Trial Outcomes & Findings for Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Healthy Pediatric Participants From Birth to < 1 Year With Influenza-Like Symptoms (NCT NCT03653364)

NCT ID: NCT03653364

Last Updated: 2024-05-17

Results Overview

An 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 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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 49 participants
• Primary outcome timeframe: From Day 1 up to Day 29
• Results posted on: 2024-05-17

Participant Flow

Participants were enrolled in this study at 15 investigative sites in 7 countries (Costa Rica, Finland, Mexico, Poland, South Africa, Spain, and the United States) from 23 January 2019 to 03 April 2023.

A total of 49 pediatric participants from birth to <1 year with influenza-like symptoms were enrolled in this study to receive baloxavir marboxil. Out of the 49 participants, one participant was screened and enrolled by accident but was not dosed.

Participant milestones

Measure	Baloxavir Marboxil Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Overall Study STARTED	49
Overall Study COMPLETED	46
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Baloxavir Marboxil Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Overall Study Withdrawal by Subject	1
Overall Study Enrolled in Error	1
Overall Study Death	1

Baseline Characteristics

Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Healthy Pediatric Participants From Birth to < 1 Year With Influenza-Like Symptoms

Baseline characteristics by cohort

Measure	Baloxavir Marboxil n=48 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Age, Continuous	206.5 days STANDARD_DEVIATION 106.08 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	26 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Day 1 up to Day 29

Population: Safety-evaluable population included all participants who received at least one dose of treatment regardless of whether they had any follow-up assessments.

An 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 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.

Outcome measures

Measure	Baloxavir Marboxil n=48 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	23 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	2 Participants

SECONDARY outcome

Timeframe: 0.5 to 2 hours post dose on Day 1; 24 hours (Day 2) and 72 hours (Day 4) post dose, Day 6 and Day 10

Population: Pharmacokinetics (PK)-evaluable population included all participants in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit timepoint. Overall number analyzed is the number of participants with data available for analysis. Number analyzed per timepoint are unique number of participants out of all the assessed participants with data available for analysis at specified timepoint. Different participants may have contributed data for each timepoint.

S-033447 is an active metabolite of baloxavir marboxil.

Outcome measures

Measure	Baloxavir Marboxil n=46 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Plasma Concentrations of Baloxavir Marboxil and S-033447 Baloxavir Marboxil: 0.5 to 2 hours	0.93 nanograms per milliliters (ng/mL) Standard Deviation 2.301
Plasma Concentrations of Baloxavir Marboxil and S-033447 Baloxavir Marboxil: 24 hours	0 nanograms per milliliters (ng/mL) Standard Deviation 0
Plasma Concentrations of Baloxavir Marboxil and S-033447 Baloxavir Marboxil: 72 hours	0 nanograms per milliliters (ng/mL) Standard Deviation 0
Plasma Concentrations of Baloxavir Marboxil and S-033447 Baloxavir Marboxil: Day 6	0 nanograms per milliliters (ng/mL) Standard Deviation 0
Plasma Concentrations of Baloxavir Marboxil and S-033447 Baloxavir Marboxil: Day 10	0 nanograms per milliliters (ng/mL) Standard Deviation 0
Plasma Concentrations of Baloxavir Marboxil and S-033447 S-033447: 0.5 to 2 hours	81.98 nanograms per milliliters (ng/mL) Standard Deviation 89.412
Plasma Concentrations of Baloxavir Marboxil and S-033447 S-033447: 24 hours	49.75 nanograms per milliliters (ng/mL) Standard Deviation 40.987
Plasma Concentrations of Baloxavir Marboxil and S-033447 S-033447: 72 hours	17.88 nanograms per milliliters (ng/mL) Standard Deviation 17.438
Plasma Concentrations of Baloxavir Marboxil and S-033447 S-033447: Day 6	4.72 nanograms per milliliters (ng/mL) Standard Deviation 3.649
Plasma Concentrations of Baloxavir Marboxil and S-033447 S-033447: Day 10	1.35 nanograms per milliliters (ng/mL) Standard Deviation 1.547

SECONDARY outcome

Timeframe: Up to Day 10

Population: PK-evaluable population included all participants in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit timepoint. Overall number analyzed is the number of participants with data available for analysis. Since baloxavir marboxil was barely measurable in plasma, baloxavir marboxil pharmacokinetic parameters were not determined.

S-033447 is an active metabolite of baloxavir marboxil.

Outcome measures

Measure	Baloxavir Marboxil n=46 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil and S-033447 Baloxavir Marboxil	NA nanograms/milliters*hour (ng/mL*hr) Standard Deviation NA Baloxavir marboxil was below the level of detection in plasma; hence mean and standard deviation could not be derived.
Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil and S-033447 S-033447	5070 nanograms/milliters*hour (ng/mL*hr) Standard Deviation 3520

SECONDARY outcome

Timeframe: Up to Day 10

Population: PK-evaluable population included all participants in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit timepoint. Overall number analyzed is the number of participants with data available for analysis. Since baloxavir marboxil was barely measurable in plasma, baloxavir marboxil pharmacokinetic parameters were not determined.

S-033447 is an active metabolite of baloxavir marboxil.

Outcome measures

Measure	Baloxavir Marboxil n=46 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Maximum Plasma Concentration (Cmax) of Baloxavir Marboxil and S-033447 Baloxavir Marboxil	NA nanograms/ milliters (ng/ml) Standard Deviation NA Baloxavir marboxil was below the level of detection in plasma; hence mean and standard deviation could not be derived.
Maximum Plasma Concentration (Cmax) of Baloxavir Marboxil and S-033447 S-033447	127 nanograms/ milliters (ng/ml) Standard Deviation 81.0

SECONDARY outcome

Timeframe: Up to Day 10

Population: PK-evaluable population included all participants in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit timepoint. Overall number analyzed is the number of participants with data available for analysis. Since baloxavir marboxil was barely measurable in plasma, baloxavir marboxil pharmacokinetic parameters were not determined.

S-033447 is an active metabolite of baloxavir marboxil.

Outcome measures

Measure	Baloxavir Marboxil n=46 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Time to Maximum Plasma Concentration (Tmax) of Baloxavir Marboxil and S-033447 Baloxavir Marboxil	NA hours Baloxavir marboxil was below the level of detection in plasma; hence median and full range (upper limit and lower limit) could not be derived.
Time to Maximum Plasma Concentration (Tmax) of Baloxavir Marboxil and S-033447 S-033447	4.5 hours Interval 2.0 to 14.5

SECONDARY outcome

Timeframe: Up to Day 10

Population: PK-evaluable population included all participants in the ITT population who had at least one post-dose drug concentration measurement at a scheduled visit timepoint. Overall number analyzed is the number of participants with data available for analysis. Since baloxavir marboxil was barely measurable in plasma, baloxavir marboxil pharmacokinetic parameters were not determined.

S-033447 is an active metabolite of baloxavir marboxil.

Outcome measures

Measure	Baloxavir Marboxil n=46 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Apparent Half-Life (T1/2) of Baloxavir Marboxil and S-033447 S-033447	23.1 hours Interval 13.0 to 33.4
Apparent Half-Life (T1/2) of Baloxavir Marboxil and S-033447 Baloxavir Marboxil	NA hours Baloxavir marboxil was below the level of detection in plasma; hence median and full range (upper limit and lower limit) could not be derived.

SECONDARY outcome

Timeframe: Day 1 up to Day 15

Population: Intent-to-Treat Influenza-Infected (ITTi) population is a subset of ITT participants who had a laboratory confirmation of influenza infection (polymerase chain reaction \[PCR\] result) from any swab sample collected at baseline or during the study.

Time to alleviation of influenza signs and symptoms was defined as the length of time taken from the start of treatment to the point at which all of the following criteria were met and remained for at least 21.5 hours:

• A score of 0 (no problem) or 1 (minor problem) for cough and nasal symptoms for items 14 and 15 of the Canadian Acute Respiratory Illness and Flu Scale [CARIFS]);
• A "yes" response to the following question on the CARIFS: "Since the last assessment has the participant been able to return to day care/school, or resume his or her normal daily activity in the same way as performed prior to developing the flu?";
• First return to afebrile state (tympanic temperature ≤37.2 degree Celsius [°C]).

Median time was estimated from the Kaplan-Meier curve. Participants who withdrew prior to an event of interest or did not experience resolution of symptoms were censored at the last observation time point.

Outcome measures

Measure	Baloxavir Marboxil n=15 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Time to Alleviation of Influenza Signs and Symptoms	163.7 hours Interval 122.5 to Due to low number of participants with event, the upper limit of 95% confidence interval (CI) could not be calculated.

SECONDARY outcome

Timeframe: Day 1 up to Day 15

Population: ITTi population is a subset of ITT participants who had a laboratory confirmation of influenza infection (PCR result) from any swab sample collected at baseline or during the study. Overall number analyzed is the number of participants available for analysis.

Duration of fever was defined as the length of time taken by participants to return to afebrile state [tympanic temperature ≤ 37.2°C] and remaining so for at least 21.5 hours after onset. Participants who did not have fever at baseline or whose body temperature was not collected were excluded from the analysis. Median time was estimated from the Kaplan-Meier curve.

Outcome measures

Measure	Baloxavir Marboxil n=13 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Duration of Fever	23.1 hours Interval 22.3 to 44.6

SECONDARY outcome

Timeframe: Day 1 up to Day 15

Population: ITTi population is a subset of ITT participants who had a laboratory confirmation of influenza infection (PCR result) from any swab sample collected at baseline or during the study.

The efficacy of baloxavir marboxil was evaluated by duration of symptoms i.e., alleviation of all symptoms as defined by a score of 0 [no problem] or 1 [minor problem] and remaining so for at least 21.5 hours, for all 18 symptoms (Poor appetite; Not sleeping well; Irritable, cranky, fussy; Feels unwell; Low energy, tired; Not playing well; Crying more than usual; Needing extra care; Clinginess; Headache; Sore throat; Muscle aches or pains; Fever; Cough; Nasal congestion, runny nose; Vomiting; Not interested in what's going on; Unable to get out of bed) specified in the CARIFS questionnaire. Median time was estimated from the Kaplan-Meier curve. Participants who withdrew prior to an event of interest or did not experience resolution of symptoms were censored at the last observation time point.

Outcome measures

Measure	Baloxavir Marboxil n=15 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Duration of Symptoms	163.7 hours Interval 71.0 to Due to low number of participants with event, the upper limit of 95% confidence interval (CI) could not be calculated.

SECONDARY outcome

Timeframe: Day 1 up to Day 15

Population: ITTi population is a subset of ITT participants who had a laboratory confirmation of influenza infection (PCR result) from any swab sample collected at baseline or during the study. Overall number analyzed is the number of participants with data available for analysis

Time to return to normal health and activity was defined by a 'Yes' response to the following question on the CARIFS: "Since the last assessment has the patient been able to return to day care/school or resume his or her normal daily activity in the same way as performed prior to developing the flu?" and remaining so for at least 21.5 hours.

Median time was estimated from the Kaplan-Meier curve.Participants who withdrew prior to an event of interest or did not experience resolution of symptoms were censored at the last observation time point.

Outcome measures

Measure	Baloxavir Marboxil n=14 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Time to Return to Normal Health and Activity	140.7 hours Interval 72.2 to Due to low number of participants with event, the upper limit of 95% confidence interval (CI) could not be calculated.

SECONDARY outcome

Timeframe: Day 1 up to Day 29

Population: ITTi population is a subset of ITT participants who had a laboratory confirmation of influenza infection (PCR result) from any swab sample collected at baseline or during the study.

The influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis

Outcome measures

Measure	Baloxavir Marboxil n=15 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Number of Participants With Influenza-Related Complications	0 Participants

SECONDARY outcome

Timeframe: Day 1 up to Day 29

Population: ITTi population is a subset of ITT participants who had a laboratory confirmation of influenza infection (PCR result) from any swab sample collected at baseline or during the study.

The number of participants who required antibiotics for influenza related complication are reported here.

Outcome measures

Measure	Baloxavir Marboxil n=15 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Number of Participants Requiring Antibiotics	0 Participants

SECONDARY outcome

Timeframe: Day 1 up to Day 29

Population: ITTi population is a subset of ITT participants who had a laboratory confirmation of influenza infection (PCR result) from any swab sample collected at baseline or during the study. Overall number analyzed is the number of participants with data available for analysis.

Time to cessation of viral shedding by virus titer was defined as the time, in hours, between the initiation of any study treatment and first time when the influenza virus titer was below the limit of detection (0.75 log10 tissue culture infectious dose (TCID)50/milliliters [mL]). Participants whose virus titers did not reach the limit by the last observation time point were treated as censored at that time point. One day was converted into 24 hours. Median time was estimated from the Kaplan-Meier curve.

Outcome measures

Measure	Baloxavir Marboxil n=10 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Time to Cessation of Viral Shedding by Virus Titer	24.5 hours Interval 24.2 to 68.6

SECONDARY outcome

Timeframe: Day 1 up to Day 29

Population: ITTi population is a subset of ITT participants who had a laboratory confirmation of influenza infection (PCR result) from any swab sample collected at baseline or during the study. Overall number analyzed is the number of participants with a positive virus RNA on Day 1.

Time to cessation of viral shedding by RT-PCR, in hours, was defined as the time between the initiation of study treatment and first time when the virus ribonucleic acid (RNA) by RT-PCR qualitative result was negative (no cycle threshold [Ct]-value detectable). Participants who did not have a negative result by the last observation time point were treated as censored at that time point. For the participants with multiple virus types, this endpoint was defined as the time between the initiation of the study treatment and first time when the virus RNA by RT-PCR qualitative result was negative for all virus types. One day was converted into 24 hours. Median time was estimated from the Kaplan -Meier curve. Participants with a positive virus RNA on Day 1 are included in this analysis.

Outcome measures

Measure	Baloxavir Marboxil n=14 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Time to Cessation of Viral Shedding by Reverse Transcription-Polymerase Chain Reaction (RT-PCR)	219.1 hours Interval 141.6 to 695.5

SECONDARY outcome

Timeframe: Baseline, Days 2, 4, 6, 10, and 29

Population: ITTi population is a subset of ITT participants who had a laboratory confirmation of influenza infection (PCR result) from any swab sample collected at baseline or during the study. Number analyzed per timepoint are unique number of participants out of all the assessed participants with data available for analysis at specified timepoint. Different participants may have contributed data for each timepoint.

Change from baseline in influenza virus titer (log10TCID50/mL) was defined as the change from baseline in influenza virus titer on Days 2, 4, 6, 10, and 29. If influenza virus titer was less than the lower limit of quantification (LLOQ), the virus titer was imputed as 0.749 (log10TCID50/mL). Only participants with a positive virus titer on Day 1 were included in this analysis.

Outcome measures

Measure	Baloxavir Marboxil n=15 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Change From Baseline in Influenza Virus Titer Over Time Baseline	3.58 log10 TCID 50/mL Standard Deviation 1.81
Change From Baseline in Influenza Virus Titer Over Time Change From Baseline at Day 2	-2.50 log10 TCID 50/mL Standard Deviation 1.70
Change From Baseline in Influenza Virus Titer Over Time Change From Baseline at Day 4	-2.60 log10 TCID 50/mL Standard Deviation 1.95
Change From Baseline in Influenza Virus Titer Over Time Change From Baseline at Day 6	-2.43 log10 TCID 50/mL Standard Deviation 1.40
Change From Baseline in Influenza Virus Titer Over Time Change From Baseline at Day 10	-2.83 log10 TCID 50/mL Standard Deviation 1.81
Change From Baseline in Influenza Virus Titer Over Time Change From Baseline at Day 29	-1.69 log10 TCID 50/mL Standard Deviation 1.71

SECONDARY outcome

Timeframe: Baseline, Days 2, 4, 6, and 10

Population: ITTi population is a subset of ITT participants who had a laboratory confirmation of influenza infection (PCR result) from any swab sample collected at baseline or during the study. Number analyzed per timepoint are unique number of participants out of all the assessed participants with data available for analysis at specified timepoint. Different participants may have contributed data for each timepoint.

Change from baseline in the amount of virus RNA was defined as the change from baseline in the amount of virus RNA on Days 2, 4, 6 and 10. If the amount of virus RNA is less than the lower limit of quantification, the amount of virus RNA was imputed as the relevant LLOQ (log10 viral particles per mililiter (vp/mL)). If a participant was infected with multiple virus types, the sum of virus RNA (log10 vp/mL) was used for analysis. Participants with a positive virus RNA by RT-PCR on Day 1 were included in this analysis.

Outcome measures

Measure	Baloxavir Marboxil n=15 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Change From Baseline in the Amount of Virus RNA (RT-PCR) Over Time Change From Baseline at Day 4	-1.93 log10 vp/mL Standard Deviation 1.99
Change From Baseline in the Amount of Virus RNA (RT-PCR) Over Time Baseline	6.46 log10 vp/mL Standard Deviation 1.91
Change From Baseline in the Amount of Virus RNA (RT-PCR) Over Time Change From Baseline at Day 2	-2.26 log10 vp/mL Standard Deviation 1.00
Change From Baseline in the Amount of Virus RNA (RT-PCR) Over Time Change From Baseline at Day 6	-1.76 log10 vp/mL Standard Deviation 2.40
Change From Baseline in the Amount of Virus RNA (RT-PCR) Over Time Change From Baseline at Day 10	-3.30 log10 vp/mL Standard Deviation 3.46

SECONDARY outcome

Timeframe: Baseline, Days 2, 4, 6, 10, and 29

Population: ITTi population is a subset of ITT participants who had a laboratory confirmation of influenza infection (PCR result) from any swab sample collected at baseline or during the study. Overall number analyzed is the number of participants with a positive influenza virus titer on Day 1. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Percentage of participants positive for influenza virus titer at each visit were defined as the percentage of participants whose influenza virus titer was not less than the LLOQ (0.75 log10TCID50/mL) or positive among those assessed for influenza virus titer on Days 2, 4, 6, 10 and 29. Participants with a positive influenza virus titer on Day 1 were included in this analysis.

Outcome measures

Measure	Baloxavir Marboxil n=10 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Percentage of Participants With Positive Influenza Virus Titer Over Time Day 10	0 percentage of participants
Percentage of Participants With Positive Influenza Virus Titer Over Time Day 29	0 percentage of participants
Percentage of Participants With Positive Influenza Virus Titer Over Time Baseline	100 percentage of participants
Percentage of Participants With Positive Influenza Virus Titer Over Time Day 2	40 percentage of participants
Percentage of Participants With Positive Influenza Virus Titer Over Time Day 4	20 percentage of participants
Percentage of Participants With Positive Influenza Virus Titer Over Time Day 6	30 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Days 2, 4, 6, 10, and 29

Population: ITTi population is a subset of ITT participants who had a laboratory confirmation of influenza infection (PCR result) from any swab sample collected at baseline or during the study. Overall number analyzed is the number of participants with a positive RT-PCR result on Day 1. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Percentage of participants positive by RT-PCR at each visit was defined as the percentage of participants with a positive qualitative result among those assessed by RT-PCR on Days 2, 4, 6, 10 and 29. Participants with a positive RT-PCR result on Day 1 were included in this analysis. Percentages are rounded off.

Outcome measures

Measure	Baloxavir Marboxil n=14 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Percentage of Participants Positive by RT-PCR Over Time Day 29	0 percentage of participants
Percentage of Participants Positive by RT-PCR Over Time Baseline	100 percentage of participants
Percentage of Participants Positive by RT-PCR Over Time Day 2	92.3 percentage of participants
Percentage of Participants Positive by RT-PCR Over Time Day 4	92.3 percentage of participants
Percentage of Participants Positive by RT-PCR Over Time Day 6	64.3 percentage of participants
Percentage of Participants Positive by RT-PCR Over Time Day 10	42.9 percentage of participants

SECONDARY outcome

Timeframe: Day 1 up to Day 29

Population: ITTi population is a subset of ITT participants who had a laboratory confirmation of influenza infection (PCR result) from any swab sample collected at baseline or during the study. Overall number analyzed is the number of participants with a positive virus titer on Day 1.

AUC in virus titer was calculated using the trapezoidal method. Twenty-four hours of time was converted into one day. Participants with a positive virus titer on Day 1 were included in this analysis. The LLOQ and lower limit of detection was defined as 0.75 log10TCID50/mL for flu A and 0.75 log10TCID50/mL for flu B. If a participant was infected with multiple virus types, the sum of those virus titers will be used for analysis.

Outcome measures

Measure	Baloxavir Marboxil n=10 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Area Under the Concentration-Time Curve (AUC) in Virus Titer	405.23 log10 TCID 50/mL*hours Standard Deviation 184.72

SECONDARY outcome

Timeframe: Day 1 up to Day 29

Population: ITTi population is a subset of ITT participants who had a laboratory confirmation of influenza infection (PCR result) from any swab sample collected at baseline or during the study. Overall number analyzed is the number of participants with a positive virus titer on Day 1.

AUC in virus RNA (RT-PCR) was defined as AUC of change from baseline in the amount of virus RNA (RT-PCR). AUC was calculated using the trapezoidal method similar to AUC in virus titer. Participants with a positive RT-PCR result on Day 1 were subjected to this analysis. If the amount of virus RNA is less than the lower limit of quantification, the amount of virus RNA was imputed as the relevant LLOQ (log10 viral particles per mililiter (vp/mL)). If a participant was infected with multiple virus types, the sum of those the amount of virus RNA was used for analysis.

Outcome measures

Measure	Baloxavir Marboxil n=13 Participants Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Area Under the Curve in the Amount of Virus RNA (RT-PCR)	779.06 log10 vp/mL*hours Standard Deviation 426.83

Adverse Events

Baloxavir Marboxil

Serious events: 2 serious events

Other events: 11 other events

Deaths: 1 deaths

Serious adverse events

Measure	Baloxavir Marboxil n=48 participants at risk Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Infections and infestations Lower respiratory tract infection	2.1% 1/48 • Number of events 1 • Day 1 up to Day 29 Safety-evaluable Population included all participants who received at least one dose of treatment regardless of whether they had any follow-up assessments.
Respiratory, thoracic and mediastinal disorders Choking	2.1% 1/48 • Number of events 1 • Day 1 up to Day 29 Safety-evaluable Population included all participants who received at least one dose of treatment regardless of whether they had any follow-up assessments.

Other adverse events

Measure	Baloxavir Marboxil n=48 participants at risk Participants received a single oral dose of baloxavir marboxil on Day 1 based on body weight and age.
Gastrointestinal disorders Diarrhoea	16.7% 8/48 • Number of events 9 • Day 1 up to Day 29 Safety-evaluable Population included all participants who received at least one dose of treatment regardless of whether they had any follow-up assessments.
Gastrointestinal disorders Vomiting	12.5% 6/48 • Number of events 11 • Day 1 up to Day 29 Safety-evaluable Population included all participants who received at least one dose of treatment regardless of whether they had any follow-up assessments.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER