Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as MK-4482, LAGEVRIO®, MOV, EIDD-2801
Molnupiravir · 7 trials · 5 indications
Hospitalization is defined as ≥24 hours of acute care in a hospital or similar acute care facility, including emergency rooms or facilities created to address hospitalization needs specifically for COVID-19. Hospitalization and death may be due to any cause. An MAV is defined as any unscheduled, nonroutine healthcare visit where the participant is evaluated by a licensed (according to local/national guidelines) healthcare provider. As prespecified by the protocol, the percentage of participants who experience ONE OR MORE of these 3 events (hospitalization, death, or COVID-19-related MAV) occurring from randomization through Day 29 will be presented.
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 percentage of participants with at least 1 AE will be presented.
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 percentage of participants who discontinue study intervention due to an AE will be presented.
Percentage of participants who had undetectable SARS-CoV-2 in baseline NP swabs and developed COVID-19 (laboratory-confirmed SARS-CoV-2 infection with symptoms) through Day 14 were reported.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
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.
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.
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.
The percentage of participants who were hospitalized and/or died through Day 29 is presented. Hospitalization (all cause) is defined as at least 24 hours of acute care in a hospital or similar acute care facility. Death was due to any cause. Any participants with an unknown survival status at Day 29 were treated as failure. The analysis in Part 2 was based on all participants enrolled by the pre-specified futility/early efficacy analysis and was used for demonstration of superiority to placebo for the primary efficacy outcome measure.
The number of participants with at least 1 AE is presented. 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 discontinued study intervention due to an AE is presented. 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.
Infectivity rate was defined as the number of participants with two quantifiable (≥lower limit of quantitation (LLOQ)) influenza challenge virus (A/France/759/21 \[H1N1\] strain) qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples (from nasal wash samples collected twice daily - morning and evening). Infectivity rate based on qRT-PCR in Part 1 participants from baseline (day 1 PM - afternoon) up to planned discharge from quarantine (day 8 AM - post viral inoculation) is presented. Per protocol, only data for part 1 participants were presented for this endpoint.
The number of participants with two quantifiable (≥lower limit of quantitation (LLOQ)) influenza challenge virus qRT-PCR measurements reported on ≥2 independent nasopharyngeal samples (from nasal wash samples collected twice daily - morning and evening). Infectivity rate based on qRT-PCR in Part 1 participants from day 2 PM up to day 8 post viral inoculation is presented. Per protocol, only data for part 1 participants were presented for this endpoint.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE is viral challenge-related as determined by the investigator. Number of participants experiencing ≥1 viral challenge-related AE in part 1 is presented. Per protocol, only data for part 1 participants were presented for this endpoint.
PVL was defined as the maximum viral load of influenza challenge virus from nasopharyngeal samples (nasal wash samples collected twice daily - morning and evening). PVL as determined by quantitative viral culture (QVC) was measured starting from day 1 PM (baseline) up to planned discharge from quarantine (day 8 AM). PVL of the H1N1 strain was measured by quantitative viral culture (QVC) using TCID50 plaque assay and analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for Molnupiravir PEP and placebo were presented for this endpoint.
VL-AUC is the area under the viral load-time curve of influenza challenge virus nasopharyngeal samples determined by QVC. H1N1 viral load was computed for each participant from nasopharyngeal samples collected twice daily (morning and evening) from day 2 AM to day 8 AM. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only data for Molnupiravir Tx and placebo were presented for this endpoint.
Blood for plasma samples was collected at pre-specified time points to determine the AUC0-inf of NHC.
Blood for plasma samples was collected at pre-specified time points to determine the Cmax of NHC.
An AE was 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 was therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE were reported.
The plasma AUC0-∞ of NHC is reported.
| Arm | Type | Description |
|---|---|---|
| Molnupiravir | EXPERIMENTAL | Participants will receive 800 mg molnupiravir orally every 12 hours for 5 days (a total of 10 consecutive doses) |
| Placebo | PLACEBO_COMPARATOR | Participants will receive molnupiravir-matching placebo orally every 12 hours for 5 days (a total of 10 consecutive doses) |
| Panel A: Molnupiravir Prophylaxis | EXPERIMENTAL | Participants received molnupiravir 800 mg every 12 hours for 5 days beginning on Day -1, and are inoculated with RSV-A Memphis 37b on Day 0. Participants switch to placebo beginning on the evening of Day 4 to the morning of Day 10. |
| Panel B: Molnupiravir Triggered Treatment | EXPERIMENTAL | Participants received placebo on Day -1, are inoculated with RSV-A Memphis 37b on Day 0, and continue to receive placebo until testing positive for RSV. Participants then received 800 mg of molnupiravir every 12 hours for 5 days. |
| Panel C: Matched Placebo | PLACEBO_COMPARATOR | Participants received placebo beginning on Day -1, are inoculated with RSV-A Memphis 37b on Day 0, and continue receiving placebo until the morning of Day 10. |
| Part 1: Molnupiravir 200 mg | EXPERIMENTAL | 200 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total) |
| Part 1: Molnupiravir 400 mg | EXPERIMENTAL | 400 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total) |
| Part 1: Molnupiravir 800 mg | EXPERIMENTAL | 800 mg molnupiravir administered orally every 12 hours for 5 days (10 doses total) |
| Part 1: Placebo | PLACEBO_COMPARATOR | Placebo matching molnupiravir administered orally every 12 hours for 5 days (10 doses total) |
| Part 2: Molnupiravir 800 mg | EXPERIMENTAL | 800 mg Molnupiravir (dose to be selected) administered orally every 12 hours for 5 days (10 doses total) |
| Part 2: Placebo | PLACEBO_COMPARATOR | Placebo matching molnupiravir administered orally every 12 hours for 5 days (10 doses total) |
| Panel A: Molnupiravir Post-Exposure Prophylaxis (Part 2) | EXPERIMENTAL | Molnupiravir 800 mg every 12 hours Day 0 PM through Day 5 AM, placebo molnupiravir every 12 hours Day 5 PM through Day 6 PM |
| Panel B: Molnupiravir Treatment (Part 2) | EXPERIMENTAL | Placebo molnupiravir every 12 hours Day 0 PM through Day 1 PM, molnupiravir 800 mg every 12 hours Day 2 AM through Day 6 PM |
| Panel C: Oseltamivir Treatment (Part 2) | ACTIVE_COMPARATOR | Placebo oseltamivir Day 0 PM through Day 1 PM, oseltamivir 75 mg plus placebo so the total number of capsules is always 4 per dose every 12 hours Day 2 AM through Day 6 PM |
| Panel D: Molnupiravir Placebo (Part 2) | PLACEBO_COMPARATOR | Placebo molnupiravir every 12 hours Day 0 PM through Day 6 PM |
| Virus Inoculation (Part 1 & 2) | EXPERIMENTAL | Influenza A challenge virus given once by intranasal administration |
| Panel A - Severe Renal Impairment Group | EXPERIMENTAL | Participants with severe renal impairment will receive a single oral 800 mg dose of molnupiravir. |
| Panel B - Healthy Control Group | EXPERIMENTAL | Participants in the healthy mean matched control group will receive a single oral 800 mg dose of molnupiravir. |
| Moderate Hepatic Impairment | EXPERIMENTAL | Participants with moderate hepatic impairment received a single oral dose of molnupiravir 800 mg on Day 1. |
| Healthy-Matched Control Group | EXPERIMENTAL | Healthy matched participants received a single oral dose of molnupiravir 800 mg on Day 1. |
| Name | Type | Description |
|---|---|---|
| Molnupiravir | DRUG | Molnupiravir administered orally as two 400 mg film-coated tablets every 12 hours for 5 days (a total of 10 consecutive doses) |
| Placebo | DRUG | Molnupiravir-matching placebo administered orally as two film-coated tablets every 12 hours for 5 days (a total of 10 consecutive doses) |
| RSV A Memphis 37b | BIOLOGICAL | RSV A Memphis 37b viral challenge given once by intranasal administration at a dosage of \~4 Log10 plaque forming units (PFUs). |
| Placebo molnupiravir | DRUG | Four placebo capsules matched to molnupiravir taken twice daily by mouth. |
| Placebo oseltamivir | DRUG | Placebo capsule matched to oseltamivir taken twice daily by mouth. |
| Oseltamivir | DRUG | One capsule of oseltamivir 75 mg taken twice daily by mouth. |
| Influenza A Virus | BIOLOGICAL | Influenza A challenge virus given once by intranasal administration at an inoculum concentration of between approximately 5 and 7 Log10 tissue culture infective dose 50% (TCID50/mL). |
Inclusion Criteria The main inclusion criteria include but are not limited to the following: * Is an individual of any sex/gender, ≥18 years of age * Has documentation of SARS-CoV-2 infection with sample collection ≤4 days prior to randomization * Has initial onset of signs/symptoms attributable t...
Molnupiravir is an investigational oral antiviral being studied for Coronavirus Disease 2019 (COVID-19), influenza infection, and respiratory syncytial virus (RSV). It is also being evaluated in people with renal impairment and hepatic impairment. It is a small molecule antiviral in Phase 3 development.
Molnupiravir is being developed by Merck & Company, Inc., which trades on the New York Stock Exchange under the ticker MRK. Merck is the sponsor of the clinical program studying the drug across COVID-19, influenza, RSV, and impairment populations.
Molnupiravir is in Phase 3 clinical development. The Phase 3 study NCT06667700 is currently recruiting, while earlier Phase 1 and Phase 2 studies in influenza, RSV, and renal impairment have been completed. It remains an investigational drug.
Molnupiravir has been studied in four registered trials. NCT06667700 is a recruiting Phase 3 COVID-19 study in high-risk adults. Completed trials include NCT05818124 in influenza, NCT05559905 in RSV, and NCT05386758 in severe renal impairment. Total enrollment across these studies is 7,258 participants.
Yes, MK-4482 is an alternative designation for Molnupiravir. The two names refer to the same investigational antiviral compound developed by Merck. Trial titles such as MK-4482-023 and MK-4482-019 use the MK-4482 code for the same drug.
Molnupiravir is being evaluated to prevent severe illness from Coronavirus Disease 2019 (COVID-19) in people who are high risk. The ongoing Phase 3 trial NCT06667700 is recruiting adults aged 18 and older across multiple countries including the United States, Japan, and several European nations.