A Surveillance Study of Susceptibility to Baloxavir Marboxil in Pediatric Participants With Influenza and Transmission of Influenza to Household Contacts

A Phase IIIb Multicenter, Single-arm, Open-label Surveillance Study of Susceptibility to Baloxavir Marboxil in Pediatric Patients With Influenza and Transmission of Influenza to Household Contacts

This study consists of two parts: Part A Surveillance and Part B Transmission.

The main purpose of Part A is to evaluate the prevalence of pre-dose and treatment-emergent amino acid substitutions in pediatric participants' <12 years with influenza treated with baloxavir marboxil.

Part B will include a subset of Part A participants who have household contacts (HHCs) recruited to the study. Part B will evaluate the incidence of onward influenza transmission from pediatric index participants (IPs) under 5 years of age and those aged 5 to under 12 years, treated with baloxavir marboxil, to their HHCs. Participants will no longer be enrolled to Part B Transmission as per protocol version 3.

Inclusion Criteria (Part A):

• Participants with symptoms suggestive of influenza based on investigator's judgement with diagnosis confirmed by a positive local influenza test within 24 hours before full study screening
• Participants with a negative severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) test within 48 hours before full study screening
• Time interval between onset of influenza symptoms and the start of pre-dose examinations at screening is 48 hours or less

Inclusion Criteria (Part B):

[A] IP:

• Eligible to take part in Part A
• Lives in a household with a HHC willing to be recruited as full HHC

[B] HHCs:

- Each HHC living in the home of an IP at the time of IP treatment must be screened for partial or full-study HHC eligibility

[C] Partial HHC:

• Starts screening within 1 calendar day after IP treatment
• Negative influenza and SARS-CoV-2 test at screening after IP's treatment with baloxavir marboxil
• HHC lives in a household where 1 or more HHCs meet the full-study HHC requirements AND at least 1 full-study HHC has not received the influenza vaccine within 6 months prior to screening
• HHC lives in a household where 1 or more HHCs meet the full-study HHC requirements, and at least 1 full-study HHC has not received the influenza vaccine within 6 months prior to screening.
• HHC lives with other HHCs (if applicable) who fulfill all the "partial HHC" criteria

[D] Full-study HHC:

• Fulfills the "partial HHC" criteria
• Agrees to participate in the full study
• Will reside in the IP's house for at least 12 of the next 15 days and will be present for scheduled study visits
• No influenza symptoms within 7 days prior to screening
• Does not have a moderate or worse active infections or infections requiring systemic or otherwise internally administered or otherwise internally administered antibiotic/antiviral/antifungal therapy

Exclusion Criteria (Part A):

• Participants with severe influenza virus infection requiring inpatient treatment
• Severely immunocompromised participants (including participants receiving immunosuppressant therapy, or those with cancer or human immunodeficiency virus [HIV] infection) as defined by the investigator
• Participants with concurrent (non-influenza) infections requiring systemic anti-microbial and/or anti-viral therapy at the pre-dose examinations
• Treatment with baloxavir marboxil, peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir or amantadine within 30 days prior to screening
• Treatment with an investigational influenza-specific monoclonal antibody within 6 months or 5 half-lives, whichever is longer, prior to screening
• Treatment with an investigational therapy within 30 days or 5 half-lives, whichever is longer, prior to screening
• Known hypersensitivity to baloxavir marboxil or the drug product excipients
• Females who have commenced menarche (i.e., child-bearing potential)

Exclusion Criteria (Part B):

• IPs who fulfil an exclusion criterion for Part A
• HHCs deemed to require influenza post-exposure prophylaxis with influenza antiviral treatment due to their risk of developing influenza-related complications in accordance with local guidelines or clinical practice
• HHCs diagnosed with influenza by health care professional in the past 4 weeks