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

A Phase 2a Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-4482 in Healthy Participants Inoculated With Experimental Respiratory Syncytial Virus

This is a study of molnupiravir (MK-4482) in healthy participants who have been inoculated with an experimental Respiratory Syncytial Virus (RSV) [RSV-A Memphis 37b]. It is hypothesized that treatment with the drug MK-4482 (molnupiravir) will reduce the peak viral load (PVL) in the participant compared to placebo when given either before or after RSV-A Memphis 37b inoculation.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus
• Intervention / Treatment: Drug: Molnupiravir; Drug: Placebo; Biological: RSV A Memphis 37b

Detailed Description

Participants arrive at the study center for check-in between Day -3 and Day -1. Participants receive the assigned treatment beginning on Day -1. On Day 0, all participants receive viral inoculation with RSV-A Memphis 37b. All participants depart on Day 12 and follow-up is continued until Day 28.

The study is designed with the following arms:

• Panel A: Molupiravir Prophylaxis - in this arm, participants receive molupiravir beginning on Day -1, are incoluated with RSV-A Memphis 37b on Day 0, and continue receiving molnupiravir for a total of 5 days before switching to placebo through Day 10.
• Panel B: Molupiravir Triggered Treatment - in this arm, participants receive placebo beginning on Day -1 until testing positive for RSV. Participants are inoculated with RSV-A Memphis 37b on Day 0. When participants test positive for RSV, they switch to molnupiravir for a total of 5 consecutive days before switching back to placebo through Day 10. If participants in this arm do not test positive for RSV by Day 5, they automatically switch to molnupiravir through Day 10.
• Panel C: Placebo - in this arm, all participants receive placebo beginning on Day -1, are inoculated with RSV-A Memphis 37b on Day 0, and continue receiving placebo through Day 10.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, City Of
    • London, London, City Of, United Kingdom, E1 2AX
      • hVIVO Services ( Site 0001)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Is in good health based on medical history, physical examination, vital sign measurements, spirometry, and electrocardiograms (ECGs) performed before randomization.
• Has a total body weight ≥50 kg and Body Mass Index (BMI) ≥18 kg/m^2 and ≤35 kg/m^2.
• For males, agrees to abstain from heterosexual intercourse OR use contraception unless confirmed to be azoospermic during the study and for 90 days after.
• For females, is not pregnant or breastfeeding, AND is either not a woman of childbearing potential (WOCBP) or is a WOCBP AND uses a highly effective contraceptive (low user dependency OR a user dependent hormonal method in combination with a barrier method), has a negative highly sensitive pregnancy test at screening, and has medical, menstrual, and recent sexual activity history reviewed by the investigator to decrease risk of early undetected pregnancy.

Exclusion Criteria:

• Has a history of, or currently active, symptoms or signs suggestive of upper or lower respiratory tract infection within 4 weeks prior to the first study visit.
• Has a history of clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases.
• Has a history of resolved depression and/or anxiety 1 or more years ago may be included at the discretion of the investigator.
• Has a history of cancer (malignancy).
• Has a history of rhinitis (including hay fever) which is clinically active or history of moderate to severe rhinitis, or history of seasonal allergic rhinitis likely to be active at the time of inclusion into the study and/or requiring regular nasal corticosteroids on an at least weekly basis, within 30 days of admission to quarantine.
• Has a history of atopic dermatitis/eczema which is clinically severe and/or requiring moderate to large amounts of daily dermal corticosteroids.
• If the reporting physician has diagnosed migraine can be included, provided there are no associated neurological symptoms such as hemiplegia or visual loss.
• If there is a physician diagnosed mild Irritable Bowel Syndrome not requiring regular treatment, can be included at the discretion of the investigator.
• Uses or anticipates use during study of herbal supplements within 7 days prior to Viral Challenge, any cytochrome P450 (CYP450)-inhibiting medications within 21 days prior to Viral Challenge, any over-the-counter medications (eg, ibuprofen) within 7 days prior to Viral Challenge, or any systemic anti-viral administration within 4 weeks of Viral Challenge/first dosing of study medication.
• Has evidence of receipt of vaccine within the 4 weeks prior to the planned date of viral challenge/first dosing with study medication (whichever occurs first).
• Intends to receive any vaccine before the last study visit.
• Has received any investigational drug within 3 months or 5 half-lives (whichever is greater) prior to the planned date of viral challenge/first dosing with study medication (whichever occurs first).
• Has received ≥3 investigational drugs in the past 12 months.
• Has had a prior inoculation with a virus from the same family as the challenge virus.
• Has smoked ≥10 pack years at any time (one pack of 20 cigarettes a day for 10 years).
• Has a recent history or presence of alcohol addiction, or excessive use of alcohol (weekly intake in excess of 28 units alcohol; 1 unit being a half glass of beer, a small glass of wine or a measure of spirits), or excessive consumption of xanthine-containing substances (eg, daily intake in excess of 5 cups of caffeinated drinks such as coffee, tea, cola).
• Has a lifetime history of anaphylaxis and/or a lifetime history of severe allergic reaction.
• Has any significant abnormality altering the anatomy of the nose in a substantial way or nasopharynx that may interfere with the aims of the study and, in particular, any of the nasal assessments or viral challenge.
• Has any clinically significant history of epistaxis (large nosebleeds) within the last 3 months of the first study visit and/or history of being hospitalized due to epistaxis on any previous occasion.
• Has had any nasal or sinus surgery within 3 months of the first study visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel A: Molnupiravir Prophylaxis; Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1, and are inoculated with RSV-A Memphis 37b on Day 0. Participants switch to placebo beginning on the evening of Day 4 to the morning of Day 10.	Drug: Molnupiravir; Four molnupiravir 200 mg capsules (800 mg total dose) taken twice daily by mouth.; Other Names: MK-4482; Drug: Placebo; Placebo capsule matched to molnupiravir taken twice daily by mouth.; Biological: RSV A Memphis 37b; RSV A Memphis 37b viral challenge given once by intranasal administration at a dosage of ~4 Log10 plaque forming units (PFUs).
Experimental: Panel B: Molnupiravir Triggered Treatment; Participants received placebo on Day -1, are inoculated with RSV-A Memphis 37b on Day 0, and continue to receive placebo until testing positive for RSV. Participants then received 800 mg of molnupiravir every 12 hours for 5 days.	Drug: Molnupiravir; Four molnupiravir 200 mg capsules (800 mg total dose) taken twice daily by mouth.; Other Names: MK-4482; Drug: Placebo; Placebo capsule matched to molnupiravir taken twice daily by mouth.; Biological: RSV A Memphis 37b; RSV A Memphis 37b viral challenge given once by intranasal administration at a dosage of ~4 Log10 plaque forming units (PFUs).
Placebo Comparator: Panel C: Matched Placebo; Participants received placebo beginning on Day -1, are inoculated with RSV-A Memphis 37b on Day 0, and continue receiving placebo until the morning of Day 10.	Drug: Placebo; Placebo capsule matched to molnupiravir taken twice daily by mouth.; Biological: RSV A Memphis 37b; RSV A Memphis 37b viral challenge given once by intranasal administration at a dosage of ~4 Log10 plaque forming units (PFUs).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Panel A vs Panel C: Peak Viral Load (PVL) Determined by Viral Quantitative Culture	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.	From Day 2 up to Day 12
Panel B vs. Panel C: Area Under the Viral Load-time Curve (VL-AUC) Determined by Viral Quantitative Culture	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.	From Day 2 up to Day 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All Panels: Number of Participants Who Experienced ≥1 Adverse Event (AE)	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.	From Day -1 up to Day 28
All Panels: Number of Participants Who Experienced ≥1 Serious AE (SAE)	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.	From Day -1 up to Day 28
All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related AE	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.	From Day 0 up to Day 28
All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related SAE	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.	From Day 0 up to Day 28
All Panels: Number of Participants Using Concomitant Medications From Viral Challenge Through Day 28	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.	From Day 0 up to Day 28
Panel A vs. Panel C: VL-AUC Determined by Viral Quantitative Culture	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.	From Day 2 up to Day 12
Panel A vs. Panel C: VL-AUC Determined by Real-time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR)	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.	Day 2 up through Day 12
Panel A vs. Panel C: PVL Determined by qRT-PCR	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.	Day 2 up through Day 12
Panel A vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores (TSS-AUC)	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.	From Day -1 up to Day 12
Panel A vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores Change From Baseline (TSS-AUC-CFB)	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.	Baseline (Day -1) and up to Day 12
Panel A vs. Panel C: Peak Total Symptom Scores	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.	From Day -1 up to Day 12
Panel A vs. Panel C: Peak Daily Symptom Score	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.	From Day 2 up to Day 12
Panel A vs. Panel C: Percentage of Participants With Respiratory Syncytial Virus (RSV) Infection Based on qRT-PCR	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.	From Day 2 up to Day 12
Panel A vs. Panel C: Percentage of Participants With RSV Infection Based on Cell Culture Measurement of Nasal Sample	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.	From Day 2 up to Day 12
Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Symptomatic RSV Infection	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.	From Day 2 up to Day 12
Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Moderately Severe Symptomatic RSV Infection	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.	From Day 2 up to Day 12
Panel A vs. Panel C: Percentage of Participants With Culture-Confirmed Symptomatic RSV Infection	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.	From Day 2 up to Day 12
Panel B vs. Panel C: PVL Determined by Viral Quantitative Culture	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.	From Day 2 up to Day 12
Panel B vs. Panel C: Time to Negative Test by Viral Quantitative Culture	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.	From Day 2 up to Day 12
Panel B vs. Panel C: VL-AUC Determined by qRT-PCR	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.	From Day 2 up to Day 12
Panel B vs. Panel C: PVL Determined by qRT-PCR	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.	From Day 2 up to Day 12
Panel B vs. Panel C: Time to Negative Test by qRT-PCR	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.	From Day 2 up to Day 12
Panel B vs. Panel C: TSS-AUC	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.	From Day -1 up to Day 12
Panel B vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores Change From Baseline (TSS-AUC-CFB)	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.	Baseline (Day -1) and up to Day 12
Panel B vs. Panel C: Peak TSS	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.	From Day -1 up to Day 12
Panel B vs. Panel C: Peak Daily Symptom Score	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.	From Day -1 up to Day 12
Panel B vs. Panel C: Time to Symptom Resolution	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.	From Day -1 up to Day 12
Panels A & B: Maximum Plasma Concentration (Cmax) of N-Hydroxycytidine (NHC)	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.	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
Panels A & B: Time to Maximum Plasma Concentration (Tmax) of NHC	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.	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
Panels A & B: Area Under the Plasma Concentration Curve From 0 to 12 Hours Postdose (AUC0-12) of NHC	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.	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
Panels A & B: Trough Concentration (Ctrough) of NHC	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.	Day 2 at 12 hours predose (Panel A) or Day 6 at 12 hours predose (Panel B)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Cheng MH, Mann AJ, Maas BM, Zhao T, Bevan M, Schaeffer AK, Liao LE, Catchpole AP, Hilbert DW, Aubrey Stoch S, De Anda CS. A Phase 2a, Randomized, Placebo-Controlled Human Challenge Trial to Evaluate the Efficacy and Safety of Molnupiravir in Healthy Participants Inoculated with Respiratory Syncytial Virus. Pulm Ther. 2025 Jun;11(2):285-304. doi: 10.1007/s41030-025-00289-z. Epub 2025 Apr 2.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2022
• Primary Completion (Actual): April 18, 2023
• Study Completion (Actual): June 8, 2023

Study Registration Dates

• First Submitted: September 26, 2022
• First Submitted That Met QC Criteria: September 26, 2022
• First Posted (Actual): September 29, 2022

Study Record Updates

• Last Update Posted (Actual): July 18, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Virus Diseases; Anti-Infective Agents; Antiviral Agents; Molnupiravir
• Other Study ID Numbers: 4482-017; MK-4482-017 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes