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

NCT05818124 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 4482-019
• Study Type: interventional
• Target: 161
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Influenza Infection

Outcome Measures

Primary Outcomes (5)

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

  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.

  From Day 1 PM up to Day 8 post viral inoculation

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

  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.

  From Day 2 PM up to Day 8 post viral inoculation

• Part 1: Number of Participants Experiencing ≥1 Viral Challenge-related 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. 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.

  Up to approximately 31 days

• 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)

  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.

  From Day 1 PM up to Day 8 post viral inoculation

• 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)

  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.

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

Secondary Outcomes (79)

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

  From Day 1 PM up to Day 8 post viral inoculation

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

  From Day 2 PM Up to Day 8 post viral inoculation

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

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

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

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

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

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

Study Arms (5)

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

Drug: Molnupiravir; Drug: Placebo molnupiravir; Biological: Influenza A Virus

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

Drug: Molnupiravir; Drug: Placebo molnupiravir; Biological: Influenza A Virus

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

Drug: Placebo oseltamivir; Drug: Oseltamivir; Biological: Influenza A Virus

Panel D: Molnupiravir Placebo (Part 2)

PLACEBO COMPARATOR

Placebo molnupiravir every 12 hours Day 0 PM through Day 6 PM

Drug: Placebo molnupiravir; Biological: Influenza A Virus

Virus Inoculation (Part 1 & 2)

EXPERIMENTAL

Influenza A challenge virus given once by intranasal administration

Biological: Influenza A Virus

Interventions

Molnupiravir DRUG

Four molnupiravir 200 mg capsules (800 mg total dose) taken twice daily by mouth.

Also known as: MK-4482

Panel A: Molnupiravir Post-Exposure Prophylaxis (Part 2); Panel B: Molnupiravir Treatment (Part 2)

Placebo molnupiravir DRUG

Four placebo capsules matched to molnupiravir taken twice daily by mouth.

Panel A: Molnupiravir Post-Exposure Prophylaxis (Part 2); Panel B: Molnupiravir Treatment (Part 2); Panel D: Molnupiravir Placebo (Part 2)

Placebo oseltamivir DRUG

Placebo capsule matched to oseltamivir taken twice daily by mouth.

Panel C: Oseltamivir Treatment (Part 2)

Oseltamivir DRUG

One capsule of oseltamivir 75 mg taken twice daily by mouth.

Panel C: Oseltamivir Treatment (Part 2)

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).

Panel A: Molnupiravir Post-Exposure Prophylaxis (Part 2); Panel B: Molnupiravir Treatment (Part 2); Panel C: Oseltamivir Treatment (Part 2); Panel D: Molnupiravir Placebo (Part 2); Virus Inoculation (Part 1 & 2)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (1)

hVIVO Services ( Site 0001)

London, London, City of, E1 2AX, United Kingdom

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Interventions

molnupiravir; Oseltamivir

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2023
• First Posted: April 18, 2023
• Study Start: August 21, 2023
• Primary Completion: June 28, 2024
• Study Completion: June 28, 2024
• Last Updated: August 6, 2025
• Results First Posted: August 6, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)