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

NCT05818124
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Phase
Phase 1
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Recruitment status
Completed
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Participants
161
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Lead sponsor
Merck Sharp & Dohme LLC
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Start date
2023-08-21
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Number of sites
1
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Summary
This is a phase 2a double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of molnupiravir (MK-4482) in healthy participants inoculated with experimental influenza virus. The primary hypotheses are that MK-4482 initiated 12 hours following intranasal inoculation of the influenza challenge virus reduces the peak viral load compared to placebo and that MK-4482 initiated 2 days following intranasal inoculation of the influenza challenge virus reduces the viral load area under the curve (AUC) compared to placebo.
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Short title
Efficacy and Safety of Molnupiravir in Healthy Participants Inoculated With Experimental Influenza Virus (MK-4482-019)
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Official title
A Phase 2a Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-4482 in Healthy Participants Inoculated With Experimental Influenza Virus
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Control arm
Placebo
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Registry reports results
Yes
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Listing at source
Listed
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Recruitment status
Completed
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Phase
Phase 1
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Study type
Interventional
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Completion date
2024-06-28
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First posted
2023-04-18
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Registry last updated
2025-08-06
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Primary completion date
2024-06-28
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Start date
2023-08-21
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Actual participants
161
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Participants
161
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Participant count basis
Actual
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Protocol amendments
3
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Number of sites
1
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Merck Sharp & Dohme LLC
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05818124
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ClinicalTrials.gov ID
NCT05818124
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Double masking
Masked roles
Participants, Investigators
Sources for study design
clinicaltrials.gov

  1. Part 1: Infectivity Rate Based on Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) From Day 1 PM Through Day 8 AM

    Timeframe: From Day 1 PM up to Day 8 post viral inoculation

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

  2. Part 1: Infectivity Rate Based on Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) From Day 2 PM Through Day 8 AM

    Timeframe: From Day 2 PM up to Day 8 post viral inoculation

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

  3. Part 1: Number of Participants Experiencing ≥1 Viral Challenge-related Adverse Event (AE)

    Timeframe: Up to approximately 31 days

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

  4. Part 2: Peak Viral Load (PVL) Determined by Quantitative Viral Culture Tissue Culture Infective Dose 50% (TCID50) Assay From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)

    Timeframe: From Day 1 PM up to Day 8 post viral inoculation

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

  5. Part 2: Area Under the Viral Load-Time Curve (VL-AUC) Determined by QVC (TCID50 Assay) From Day 2 AM Through Day 8 AM After Intranasal Inoculation (Molnupiravir Tx and Placebo)

    Timeframe: Days 2, 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation

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

  1. Part 1: QVC-Confirmed Influenza Infection From Day 1 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 1 PM up to Day 8 post viral inoculation

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

  2. Part 1: QVC-Confirmed Influenza Infection From Day 2 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 2 PM Up to Day 8 post viral inoculation

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

  3. Part 1: VL-AUC Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: Day 1 PM, Days 2, 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation

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

  4. Part 1: VL-AUC Determined by qRT-PCR From Day 2 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: Day 2 PM, Days 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation

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

  5. Part 1: VL-AUC Determined by Quantitative Viral Culture (TCID50 Assay) From Day 1 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: Day 1 PM, Days 2, 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation

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

  6. Part 1: VL-AUC Determined by Quantitative Viral Culture (TCID50 Assay) From Day 2 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: Day 2 PM, Days 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation

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

  7. Part 1: PVL Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 1 PM up to Day 8 post viral inoculation

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

  8. Part 1: PVL Determined by qRT-PCR From Day 2 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 2 PM up to Day 8 post viral inoculation

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

  9. Part 1: PVL Determined by Quantitative Viral Culture (TCID50 Assay) From Day 1 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 1 PM up to Day 8 post viral inoculation

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

  10. Part 1: PVL Determined by Quantitative Viral Culture (TCID50 Assay) From Day 2 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 2 PM up to Day 8 post viral inoculation

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

  11. Part 1: Duration in Days of Quantifiable Influenza Infection by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 1 PM up to Day 8 post viral inoculation

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

  12. Part 1: Duration in Days of Quantifiable Influenza Infection by qRT-PCR From Day 2 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 2 PM up to Day 8 post viral inoculation

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

  13. Part 1: Duration in Days of Quantifiable Influenza Infection by QVC (TCID50 Assay) Confirmed Infection From Day 1 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 1 PM up to Day 8 post viral inoculation

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

  14. Part 1: Duration in Days of Quantifiable Influenza Infection by QVC Confirmed Infection From Day 2 PM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 2 PM up to Day 8 post viral inoculation

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

  15. Part 1: Area Under the Total Symptom Score-Time Curve (TSS-AUC) From Day 1 AM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 1 AM up to Day 8 post viral inoculation

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

  16. Part 1: Area Under the Total Symptom Score-Time Curve (TSS-AUC) From Day 2 AM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 2 AM up to Day 8 post viral inoculation

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

  17. Part 1: Peak Total Symptom Score (TSS) From Day 1 AM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 1 AM up to Day 8 post viral inoculation

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

  18. Part 1: Peak Total Symptom Score (TSS) From Day 2 AM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 2 AM up to Day 8 post viral inoculation

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

  19. Part 1: Daily Maximum TSS From Day 1 AM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 1 AM up to Day 8 post viral inoculation

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

  20. Part 1: Duration in Days of Grade ≥2 Symptoms From Day 1 AM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 1 AM up to Day 8 post viral inoculation

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

  21. Part 1: Duration of Grade ≥2 Symptoms From Day 2 AM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 2 AM up to Day 8 post viral inoculation

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

  22. Part 1: Time to Symptom Resolution From Day 1 AM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 1 AM up to Day 8 post viral inoculation

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

  23. Part 1: Time to Symptom Resolution From Day 2 AM Through Discharge From Quarantine (Day 8 AM) After Intranasal Inoculation

    Timeframe: From Day 2 AM up to Day 8 post viral inoculation

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

  24. Part 1: Time to Peak TSS From Day 1 AM Through Day 8 AM After Intranasal Inoculation

    Timeframe: From Day 1 AM up to Day 8 post viral inoculation

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

  25. Part 2: VL-AUC Determined by qRT-PCR From Day 1 PM Through Day 8 AM After Intranasal Inoculation (Molnupiravir PEP and Placebo)

    Timeframe: Day 1 PM, Days 2, 3, 4, 5, 6, 7 - twice daily (AM and PM), and day 8 AM post viral inoculation

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

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Sex
All
Age groups
Adults
Minimum age
18 Years
Maximum age
55 Years
Healthy volunteers
Yes

  • Is in good health based on medical history, physical examination, vital sign measurements, spirometry, and electrocardiograms performed before inoculation.
  • Has a total body weight ≥50 kg and Body Mass Index (BMI) ≥18 kg/m^2 and ≤35 kg/m^2.
  • For males: abstains from heterosexual intercourse as their preferred and usual lifestyle and agrees to remain abstinent OR uses contraception unless confirmed to be azoospermic.
  • For participants assigned female sex at birth: is not pregnant or breastfeeding, AND is either not a person of childbearing potential (POCBP) or is a POCBP AND uses a contraceptive method that is highly effective (low user dependency method, OR a user dependent hormonal method in combination with barrier method), or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle, has a negative highly sensitive pregnancy test, abstains from breastfeeding, and has medical, menstrual, and recent sexual activity history reviewed by the investigator to decrease risk of early undetected pregnancy.

  • Has a history of, or has currently active, symptoms or signs suggestive of upper or lower respiratory tract infection within 4 weeks prior to admission to quarantine.
  • Has a history of clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or diseases.
  • Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy visit, or expected during the conduct of the study, or has a history of clinically significant psychiatric disorder of the last 5 years.
  • Has a history of cancer.
  • Has a history of rhinitis 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 prior to 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.
  • Has a diagnosis of cluster headache/migraine or is receiving prophylaxis against migraine.
  • Has a lifetime history of anaphylaxis and/or a lifetime history of severe allergic reaction. Significant intolerance to any food or drug in the last 12 months.
  • Has had major surgery and/or donated or lost 1 unit of blood within 3 months prior to the prestudy visit.
  • Uses or anticipates the use of concomitant medications, including vitamins or herbal and dietary supplements from approximately 2 weeks prior to the planned date of viral challenge until the poststudy visit.
  • Has evidence of receipt of vaccine within the 4 weeks prior to the planned date of viral challenge.
  • Intends to receive any vaccine(s) before the last day of follow-up.
  • Has received any investigational drug within 3 months prior to the planned date of viral challenge.
  • Has received 3 or more investigational drugs within the previous 12 months prior to the planned date of viral challenge.
  • Has had prior inoculation with a virus from the same virus subtype as the challenge virus.
  • Has had prior inoculation with a virus from the same virus-family as the challenge virus in the last 12 months.
  • Has had prior participation in another human viral challenge study with a respiratory virus in the preceding 3 months, taken from the date of viral challenge in the previous study to the date of expected viral challenge in this study.
  • Has smoked ≥10 pack-years at any time.
  • Has a recent history or presence of alcohol addiction, or excessive use of alcohol.
  • Consumes excessive amounts, defined as more than 6 servings of caffeinated beverages or xanthine-containing products.
  • 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.
  • Has had any nasal or sinus surgery within 3 months.
  • Is a regular user of cannabis or any illicit drugs, or has a history of drug abuse within approximately 1 year.
Sources for eligibility
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  • hVIVO Services ( Site 0001)London, United Kingdom
Sources for sites
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Sources for references
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Related records

Drugs (2)

Lead sponsors (1)