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

NCT ID: NCT05559905

Last Updated: 2025-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-02
• Study Completion Date: 2023-06-08

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.

Conditions

Respiratory Syncytial Virus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Panel A: Molnupiravir Prophylaxis

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.

Group Type: EXPERIMENTAL

Molnupiravir

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Placebo capsule matched to molnupiravir taken twice daily by mouth.

RSV A Memphis 37b

Intervention Type: BIOLOGICAL

RSV A Memphis 37b viral challenge given once by intranasal administration at a dosage of \~4 Log10 plaque forming units (PFUs).

Panel B: Molnupiravir Triggered Treatment

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.

Group Type: EXPERIMENTAL

Molnupiravir

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Placebo capsule matched to molnupiravir taken twice daily by mouth.

RSV A Memphis 37b

Intervention Type: BIOLOGICAL

RSV A Memphis 37b viral challenge given once by intranasal administration at a dosage of \~4 Log10 plaque forming units (PFUs).

Panel C: Matched Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsule matched to molnupiravir taken twice daily by mouth.

RSV A Memphis 37b

Intervention Type: BIOLOGICAL

RSV A Memphis 37b viral challenge given once by intranasal administration at a dosage of \~4 Log10 plaque forming units (PFUs).

Interventions

Molnupiravir

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

Intervention Type: DRUG

Placebo

Placebo capsule matched to molnupiravir taken twice daily by mouth.

Intervention Type: DRUG

RSV A Memphis 37b

RSV A Memphis 37b viral challenge given once by intranasal administration at a dosage of \~4 Log10 plaque forming units (PFUs).

Intervention Type: BIOLOGICAL

Other Intervention Names

MK-4482

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

hVIVO Services ( Site 0001)

London, London, City of, United Kingdom

Countries

United Kingdom

References

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.

Reference Type: RESULT

PMID: 40175624 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

MK-4482-017

Identifier Type: OTHER

Identifier Source: secondary_id

4482-017

Identifier Type: -

Identifier Source: org_study_id