Study to Assess the Efficacy of Baloxavir Marboxil Versus Placebo to Reduce Onward Transmission of Influenza A or B in Households

INCLUSION CRITERIA:

Index Patients (IPs):

• Able to comply with the study protocol per investigator judgment.

• Diagnosed with acute influenza infection by investigator.

• Polymerase chain reaction [PCR] (+) or Rapid Influenza Diagnostic Test [RIDT] (+)for influenza A/B based on cobas® SARS-CoV-2 and influenza A/B or otherpoint-of-care / local laboratory results.

• PCR (-) or antigen test (-) for SARS-CoV-2 based on cobas® SARS-CoV-2 and InfluenzaA/B test or other point-of-care / local laboratory result

• Presence of (a) fever (>=38.0 °C per tympanic or rectal thermometer; >=37.5 °C peraxillary, oral or forehead/temporal thermometer) or (b) any influenza symptoms (cough, sore throat, nasal congestion, headache, feverishness or chills, muscle orjoint pain, fatigue).

• The time interval between the onset of fever or influenza symptoms and the pre-doseexaminations is 48 hours or less.

• IP lives in a household where: (1) No HHC is known to have been diagnosed withinfluenza or SARS-CoV-2 infection by a healthcare professional (HCP) in the past 4weeks; (2) All HHCs are expected to meet the key HHC inclusion criteria; (3) >=1HHCs are expected to participate in the full study who have not received theinfluenza vaccine within 6 months prior to screening.

• Women of childbearing potential: Agreement to remain abstinent (refrain fromheterosexual intercourse) or use contraceptive measures specified in the protocol

All HHCs (Part 1):

• PCR (-) or RIDT (-) based on cobas® SARS-CoV-2 and influenza A/B or other localpoint-of-care / local laboratory result.

• PCR (-) or antigen test (-) for SARS-CoV-2 based on cobas® SARS-CoV-2 and InfluenzaA/B or other POC / local laboratory result.

• HHC lives with no HHC who will be present in the home at any time during the studyand who meets any HHC exclusion criteria.

• HHC lives with no HHC who does not meet HHC inclusion criteria (part 1).

• HHC lives in a household where ≥1 HHCs meet all of the following: Start screeningwithin 24 hours after IP randomization; Have NOT received the influenza vaccinewithin 6 months prior to screening; and Fulfill full study HHC inclusion criteriapart 2.

Full study HHCs (part 2) intended for full study must meet the following additional criteria for study entry:

• Agree to participate in the full study.

• Able to comply with the study protocol per investigator judgment

• No influenza symptoms within 7 days prior to screening. Alternatively, mild symptomsare permissible if determined by the investigator to be due to a preexistingcondition.

• Temperature <38.0 °C (tympanic).

• Will reside in the index patient's house for at least 7 of the next 9 days and willbe present for scheduled study visits.

• Willing and able to measure and record temperature, or have another household memberperform the task on his or her behalf. Furthermore, a responsible adult will assumeresponsibility to oversee or perform this task on behalf of minors.

• In the 6 months prior to screening: a) Has not been diagnosed with influenza by ahealthcare professional b) Has not received BXM, peramivir, laninamivir,oseltamivir, zanamivir, rimantadine, umifenovir, favipiravir or amantadine.

• Does not have a moderate or worse active infections OR infections requiring systemic (e.g., oral or intravenous) or otherwise internally administered (e.g., inhaled,intrathecal) antibiotic/antiviral/antifungal therapy, (topical therapies for mildexternal infections allowed).

EXCLUSION CRITERIA:

IPs:

• IPs with severe influenza virus infection requiring inpatient treatment.

• IPs judged by the investigator to be at high risk for complications of influenza.

• IP is ≥12 years old and unable to swallow tablets (not applicable to IPs 5 to 11year olds who will receive oral suspension).

• Women who are breastfeeding or have a positive pregnancy test in the pre-doseexaminations.

• IPs with concurrent (non-influenza) infections requiring systemic antimicrobialand/or antiviral therapy at the pre-dose examinations.

• IPs who have received baloxavir marboxil, peramivir, laninamivir, oseltamivir,zanamivir, rimantadine, umifenovir, favipiravir or amantadine, or an investigationaldrug, within 30 days or 5 drug-elimination half-lives, whichever is longer, prior toscreening.

• IPs who have received an investigational monoclonal antibody for a viral disease inthe last year.

• Known hypersensitivity to baloxavir marboxil or the drug product excipients.

• IP previously included in the study

• IP lives with an HHC who, based on available information, meets the HHC exclusioncriteria

HHC:

• Pregnant or within 2 weeks post-partum at screening.

• Immunocompromised.

• Less than 2 years old.

• Who have received an investigational therapy within the 30 days or 5 drugelimination half-lives, whichever is longer, prior to screening.

• Diagnosed with influenza or SARS-CoV-2 infection by a healthcare professional in thepast 4 weeks.

• HHC who plans to arrive home after 24 hours post IP randomization to Day 9 and isnot willing to be consented as soon as possible upon arrival.

• HHC previously included in the study.