Study to Assess Efficacy and Safety of Baloxavir Marboxil... | NCT03684044

ID	Type	Description	Link
2018-001416-30	EudraCT Number

Label	Type	Description	Intervention Names
Baloxavir Marboxil	Experimental	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.	Drug: Baloxavir Marboxil
Placebo	Placebo Comparator	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.	Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Baloxavir Marboxil	Drug	Baloxavir marboxil will be administered as a weight-based dose on Days 1 and 4. A third dose will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5.

Measure	Description	Time Frame
Time to Clinical Improvement	Time to Clinical Improvement (TTCI) is defined as Time to Hospital Discharge OR Time to NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.	Up to Day 35

Measure	Description	Time Frame
Response Rates of the 6-Point Ordinal Scale at Day 7	The ordinal scale categories are: Category 1) Discharged (or "ready for discharge") Category 2) Non-ICU hospital ward (or "ready for hospital ward") not requiring supplemental oxygen/non-invasive ventilation Category 3) Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen/non-invasive ventilation Category 4) ICU without mechanical (invasive) ventilation (or "ready for ICU admission") Category 5) Mechanical (invasive) ventilation Category 6) Death

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Torrance Memorial Medical Center		Torrance	California	90505	United States
Denver Health Medical Center

PubMed Identifier	Type	Citation	Retractions
36171475	Derived	Stannard HL, Mifsud EJ, Wildum S, Brown SK, Koszalka P, Shishido T, Kojima S, Omoto S, Baba K, Kuhlbusch K, Hurt AC, Barr IG. Assessing the fitness of a dual-antiviral drug resistant human influenza virus in the ferret model. Commun Biol. 2022 Sep 28;5(1):1026. doi: 10.1038/s42003-022-04005-4.
35085510	Derived

ID	Title	Description
FG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 30, 2019	Sep 9, 2020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Time to Clinical Improvement

Time to Clinical Improvement (TTCI) is defined as Time to Hospital Discharge OR Time to NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.

Participants were reverse transcriptase-polymerase chain reaction (RT-PCR) positive for influenza at any time point

Posted

Median

95% Confidence Interval

hours

Up to Day 35

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants	OG000208 OG001114

Title

Denominators

Categories

Title	Measurements
	OG00097.5(75.9 to 117.2) OG001100.2(75.9 to 144.4)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Gehan Wilcoxon	The Gehan Wilcoxon test was used to analyze the TTCI data because the proportional hazards assumption was violated	0.4666		Median Difference (Net)	-2.7			2-Sided	95	-53.4	25.9					Superiority

Secondary

Response Rates of the 6-Point Ordinal Scale at Day 7

The ordinal scale categories are:

Category 1) Discharged (or "ready for discharge") Category 2) Non-ICU hospital ward (or "ready for hospital ward") not requiring supplemental oxygen/non-invasive ventilation Category 3) Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen/non-invasive ventilation Category 4) ICU without mechanical (invasive) ventilation (or "ready for ICU admission") Category 5) Mechanical (invasive) ventilation Category 6) Death

All participants who were RT-PCR positive for influenza and were not discontinued or lost to follow up prior to day 7.

Posted

Number

percentage of participants

Day 7

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Secondary

Time to Clinical Response

Time to Clinical Response is based on temperature ranges, oxygen saturation, respiratory status, heart rate, and hospitalization status.

Participants were RT-PCR positive for influenza at any time point

Posted

Median

95% Confidence Interval

hours

Up to Day 35

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants

Secondary

Percentage of Participants on Mechanical Ventilation

Participants were RT-PCR positive for influenza at any time point

Posted

Number

percentage of participants

Up to Day 35

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants

Secondary

Duration of Mechanical Ventilation

Participants were RT-PCR positive for influenza at any time point

Posted

Median

Full Range

hours

Up to Day 35

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants Requiring ICU Stay

Participants were RT-PCR positive for influenza at any time point

Posted

Number

percentage of participants

Up to Day 35

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants

Secondary

Duration of ICU Stay

Participants were RT-PCR positive for influenza at any time point

Posted

Median

Full Range

hours

Up to Day 35

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants	OG000

Secondary

Time to Clinical Failure

Time to clinical failure, defined as the time to death, mechanical ventilation, or ICU admission, corresponding to ordinal scale categories 6, 5, and 4, respectively, from baseline

Participants were RT-PCR positive for influenza at any time point

Posted

Median

95% Confidence Interval

hours

Up to Day 35

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts

Secondary

Time to Hospital Discharge

Participants were RT-PCR positive for influenza at any time point

Posted

Median

95% Confidence Interval

hours

Up to Day 35

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants

Secondary

Percentage of Participants With Post-Treatment Influenza-Related Complications

Influenza-related complications included pneumonia, myositis or rhabdomyolysis, encephalitis or encephalopathy, myocarditis and/or pericarditis, otitis media, sinusitis, exacerbation of COPD/asthma, sepsis, acute lung injury or acute respiratory distress syndrome.

Participants were RT-PCR positive for influenza at any time point

Posted

Number

percentage of participants

Up to Day 35

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Secondary

Mortality Rate at Day 7

Participants were RT-PCR positive for influenza at any time point

Posted

Number

95% Confidence Interval

percentage of participants

Up to Day 7

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants

Secondary

Mortality Rate at Day 28

Participants were RT-PCR positive for influenza at any time point

Posted

Number

95% Confidence Interval

percentage of participants

Up to Day 28

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants

Secondary

Time to NEWS2 of ≤ 2 Maintained for 24 Hours

A score of 0 (Range 0 - 3) indicates normal health conditions.

Participants were RT-PCR positive for influenza at any time point

Posted

Median

95% Confidence Interval

hours

Up to Day 35

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants

Secondary

Time to Cessation of Viral Shedding by Virus Titer

Time to cessation of viral shedding by virus titer is defined as the time, in hours, between the initiation of study treatment and first time when the influenza virus titer is below the limit of detection (0.75 log10 TCID50/mL)

Participants were RT-PCR positive for influenza at any time point and with a positive virus titer on Day 1

Posted

Median

95% Confidence Interval

hours

Screening (baseline) and on Days 2, 3, 4, 5, 7, and 10

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Secondary

Change From Baseline in Influenza Virus Titer at Each Timepoint

Influenza virus titer is the quantity of influenza virus in a given volume within the samples obtained from nasal swabs. If influenza virus titer was less than the lower limit of quantification, the virus titer was imputed as 0.749 (log10TCID50/mL). A lower value indicates lower viral titer.

Participants were RT-PCR positive for influenza at any time point and with a positive virus titer on Day 1

Posted

Number

log10 TCID50/ml

Days 2, 3, 4, 5, 7, and 10

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Secondary

Percentage of Participants With Positive Influenza Virus Titer at Each Timepoint

Influenza virus titer is the quantity of influenza virus in a given volume within the samples obtained from nasal swabs. If influenza virus titer was less than the lower limit of quantification, the virus titer was imputed as 0.749 (log10 TCID50/mL). A lower value indicates lower viral titer.

Participants were RT-PCR positive for influenza at any time point and with a positive virus titer on Day 1.

Posted

Number

percentage of participants

Days 2, 3, 4, 5, 7, and 10

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Secondary

Area Under the Curve in Virus Titer

Participants with a positive virus titer on Day 1

Posted

Mean

Standard Deviation

log10 TCID50/mL*hours

Days 1, 2, 3, 4, 5, 7, and 10

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants

Secondary

Time to Cessation of Viral Shedding by RT-PCR

Time to cessation of viral shedding by RT-PCR, in hours, is defined as the time between the initiation of study treatment and first time when the virus RNA by RT-PCR is below the limit of detection (2.05 for flu A and 2.83 for flu B log10 virus particles/mL)

Participants were RT-PCR positive for influenza on Day 1

Posted

Median

95% Confidence Interval

hours

Screening (baseline) and on Days 2, 3, 4, 5, 7, and 10

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Secondary

Change From Baseline in the Amount of Virus RNA (RT-PCR) at Each Timepoint

If the amount of virus RNA was less than the lower limit of quantification, the amount of virus RNA was imputed as 2.18 for flu A and 2.93 for flu B (log10 virus particles/mL)

Participants were RT-PCR positive for influenza on Day 1

Posted

Number

log10 virus particles/mL

Days 2, 3, 4, 5, 7, and 10

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units

Secondary

Percentage of Participants Positive by RT-PCR at Each Timepoint

If the amount of virus RNA was less than the lower limit of quantification, the amount of virus RNA was imputed as 2.18 for flu A and 2.93 for flu B (log10 virus particles/mL)

Participants were RT-PCR positive for influenza on Day 1

Posted

Number

percentage of participants

Days 2, 3, 4, 5, 7, and 10

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts

Secondary

Area Under the Curve in the Amount of Virus RNA (RT-PCR)

Participants were RT-PCR positive for influenza on Day 1.

Posted

Mean

Standard Deviation

log10 virus particles/mL*hours

Days 1, 2, 3, 4, 5, 7, and 10

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants

Secondary

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A serious adverse event (SAE) is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.

Posted

Number

percentage of participants

Up to Day 35

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Secondary

Percentage of Participants With AEs and SAEs Leading to Discontinuation From Treatment

Discontinuation from study treatment.

Posted

Number

percentage of participants

Up to Day 35

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants

Secondary

Percentage of Participants With Any Post-Treatment ALT and AST Above Baseline and >3 × ULN, >5 × ULN, >10 × ULN

ALT = alanine aminotransferase AST = aspartate transaminase

Posted

Number

percentage of participants

Up to Day 35

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
OG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants

Secondary

Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points

Participants who provided informed consent to intensive PK sampling in the Baloxavir Marboxil arm.

Posted

Mean

Standard Deviation

ng/mL

Day 1, 2, 4, 5, 7 and 8

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants	OG000

Secondary

Area Under the Concentration to Time Curve From Time 0 to 72 Hours (AUC0-72) of Baloxavir

Participants who provided informed consent to intensive pharmacokinetic (PK) sampling in the Baloxavir Marboxil arm.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours(h)*nanogram(ng)/milliliter (mL)

0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants	OG000

Secondary

Maximum Plasma Concentration (Cmax) of Baloxavir

Participants who provided informed consent to intensive PK sampling in the Baloxavir Marboxil arm.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants	OG000

Secondary

Apparent Half-Life (T1/2) of Baloxavir

Participants who provided informed consent to intensive PK sampling and had a sufficient number of samples available for analysis

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours (h)

0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants	OG000

Secondary

Concentration at 24 Hours (C24) of Baloxavir

Participants who provided informed consent to intensive PK sampling in the Baloxavir Marboxil arm

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8

ID	Title	Description
OG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Atrial fibrillation	Cardiac disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Bradycardia	Cardiac disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Cardiac failure	Cardiac disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0011 events1 affected124 at risk
Congestive cardiomyopathy	Cardiac disorders	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Constipation	Gastrointestinal disorders	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA version 23.0	Non-systematic Assessment	EG0002 events2 affected239 at risk EG0010 events0 affected124 at risk
Graft versus host disease	Immune system disorders	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Asymptomatic bacteriuria	Infections and infestations	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Bronchitis	Infections and infestations	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Cellulitis	Infections and infestations	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Device related infection	Infections and infestations	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Endocarditis	Infections and infestations	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Lower respiratory tract infection viral	Infections and infestations	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Pneumonia	Infections and infestations	MedDRA version 23.0	Non-systematic Assessment	EG0007 events7 affected239 at risk EG0015 events5 affected124 at risk
Pneumonia bacterial	Infections and infestations	MedDRA version 23.0	Non-systematic Assessment	EG0002 events2 affected239 at risk EG0011 events1 affected124 at risk
Pneumonia viral	Infections and infestations	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Sepsis	Infections and infestations	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Septic shock	Infections and infestations	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Superinfection viral	Infections and infestations	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Fall	Injury, poisoning and procedural complications	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Hepatic enzyme increased	Investigations	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Gout	Metabolism and nutrition disorders	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Cerebral artery embolism	Nervous system disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Encephalopathy	Nervous system disorders	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Device malfunction	Product Issues	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.0	Non-systematic Assessment	EG0002 events2 affected239 at risk EG0011 events1 affected124 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.0	Non-systematic Assessment	EG0002 events1 affected239 at risk EG0010 events0 affected124 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.0	Non-systematic Assessment	EG0004 events3 affected239 at risk EG0010 events0 affected124 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0012 events2 affected124 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0011 events1 affected124 at risk
Aortic aneurysm rupture	Vascular disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Hypotension	Vascular disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk
Orthostatic hypotension	Vascular disorders	MedDRA version 23.0	Non-systematic Assessment	EG0000 events0 affected239 at risk EG0011 events1 affected124 at risk
Peripheral ischaemia	Vascular disorders	MedDRA version 23.0	Non-systematic Assessment	EG0001 events1 affected239 at risk EG0010 events0 affected124 at risk

ID	Term
D012141	Respiratory Tract Infections
D007239	Infections
D009976	Orthomyxoviridae Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D012140	Respiratory Tract Diseases

ID	Title	Description
BG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
BG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Baloxavir Marboxil	Participants will receive at least two doses of baloxavir marboxil on Days 1 and 4. A third dose of Baloxavir will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with standard of care (SOC) NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.	4	239	29	239	44	239
EG001	Placebo	Participants will receive at least two doses of placebo on Day 1 and 4. A third dose of placebo will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5. Study treatment will be given in combination with SOC NAI (i.e., oseltamivir, zanamivir, or peramivir) in accordance with local clinical practice.	7	124	19	124	27	124