Study to Assess Efficacy and Safety of Baloxavir Marboxil In Combination With Standard-of-Care Neuraminidase Inhibitor In Hospitalized Participants With Severe Influenza

Inclusion Criteria:

- Adult participants: Signed informed consent by any participant capable of giving
consent, or, where the participant is not capable of giving consent, by his or her
legal/authorized representative

- Adolescent participants not able to legally consent: written informed consent for
study participation is obtained from participant's parents or legal guardian, with
assent as appropriate by the participant, depending on the participant's level of
understanding and capability to provide assent

- Participants who require hospitalization for severe influenza or acquire influenza
during hospitalization, the severity of which requires an extension of hospitalization

- Diagnosis of influenza A and/or B by a positive Rapid Influenza Diagnostic Test (RIDT)
or reverse transcriptase-polymerase chain reaction (RT-PCR)

- The time interval between the onset of symptoms and randomization is within 96 hours

- A score of ≥4 based on the NEWS2

- Participants will require objective criteria of seriousness defined by at least one of
the following criteria:

- Requires ventilation or supplemental oxygen to support respiration

- Has a complication related to influenza that requires hospitalization (e.g.,
pneumonia, CNS involvement, myositis, rhabdomyolysis, acute exacerbation of
chronic kidney disease, asthma or chronic obstructive pulmonary disease [COPD],
severe dehydration, myocarditis, pericarditis, exacerbation of ischemic heart
disease)

- For women of childbearing potential: Agreement to remain abstinent or use
contraceptive methods with a failure rate of < 1% per year during the treatment period
and for 28 days after the last dose of study treatment. Hormonal contraceptive methods
must be supplemented by a barrier method.

Exclusion Criteria:

- Participants who have received more than 48 hours of antiviral treatment for influenza
prior to screening

- Participants who have received baloxavir marboxil for the current influenza infection

- Known contraindication to neuraminidase inhibitors

- Participants hospitalized for exclusively social reasons (e.g., lack of caregivers at
home)

- Participants expected to die or be discharged within 48 hours, according to the
investigator's judgement

- Participants weighing < 40 kg

- Participants with known severe renal impairment (estimated glomerular filtration rate
< 30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis,
peritoneal dialysis

- Participants with any of the following laboratory abnormalities detected within 24
hours prior to or during screening (according to local laboratory reference ranges:

- ALT or AST level > 5 times the upper limit of normal (ULN) OR

- ALT or AST > 3 times the ULN and total bilirubin level > 2 times the ULN

- Pregnant or breastfeeding, or positive pregnancy test in a predose examination, or
intending to become pregnant during the study or within 28 days after the last dose of
study treatment

- Exposure to an investigational drug within 5 half-lives or 30 days (whichever is
longer) of randomization

- Any serious medical condition or abnormality in clinical laboratory tests that, in the
investigator's judgment, precludes the participant's safe participation in and
completion of the study