemental oxygen at Day 29. Participants who reached a score of 7 on the ordinal scale for clinical severity who were discharged to hospice care before or on Day 29 were considered as not discharged at Day 29. Participants with a missing oxygen-free recovery status at Day 29 were considered as not having an oxygen-free recovery.

Fit for discharge is defined as achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with an ordinal scale score of 7 must not have been discharged to hospice care to be considered as fit for discharge. Participants with a missing clinical severity score at Day 29 were considered as not having met the event at Day 29.

The clinical severity status 8-point ordinal scale scores are:

1. Death
2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
3. Hospitalized, on noninvasive ventilation or high-flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

All-cause mortality is death due to any cause. Participants with an unknown alive/death status on Day 29 were considered alive for this analysis, with the exception of patients with a score of 7 who were discharged to hospice care before or on Day 29.

The clinical severity status 8-point ordinal scale scores are:

1. Death
2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
3. Hospitalized, on noninvasive ventilation or high flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

Participants with a score of 7 who were discharged to hospice care are counted with participants with a score of 1 (death) for this endpoint.

The worst post-baseline score (lower scores are worse) through Day 29 in the clinical severity status 8-point ordinal scale, derived from all scores recorded after baseline up to and including Day 29. Participants with a score of 7 discharged to hospice care are considered as having a score of 1 (death) instead of a score of 7 for this endpoint.

The clinical severity status 8-point ordinal scale scores are:

1. Death
2. Hospitalized, on invasive mechanical ventilation or ECMO
3. Hospitalized, on noninvasive ventilation or high flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

Number of ICU days is the sum of the duration of any episode of ICU admission between Day 1 and Day 29, both inclusive. The number of ICU days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30 (worst possible outcome).

Number of invasive mechanical ventilator days is the sum of the duration of any episode of invasive mechanical ventilator admission between Day 1 and Day 29, both inclusive. The number of invasive mechanical ventilator days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30.

Clinical recovery is defined as being fit for discharge, i.e., the achievement of a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who discontinued the study on or before Days 8, 15, or 29 or with a missing clinical recovery status were considered as not having clinical recovery at each respective time point.

Clinical severity status 8-point ordinal scale:

1. Death
2. Hospitalized, on invasive mechanical ventilation or ECMO
3. Hospitalized, on noninvasive ventilation or high-flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

Sustained clinical recovery is defined as being fit for discharge (achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale) by Day 29, without re-hospitalization by Day 60. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who died or discontinued from study or with a missing clinical recovery status at Day 60 were not considered having sustained clinical recovery.

Clinical severity status 8-point ordinal scale:

1. Death
2. Hospitalized, on invasive mechanical ventilation or ECMO
3. Hospitalized, on noninvasive ventilation or high flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to study treatment. A TEAE is an AE that occurs after the first dose of study drug. A Serious AE is any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, resulted in persistent disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may jeopardize the patient or require intervention to prevent an outcome listed above.

The Investigator assessed the intensity of each AE according to the Common Terminology Criteria for Adverse Events (CTCAE):

• Grade 1 Mild; asymptomatic or mild symptoms;
• Grade 2 Moderate; minimal, local or noninvasive intervention indicated;
• Grade 3 Severe or medically significant, not immediately life-threatening;
• Grade 4 Life-threatening; urgent intervention indicated;
• Grade 5 Death due to AE.

Oxygen-free recovery at Day 29 is defined as being alive, discharged, and not receiving supplemental oxygen at Day 29. Participants who reached a score of 7 on the ordinal scale for clinical severity who were discharged to hospice care before or on Day 29 were considered as not discharged at Day 29. Participants with a missing oxygen-free recovery status at Day 29 were considered as not having an oxygen-free recovery.

Fit for discharge is defined as achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with an ordinal scale score of 7 must not have been discharged to hospice care to be considered as fit for discharge. Participants with a missing clinical severity score at Day 29 were considered as not having met the event at Day 29.

The clinical severity status 8-point ordinal scale scores are:

1. Death
2. Hospitalized, on invasive mechanical ventilation or ECMO
3. Hospitalized, on noninvasive ventilation or high-flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

All-cause mortality is death due to any cause. Participants with an unknown alive/death status on Day 29 were considered alive for this analysis, with the exception of patients with a score of 7 who were discharged to hospice care before or on Day 29.

The clinical severity status 8-point ordinal scale scores are:

1. Death
2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
3. Hospitalized, on noninvasive ventilation or high flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

Participants with a score of 7 who were discharged to hospice care are counted with participants with a score of 1 (death) for this endpoint.

The worst post-baseline score (lower scores are worse) through Day 29 in the clinical severity status 8-point ordinal scale, derived from all scores recorded after baseline up to and including Day 29. Participants with a score of 7 discharged to hospice care are considered as having a score of 1 (death) instead of a score of 7 for this endpoint.

The clinical severity status 8-point ordinal scale scores are:

1. Death
2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
3. Hospitalized, on noninvasive ventilation or high flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

Number of ICU days is the sum of the duration of any episode of ICU admission between Day 1 and Day 29, both inclusive. The number of ICU days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30 (worst possible outcome).

Number of invasive mechanical ventilator days is the sum of the duration of any episode of invasive mechanical ventilator admission between Day 1 and Day 29, both inclusive. The number of invasive mechanical ventilator days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30.

Clinical recovery is defined as being fit for discharge, i.e., the achievement of a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who discontinued the study on or before Days 8, 15, or 29 or with a missing clinical recovery status were considered as not having clinical recovery at each respective time point.

Clinical severity status 8-point ordinal scale:

1. Death
2. Hospitalized, on invasive mechanical ventilation or ECMO
3. Hospitalized, on noninvasive ventilation or high-flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

Sustained clinical recovery is defined as being fit for discharge (achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale) by Day 29, without re-hospitalization by Day 60. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who died or discontinued from study or with a missing clinical recovery status at Day 60 were not considered having sustained clinical recovery.

Clinical severity status 8-point ordinal scale:

1. Death
2. Hospitalized, on invasive mechanical ventilation or ECMO
3. Hospitalized, on noninvasive ventilation or high flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to study treatment. A TEAE is an AE that occurs after the first dose of study drug. A serious AE is any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, resulted in persistent disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may jeopardize the patient or require intervention to prevent an outcome listed above.

The Investigator assessed the intensity of each AE according to the CTCAE grades:

• Grade 1 Mild; asymptomatic or mild symptoms;
• Grade 2 Moderate; minimal, local or noninvasive intervention indicated;
• Grade 3 Severe or medically significant, not immediately life-threatening;
• Grade 4 Life-threatening; urgent intervention indicated;
• Grade 5 Death due to AE.

Oxygen-free recovery at Day 29 is defined as being alive, discharged, and not receiving supplemental oxygen at Day 29. Participants who reached a score of 7 on the ordinal scale for clinical severity who were discharged to hospice care before or on Day 29 were considered as not discharged at Day 29. Participants with a missing oxygen-free recovery status at Day 29 were considered as not having an oxygen-free recovery.

Fit for discharge is defined as achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with an ordinal scale score of 7 must not have been discharged to hospice care to be considered as fit for discharge. Participants with a missing clinical severity score at Day 29 were considered as not having met the event at Day 29.

The clinical severity status 8-point ordinal scale scores are:

1. Death
2. Hospitalized, on invasive mechanical ventilation or ECMO
3. Hospitalized, on noninvasive ventilation or high-flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

All-cause mortality is death due to any cause. Participants with an unknown alive/death status on Day 29 were considered alive for this analysis, with the exception of patients with a score of 7 who were discharged to hospice care before or on Day 29.

The clinical severity status 8-point ordinal scale scores are:

1. Death
2. Hospitalized, on invasive mechanical ventilation or ECMO
3. Hospitalized, on noninvasive ventilation or high flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

Participants with a score of 7 who were discharged to hospice care are counted with participants with a score of 1 (death) for this endpoint.

The worst post-baseline score (lower scores are worse) through Day 29 in the clinical severity status 8-point ordinal scale scores, derived from all scores recorded after baseline up to and including Day 29. Participants with a score of 7 discharged to hospice care were considered as having a score of 1 (death) instead of a score of 7 for this endpoint.

The clinical severity status 8-point ordinal scale scores scores are:

1. Death
2. Hospitalized, on invasive mechanical ventilation or ECMO
3. Hospitalized, on noninvasive ventilation or high flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

Number of ICU days is the sum of the duration of any episode of ICU admission between Day 1 and Day 29, both inclusive. The number of ICU days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30 (worst possible outcome).

Number of invasive mechanical ventilator days is the sum of the duration of any episode of invasive mechanical ventilator admission between Day 1 and Day 29, both inclusive. The number of invasive mechanical ventilator days of participants who died before or on Day 29 as well as of participants with a score of 7 on the clinical severity status 8-point ordinal scale who were discharged to hospice care by Day 29 was set to 30.

Clinical recovery is defined as being fit for discharge, i.e., the achievement of a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who discontinued the study on or before Days 8, 15, or 29 or with a missing clinical recovery status were considered as not having clinical recovery at each respective time point.

Clinical severity status 8-point ordinal scale:

1. Death
2. Hospitalized, on invasive mechanical ventilation or ECMO
3. Hospitalized, on noninvasive ventilation or high-flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

Sustained clinical recovery is defined as being fit for discharge (achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale) by Day 29, without re-hospitalization by Day 60. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who died or discontinued from study or with a missing clinical recovery status at Day 60 were not considered having sustained clinical recovery.

Clinical severity status 8-point ordinal scale:

1. Death
2. Hospitalized, on invasive mechanical ventilation or ECMO
3. Hospitalized, on noninvasive ventilation or high flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care
6. Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care
7. Not hospitalized, limitation on activities and/or requiring home oxygen
8. Not hospitalized, no limitations on activities

An adverse event is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to study treatment. A TEAE is an AE that occurs after the first dose of study drug. A serious AE is any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, resulted in persistent disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may jeopardize the patient or require intervention to prevent an outcome listed above.

The Investigator assessed the intensity of each AE according to the CTCAE grades:

• Grade 1 Mild; asymptomatic or mild symptoms;
• Grade 2 Moderate; minimal, local or noninvasive intervention indicated;
• Grade 3 Severe or medically significant, not immediately life-threatening;
• Grade 4 Life-threatening; urgent intervention indicated;
• Grade 5 Death due to AE.