Evaluate the effect of 2 dose levels of VIS410 + oseltamivir on clinical status using a seven-level ordinal scale. Comparison between treatment groups and between all VIS410 recipients versus placebo were assessed.

Modified Intent to treat (MITT) population. All participants of the safety population that have an assessment of O2 support after randomization and are confirmed influenza A positive. Participants will be analyzed based on the treatment to which they were randomized, irrespective of what they actually received. This population was selected for the analysis of the primary endpoint to maintain the benefits of randomization and avoid the bias associated with the non-random loss of the participants

Safety and tolerability of 2 dose levels of a single intravenous (IV) dose of VIS410 when administered in combination with oseltamivir in hospitalized participants with influenza A infection. Data presents the count of participants who experienced an adverse event (AE) or serious treatment emergent adverse events (TEAE).

Safety Population: Included all ITT participants (participants who randomized to treatment) who received IV study drug. Participants were grouped according to the actual treatment received.

Time to cessation of O2 support in patients with supplemental oxygen with baseline room air <= 92%. Patients with treatment resulting in a stable SpO2 by pulse oximetry. Stable SpO2 is defined as two consecutive SpO2 values of >92% on room air that are at least 8 hours apart.

Modified intent to treat population (MITT), number of participants who had cessation of oxygen support.

Time to cessation of oxygen support in all patients with supplemental oxygen (regardless of oxygen saturation).

Modified intent to treat population (MITT), number of participants who had cessation of oxygen support. NE = not estimable.

The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in peak viral load by qRT-PCR from nasopharyngeal swabs through Day 14

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment. All efficacy analyses including the primary efficacy analyses were performed in the MITT population

The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in nasopharyngeal qRT-PCR area under the viral load-time curve (AUC) from baseline to Day 5.

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in nasopharyngeal qRT-PCR area under the viral load-time curve (AUC) from baseline to Day 7.

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

The difference between VIS410 + oseltamivir and oseltamivir alone treatment groups in nasopharyngeal qRT-PCR area under the viral load-time curve (AUC) from baseline to Day 14.

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Number of days from the end of infusion until virus is no longer detectable (at or below the limit of detection) with no samples following that are greater than the BLQ through the Day 14 (quantitative reverse-transcription polymerase chain reaction - qRT-PCR)

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Number of participants in whom peak viral load is observed post-baseline based on quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Post-baseline was considered the day 3 sample or later.

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Peak viral load based on TCID50 from nasopharyngeal swabs

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Number of participants in whom peak viral load occurred post-baseline measured by TCID50. Post-baseline was considered the day 3 sample or later.

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

The area under the viral load-time curve (AUC) for VIS410 + oseltamivir and oseltamivir alone treatment groups from baseline to Day 5 measured by TCID50 from nasopharyngeal swabs.

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

The area under the viral load-time curve (AUC) for VIS410 + oseltamivir and oseltamivir alone treatment groups from baseline to Day 7 measured by TCID50 from nasopharyngeal swabs.

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Number of participants negative for viral titer by study day determined by TCID50 on nominal days 3, 5, 7

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment, who also had a positive baseline viral culture based on TCID50.

Number of days from the end of infusion until virus is no longer detectable (at or below the limit of detection) with no samples following that are greater than the BLQ through the Day 7 (TCID50)

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by TCID50 in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment, who also had a positive baseline viral culture based on TCID50.

Number of days from the onset of symptoms until virus is no longer detectable (at or below the limit of detection) with no samples following that are greater than the BLQ through the Day 7 (TCID50)

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by TCID50 in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment, who also had a positive baseline viral culture based on TCID50.

Median time to clinical response defined by resolution of at least 4 of 5 vital signs:

• Afebrile with core temperature ≤ 37.8°C, without use of antipyretics (oral ≤ 37.2°C)
• Oxygen saturation ≥ 95% on room air without support or a return to preinfection status, if pre-infection status was < 95%
• Pulse rate ≤ 100/min
• Systolic blood pressure ≥ 90 mm/Hg, without vasopressor use
• Respiratory rate ≤ 24 beats per minute

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Median time to clinical response defined by resolution of at all 5 vital signs:

• Afebrile with core temperature ≤ 37.8°C, without use of antipyretics (oral ≤ 37.2°C)
• Oxygen saturation ≥ 95% on room air without support or a return to pre-infection status, if pre-infection status was < 95%
• Pulse rate ≤ 100/min
• Systolic blood pressure ≥ 90 mm/Hg, without vasopressor use
• Respiratory rate ≤ 24 beats per minute

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Summary of area under the curve (AUC) over time for seven-level ordinal scale. Area under the curve (AUC) is calculated using the linear trapezoidal rule. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities. Time frame is from baseline to day 7. Therefore, maximum and minimum values possible for the AUC Clinical Status Ordinal Scale scores range from 7 to 49.

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment

Summary of area under the curve (AUC) over time for seven-level ordinal scale. Area under the curve (AUC) is calculated using the linear trapezoidal rule. Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities. Time frame is from baseline to day 14. Therefore, maximum and minimum values possible for the AUC Clinical Status Ordinal Scale scores range from 14 to 98.

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment

Summary of Clinical Outcome on Seven-Level Ordinal Scale through Day 14. Worst post-baseline assessment observed.

Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities.

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Total number of days on ventilation for participants who used ventilation, including participants on ventilation at baseline

Participants requiring ventilation from the mITT population. The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Total number of days on ventilation for participations who used ventilation, including participants on ventilation at baseline. Better and worse outcome groups defined based on the Seven-Level Ordinal Scale scores, "<= 4 Seven-Level Ordinal Scale Score" is better; "> 4 Seven-Level Ordinal Scale Score" is worse group.

Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities.

Participants requiring ventilation from the mITT population. The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Total number of days in intensive care (ICU) for participants who admitted to the ICU, including participants in ICU at baseline

Participants admitted to the ICU from the mITT population. The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Total number of days in intensive care for participants who admitted to ICU, including participants in ICU at baseline. Better and worse outcome groups defined based on the Seven-Level Ordinal Scale scores, "<= 4 Seven-Level Ordinal Scale Score" is better; "> 4 Seven-Level Ordinal Scale Score" is worse group.

Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities.

Participants requiring ventilation from the mITT population. The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Number of days until resumption of usual activities by treatment group

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Number of patients experiencing all-cause and attributable mortality rates at Day 14. Attributable mortality was derived from the Complication of Influenza eCRF; all-cause mortality was derived from Complication of Influenza, Seven-Level Ordinal Scale, AE and Study Completion eCRFs

The safety population included all ITT participants who received IV study drug. Participants were grouped according to the actual treatment received.

Number of patients experiencing all-cause and attributable mortality by Day 28. Attributable mortality was derived from the Complication of Influenza eCRF; all-cause mortality was derived from Complication of Influenza, Seven-Level Ordinal Scale, AE and Study Completion eCRFs

The safety population included all ITT participants who received IV study drug. Participants were grouped according to the actual treatment received.

Number of patients experiencing all-cause and attributable mortality by Day 56. Attributable mortality was derived from the Complication of Influenza eCRF; all-cause mortality was derived from Complication of Influenza, Seven-Level Ordinal Scale, AE and Study Completion eCRFs

The safety population included all ITT participants who received IV study drug. Participants were grouped according to the actual treatment received.

Total number of days in hospital and/or ICU from admission to discharge

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Total number of days in hospital or intensive care for participations who were admitted to Hospital/ICU, including participants in Hospital/ICU at baseline. Better and worse outcome groups defined based on the Seven-Level Ordinal Scale scores, "<= 4 Seven-Level Ordinal Scale Score" is better; "> 4 Seven-Level Ordinal Scale Score" is worse group.

Seven-Level Ordinal Scale is a hierarchical scale with the classifications presented from the worst clinical outcome to the best clinical outcome in descending order with 7=death, 6=Intensive care unit (ICU) stay with mechanical ventilation , 5=ICU stay without mechanical ventilation, 4=Non-ICU hospitalization with supplemental oxygen, 3=Non-ICU hospitalization without supplemental oxygen, 2=Discharge with partial resumption of normal activities, 1=Discharge with full resumption of normal activities.

Participants requiring ventilation from the mITT population. The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Number of participants with rehospitalization due to influenza A relapse

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Summary of influenza symptom complications, including baseline and incident complications

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.

Summary of Serum VIS410 Pharmacokinetic Parameters in PK Population by maximum concentration (Cmax) of VIS410 in participant's serum.

The PK population included all participants who received IV study drug and had at least 1 PK parameter that could be calculated.

Summary of Serum VIS410 Pharmacokinetic Parameters in PK Population by the area under the concentration/time curve from 0 to infinity (AUC0-inf) of VIS410 in participant's serum.

The PK population included all participants who received IV study drug and had at least 1 PK parameter that could be calculated.

Summary of Serum VIS410 Pharmacokinetic Parameters in PK Population by the clearance rate (Cl) of VIS410 in participant's serum.

The PK population included all participants who received IV study drug and had at least 1 PK parameter that could be calculated.

Summary of Serum VIS410 Pharmacokinetic Parameters in PK Population by the half-life (t1/2) of VIS410 in participant's serum.

The PK population included all participants who received IV study drug and had at least 1 PK parameter that could be calculated.

Summary of the maximum fold increase for anti-VIS410 antibody testing for VIS410 groups and placebo.

The modified ITT (MITT) population included all participants who received IV study drug and were confirmed influenza A positive by qRT-PCR in central lab analysis of pre-dose Day 1 and/or post-dose Day 1. Participants were grouped according to the randomly assigned treatment.