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

A Phase IIIB, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Clinical Efficacy Study of Baloxavir Marboxil for the Reduction of Direct Transmission of Influenza From Otherwise Healthy Patients to Household Contacts

Otherwise healthy index patients (IP) are randomized to either baloxavir marboxil or placebo if their influenza symptoms onset was within 48 hours of screening. Their households are enrolled within 24 hours of randomization if at least 1 household contacts (HHC) have not received influenza vaccine within 6 months of screening and if all HHC screen negative for influenza infection. The main endpoints are assessed based on multiple respiratory swabs, obtained from both IP and HHC up to 9 (+/-1) days post IP randomization, and through the assessment of symptoms.

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 other point-of-care / local laboratory results.
• PCR (-) or antigen test (-) for SARS-CoV-2 based on cobas® SARS-CoV-2 and Influenza A/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 per axillary, oral or forehead/temporal thermometer) or (b) any influenza symptoms (cough, sore throat, nasal congestion, headache, feverishness or chills, muscle or joint pain, fatigue).
• The time interval between the onset of fever or influenza symptoms and the pre-dose examinations is 48 hours or less.
• IP lives in a household where: (1) No HHC is known to have been diagnosed with influenza or SARS-CoV-2 infection by a healthcare professional (HCP) in the past 4 weeks; (2) All HHCs are expected to meet the key HHC inclusion criteria; (3) >=1 HHCs are expected to participate in the full study who have not received the influenza vaccine within 6 months prior to screening.
• Women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual 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 local point-of-care / local laboratory result.
• PCR (-) or antigen test (-) for SARS-CoV-2 based on cobas® SARS-CoV-2 and Influenza A/B or other POC / local laboratory result.
• HHC lives with no HHC who will be present in the home at any time during the study and 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 screening within 24 hours after IP randomization; Have NOT received the influenza vaccine within 6 months prior to screening; and Fulfill full study HHC inclusion criteria part 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 symptoms are permissible if determined by the investigator to be due to a preexisting condition.
• Temperature <38.0 °C (tympanic).
• Will reside in the index patient's house for at least 7 of the next 9 days and will be present for scheduled study visits.
• Willing and able to measure and record temperature, or have another household member perform the task on his or her behalf. Furthermore, a responsible adult will assume responsibility 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 a healthcare 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 mild external 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 11 year olds who will receive oral suspension).
• Women who are breastfeeding or have a positive pregnancy test in the pre-dose examinations.
• IPs with concurrent (non-influenza) infections requiring systemic antimicrobial and/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 investigational drug, within 30 days or 5 drug-elimination half-lives, whichever is longer, prior to screening.
• IPs who have received an investigational monoclonal antibody for a viral disease in the 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 exclusion criteria

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 drug elimination half-lives, whichever is longer, prior to screening.
• Diagnosed with influenza or SARS-CoV-2 infection by a healthcare professional in the past 4 weeks.
• HHC who plans to arrive home after 24 hours post IP randomization to Day 9 and is not willing to be consented as soon as possible upon arrival.
• HHC previously included in the study.