Trial Outcomes & Findings for Respiratory Syncytial Virus (RSV) Human Challenge Study of Molnupiravir in Healthy Participants (MK-4482-017) (NCT NCT05559905)

NCT ID: NCT05559905

Last Updated: 2025-07-18

Results Overview

PVL was defined as the maximum viral load during a specified time period. PVL determined by viral quantitative culture (plaque assay) was measured from Day 2 up to Day 12 (end of participant quarantine). PVL (on the log10 scale) of RSV A Memphis 37b determined by viral quantitative culture (plaque assay) between Day 2 and Day 12 am after intranasal inoculation (Day 0) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 116 participants
• Primary outcome timeframe: From Day 2 up to Day 12
• Results posted on: 2025-07-18

Participant Flow

Participants in the lower quartile for immunogenicity to the RSV A Memphis 37b as determined by a serum microneutralization assay were screened for eligibility for this study.

Participant milestones

Measure	Panel A: Molnupiravir Prophylaxis Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel B: Molnupiravir Triggered Treatment Participants received placebo on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued to receive placebo until testing positive for RSV. Participants then received 800 mg of molnupiravir every 12 hours for 5 days.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Overall Study STARTED	40	36	40
Overall Study Started Study Medication	39	36	40
Overall Study COMPLETED	38	36	40
Overall Study NOT COMPLETED	2	0	0

Reasons for withdrawal

Measure	Panel A: Molnupiravir Prophylaxis Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel B: Molnupiravir Triggered Treatment Participants received placebo on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued to receive placebo until testing positive for RSV. Participants then received 800 mg of molnupiravir every 12 hours for 5 days.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Overall Study Withdrawal by Subject	1	0	0
Overall Study Not Reported	1	0	0

Baseline Characteristics

Respiratory Syncytial Virus (RSV) Human Challenge Study of Molnupiravir in Healthy Participants (MK-4482-017)

Baseline characteristics by cohort

Measure	Panel A: Molnupiravir Prophylaxis n=40 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel B: Molnupiravir Triggered Treatment n=36 Participants Participants received placebo on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued to receive placebo until testing positive for RSV. Participants then received 800 mg of molnupiravir every 12 hours for 5 days.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Total n=116 Participants Total of all reporting groups
Age, Continuous	26.6 Years STANDARD_DEVIATION 5.4 • n=5 Participants	28.7 Years STANDARD_DEVIATION 8.2 • n=7 Participants	26.8 Years STANDARD_DEVIATION 6.9 • n=5 Participants	27.3 Years STANDARD_DEVIATION 6.9 • n=4 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	13 Participants n=7 Participants	17 Participants n=5 Participants	45 Participants n=4 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	23 Participants n=7 Participants	23 Participants n=5 Participants	71 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=5 Participants	35 Participants n=7 Participants	40 Participants n=5 Participants	115 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	15 Participants n=4 Participants
Race (NIH/OMB) White	32 Participants n=5 Participants	25 Participants n=7 Participants	29 Participants n=5 Participants	86 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel A or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, and had available PVL viral quantitative culture data. Per protocol, Panel B was not included in this analysis.

PVL was defined as the maximum viral load during a specified time period. PVL determined by viral quantitative culture (plaque assay) was measured from Day 2 up to Day 12 (end of participant quarantine). PVL (on the log10 scale) of RSV A Memphis 37b determined by viral quantitative culture (plaque assay) between Day 2 and Day 12 am after intranasal inoculation (Day 0) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=32 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=34 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel A vs Panel C: Peak Viral Load (PVL) Determined by Viral Quantitative Culture	2.55 log10 plaque forming units (PFU)/mL Interval 1.81 to 3.3	2.84 log10 plaque forming units (PFU)/mL Interval 2.12 to 3.57	—

PRIMARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel B or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, were determined to be RSV infected, and had available VL-AUC viral quantitative culture data. Per protocol, Panel A was not included in this analysis.

VL-AUC between Day 2 and Day 12 after intranasal inoculation (Day 0) was computed for each participant, based on RSV viral load determined by viral quantitative culture (plaque assay) from nasal wash samples collected twice daily (morning and evening). In order to calculate the AUC, the actual time that the assessment was collected was used within the AUC calculation. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only Panel B (treatment) and Panel C (placebo) were included in the model. For both panels, only the participants with RSV infection were included.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=20 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=25 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel B vs. Panel C: Area Under the Viral Load-time Curve (VL-AUC) Determined by Viral Quantitative Culture	7.02 day*log10 PFU/mL Interval 3.91 to 10.14	9.72 day*log10 PFU/mL Interval 6.93 to 12.5	—

SECONDARY outcome

Timeframe: From Day -1 up to Day 28

Population: All participants who received at least one dose of treatment.

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 who experienced an AE is reported.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=39 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=36 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
All Panels: Number of Participants Who Experienced ≥1 Adverse Event (AE)	13 Participants	15 Participants	13 Participants

SECONDARY outcome

Timeframe: From Day -1 up to Day 28

Population: All participants who received at least one dose of treatment.

An SAE is any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires hospitalization or prolongs existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly or birth defect; or is another important medical event such as invasive/malignant cancers or substance abuse/dependency. The number of participants who experienced an SAE is reported.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=39 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=36 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
All Panels: Number of Participants Who Experienced ≥1 Serious AE (SAE)	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 0 up to Day 28

Population: All participants who received at least one dose of treatment.

A viral challenge-related AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that was considered related to the viral challenge (inoculation). The number of participants who experienced AEs related to the viral challenge from viral challenge (Day 0) up to the Day 28 follow-up is reported.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=39 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=36 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related AE	1 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: From Day 0 up to Day 28

Population: All participants who received at least one dose of treatment.

A viral challenge-related SAE was defined as any untoward medical occurrence that, at any dose, resulted in death; was life-threatening; required hospitalization or prolonged existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly or birth defect; or was another important medical event, that was considered related to the viral challenge (inoculation). The number of participants who experienced SAEs related to the viral challenge from viral challenge (Day 0) up to the Day 28 follow-up is reported.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=39 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=36 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related SAE	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Day 0 up to Day 28

Population: All participants who received at least one dose of treatment.

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 using concomitant medications from viral challenge (Day 0) up through Day 28 is reported.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=39 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=36 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
All Panels: Number of Participants Using Concomitant Medications From Viral Challenge Through Day 28	6 Participants	7 Participants	7 Participants

SECONDARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel A or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, and had available VL-AUC viral quantitative culture data. Per protocol, Panel B was not included in the analysis.

VL-AUC between Day 2 and Day 12 after intranasal inoculation (Day 0) was computed for each participant, based on RSV viral load determined by viral quantitative culture (plaque assay) from nasal wash samples collected twice daily (morning and evening). In order to calculate the AUC, the actual time that the assessment was collected was used within the AUC calculation. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=32 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=34 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel A vs. Panel C: VL-AUC Determined by Viral Quantitative Culture	7.56 day*log10 PFU/mL Interval 4.95 to 10.17	8.17 day*log10 PFU/mL Interval 5.64 to 10.7	—

SECONDARY outcome

Timeframe: Day 2 up through Day 12

Population: All randomized participants in Panel A or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into and who received the viral inoculation. Per protocol, Panel B was not included in the analysis.

VL-AUC between Day 2 and Day 12 after intranasal inoculation (Day 0) was computed for each participant, based on RSV viral load determined by qRT-PCR from nasal wash samples collected twice daily (morning and evening). In order to calculate the AUC, the actual time that the assessment was collected was used within the AUC calculation. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=39 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel A vs. Panel C: VL-AUC Determined by Real-time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR)	17.62 day*log10 copies/mL Interval 11.7 to 25.53	19.54 day*log10 copies/mL Interval 13.7 to 25.39	—

SECONDARY outcome

Timeframe: Day 2 up through Day 12

Population: All randomized participants in Panel A or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, and had available PVL qRT-PCR data. Per protocol, Panel B was not included in this analysis.

PVL was defined as the maximum viral load during a specified time period. PVL as determined by qRT-PCR was measured starting from Day 2 up to planned discharge from quarantine (Day 12 am). Nasal wash samples were collected and tested for RSV viral load by qRT-PCR twice daily from Day 2 through Day 11. A single nasal wash sample for RSV viral load by qRT-PCR was collected on Day 12. PVL by qRT-PCR was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=39 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel A vs. Panel C: PVL Determined by qRT-PCR	4.66 day*log10 copies/mL Interval 3.66 to 5.66	4.80 day*log10 copies/mL Interval 3.81 to 5.79	—

SECONDARY outcome

Timeframe: From Day -1 up to Day 12

Population: All randomized participants in Panel A or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, and had available TSS data. Per protocol, Panel B was not included in this 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"). 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 12 (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 Panel A (prophylaxis) and Panel C (placebo) were included in the model. TSS-AUC measured from 10 symptoms within the graded symptom scoring was reported.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel A vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores (TSS-AUC)	7.5 Scores on a Scale*Days Interval 4.18 to 10.81	9.59 Scores on a Scale*Days Interval 6.36 to 12.82	—

SECONDARY outcome

Timeframe: Baseline (Day -1) and up to Day 12

Population: All randomized participants in Panel A or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, and had available TSS data. Per protocol, Panel B was not included in this analysis.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("absence") 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. 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 12 (quarantine discharge) using the Trapezoidal rule. TSS-AUC-CFB was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model. TSS-AUC-CFB was defined as the change from baseline in TSS-AUC from Day -1 up to Day 12. TSS-AUC-CFB measured from 10 symptoms within the graded symptom scoring was reported.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel A vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores Change From Baseline (TSS-AUC-CFB)	6.84 Scores on a Scale*Days Interval 4.03 to 9.66	8.66 Scores on a Scale*Days Interval 5.92 to 11.41	—

SECONDARY outcome

Timeframe: From Day -1 up to Day 12

Population: All randomized participants in Panel A or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, and had available TSS data. Per protocol, Panel B was not included in this 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. 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. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model. Peak TSS measured from 10 symptoms within the graded symptom scoring was reported.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel A vs. Panel C: Peak Total Symptom Scores	2.74 Scores on a Scale Interval 1.85 to 3.62	3.20 Scores on a Scale Interval 2.33 to 4.07	—

SECONDARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel A or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, and had available TSS data. Per protocol, Panel B was not included in this 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. 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. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the analysis. Peak daily sums of symptom score measured from 10 symptoms within the graded symptom scoring were reported for Panels A and C.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel A vs. Panel C: Peak Daily Symptom Score Day 2	0.8 Scores on a Scale Standard Deviation 1.13	1.1 Scores on a Scale Standard Deviation 1.36	—
Panel A vs. Panel C: Peak Daily Symptom Score Day 3	0.6 Scores on a Scale Standard Deviation 0.88	0.9 Scores on a Scale Standard Deviation 1.24	—
Panel A vs. Panel C: Peak Daily Symptom Score Day 4	0.7 Scores on a Scale Standard Deviation 0.98	1.0 Scores on a Scale Standard Deviation 1.56	—
Panel A vs. Panel C: Peak Daily Symptom Score Day 5	0.8 Scores on a Scale Standard Deviation 1.22	1.4 Scores on a Scale Standard Deviation 1.90	—
Panel A vs. Panel C: Peak Daily Symptom Score Day 6	1.2 Scores on a Scale Standard Deviation 1.41	2.1 Scores on a Scale Standard Deviation 2.82	—
Panel A vs. Panel C: Peak Daily Symptom Score Day 7	1.4 Scores on a Scale Standard Deviation 1.52	1.9 Scores on a Scale Standard Deviation 3.02	—
Panel A vs. Panel C: Peak Daily Symptom Score Day 8	1.7 Scores on a Scale Standard Deviation 2.24	1.8 Scores on a Scale Standard Deviation 2.22	—
Panel A vs. Panel C: Peak Daily Symptom Score Day 9	1.4 Scores on a Scale Standard Deviation 1.67	1.3 Scores on a Scale Standard Deviation 1.90	—
Panel A vs. Panel C: Peak Daily Symptom Score Day 10	0.9 Scores on a Scale Standard Deviation 1.83	0.8 Scores on a Scale Standard Deviation 1.58	—
Panel A vs. Panel C: Peak Daily Symptom Score Day 11	0.7 Scores on a Scale Standard Deviation 1.21	0.5 Scores on a Scale Standard Deviation 1.02	—
Panel A vs. Panel C: Peak Daily Symptom Score Day 12	0.3 Scores on a Scale Standard Deviation 0.76	0.3 Scores on a Scale Standard Deviation 0.56	—

SECONDARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel A or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, and had available RSV infection qRT-PCR data. Per protocol, Panel B was not included in this analysis.

A qRT-PCR-confirmed RSV infection was defined as 2 quantifiable (≥ lower limit of quantification [LLOQ]) qRT-PCR measurements (reported on 2 or more independent samples over 2 days), from Day 2 up to Day 12. The number of participants with qRT-PCR-confirmed RSV infection is reported. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the analysis.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel A vs. Panel C: Percentage of Participants With Respiratory Syncytial Virus (RSV) Infection Based on qRT-PCR	68.42 Percentage of Participants Interval 51.35 to 82.5	65.00 Percentage of Participants Interval 48.32 to 79.37	—

SECONDARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel A or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, and had at least 1 available positive RSV cell culture measurement data. Per protocol, Panel B was not included in this analysis.

RSV infection based on cell culture measurement was defined as at least one positive (≥ LLOQ) cell culture measurement in nasal swab samples. The percentage of participants with at least one positive (≥ LLOQ) cell culture measurement in nasal swab samples is reported. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the analysis.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel A vs. Panel C: Percentage of Participants With RSV Infection Based on Cell Culture Measurement of Nasal Sample	57.89 Percentage of Participants Interval 40.82 to 73.69	55.00 Percentage of Participants Interval 38.49 to 70.74	—

SECONDARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel A or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, and had available RSV symptomatic infection data. Per protocol, Panel B was not included in this analysis.

Symptomatic RSV infection was defined as 2 quantifiable (≥LLOQ) qRT-PCR measurements reported on 2 or more days and either one or more clinical symptoms of any grade from two different categories in the symptom scoring system (upper respiratory, lower respiratory, systemic) or one grade 2 symptom from any category. The percentage of participants with qRT-PCR-confirmed symptomatic RSV infection is reported. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the analysis.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Symptomatic RSV Infection	47.37 Percentage of Participants Interval 30.98 to 64.18	50.00 Percentage of Participants Interval 33.8 to 66.2	—

SECONDARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel A or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, and had available RSV symptomatic infection data. Per protocol, Panel B was not included in this analysis.

Moderately severe symptomatic RSV infection was defined as 2 quantifiable (≥LLOQ) qRT-PCR measurements reported on 2 or more consecutive days and any symptom scores of grade ≥2 at a single time point. The percentage of participants with qRT-PCR-confirmed moderately severe symptomatic RSV infection is reported. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the analysis.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Moderately Severe Symptomatic RSV Infection	26.32 Percentage of Participants Interval 13.4 to 43.1	42.50 Percentage of Participants Interval 27.04 to 59.11	—

SECONDARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel A or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, and had available RSV symptomatic infection data. Per protocol, Panel B was not included in this analysis.

Culture-confirmed symptomatic RSV infection was defined by 1 quantifiable (≥LLOQ) cell culture measurement from Day 2 up to Day 12, and either one or more clinical symptoms of any grade from two different categories in the symptom scoring system (upper respiratory, lower respiratory, systemic) or one grade 2 symptom from any category. The percentage of participants with culture confirmed symptomatic RSV infection is reported. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the analysis.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=40 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel A vs. Panel C: Percentage of Participants With Culture-Confirmed Symptomatic RSV Infection	42.11 Percentage of Participants Interval 26.31 to 59.18	45.00 Percentage of Participants Interval 29.26 to 61.51	—

SECONDARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel B or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, were determined to be RSV infected, and had available PVL viral quantitative culture data. Per protocol, Panel A was not included in this analysis.

PVL was defined as the maximum viral load during a specified time period. PVL as determined by viral quantitative culture was measured starting from Day 2 up to planned discharge from quarantine (Day 12 am). PVL (on the log10 scale) of RSV A Memphis 37b determined by viral quantitative culture (plaque assay) between Day 2 and Day 12 am after intranasal inoculation (Day 0) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only Panel B (treatment) and Panel C (placebo) are included in the model. For both panels, only the participants with RSV infection were included in the analysis.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=20 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=25 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel B vs. Panel C: PVL Determined by Viral Quantitative Culture	2.85 log10 PFU/mL Interval 1.96 to 3.74	3.53 log10 PFU/mL Interval 2.74 to 4.33	—

SECONDARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel B or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, were determined to be RSV infected, and had available negative test by viral quantitative culture data. Per protocol, Panel A was not included in this analysis.

The time to negative test was defined as length of time in days between the date and time of the first MK-4482 administration to the date and time of first confirmed negative test after peak viral culture measurement. A negative test is a result below the low limit of quantification (LLOQ) by viral quantitative culture (plaque assay). The Kaplan-Meier estimate median in days is reported. Per protocol, only Panel B (treatment) and Panel C (placebo) are included in the model. For both panels, only the participants with RSV infection were included in the analysis.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=16 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=19 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel B vs. Panel C: Time to Negative Test by Viral Quantitative Culture	5.0 Days Interval 4.0 to N/A: Upper limit of 95% confidence interval was not reached due to insufficient number of events (i.e. participants with negative test).	5.0 Days Interval 4.0 to 6.0	—

SECONDARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel B or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, were determined to be RSV infected, and had available VL-AUC qRT-PCR data. Per protocol, Panel A was not included in this analysis.

VL-AUC between Day 2 and Day 12 after intranasal inoculation (Day 0) was computed for each participant, based on RSV viral load determined by qRT-PCR from nasal wash samples collected twice daily (morning and evening). In order to calculate the AUC, the actual time that the assessment was collected was used within the AUC calculation. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only Panel B (treatment) and Panel C (placebo) are included in the model. For both panels, only the participants with RSV infection were included in the analysis.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=23 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=26 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel B vs. Panel C: VL-AUC Determined by qRT-PCR	20.58 days*log10 copies/mL Interval 13.0 to 28.16	26.51 days*log10 copies/mL Interval 19.38 to 33.64	—

SECONDARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel B or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, were determined to be RSV infected, and had available PVL qRT-PCR data. Per protocol, Panel A was not included in this analysis.

PVL was defined as the maximum viral load during a specified time period. PVL as determined by qRT-PCR was measured starting from Day 2 up to planned discharge from quarantine (Day 12 am). Nasal wash samples were collected and tested for RSV viral load by qRT-PCR twice daily from Day 2 through Day 11. A single nasal wash sample for RSV viral load by qRT-PCR was collected on Day 12. PVL by qRT-PCR were analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only Panel B (treatment) and Panel C (placebo) are included in the model. For both panels, only the participants with RSV infection were included in the analysis.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=23 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=26 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel B vs. Panel C: PVL Determined by qRT-PCR	5.43 log10 PFU/mL Interval 4.3 to 6.56	6.02 log10 PFU/mL Interval 4.95 to 7.08	—

SECONDARY outcome

Timeframe: From Day 2 up to Day 12

Population: All randomized participants in Panel B or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, were determined to be RSV infected, and had available negative test qRT-PCR data. Per protocol, Panel A was not included in this analysis.

The time (days) to confirmed negative test by qRT-PCR was defined as the length of time between the date and time of the first investigational medicinal product (IMP) administration to the date and time of first confirmed undetectable (<LLOQ) qRT-PCR result after peak qRT-PCR measurement. The time to negative test starting at Day 2 to first confirmed undetectable (<LLOQ) assessment after peak measure is reported. Per protocol, only Panel B (treatment) and Panel C (placebo) are included in the model. For both panels, only the participants with RSV infection were included in the analysis.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=20 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=24 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel B vs. Panel C: Time to Negative Test by qRT-PCR	NA Days Interval 6.0 to N/A: Upper limit of 95% confidence interval was not reached due to insufficient number of events (i.e. participants with negative test).	9.0 Days Interval 7.0 to N/A: Upper limit of 95% confidence interval was not reached due to insufficient number of events (i.e. participants with negative test).	—

SECONDARY outcome

Timeframe: From Day -1 up to Day 12

Population: All randomized participants in Panel B or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, were determined to be RSV infected, and had available TSS data. Per protocol, Panel A was not included in this 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"). 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 12 (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 Panel B and Panel C are included in the model, and only participants with RSV infection were included in the analysis. TSS-AUC measured from 10 symptoms within the graded symptom scoring was reported.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=23 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=26 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel B vs. Panel C: TSS-AUC	4.74 Scores on a Scale*Days Interval 1.76 to 7.72	6.57 Scores on a Scale*Days Interval 3.76 to 9.37	—

SECONDARY outcome

Timeframe: Baseline (Day -1) and up to Day 12

Population: All randomized participants in Panel B or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, were determined to be RSV infected, and had available TSS data. Per protocol, Panel A was not included in this analysis.

Participants used a symptom diary card to record the daily severity of 10 clinical symptoms on a scale ranging from 0 ("absence") 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. 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 12 (quarantine discharge) using the Trapezoidal rule. TSS-AUC-CFB was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only Panel B and Panel C are included in the model, and only the participants with RSV infection were included in the analysis. TSS-AUC-CFB was defined as the change from baseline in TSS-AUC from Day -1 up to Day 12. TSS-AUC-CFB measured from 10 symptoms within the graded symptom scoring was reported.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=23 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=26 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel B vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores Change From Baseline (TSS-AUC-CFB)	2.60 Scores on a Scale*Days Interval -1.02 to 6.23	2.74 Scores on a Scale*Days Interval -0.67 to 6.15	—

SECONDARY outcome

Timeframe: From Day -1 up to Day 12

Population: All randomized participants in Panel B or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, were determined to be RSV infected, and had available TSS data. Per protocol, Panel A was not included in this 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. The highest total symptom score (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 was reported for Panels B and C. Per protocol, only Panel B (treatment) and Panel C (placebo) are included in the model. For both panels, only the participants with RSV infection were included in the analysis.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=23 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=26 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel B vs. Panel C: Peak TSS	3.00 Score on a Scale Interval 1.61 to 4.39	3.62 Score on a Scale Interval 2.31 to 4.92	—

SECONDARY outcome

Timeframe: From Day -1 up to Day 12

Population: All randomized participants in Panel B or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, were determined to be RSV infected, and had available TSS data. Per protocol, Panel A was not included in this 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. 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. Peak daily sums of symptom score measured from 10 symptoms within the graded symptom scoring were reported for Panels B and C. Per protocol, only Panel B (treatment) and Panel C (placebo) are included in the model. For both panels, only the participants with RSV infection were included in the analysis.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=23 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=26 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel B vs. Panel C: Peak Daily Symptom Score Day 1	0.6 Score on a Scale Standard Deviation 0.90	1.4 Score on a Scale Standard Deviation 1.6	—
Panel B vs. Panel C: Peak Daily Symptom Score Day 2	1.3 Score on a Scale Standard Deviation 1.89	2.0 Score on a Scale Standard Deviation 2.18	—
Panel B vs. Panel C: Peak Daily Symptom Score Day 3	1.5 Score on a Scale Standard Deviation 1.68	2.3 Score on a Scale Standard Deviation 2.31	—
Panel B vs. Panel C: Peak Daily Symptom Score Day 4	2.1 Score on a Scale Standard Deviation 2.44	2.7 Score on a Scale Standard Deviation 3.26	—
Panel B vs. Panel C: Peak Daily Symptom Score Day 5	1.8 Score on a Scale Standard Deviation 2.67	2.5 Score on a Scale Standard Deviation 3.37	—
Panel B vs. Panel C: Peak Daily Symptom Score Day 6	1.4 Score on a Scale Standard Deviation 2.29	1.5 Score on a Scale Standard Deviation 2.06	—
Panel B vs. Panel C: Peak Daily Symptom Score Day 7	0.7 Score on a Scale Standard Deviation 1.33	1.2 Score on a Scale Standard Deviation 2.12	—
Panel B vs. Panel C: Peak Daily Symptom Score Day 8	0.5 Score on a Scale Standard Deviation 1.08	0.7 Score on a Scale Standard Deviation 1.48	—
Panel B vs. Panel C: Peak Daily Symptom Score Day 9	1.0 Score on a Scale Standard Deviation 1.26	0.8 Score on a Scale Standard Deviation 1.42	—
Panel B vs. Panel C: Peak Daily Symptom Score Day 10	0.7 Score on a Scale Standard Deviation 1.15	0.5 Score on a Scale Standard Deviation 1.00	—
Panel B vs. Panel C: Peak Daily Symptom Score Day 11	1.0 Score on a Scale Standard Deviation 1.41	0.0 Score on a Scale Standard Deviation 0	—

SECONDARY outcome

Timeframe: From Day -1 up to Day 12

Population: All randomized participants in Panel B or Panel C who received 1 dose of the correct clinical material corresponding to the treatment group the participants were randomized into, who received the viral inoculation, were determined to be RSV infected, and had available symptom resolution data. Per protocol, Panel A was not included in this 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. Symptom resolution was defined as a participant scoring 0 for the total symptom score for a 24-hour period (e.g., a minimum of three consecutive symptom diary cards, each with a score of 0 after their peak symptom score. The time in days to symptom resolution by treatment group, as measured from 10 symptoms within the graded daily symptom scoring system, was reported. Per protocol, only Panel B (treatment) and Panel C (placebo) are included in the model. For both panels, only the participants with RSV infection were included in the analysis.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=17 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=18 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panel B vs. Panel C: Time to Symptom Resolution	6.0 Days Interval 4.0 to 8.0	8.5 Days Interval 6.0 to N/A: Upper limit of 95% confidence interval was not reached due to insufficient number of events (i.e. participants with negative test).	—

SECONDARY outcome

Timeframe: Day -1: Predose and 12 hours postdose; Days 2, 5, and 6: 12 hours postdose; Days 4 and 7: predose and 0.5, 1.5, 4, 8, and 12 hours postdose

Population: All randomized participants in Panels A and B who received at least one dose of molnupiravir and received viral inoculation, with available measurements and without important protocol deviations. Per protocol, Panel C participants receiving placebo were not included in the analysis.

NHC is the pharmacologically active moiety of molnupiravir 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. Cmax of NHC was reported for participants receiving molnupiravir in Panels A and B.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=36 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panels A & B: Maximum Plasma Concentration (Cmax) of N-Hydroxycytidine (NHC)	3640 ng/mL Geometric Coefficient of Variation 33.5	3010 ng/mL Geometric Coefficient of Variation 111.5	—

SECONDARY outcome

Timeframe: Day -1: Predose and 12 hours postdose; Days 2, 5, and 6: 12 hours postdose; Days 4 and 7: predose and 0.5, 1.5, 4, 8, and 12 hours postdose

Population: All randomized participants in Panels A and B who received at least one dose of molnupiravir and received viral inoculation, with available measurements and without important protocol deviations. Per protocol, Panel C participants receiving placebo were not included in the analysis.

NHC is the pharmacologically active moiety of molnupiravir 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. Tmax of NHC was reported for participants receiving molnupiravir in Panels A and B.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=36 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panels A & B: Time to Maximum Plasma Concentration (Tmax) of NHC	1.47 hr Interval 1.33 to 1.97	1.48 hr Interval 0.0 to 2.13	—

SECONDARY outcome

Timeframe: Day -1: Predose and 12 hours postdose; Days 2, 5, and 6: 12 hours postdose; Days 4 and 7: predose and 0.5, 1.5, 4, 8, and 12 hours postdose

Population: All randomized participants in Panels A and B who received at least one dose of molnupiravir and received viral inoculation, with available measurements and without important protocol deviations. Per protocol, Panel C participants receiving placebo were not included in the analysis.

NHC is the pharmacologically active moiety of molnupiravir 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). AUC0-12 was reported for participants receiving molnupiravir in Panels A and B.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=36 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panels A & B: Area Under the Plasma Concentration Curve From 0 to 12 Hours Postdose (AUC0-12) of NHC	9270 hr*ng/mL Geometric Coefficient of Variation 28.4	8100 hr*ng/mL Geometric Coefficient of Variation 87.9	—

SECONDARY outcome

Timeframe: Day 2 at 12 hours predose (Panel A) or Day 6 at 12 hours predose (Panel B)

Population: All randomized participants in Panels A and B who received at least one dose of molnupiravir and received viral inoculation, with available measurements and without important protocol deviations. Per protocol, Panel C participants receiving placebo were not included in the analysis.

NHC is the pharmacologically active moiety of molnupiravir 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 Cmax. Ctrough of NHC in plasma was reported for participants receiving molnupiravir in Panels A and B.

Outcome measures

Measure	Panel A: Molnupiravir Prophylaxis n=38 Participants Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1 and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel C: Matched Placebo n=36 Participants Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.	Panel C: Matched Placebo Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Panels A & B: Trough Concentration (Ctrough) of NHC	25.1 ng/mL Geometric Coefficient of Variation 55.6	19.8 ng/mL Geometric Coefficient of Variation 66.8	—

Adverse Events

Panel A: Molnupiravir Prophylaxis

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Panel B: Molnupiravir Triggered Treatment

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Panel C: Matched Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Panel A: Molnupiravir Prophylaxis n=39 participants at risk Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1, and were inoculated with RSV-A Memphis 37b on Day 0. Participants switched to placebo beginning on the evening of Day 4 to the morning of Day 10.	Panel B: Molnupiravir Triggered Treatment n=36 participants at risk Participants received placebo on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued to receive placebo until testing positive for RSV. Participants then received 800 mg of molnupiravir every 12 hours for 5 days.	Panel C: Matched Placebo n=40 participants at risk Participants received placebo beginning on Day -1, were inoculated with RSV-A Memphis 37b on Day 0, and continued receiving placebo until the morning of Day 10.
Infections and infestations Upper respiratory tract infection	2.6% 1/39 • Number of events 1 • Day -1 up to Day 28 All-Cause Mortality is reported for all randomized participants. Serious adverse events and non-serious (other) adverse events are reported for all participants that received at least one dose of study treatment.	5.6% 2/36 • Number of events 2 • Day -1 up to Day 28 All-Cause Mortality is reported for all randomized participants. Serious adverse events and non-serious (other) adverse events are reported for all participants that received at least one dose of study treatment.	0.00% 0/40 • Day -1 up to Day 28 All-Cause Mortality is reported for all randomized participants. Serious adverse events and non-serious (other) adverse events are reported for all participants that received at least one dose of study treatment.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data. In this case, a coordinating investigator will be designated by mutual agreement. If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. Authorship will be determined by mutual agreement and in line with ICMJE authorship requirements.
• Publication restrictions are in place

Restriction type: OTHER