Trial Outcomes & Findings for Efficacy and Safety of Molnupiravir in Healthy Participants Inoculated With Experimental Influenza Virus (MK-4482-019) (NCT NCT05818124)

This was a 2-part study in healthy participants. Part 1 was an open label validation study to confirm that Part 2 can proceed using the same challenge strain.

Before viral inoculation on Day 0, participants had serosuitability confirmed by negative hemagglutination inhibition and quarantined participants underwent additional screening to exclude those with respiratory pathogens, and participants who were excluded at this time did not receive study intervention.

Efficacy and Safety of Molnupiravir in Healthy Participants Inoculated With Experimental Influenza Virus (MK-4482-019)

Infectivity rate was defined as the number of participants with two quantifiable (≥lower limit of quantitation (LLOQ)) influenza challenge virus (A/France/759/21 \[H1N1\] strain) qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples (from nasal wash samples collected twice daily - morning and evening). Infectivity rate based on qRT-PCR in Part 1 participants from baseline (day 1 PM - afternoon) up to planned discharge from quarantine (day 8 AM - post viral inoculation) is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

The number of participants with two quantifiable (≥lower limit of quantitation (LLOQ)) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples (from nasal wash samples collected twice daily - morning and evening). Infectivity rate based on qRT-PCR in Part 1 participants from day 2 PM up to day 8 post viral inoculation is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE is viral challenge-related as determined by the investigator. Number of participants experiencing ≥1 viral challenge-related AE in part 1 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening). PVL as determined by quantitative viral culture (QVC) was measured starting from day 1 PM (baseline) up to planned discharge from quarantine (day 8 AM). PVL of the H1N1 strain was measured by quantitative viral culture (QVC) using TCID50 plaque assay and analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples determined by QVC. H1N1 viral load was computed for each participant from nasopharyngeal samples collected twice daily (morning and evening) from day 2 AM to day 8 AM. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for Molnupiravir Tx and placebo were presented for this endpoint.

QVC-Confirmed Influenza Infection was defined as the number of participants with one quantifiable ≥LLOQ influenza challenge virus measurement from QVC (plaque assay) of nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening). QVC confirmed influenza infection in Part 1 participants from day 1 PM up to day 8 post viral inoculation is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

QVC-Confirmed Influenza Infection was defined as the number of participants with one quantifiable ≥LLOQ influenza challenge virus measurement from QVC (plaque assay) of nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening). QVC confirmed influenza infection in Part 1 participants from day 2 PM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples determined by qRT-PCR. H1N1 viral load was computed for each participant from nasopharyngeal samples collected twice daily (morning and evening) from day 1 PM to day 8 AM. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for part 1 participants were presented for this endpoint.

VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples determined by qRT-PCR. H1N1 viral load was computed for each participant from nasopharyngeal samples collected twice daily (morning and evening) from day 2 PM to day 8 AM. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for part 1 participants were presented for this endpoint. VL-AUC by qRT-PCR in Part 1 participants from day 2 PM up to day 8 is presented.

VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples determined by QVC. H1N1 viral load was computed for each participant from nasophayngeal samples collected twice daily (morning and evening) from day 1 PM to day 8 AM. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for part 1 participants were presented for this endpoint. VL-AUC by QVC in Part 1 participants from day 1 PM up to day 8 is presented.

VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples determined by QVC. H1N1 viral load was computed for each participant from nasopharyngeal samples collected twice daily (morning and evening) from day 1 PM to day 8 AM. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for part 1 participants were presented for this endpoint. VL-AUC by QVC in Part 1 participants from day 2 PM up to day 8 is presented.

PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening) from day 1 PM (baseline) through day 8 AM. PVL of the H1N1 strain was measured by qRT-PCR and analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for part 1 participants were presented for this endpoint.

PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening) from day 2 PM (baseline) through day 8 AM. PVL of the H1N1 strain was measured by qRT-PCR and analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for part 1 participants were presented for this endpoint.

PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening) from day 1 PM (baseline) through day 8 AM. PVL of the H1N1 strain was measured by QVC and analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for part 1 participants were presented for this endpoint.

PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening) from day 2 PM (baseline) through day 8 AM. PVL of the H1N1 strain was measured by QVC and analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for part 1 participants were presented for this endpoint.

Duration in days of quantifiable influenza infection was defined as the time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure (after which there are no more confirmed quantifiable samples) determined by qRT-PCR from nasal wash samples collected twice daily (morning and evening). Duration of Quantifiable Influenza by qRT-PCR in Part 1 participants from day 1 PM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

Duration in days of quantifiable influenza infection was defined as the time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples) determined by qRT-PCR from nasal wash samples collected twice daily (morning and evening). Duration of Quantifiable Influenza by qRT-PCR in Part 1 participants from day 2 PM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

Duration in days of quantifiable influenza infection was defined as the time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples) determined by QVC (plaque assay) from nasal wash samples collected twice daily (morning and evening). Duration of Quantifiable Influenza by QVC in Part 1 participants from day 1 PM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

Duration in days of quantifiable influenza infection was defined as the time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples) determined by QVC (plaque assay) from nasal wash samples collected twice daily (morning and evening). Duration of Quantifiable Influenza by QVC in Part 1 participants from day 2 PM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom was used to obtain a total symptom score (TSS). TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. TSS were used to calculate the AUC for each participant based on the available non-missing calculated total symptom scores between Day 1 until Day 8 (quarantine discharge) using the Trapezoidal rule. TSS-AUC measured from 10 symptoms assessed 3 times daily within the graded symptom scoring was reported. TSS-AUC in Part 1 participants from day 1 AM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom was used to obtain TSS. Total symptom scores (TSS) ranged from 0 to 31, with higher scores indicating greater symptom severity. TSS were used to calculate the AUC for each participant based on the available non-missing calculated total symptom scores between Day 2 until Day 8 (quarantine discharge) using the Trapezoidal rule. TSS-AUC in Part 1 participants from day 2 AM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom was used to obtain a total symptom score (TSS). TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. The highest TSS (defined as the sum of all 10 individual composite symptoms) was summarized by treatment group and analyzed using a linear model with treatment group as a fixed categorical effect. Peak TSS measured from 10 symptoms within the graded symptom scoring system collected 3 times daily was reported. Peak TSS in Part 1 participants from day 1 AM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom was used to obtain TSS. TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. The highest TSS (defined as the sum of all 10 individual composite symptoms) was summarized by treatment group and analyzed using a linear model with treatment group as a fixed categorical effect. Peak TSS measured from 10 symptoms within the graded symptom scoring system collected 3 times daily was reported. Peak TSS in Part 1 participants from day 2 AM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom was used to obtain TSS. TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. Maximum TSS on each day, measured by graded symptom scoring system collected 3 times daily were reported. Daily maximum TSS in Part 1 participants from day 1 AM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from Grade 0 ("no symptoms") to Grade 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from Grade 0 ("no symptoms") to Grade 4 ("symptoms at rest"). Duration of Grade 2 symptoms is defined as the duration in days from the first occurrence of a Grade 2 or higher symptom until the first 24 hours period where no Grade 2 or higher symptoms are recorded. Duration in days of grade ≥2 Symptoms in part 1 participants from day 1 AM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from Grade 0 ("no symptoms") to Grade 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from Grade 0 ("no symptoms") to Grade 4 ("symptoms at rest"). Duration of Grade 2 symptoms is defined as the duration in days from the first occurrence of a Grade 2 or higher symptom until the first 24 hours period where no Grade 2 or higher symptoms are recorded. Duration in days of grade ≥2 Symptoms in part 1 participants from day 2 AM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. Time in days to symptom resolution was defined as the time in days from the beginning of the specified time frame until the beginning of a 24-hour period with no symptoms above the baseline maximum TSS, as measured by graded symptom scoring system collected 3 times daily. Baseline maximum is defined as the maximum TSS on Day -1 (1 day prior to intranasal inoculation). Time in days to symptom resolution in part 1 participants from day 1 AM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. Time in days to symptom resolution was defined as the time (in days) from the beginning of the specified time frame until the beginning of a 24-hour period with no symptoms above the baseline maximum TSS, as measured by graded symptom scoring system collected 3 times daily. Baseline maximum is defined as the maximum TSS on Day -1 (1 day prior to intranasal inoculation). Time in days to symptom resolution in part 1 participants from day 2 AM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom was used to obtain TSS. TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. The highest total symptom score recorded on each day, across the three assessments, for each participant was summarized descriptively by treatment group and assessment day. Time to peak TSS was defined as the time from the assessment at Day 1 AM until the highest total symptom score was calculated. Time to peak TSS in Part 1 participants from day 1 AM up to day 8 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.

VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples determined by qRT-PCR. H1N1 viral load was computed for each participant from nasopharyngeal samples collected twice daily (morning and evening) from day 1 PM to day 8 AM. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples determined by QVC. H1N1 viral load was computed for each participant from nasophayngeal samples collected twice daily (morning and evening) from day 1 PM to day 8 AM. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening) from day 1 PM (baseline) through day 8 AM. PVL of the H1N1 strain was measured by qRT-PCR and analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

The percentage of participants with two quantifiable (≥ LLOQ) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening) within 48 hrs of each other, starting from baseline (Day 1 PM) up to planned discharge from quarantine (Day 8, AM). qRT-PCR-confirmed influenza infection in Part 2 participants from day 1 PM up to day 8 is presented. Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

The percentage of participants with two quantifiable (≥ LLOQ) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening) within 48 h of each other, starting from baseline (Day 1 PM) up to planned discharge from quarantine (Day 8, AM) AND total symptom score (TSS) ≥2 at ≥1 time point following inoculation. Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom is used to obtain TSS. Total symptom scores (TSS) ranged from 0 to 31, with higher scores indicating greater symptom severity. Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

The percentage of participants with two quantifiable (≥ LLOQ) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening) over 2 days AND any symptom of Grade ≥2 at ≥1 timepoint following inoculation. Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from Grade 0 ("no symptoms") to Grade 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from Grade 0 ("no symptoms") to Grade 4 ("symptoms at rest"). Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

Percentage of participants with qRT-PCR-confirmed febrile influenza infection was defined as the percentage of participants with two quantifiable (≥ LLOQ) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening) over 2 days, starting from baseline (Day 1 PM) up to planned discharge from quarantine (Day 8, am) AND a temperature of ≥37.9°C at ≥1 time point following inoculation. Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

Percentage of participants with QVC confirmed influenza infection was defined as the percentage of participants with one quantifiable ≥LLOQ influenza challenge virus measurement from QVC (TCID50 assay) from a nasopharyngeal sample (nasal wash samples collected twice daily - morning and evening). Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

Percentage of participants with QVC (TCID50 assay) confirmed symptomatic influenza infection was defined as the percentage of participants with one quantifiable ≥LLOQ influenza challenge virus measurement from quantitative viral culture from a nasopharyngeal sample (nasal wash samples collected twice daily - morning and evening) AND TSS ≥2 at ≥1 time point following inoculation. Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom is used to obtain a total symptom score (TSS). TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

Duration of quantifiable infection was defined as the time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure (after which there are no more confirmed quantifiable samples) determined by qRT-PCR. Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

Duration of quantifiable infection was defined as the time in days from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples) determined by QVC (TCID50 assay). Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

Time to confirmed negative test was defined as the time in days from baseline until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure (after which there are no more confirmed quantifiable samples) as determined by qRT-PCR from nasal wash samples collected twice daily (morning and evening). Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

Time to confirmed negative test was defined as the time in days from baseline until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure (after which there are no more confirmed quantifiable samples) as determined by QVC (TCID50 assay) from nasal wash samples collected twice daily (morning and evening). Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

Time to PVL was defined as the time in days from the baseline until the PVL measurement as determined by qRT-PCR from nasal wash samples collected twice daily (morning and evening). PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples. Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

Time to PVL was defined as the time in days from the baseline until the PVL measurement as determined by QVC (TCID50 assay) from nasal wash samples collected twice daily (morning and evening). PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples. Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.

VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples determined by qRT-PCR. H1N1 viral load was computed for each participant from nasophayngeal samples collected twice daily (morning and evening) from day 1 PM to day 8 AM. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for Molnupiravir Tx and placebo were presented for this endpoint.

VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples determined by qRT-PCR. H1N1 viral load was computed for each participant from nasophayngeal samples collected twice daily (morning and evening) from day 1 PM to day 8 AM. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for OTV Tx and placebo were presented for this endpoint.

VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples determined by QVC. H1N1 viral load was computed for each participant from nasophayngeal samples collected twice daily (morning and evening) from day 1 PM to day 8 AM. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for Molnupiravir Tx and placebo were presented for this endpoint.

VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples determined by QVC. H1N1 viral load was computed for each participant from nasopharyngeal samples collected twice daily (morning and evening) from day 1 PM to day 8 AM. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for OTV Tx and placebo were presented for this endpoint.

PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening). PVL as determined by quantitative viral culture (QVC) was measured starting from day 1 PM (baseline) up to planned discharge from quarantine (day 8 AM). PVL of the H1N1 strain was measured by quantitative viral culture (QVC) using TCID50 assay and analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for Molnupiravir Tx and placebo were presented for this endpoint.

PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening). PVL as determined by quantitative viral culture (QVC) was measured starting from day 1 PM (baseline) up to planned discharge from quarantine (day 8 AM). PVL of the H1N1 strain was measured by quantitative viral culture (QVC) using TCID50 assay and analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for OTV Tx and placebo were presented for this endpoint.

PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening) from day 1 PM (baseline) through day 8 AM. PVL of the H1N1 strain was measured by qRT-PCR and analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for Molnupiravir Tx and placebo were presented for this endpoint.

PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening) from day 1 PM (baseline) through day 8 AM. PVL of the H1N1 strain was measured by qRT-PCR and analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for OTV Tx and placebo were presented for this endpoint.

Duration of quantifiable infection was defined as the time from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure (after which there are no more confirmed quantifiable samples) determined by qRT-PCR. Per protocol, only data for Molnupiravir Tx, OTV Tx and placebo were presented for this endpoint.

Time from the first quantifiable (≥LLOQ) influenza challenge virus measurement until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure after which there are no more confirmed quantifiable samples) determined by QVC (TCID50 assay). Per protocol, only data for Molnupiravir Tx, OTV Tx and placebo were presented for this endpoint.

Time to confirmed negative test was defined as the time in days from baseline until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure (after which there are no more confirmed quantifiable samples) as determined by qRT-PCR from nasal wash samples collected twice daily (morning and evening). Per protocol, only data for Molnupiravir Tx and placebo were presented for this endpoint.

Time to confirmed negative test was defined as the time in days from baseline until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure (after which there are no more confirmed quantifiable samples) as determined by qRT-PCR from nasal wash samples collected twice daily (morning and evening). Per protocol, only data for OTV Tx and placebo were presented for this endpoint.

Time to confirmed negative test was defined as the time in days from baseline until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure (after which there are no more confirmed quantifiable samples) as determined by QVC (TCID50 assay) from nasal wash samples collected twice daily (morning and evening). Per protocol, only data for Molnupiravir Tx and placebo were presented for this endpoint.

Time to confirmed negative test was defined as the time from baseline until the first confirmed unquantifiable (\<LLOQ detected or not detected) assessment after the peak measure (after which there are no more confirmed quantifiable samples) as determined by QVC (TCID50 assay) from nasal wash samples collected twice daily (morning and evening). Per protocol, only data for OTV Tx and placebo were presented for this endpoint.

Time to PVL was defined as the time in days from the baseline until the PVL measurement as determined by qRT-PCR from nasal wash samples collected twice daily (morning and evening). PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples. Per protocol, only data for Molnupiravir Tx, OTV Tx and placebo were presented for this endpoint.

Time to PVL was defined as the time in days from the baseline until the PVL measurement as determined by QVC (TCID50 assay) from nasal wash samples collected twice daily (morning and evening). PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples. Per protocol, only data for Molnupiravir Tx, OTV Tx and placebo were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom was used to obtain TSS. Total symptom scores (TSS) ranged from 0 to 31, with higher scores indicating greater symptom severity. TSS were used to calculate the AUC for each participant based on the available non-missing calculated total symptom scores between Day 2 until Day 8 (quarantine discharge) using the Trapezoidal rule. TSS-AUC measured from 10 symptoms assessed 3 times daily within the graded symptom scoring was reported. Per protocol, only Molnupiravir Tx and placebo were included in the model.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). Total symptom scores (TSS) ranged from 0 to 31, with higher scores indicating greater symptom severity. For each participant, the sum of grade values for each symptom was used to obtain a total symptom score (TSS). TSS were used to calculate the AUC for each participant based on the available non-missing calculated total symptom scores between Day 2 until Day 8 (quarantine discharge) using the Trapezoidal rule. TSS-AUC was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only OTV Tx and placebo were included in the model. TSS-AUC measured from 10 symptoms within the graded symptom scoring was reported.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom was used to obtain TSS. TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. The highest TSS (defined as the sum of all 10 individual composite symptoms) was summarized by treatment group and analyzed using a linear model with treatment group as a fixed categorical effect. Peak TSS measured from 10 symptoms within the graded symptom scoring system collected 3 times daily was reported. Per protocol, only Molnupiravir Tx and placebo were reported for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom was used to obtain TSS. TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. The highest TSS (defined as the sum of all 10 individual composite symptoms) was summarized by treatment group and analyzed using a linear model with treatment group as a fixed categorical effect. Peak TSS measured from 10 symptoms within the graded symptom scoring system collected 3 times daily was reported was reported. Per protocol, only OTV Tx and Placebo were reported for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. For each participant, the sum of grade values for each symptom was used to obtain TSS. Maximum TSS on each day, measured by graded symptom scoring system collected 3 times daily were reported. Per protocol, only Molnupiravir Tx, OTV Tx and Placebo were reported for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. For each participant, the sum of grade values for each symptom was used to obtain TSS. Maximum TSS on each day, measured by graded symptom scoring system collected 3 times daily were reported. Per protocol, only Molnupiravir PEP and Placebo were included in the model.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from Grade 0 ("no symptoms") to Grade 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from Grade 0 ("no symptoms") to Grade 4 ("symptoms at rest"). Duration in days of Grade ≥2 symptoms was defined as the duration of time in days from the first occurrence of any symptom assigned Grade 2 or higher, to the beginning of the first 24-hour period without any symptom assigned Grade 2 or higher, after the peak TSS. Per protocol, Molnupiravir Tx, OTV Tx and Placebo were included in the analysis.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. Time in days to symptom resolution was defined as the time in days until the beginning of a 24-hour period with no symptoms above the baseline maximum TSS, as measured by graded symptom scoring system collected 3 times daily. Baseline maximum is defined as the maximum TSS on Day -1 (1 day prior to intranasal inoculation). Per protocol, only Molnupiravir Tx, OTV Tx and Placebo were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom was used to obtain TSS. TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. The highest total symptom score recorded on each day, across the three assessments, for each participant was summarized descriptively by treatment group and assessment day. Time to peak TSS was defined as the time from the assessment at Day 2 AM until the highest total symptom score was calculated. Per protocol, only Molnupiravir Tx, OTV Tx and Placebo were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom was used to obtain TSS. Total symptom scores (TSS) ranged from 0 to 31, with higher scores indicating greater symptom severity. TSS were used to calculate the AUC for each participant based on the available non-missing calculated total symptom scores between Day 1 until Day 8 (quarantine discharge) using the Trapezoidal rule. Per protocol, only Molnupiravir PEP and Placebo was included in the model.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom is used to obtain TSS. TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. The highest TSS (defined as the sum of all 10 individual composite symptoms) was summarized by treatment group and analyzed using a linear model with treatment group as a fixed categorical effect. Peak TSS measured from 10 symptoms within the graded symptom scoring system collected 3 times daily was reported. Per protocol, only Molnupiravir PEP and Placebo were presented for this endpoint.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from Grade 0 ("no symptoms") to Grade 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from Grade 0 ("no symptoms") to Grade 4 ("symptoms at rest"). Duration of Grade 2 symptoms is defined as the duration in days from the first occurrence of a Grade 2 or higher symptom until the first 24 hours period where no Grade 2 or higher symptoms are recorded. Per protocol, Molnupiravir PEP and Placebo were included in the analysis.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. Time in days to symptom resolution was defined as the time in days from the beginning of the specified time frame until the beginning of a 24-hour period with no symptoms above the baseline maximum TSS, as measured by graded symptom scoring system collected 3 times daily. Baseline maximum is defined as the maximum TSS on Day -1 (1 day prior to intranasal inoculation). Per protocol, only Molnupiravir PEP and Placebo are reported.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("no symptoms") to 3 ("bothersome and interferes with activities"), with the exception of "shortness of breath" symptom which was scored from 0 ("no symptoms") to 4 ("symptoms at rest"). For each participant, the sum of grade values for each symptom is used to obtain TSS. TSS ranged from 0 to 31, with higher scores indicating greater symptom severity. Time in days to peak TSS was defined as the time from baseline to the time of peak TSS measured by the graded symptom scoring system collected 3 times daily. Per protocol, only Molnupiravir PEP and Placebo are reported.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with one or more AEs are presented. Per protocol, only Molnupiravir PEP and Molnupiravir Tx are reported.

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued study treatment due to an AE are presented. Per protocol, only Molnupiravir PEP and Molnupiravir Tx are reported.

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE is viral challenge-related as determined by investigator. The number of participants with one or more viral challenge-related AEs are presented.

Concomitant medications were defined as any prescription medications, over the counter drugs or dietary supplements that a participant happened to be taking while on study, in addition to molnupiravir. The number of participants who use at least 1 concomitant medication from viral challenge (Day 0) through Day 28 were reported. Per protocol, only Molnupiravir PEP, Molnupiravir Tx, OTV Tx and Placebo were reported.

NHC is the pharmacologically active moiety of molnupiravir (MK-4482) and therefore its primary pharmacokinetic measure. Cmax was defined as the peak concentration of NHC over the dosing interval. Plasma samples were collected at multiple time points pre-and post-administration and used to determine Cmax following oral administration of Molnupiravir. Per protocol, Cmax for only Molnupiravir PEP and Molnupiravir Tx were reported.

NHC is the pharmacologically active moiety of molnupiravir (MK-4482) and therefore its primary pharmacokinetic measure. Tmax was defined as the time to peak concentration. Plasma samples were collected at multiple time points pre-and post-administration and used to determine Tmax following oral administration of Molnupiravir. Per protocol, Tmax for only Molnupiravir PEP and Molnupiravir Tx were reported.

NHC is the pharmacologically active moiety of molnupiravir (MK-4482) and therefore its primary pharmacokinetic measure. Plasma samples were collected at multiple time points pre-and post-administration and used to determine the area under the plasma concentration curve from time 0 to 12 hours (AUC0-12) following oral administration of Molnupiravir. Per protocol, AUC0-12 for only Molnupiravir PEP and Molnupiravir Tx were reported.

NHC is the pharmacologically active moiety of molnupiravir (MK-4482) and therefore its primary pharmacokinetic measure. AUC0-last is a measure of total exposure to Molnupiravir in plasma from the start of dosing to the time of the last quantifiable (\<LLOQ\]) sample. Per protocol, AUC0-Last for only Molnupiravir PEP and Molnupiravir Tx were reported.

NHC is the pharmacologically active moiety of molnupiravir (MK-4482) and therefore its primary pharmacokinetic measure. The trough concentration (Ctrough) was defined as the lowest concentration before the next dose. Plasma samples were collected at multiple time points pre-and post-administration and used to determine Ctrough. Per protocol, Ctrough for only Molnupiravir PEP and Molnupiravir Tx were reported.

NHC is the pharmacologically active moiety of molnupiravir (MK-4482) and therefore its primary pharmacokinetic measure. t1/2 is the amount of time required to clear 50% of NHC following the oral administration of Molnupiravir. Per protocol, t1/2 for only Molnupiravir PEP and Molnupiravir Tx were reported.