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

The virological transmission was determined based on Polymerase Chain Reaction Positive (PCR+) influenza test results. The adjusted incidence (cumulative proportion of events by Day 5) rate is reported here. This is defined as percentage of HHCs who tested PCR+ for influenza by Day 5 post IP randomization with virus subtype matching with that of the respective IP, irrespective of being symptomatic or asymptomatic. The adjusted incidence rates presented were estimated using a generalized estimating equations (GEE) approach.

Time frame: Baseline (Day 1) to Day 5

Population: The primary household contacts analysis set (PAS-HC) included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B, received the study drug, and where all contacts were PCR negative at baseline.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of 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.

Time frame: Baseline up to Day 9 (for IPs ≥12 years old) and Day 21 (for IPs <12 years old)

Population: Safety IP Set included all randomized participants who received at least one dose of study treatment. One participant was randomized to placebo but received baloxavir and is counted in the Baloxavir arm.

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 or incapacity, is a congenital anomaly or birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.

Time frame: Baseline up to Day 9 (for IPs ≥12 years old) and Day 21 (for IPs <12 years old)

Population: Safety IP Set included all randomized participants who received at least one dose of study treatment. One participant was randomized to placebo but received baloxavir and is counted in the Baloxavir arm.

The adjusted incidence (cumulative proportion of events by Day 9) rate is reported here. This is defined as percentage of HHCs who tested PCR+ for influenza by Day 9 post IP randomization and developed symptoms at any time during the study. The adjusted incidence rates presented were estimated using a GEE approach. HHCs ≥12 years were symptomatic if they had (1) a temperature ≥38.0°C and one respiratory symptom (cough, sore throat, nasal congestion) or (2) one respiratory and one systemic symptom (headache, chills, muscle/joint pain, fatigue), with or without fever. HHCs ≥2 and \<12 years were symptomatic if the presence of temperature was ≥38.0°C and had upper respiratory symptoms (cough, nasal congestion, rhinorrhea). Symptoms must be either new or have worsened versus baseline in HHC with baseline symptoms due to a preexisting comorbidity.

Time frame: Baseline (Day 1) to Day 9

Population: PAS-HC included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B and received study drug and where all contacts were PCR negative at baseline. Overall number analyzed is the number of participants with data available for analysis.

Virological infection was defined as HHCs who tested PCR+ for influenza by Day 9 post IP randomization based on PCR influenza test results. The adjusted incidence (cumulative proportion of events by Day 9) rate is reported here. This is defined as percentage of HHCs who met the virological infection by Day 9 endpoint. The adjusted incidence rates presented were estimated using a GEE approach.

Time frame: Baseline (Day 1) to Day 9

Population: PAS-HC included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B and received study drug and where all contacts were PCR negative at baseline. Overall number analyzed is the number of participants with data available for analysis.

The adjusted incidence (cumulative proportion of events by Day 5) rate is reported here. This is defined as percentage of HHCs who tested PCR+ for influenza by Day 5 post IP randomization with virus subtype matching with that of respective IP, & developed symptoms at any time during the study. The adjusted incidence rates presented were estimated using a GEE approach. HHCs ≥12 years old were symptomatic if 1. Presence of temperature ≥38.0 Celsius (C) and 1 respiratory symptom (cough, sore throat, nasal congestion) or 2. Presence of 1 respiratory symptom and 1 general systemic symptom (headache, feverishness or chills, muscle or joint pain, fatigue), with/without a fever. HHCs ≥2 and \<12 years old were symptomatic if the presence of temperature was ≥38.0°C and had upper respiratory tract infection signs or symptoms (cough, nasal congestion, or rhinorrhea). Symptoms must be either new or have worsened versus baseline in HHC with baseline symptoms due to a preexisting comorbidity.

Time frame: Baseline (Day 1) to Day 5

Population: PAS-HC included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B, received the study drug, and where all contacts were PCR negative at baseline.

The adjusted incidence (cumulative proportion of events by Day 9) rate is reported here. This is defined as percentage of HHCs who met the virological transmission by Day 9 endpoint and developed symptoms at any time during the study. The adjusted incidence rates presented were estimated using a GEE approach. HHCs ≥12 years were symptomatic if they had 1. temperature ≥38.0°C and one respiratory symptom (cough, sore throat, nasal congestion) or 2. one respiratory and one general systemic symptom (headache, feverishness or chills, muscle or joint pain, fatigue), with or without fever. HHCs ≥2 and \<12 years were symptomatic if the presence of temperature was ≥38.0°C and had upper respiratory symptoms (headache, feverishness or chills, muscle or joint pain, fatigue). Symptoms must be either new or have worsened versus baseline in HHC with baseline symptoms due to a preexisting comorbidity.

Time frame: Baseline (Day 1) to Day 9

Population: PAS-HC included unvaccinated HHCs who were linked to households where IP was baseline PCR+ for influenza A or B, received study drug, and where all contacts were PCR negative at baseline. Overall number analyzed is the number of participants with data available for analysis.

The adjusted incidence (cumulative proportion of events by Day 9) rate is reported here. This is defined as percentage of HHCs who tested PCR+ for influenza by Day 9 post IP randomization with virus subtype matching with the respective IP, irrespective of being symptomatic or asymptomatic including: 1. all HHC meeting primary endpoint, AND 2. all HHC cases detected after Day 5 meeting the following criteria: 2a. included HHC case was in an HH where another HHC had already met the primary endpoint OR 2b. included HHC case was PCR+ bearing an amino acid substitution of isoleucine for another amino acid at position 38 (I38X) in the polymerase acidic (PA) protein (PA/I38X substitution) or amino acid substitution of threonine to lysine at position 20 in the PA protein for influenza B only (PA/T20K). The adjusted incidence rates presented were estimated using a GEE approach.

Time frame: Baseline (Day 1) to Day 9

Population: PAS-HC analysis set included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B, received the study drug, and where all contacts were PCR negative at baseline. Overall number analyzed included number of HHCs with data available for analysis.

Percentage of HHs with at least one HHC who meets the endpoint of any symptomatic infection by Day 9 are reported here. HHCs ≥12 years were symptomatic if they had 1. a temperature ≥38.0°C &1 respiratory symptom (cough, sore throat, nasal congestion) or 2. 1 respiratory & 1 systemic symptom (headache, chills, muscle/joint pain, fatigue), with/without fever. HHCs ≥2 & \<12 years were symptomatic if the temperature was ≥38.0°C & had upper respiratory symptoms (cough, nasal congestion, rhinorrhea). Symptoms must be new or have worsened versus baseline in HHC with baseline symptoms due to preexisting comorbidity. 'Number of participants analyzed' is the number of IPs in the PAS-IP set.

Time frame: Baseline (Day 1) to Day 9

Population: PAS-HH included all households of randomized IPs that were PCR+ at screening and with at least one HHC enrolled for the full study. The IPs should be a part of the PAS-IP which includes all randomized IPs with at least one HHC in the PAS-HC. PAS-HC included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B, received the study drug, and where all contacts were PCR negative at baseline.

Virological infection at the HH level was defined as the HHs with at least one HHC who met the endpoint of any virological infection by Day 9. 'Number of participants analyzed' is the number of IPs in the PAS-IP set.

Time frame: Baseline (Day 1) to Day 9

Population: PAS-HH included all households of randomized IPs that were PCR+ at screening and with at least one HHC enrolled for the full study. The IPs should be a part of the PAS-IP which includes all randomized IPs with at least one HHC in the PAS-HC. PAS-HC included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B, received the study drug, and where all contacts were PCR negative at baseline.

Percentage of HHs with at least one HHC who meets the symptomatic transmission by Day 5 endpoint are reported here. 'Number of participants analyzed' is the number of IPs in the PAS-IP set.

Time frame: Baseline (Day 1) to Day 5

Population: PAS-HH included all households of randomized IPs that were PCR+ at screening and with at least one HHC enrolled for the full study. The IPs should be a part of the PAS-IP which includes all randomized IPs with at least one HHC in the PAS-HC. PAS-HC included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A or B, received the study drug, and where all contacts were PCR negative at baseline.

Percentage of households with at least one HHC who met the primary endpoint of virological transmission by Day 5 are reported here. 'Number of participants analyzed' is the number of IPs in the PAS-IP set.

Time frame: Baseline (Day 1) to Day 5

Population: Primary Households Analysis Set (PAS-HH) included all households of randomized IPs that were PCR+ at screening and with at least one HHC enrolled for the full study. IPs should be a part of the Primary Index Patients Analysis Set (PAS-IP) which includes all randomized IPs with at least 1 HHC in the PAS-HC. PAS-HC included unvaccinated HHCs who were linked to households where the IP was baseline PCR+ for influenza A/B, received study drug, and where all contacts were PCR negative at baseline.