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

NCT05559905 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 4482-017MK-4482-017
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

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.

Conditions

Respiratory Syncytial Virus

Outcome Measures

Primary Outcomes (2)

• Panel A vs Panel C: Peak Viral Load (PVL) Determined by Viral Quantitative Culture

  PVL was defined as the maximum viral load during a specified time period. PVL determined by viral quantitative culture (plaque assay) was measured from Day 2 up to Day 12 (end of participant quarantine). PVL (on the log10 scale) of RSV A Memphis 37b determined by viral quantitative culture (plaque assay) between Day 2 and Day 12 am after intranasal inoculation (Day 0) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only Panel A (prophylaxis) and Panel C (placebo) were included in the model.

  From Day 2 up to Day 12

• Panel B vs. Panel C: Area Under the Viral Load-time Curve (VL-AUC) Determined by Viral Quantitative Culture

  VL-AUC between Day 2 and Day 12 after intranasal inoculation (Day 0) was computed for each participant, based on RSV viral load determined by viral quantitative culture (plaque assay) from nasal wash samples collected twice daily (morning and evening). In order to calculate the AUC, the actual time that the assessment was collected was used within the AUC calculation. VL-AUC (on the log10 scale) was analyzed using a linear model with treatment group as a fixed categorical effect. Per protocol, only Panel B (treatment) and Panel C (placebo) were included in the model. For both panels, only the participants with RSV infection were included.

  From Day 2 up to Day 12

Secondary Outcomes (31)

• All Panels: Number of Participants Who Experienced ≥1 Adverse Event (AE)

  From Day -1 up to Day 28

• All Panels: Number of Participants Who Experienced ≥1 Serious AE (SAE)

  From Day -1 up to Day 28

• All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related AE

  From Day 0 up to Day 28

• All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related SAE

  From Day 0 up to Day 28

• All Panels: Number of Participants Using Concomitant Medications From Viral Challenge Through Day 28

  From Day 0 up to Day 28

Study Arms (3)

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.

Drug: Molnupiravir; Drug: Placebo; Biological: RSV A Memphis 37b

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.

Drug: Molnupiravir; Drug: Placebo; Biological: RSV A Memphis 37b

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.

Drug: Placebo; Biological: RSV A Memphis 37b

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 Prophylaxis; Panel B: Molnupiravir Triggered Treatment

Placebo DRUG

Placebo capsule matched to molnupiravir taken twice daily by mouth.

Panel A: Molnupiravir Prophylaxis; Panel B: Molnupiravir Triggered Treatment; Panel C: Matched Placebo

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).

Panel A: Molnupiravir Prophylaxis; Panel B: Molnupiravir Triggered Treatment; Panel C: Matched Placebo

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 (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.

You may not qualify if:

• 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 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).

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (1)

hVIVO Services ( Site 0001)

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

Location

Related Publications (1)

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

  PMID: 40175624 RESULT

Related Links

• Merck Clinical Trials Information

MeSH Terms

Interventions

molnupiravir

Results Point of Contact

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

ClinicalTrialsDisclosure@merck.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 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2022
• First Posted: September 29, 2022
• Study Start: November 2, 2022
• Primary Completion: April 18, 2023
• Study Completion: June 8, 2023
• Last Updated: July 18, 2025
• Results First Posted: May 20, 2024

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)