A Study to Evaluate the Pharmacokinetics, Safety, and Antiviral Activity of JNJ-63623872 in Combination With Oseltamivir in Adult, and Elderly Hospitalized Participants With Influenza A Infection

An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with treatment and therefore can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with use of a medicinal product, whether or not related to that medicinal product. TEAEs were defined as AEs that were reported or worsened on after start of study drug(s) dosing through safety follow-up visit. A serious adverse event (SAE) is any untoward medical occurrence that at any dose resulting in any of following outcomes: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

Time to influenza A viral negativity was determined based on quantitative reverse transcription polymerase chain reaction (qRT-PCR). A participant was considered influenza A viral negative at the time point that the first negative nasal midturbinate (MT) swab was recorded (in days). Viral Load Limit of detection (LOD) = 2.18 log10 viral particles per milliliter (vp/mL). Results less than (<) limit of quantification (LOQ) and greater than (>) LOD (target detected) are imputed with 2.12 log10 vp/mL, results <LOD (target not detected) are imputed with 0 log10 vp/mL.

Influenza viral load over time (Log 10 viral particles per milliliter [vp/mL]) was measured by qRT-PCR. Viral Load LOD = 2.18 log10 vp/mL. Results < LOQ and > LOD (target detected) are imputed with 2.12 log10 vp/mL and results <LOD (target not detected) are imputed with 0 log10 vp/mL.

Rate of decline in viral load (Log10 viral particles per milliliter per day [log10 vp/mL/day]) during treatment was measured by qRT-PCR. Viral Load Limit of quantification (LOQ) = 2.18 log10 vp/mL, LOD = 2.05 log10 vp/mL. Results < LOQ and greater than > LOD (target detected) are imputed with 2.12 log10 vp/mL. Results <LOD (target not detected) are imputed with 0 log10 vp/mL.

Viral load AUC was determined by qRT-PCR assay of nasal swabs. Viral Load LOQ = 2.18 log10 vp/mL, LOD = 2.05 log10 vp/mL. Results <LOQ and >LOD (target detected) are imputed with 2.12 log10 vp/mL. Results <LOD (target not detected) are imputed with 0 log10 vp/mL.

Percentage of participants with following Influenza Complications: bacterial pneumonia (culture confirmed where possible), bacterial superinfections, respiratory failure, pulmonary disease (example, asthma, chronic obstructive pulmonary disease [COPD]), cardiovascular and cerebrovascular disease (example, myocardial infarction, congestive heart failure [CHF], arrhythmia, stroke) and all complications were reported.

FLU-PRO assesses 32 influenza symptoms in each of the following body areas (domains): Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal and Body/Systemic . Participants rate each symptom on a 5-point ordinal scale, with higher scores indicating a more frequent sign or symptom. For 27 of the items, the scale is as follows: 0 ("Not at all"), 1 ("A little bit"), 2 ("Somewhat"), 3 ("Quite a bit"), and 4 ("Very much"). For 5 items, severity is assessed in terms of numerical frequency, that is (i.e), vomiting or diarrhea (0 times, 1 time, 2 times, 3 times, or 4 or more times); with frequency of sneezing, coughing, and coughed up mucus or phlegm evaluated on a scale from 0 ("Never") to 4 ("Always").The FLU-PRO total score is computed as a mean score across all 32 items comprising the instrument. Total scores can range from 0 (symptom free) to 4 (very severe symptoms).

Time to improvement of vital signs was defined as the time from first study treatment to when at least 4 of 5 symptoms (temperature, blood oxygen saturation, heart rate, systolic blood pressure, and respiration rate) had recovered, including normalization of temperature and blood oxygen saturation. Resolution criteria for vital signs: for Temperature: oral temperature less than or equal to (<=) 36.5 degree Celsius (C) for elderly and <=37.2 C for adults; for oxygen saturation: greater than or equal to (>=) 92 percent (%) on room air without supplemental oxygen; for respiratory rate: <= 24 per minutes; for heart rate: <= 100 per minutes and for systolic blood pressure: >= 90 millimeters of mercury (mmHg).

The time to improvement of respiratory status was defined as the time from first study treatment until the first assessment of a successive series of 3 recording where normalization of blood oxygen saturation and respiration rate occurred at respiration rate <=24 per minutes).

The ordinal scale was used to assess participant's clinical outcome. It consists of 6 categories or clinical states that are exhaustive, mutually exclusive, and ordered, where 1- Death, 2- Admitted to intensive care unit (ICU) or mechanically ventilated/ extracorporeal membrane oxygenation (ECMO), 3- Non-ICU plus supplemental oxygen, 4- Non-ICU plus no supplemental oxygen, 5- Not hospitalized, but unable to continue activity, 6- Not hospitalized (NH) and continues activities.

Number of participants with emergence (from baseline) of drug resistance mutations detected by genotype or phenotype were reported.

Time to return to premorbid functional status (time to return usual activities) was defined as time in hours from the first dose of investigational product till the first one of 2 successive cases where the response is 'Yes' on FLU-PRO additional question 7 (Have you returned to your usual activities today?).

Time to hospital discharge was calculated from the date of first study drug intake during hospitalization up to date of discharge.

Time to return to usual health was defined as the time in hours from the first dose of investigational product till the first one of 2 successive cases where the response is 'Yes' on FLU-PRO additional question 9 (Have you returned to your health today?).

Time to significant reduction in influenza symptom severity (mild/none) is time from first dose of investigational drug until first of 2 successive recordings in which total score for each of 2 recordings is lower or equal to 1 and all domain scores is lower or equal to 1. FLU-PRO assesses 32 influenza symptoms in body areas (domains): Nose, throat, eyes, chest, gastrointestinal, body. Participants rate each symptom on 5-point scale, with higher scores indicates more frequent symptom. For 27 of items, scale is as follows: 0 (Not at all), 1 (A little bit), 2 (Somewhat), 3 (Quite a bit), 4 (Very much). For 5 items, severity is assessed in terms of numerical frequency, i.e, vomiting/diarrhea (0 times, 1 time, 2 times, 3 times, or 4 or more times); with frequency of sneezing, coughing and coughed up mucus or phlegm evaluated on scale from 0=Never to 4=Always. FLU-PRO total score is computed as mean score across all 32 items and ranges from 0 (symptom free) to 4 (very severe symptoms).

Percentage of participants with significant reduction in influenza symptom severity was defined as time from first dose of investigational product until first of 2 successive recordings in which FLU-PRO total score for each of 2 recordings <= to 1 and all FLU-PRO domain scores is <=1. FLU-PRO assesses 32 influenza symptoms in body areas (domains): Nose, throat, eyes, chest, gastrointestinal, body. Participants rate each symptom on a 5-point ordinal scale, with higher scores indicates more frequent symptom. For 27 of items, scale is as follows: 0 (Not at all), 1 (A little bit), 2 (Somewhat), 3 (Quite a bit), 4 (Very much). For 5 items, severity is assessed as numerical frequency i.e, vomiting or diarrhea (0-4 or more times); with frequency of sneezing, coughing, coughed up mucus or phlegm evaluated on a scale from 0 (Never)-4 (Always). FLU-PRO total score is computed as a mean score across all 32 items comprising instrument and ranges from 0 (symptom free) to 4 (very severe symptoms).