Respiratory Syncytial Virus
Conditions
Brief summary
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.
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.
Interventions
DRUGMolnupiravir
Four molnupiravir 200 mg capsules (800 mg total dose) taken twice daily by mouth.
DRUGPlacebo
Placebo capsule matched to molnupiravir taken twice daily by mouth.
BIOLOGICALRSV A Memphis 37b
RSV A Memphis 37b viral challenge given once by intranasal administration at a dosage of \ 4 Log10 plaque forming units (PFUs).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Panel A vs Panel C: Peak Viral Load (PVL) Determined by Viral Quantitative Culture | From Day 2 up to Day 12 | 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. |
| Panel B vs. Panel C: Area Under the Viral Load-time Curve (VL-AUC) Determined by Viral Quantitative Culture | From Day 2 up to Day 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related AE | From Day 0 up to Day 28 | 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. |
| All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related SAE | From Day 0 up to Day 28 | 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. |
| All Panels: Number of Participants Using Concomitant Medications From Viral Challenge Through Day 28 | From Day 0 up to 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. |
| Panel A vs. Panel C: VL-AUC Determined by Viral Quantitative Culture | From Day 2 up to Day 12 | 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. |
| Panel A vs. Panel C: VL-AUC Determined by Real-time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) | Day 2 up through Day 12 | 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. |
| Panel A vs. Panel C: PVL Determined by qRT-PCR | Day 2 up through Day 12 | 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. |
| Panel A vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores (TSS-AUC) | From Day -1 up to Day 12 | 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. |
| Panel A vs. Panel C: Peak Total Symptom Scores | From Day -1 up to Day 12 | 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. |
| Panel A vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores Change From Baseline (TSS-AUC-CFB) | Baseline (Day -1) and up to Day 12 | 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. |
| Panel A vs. Panel C: Peak Daily Symptom Score | From Day 2 up to Day 12 | 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. |
| Panel A vs. Panel C: Percentage of Participants With Respiratory Syncytial Virus (RSV) Infection Based on qRT-PCR | From Day 2 up to Day 12 | 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. |
| Panel A vs. Panel C: Percentage of Participants With RSV Infection Based on Cell Culture Measurement of Nasal Sample | From Day 2 up to Day 12 | 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. |
| Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Symptomatic RSV Infection | From Day 2 up to Day 12 | 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. |
| Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Moderately Severe Symptomatic RSV Infection | From Day 2 up to Day 12 | 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. |
| All Panels: Number of Participants Who Experienced ≥1 Adverse Event (AE) | From Day -1 up to Day 28 | 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. |
| Panel B vs. Panel C: PVL Determined by Viral Quantitative Culture | From Day 2 up to Day 12 | 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. |
| Panel B vs. Panel C: Time to Negative Test by Viral Quantitative Culture | From Day 2 up to Day 12 | 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. |
| Panel B vs. Panel C: VL-AUC Determined by qRT-PCR | From Day 2 up to Day 12 | 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. |
| Panel B vs. Panel C: PVL Determined by qRT-PCR | From Day 2 up to Day 12 | 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. |
| Panel B vs. Panel C: Time to Negative Test by qRT-PCR | From Day 2 up to Day 12 | 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. |
| Panel B vs. Panel C: TSS-AUC | From Day -1 up to Day 12 | 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. |
| Panel B vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores Change From Baseline (TSS-AUC-CFB) | Baseline (Day -1) and up to Day 12 | 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. |
| Panel B vs. Panel C: Peak TSS | From Day -1 up to Day 12 | 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. |
| Panel B vs. Panel C: Peak Daily Symptom Score | From Day -1 up to Day 12 | 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. |
| Panel B vs. Panel C: Time to Symptom Resolution | From Day -1 up to Day 12 | 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. |
| Panels A & B: Maximum Plasma Concentration (Cmax) of N-Hydroxycytidine (NHC) | 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 | 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. |
| Panels A & B: Time to Maximum Plasma Concentration (Tmax) of NHC | 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 | 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. |
| Panels A & B: Area Under the Plasma Concentration Curve From 0 to 12 Hours Postdose (AUC0-12) of NHC | 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 | 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. |
| Panels A & B: Trough Concentration (Ctrough) of NHC | Day 2 at 12 hours predose (Panel A) or Day 6 at 12 hours predose (Panel B) | 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. |
| Panel A vs. Panel C: Percentage of Participants With Culture-Confirmed Symptomatic RSV Infection | From Day 2 up to Day 12 | 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. |
| All Panels: Number of Participants Who Experienced ≥1 Serious AE (SAE) | From Day -1 up to Day 28 | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 40 |
| 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. | 36 |
| 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. | 40 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Not Reported | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Panel A: Molnupiravir Prophylaxis | Panel B: Molnupiravir Triggered Treatment | Panel C: Matched Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 26.6 Years STANDARD_DEVIATION 5.4 | 28.7 Years STANDARD_DEVIATION 8.2 | 26.8 Years STANDARD_DEVIATION 6.9 | 27.3 Years STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 35 Participants | 40 Participants | 115 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 7 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 4 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 32 Participants | 25 Participants | 29 Participants | 86 Participants |
| Sex: Female, Male Female | 15 Participants | 13 Participants | 17 Participants | 45 Participants |
| Sex: Female, Male Male | 25 Participants | 23 Participants | 23 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 36 | 0 / 40 |
| other Total, other adverse events | 1 / 39 | 2 / 36 | 0 / 40 |
| serious Total, serious adverse events | 0 / 39 | 0 / 36 | 0 / 40 |
Outcome results
Primary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel A vs Panel C: Peak Viral Load (PVL) Determined by Viral Quantitative Culture | 2.55 log10 plaque forming units (PFU)/mL |
| Panel C: Matched Placebo | Panel A vs Panel C: Peak Viral Load (PVL) Determined by Viral Quantitative Culture | 2.84 log10 plaque forming units (PFU)/mL |
Comparison: Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model. The mean PVL in each group and the differences in mean PVL between MK-4482 and placebo and the corresponding 2- sided 95% CI were computed based on the linear model.p-value: 0.57890% CI: [-1.16, 0.58]ANOVA
Primary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | 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 |
| Panel C: Matched Placebo | Panel B vs. Panel C: Area Under the Viral Load-time Curve (VL-AUC) Determined by Viral Quantitative Culture | 9.72 day*log10 PFU/mL |
Comparison: 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 in the analysis. The mean VL-AUC in each group and the differences in mean VL-AUC between MK-4482 and placebo and the corresponding 2-sided 95% CI were computed based on the linear model.p-value: 0.20190% CI: [-6.17, -0.79]ANOVA
Secondary
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.
Time frame: From Day 0 up to Day 28
Population: All participants who received at least one dose of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | All Panels: Number of Participants Using Concomitant Medications From Viral Challenge Through Day 28 | 6 Participants |
| Panel C: Matched Placebo | All Panels: Number of Participants Using Concomitant Medications From Viral Challenge Through Day 28 | 7 Participants |
| Panel C: Matched Placebo | All Panels: Number of Participants Using Concomitant Medications From Viral Challenge Through Day 28 | 7 Participants |
Secondary
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.
Time frame: From Day -1 up to Day 28
Population: All participants who received at least one dose of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | All Panels: Number of Participants Who Experienced ≥1 Adverse Event (AE) | 13 Participants |
| Panel C: Matched Placebo | All Panels: Number of Participants Who Experienced ≥1 Adverse Event (AE) | 15 Participants |
| Panel C: Matched Placebo | All Panels: Number of Participants Who Experienced ≥1 Adverse Event (AE) | 13 Participants |
Secondary
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.
Time frame: From Day -1 up to Day 28
Population: All participants who received at least one dose of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | All Panels: Number of Participants Who Experienced ≥1 Serious AE (SAE) | 0 Participants |
| Panel C: Matched Placebo | All Panels: Number of Participants Who Experienced ≥1 Serious AE (SAE) | 0 Participants |
| Panel C: Matched Placebo | All Panels: Number of Participants Who Experienced ≥1 Serious AE (SAE) | 0 Participants |
Secondary
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.
Time frame: From Day 0 up to Day 28
Population: All participants who received at least one dose of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related AE | 1 Participants |
| Panel C: Matched Placebo | All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related AE | 1 Participants |
| Panel C: Matched Placebo | All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related AE | 1 Participants |
Secondary
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.
Time frame: From Day 0 up to Day 28
Population: All participants who received at least one dose of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related SAE | 0 Participants |
| Panel C: Matched Placebo | All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related SAE | 0 Participants |
| Panel C: Matched Placebo | All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related SAE | 0 Participants |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | 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 |
| Panel C: Matched Placebo | Panel A vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores Change From Baseline (TSS-AUC-CFB) | 8.66 Scores on a Scale*Days |
Comparison: Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model. The TSS-AUC-CFB in each group and the differences in mean TSS-AUC-CFB between MK-4482 and placebo and the corresponding 2- sided 95% CI were computed based on the linear model.p-value: 0.3690% CI: [-5.11, 1.47]ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores (TSS-AUC) | 7.5 Scores on a Scale*Days |
| Panel C: Matched Placebo | Panel A vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores (TSS-AUC) | 9.59 Scores on a Scale*Days |
Comparison: Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model. The TSS-AUC in each group and the differences in mean TSS-AUC between MK-4482 and placebo and the corresponding 2- sided 95% CI were computed based on the linear model.p-value: 0.37190% CI: [-5.97, 1.78]ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Peak Daily Symptom Score | Day 5 | 0.8 Scores on a Scale | Standard Deviation 1.22 |
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Peak Daily Symptom Score | Day 8 | 1.7 Scores on a Scale | Standard Deviation 2.24 |
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Peak Daily Symptom Score | Day 4 | 0.7 Scores on a Scale | Standard Deviation 0.98 |
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Peak Daily Symptom Score | Day 9 | 1.4 Scores on a Scale | Standard Deviation 1.67 |
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Peak Daily Symptom Score | Day 6 | 1.2 Scores on a Scale | Standard Deviation 1.41 |
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Peak Daily Symptom Score | Day 10 | 0.9 Scores on a Scale | Standard Deviation 1.83 |
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Peak Daily Symptom Score | Day 3 | 0.6 Scores on a Scale | Standard Deviation 0.88 |
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Peak Daily Symptom Score | Day 11 | 0.7 Scores on a Scale | Standard Deviation 1.21 |
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Peak Daily Symptom Score | Day 7 | 1.4 Scores on a Scale | Standard Deviation 1.52 |
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Peak Daily Symptom Score | Day 12 | 0.3 Scores on a Scale | Standard Deviation 0.76 |
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Peak Daily Symptom Score | Day 2 | 0.8 Scores on a Scale | Standard Deviation 1.13 |
| Panel C: Matched Placebo | Panel A vs. Panel C: Peak Daily Symptom Score | Day 12 | 0.3 Scores on a Scale | Standard Deviation 0.56 |
| Panel C: Matched Placebo | Panel A vs. Panel C: Peak Daily Symptom Score | Day 2 | 1.1 Scores on a Scale | Standard Deviation 1.36 |
| Panel C: Matched Placebo | Panel A vs. Panel C: Peak Daily Symptom Score | Day 3 | 0.9 Scores on a Scale | Standard Deviation 1.24 |
| Panel C: Matched Placebo | Panel A vs. Panel C: Peak Daily Symptom Score | Day 4 | 1.0 Scores on a Scale | Standard Deviation 1.56 |
| Panel C: Matched Placebo | Panel A vs. Panel C: Peak Daily Symptom Score | Day 5 | 1.4 Scores on a Scale | Standard Deviation 1.9 |
| Panel C: Matched Placebo | Panel A vs. Panel C: Peak Daily Symptom Score | Day 6 | 2.1 Scores on a Scale | Standard Deviation 2.82 |
| Panel C: Matched Placebo | Panel A vs. Panel C: Peak Daily Symptom Score | Day 7 | 1.9 Scores on a Scale | Standard Deviation 3.02 |
| Panel C: Matched Placebo | Panel A vs. Panel C: Peak Daily Symptom Score | Day 8 | 1.8 Scores on a Scale | Standard Deviation 2.22 |
| Panel C: Matched Placebo | Panel A vs. Panel C: Peak Daily Symptom Score | Day 9 | 1.3 Scores on a Scale | Standard Deviation 1.9 |
| Panel C: Matched Placebo | Panel A vs. Panel C: Peak Daily Symptom Score | Day 10 | 0.8 Scores on a Scale | Standard Deviation 1.58 |
| Panel C: Matched Placebo | Panel A vs. Panel C: Peak Daily Symptom Score | Day 11 | 0.5 Scores on a Scale | Standard Deviation 1.02 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Peak Total Symptom Scores | 2.74 Scores on a Scale |
| Panel C: Matched Placebo | Panel A vs. Panel C: Peak Total Symptom Scores | 3.20 Scores on a Scale |
Comparison: Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model. The mean peak TSS in each group and the differences in mean peak TSS between MK-4482 and placebo and the corresponding 2- sided 95% CI was computed based on the linear model.p-value: 0.45990% CI: [-1.5, 0.57]ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Percentage of Participants With Culture-Confirmed Symptomatic RSV Infection | 42.11 Percentage of Participants |
| Panel C: Matched Placebo | Panel A vs. Panel C: Percentage of Participants With Culture-Confirmed Symptomatic RSV Infection | 45.00 Percentage of Participants |
95% CI: [-25.69, 19.37]
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Moderately Severe Symptomatic RSV Infection | 26.32 Percentage of Participants |
| Panel C: Matched Placebo | Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Moderately Severe Symptomatic RSV Infection | 42.50 Percentage of Participants |
95% CI: [-36.77, 5.64]
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Symptomatic RSV Infection | 47.37 Percentage of Participants |
| Panel C: Matched Placebo | Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Symptomatic RSV Infection | 50.00 Percentage of Participants |
95% CI: [-25.07, 19.91]
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Percentage of Participants With Respiratory Syncytial Virus (RSV) Infection Based on qRT-PCR | 68.42 Percentage of Participants |
| Panel C: Matched Placebo | Panel A vs. Panel C: Percentage of Participants With Respiratory Syncytial Virus (RSV) Infection Based on qRT-PCR | 65.00 Percentage of Participants |
95% CI: [-18.28, 24.5]
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: Percentage of Participants With RSV Infection Based on Cell Culture Measurement of Nasal Sample | 57.89 Percentage of Participants |
| Panel C: Matched Placebo | Panel A vs. Panel C: Percentage of Participants With RSV Infection Based on Cell Culture Measurement of Nasal Sample | 55.00 Percentage of Participants |
95% CI: [-19.37, 25.69]
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: PVL Determined by qRT-PCR | 4.66 day*log10 copies/mL |
| Panel C: Matched Placebo | Panel A vs. Panel C: PVL Determined by qRT-PCR | 4.80 day*log10 copies/mL |
Comparison: Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model. The mean PVL in each group and the differences in mean PVL between MK-4482 and placebo and the corresponding 2- sided 95% CI were computed based on the linear model.p-value: 0.84990% CI: [-1.31, 1.04]ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | 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 |
| Panel C: Matched Placebo | Panel A vs. Panel C: VL-AUC Determined by Real-time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) | 19.54 day*log10 copies/mL |
Comparison: Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model. The mean VL-AUC in each group and the differences in mean VL-AUC between MK-4482 and placebo and the corresponding 2-sided 95% CI were computed based on the linear model.p-value: 0.64690% CI: [-8.88, 5.02]ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel A vs. Panel C: VL-AUC Determined by Viral Quantitative Culture | 7.56 day*log10 PFU/mL |
| Panel C: Matched Placebo | Panel A vs. Panel C: VL-AUC Determined by Viral Quantitative Culture | 8.17 day*log10 PFU/mL |
Comparison: Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model. The mean VL-AUC in each group and the differences in mean VL-AUC between MK-4482 and placebo and the corresponding 2-sided 95% CI were computed based on the linear model.p-value: 0.73690% CI: [-3.65, 2.42]ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | 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 |
| Panel C: Matched Placebo | Panel B vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores Change From Baseline (TSS-AUC-CFB) | 2.74 Scores on a Scale*Days |
Comparison: Per protocol, only Panel B (treatment) and Panel C (placebo) were included in the model. The TSS-AUC-CFB in each group and the differences in mean TSS-AUC-CFB between MK-4482 and placebo and the corresponding 2- sided 95% CI were computed based on the linear model.p-value: 0.95890% CI: [-4.28, 4.02]ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Peak Daily Symptom Score | Day 9 | 1.0 Score on a Scale | Standard Deviation 1.26 |
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Peak Daily Symptom Score | Day 1 | 0.6 Score on a Scale | Standard Deviation 0.9 |
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Peak Daily Symptom Score | Day 2 | 1.3 Score on a Scale | Standard Deviation 1.89 |
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Peak Daily Symptom Score | Day 3 | 1.5 Score on a Scale | Standard Deviation 1.68 |
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Peak Daily Symptom Score | Day 4 | 2.1 Score on a Scale | Standard Deviation 2.44 |
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Peak Daily Symptom Score | Day 5 | 1.8 Score on a Scale | Standard Deviation 2.67 |
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Peak Daily Symptom Score | Day 6 | 1.4 Score on a Scale | Standard Deviation 2.29 |
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Peak Daily Symptom Score | Day 7 | 0.7 Score on a Scale | Standard Deviation 1.33 |
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Peak Daily Symptom Score | Day 8 | 0.5 Score on a Scale | Standard Deviation 1.08 |
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Peak Daily Symptom Score | Day 10 | 0.7 Score on a Scale | Standard Deviation 1.15 |
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Peak Daily Symptom Score | Day 11 | 1.0 Score on a Scale | Standard Deviation 1.41 |
| Panel C: Matched Placebo | Panel B vs. Panel C: Peak Daily Symptom Score | Day 9 | 0.8 Score on a Scale | Standard Deviation 1.42 |
| Panel C: Matched Placebo | Panel B vs. Panel C: Peak Daily Symptom Score | Day 6 | 1.5 Score on a Scale | Standard Deviation 2.06 |
| Panel C: Matched Placebo | Panel B vs. Panel C: Peak Daily Symptom Score | Day 1 | 1.4 Score on a Scale | Standard Deviation 1.6 |
| Panel C: Matched Placebo | Panel B vs. Panel C: Peak Daily Symptom Score | Day 11 | 0.0 Score on a Scale | Standard Deviation 0 |
| Panel C: Matched Placebo | Panel B vs. Panel C: Peak Daily Symptom Score | Day 2 | 2.0 Score on a Scale | Standard Deviation 2.18 |
| Panel C: Matched Placebo | Panel B vs. Panel C: Peak Daily Symptom Score | Day 7 | 1.2 Score on a Scale | Standard Deviation 2.12 |
| Panel C: Matched Placebo | Panel B vs. Panel C: Peak Daily Symptom Score | Day 3 | 2.3 Score on a Scale | Standard Deviation 2.31 |
| Panel C: Matched Placebo | Panel B vs. Panel C: Peak Daily Symptom Score | Day 10 | 0.5 Score on a Scale | Standard Deviation 1 |
| Panel C: Matched Placebo | Panel B vs. Panel C: Peak Daily Symptom Score | Day 4 | 2.7 Score on a Scale | Standard Deviation 3.26 |
| Panel C: Matched Placebo | Panel B vs. Panel C: Peak Daily Symptom Score | Day 8 | 0.7 Score on a Scale | Standard Deviation 1.48 |
| Panel C: Matched Placebo | Panel B vs. Panel C: Peak Daily Symptom Score | Day 5 | 2.5 Score on a Scale | Standard Deviation 3.37 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Peak TSS | 3.00 Score on a Scale |
| Panel C: Matched Placebo | Panel B vs. Panel C: Peak TSS | 3.62 Score on a Scale |
Comparison: 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. The mean peak TSS in each group and the differences in mean peak TSS between MK-4482 and placebo and the corresponding 2- sided 95% CI was computed based on the linear model.p-value: 0.5290% CI: [-2.21, 0.98]ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: PVL Determined by qRT-PCR | 5.43 log10 PFU/mL |
| Panel C: Matched Placebo | Panel B vs. Panel C: PVL Determined by qRT-PCR | 6.02 log10 PFU/mL |
Comparison: 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. The mean PVL in each group and the differences in mean PVL between MK-4482 and placebo and the corresponding 2- sided 95% CI were computed based on the linear model.p-value: 0.45390% CI: [-1.88, 0.71]ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: PVL Determined by Viral Quantitative Culture | 2.85 log10 PFU/mL |
| Panel C: Matched Placebo | Panel B vs. Panel C: PVL Determined by Viral Quantitative Culture | 3.53 log10 PFU/mL |
Comparison: 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. The mean PVL in each group and the differences in mean PVL between MK-4482 and placebo and the corresponding 2- sided 95% CI were computed based on the linear model.p-value: 0.25390% CI: [-1.68, 0.31]ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Time to Negative Test by qRT-PCR | NA Days |
| Panel C: Matched Placebo | Panel B vs. Panel C: Time to Negative Test by qRT-PCR | 9.0 Days |
p-value: 0.912195% CI: [0.44, 2.51]Log Rank
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Time to Negative Test by Viral Quantitative Culture | 5.0 Days |
| Panel C: Matched Placebo | Panel B vs. Panel C: Time to Negative Test by Viral Quantitative Culture | 5.0 Days |
p-value: 0.170895% CI: [0.83, 3.57]Log Rank
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: Time to Symptom Resolution | 6.0 Days |
| Panel C: Matched Placebo | Panel B vs. Panel C: Time to Symptom Resolution | 8.5 Days |
p-value: 0.045995% CI: [0.99, 5.07]Log Rank
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: TSS-AUC | 4.74 Scores on a Scale*Days |
| Panel C: Matched Placebo | Panel B vs. Panel C: TSS-AUC | 6.57 Scores on a Scale*Days |
Comparison: Per protocol, only Panel B (treatment) and Panel C (placebo) were included in the model. The TSS-AUC in each group and the differences in mean TSS-AUC between MK-4482 and placebo and the corresponding 2- sided 95% CI were computed based on the linear model.p-value: 0.37790% CI: [-5.25, 1.6]ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panel B vs. Panel C: VL-AUC Determined by qRT-PCR | 20.58 days*log10 copies/mL |
| Panel C: Matched Placebo | Panel B vs. Panel C: VL-AUC Determined by qRT-PCR | 26.51 days*log10 copies/mL |
Comparison: 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. The mean VL-AUC in each group and the differences in mean VL-AUC between MK-4482 and placebo and the corresponding 2-sided 95% CI were computed based on the linear model.p-value: 0.25790% CI: [-14.61, 2.75]ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Molnupiravir Prophylaxis | 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 |
| Panel C: Matched Placebo | Panels A & B: Area Under the Plasma Concentration Curve From 0 to 12 Hours Postdose (AUC0-12) of NHC | 8100 hr*ng/mL | Geometric Coefficient of Variation 87.9 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panels A & B: Maximum Plasma Concentration (Cmax) of N-Hydroxycytidine (NHC) | 3640 ng/mL | Geometric Coefficient of Variation 33.5 |
| Panel C: Matched Placebo | Panels A & B: Maximum Plasma Concentration (Cmax) of N-Hydroxycytidine (NHC) | 3010 ng/mL | Geometric Coefficient of Variation 111.5 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panels A & B: Time to Maximum Plasma Concentration (Tmax) of NHC | 1.47 hr |
| Panel C: Matched Placebo | Panels A & B: Time to Maximum Plasma Concentration (Tmax) of NHC | 1.48 hr |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Molnupiravir Prophylaxis | Panels A & B: Trough Concentration (Ctrough) of NHC | 25.1 ng/mL | Geometric Coefficient of Variation 55.6 |
| Panel C: Matched Placebo | Panels A & B: Trough Concentration (Ctrough) of NHC | 19.8 ng/mL | Geometric Coefficient of Variation 66.8 |