Clinical trial NCT05559905: Respiratory Syncytial Virus (RSV) Human Challenge Study of Molnupiravir in Healthy Participants (MK-4482-017)
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 Respiratory Syncytial Virus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Syncytial Virus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-09-29
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Panel A vs Panel C: Peak Viral Load (PVL) Determined by Viral Quantitative Culture
timeFrame: From Day 2 up to Day 12
measure: Panel B vs. Panel C: Area Under the Viral Load-time Curve (VL-AUC) Determined by Viral Quantitative Culture
timeFrame: From Day 2 up to Day 12
Secondary outcomes:
measure: All Panels: Number of Participants Who Experienced ≥1 Adverse Event (AE)
timeFrame: From Day -1 up to Day 28
measure: All Panels: Number of Participants Who Experienced ≥1 Serious AE (SAE)
timeFrame: From Day -1 up to Day 28
measure: All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related AE
timeFrame: From Day 0 up to Day 28
measure: All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related SAE
timeFrame: From Day 0 up to Day 28
measure: All Panels: Number of Participants Using Concomitant Medications From Viral Challenge Through Day 28
timeFrame: From Day 0 up to Day 28
measure: Panel A vs. Panel C: VL-AUC Determined by Viral Quantitative Culture
timeFrame: From Day 2 up to Day 12
measure: Panel A vs. Panel C: VL-AUC Determined by Real-time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR)
timeFrame: Day 2 up through Day 12
measure: Panel A vs. Panel C: PVL Determined by qRT-PCR
timeFrame: Day 2 up through Day 12
measure: Panel A vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores (TSS-AUC)
timeFrame: From Day -1 up to Day 12
measure: Panel A vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores Change From Baseline (TSS-AUC-CFB)
timeFrame: Baseline (Day -1) and up to Day 12
measure: Panel A vs. Panel C: Peak Total Symptom Scores
timeFrame: From Day -1 up to Day 12
measure: Panel A vs. Panel C: Peak Daily Symptom Score
timeFrame: From Day 2 up to Day 12
measure: Panel A vs. Panel C: Percentage of Participants With Respiratory Syncytial Virus (RSV) Infection Based on qRT-PCR
timeFrame: From Day 2 up to Day 12
measure: Panel A vs. Panel C: Percentage of Participants With RSV Infection Based on Cell Culture Measurement of Nasal Sample
timeFrame: From Day 2 up to Day 12
measure: Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Symptomatic RSV Infection
timeFrame: From Day 2 up to Day 12
measure: Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Moderately Severe Symptomatic RSV Infection
timeFrame: From Day 2 up to Day 12
measure: Panel A vs. Panel C: Percentage of Participants With Culture-Confirmed Symptomatic RSV Infection
timeFrame: From Day 2 up to Day 12
measure: Panel B vs. Panel C: PVL Determined by Viral Quantitative Culture
timeFrame: From Day 2 up to Day 12
measure: Panel B vs. Panel C: Time to Negative Test by Viral Quantitative Culture
timeFrame: From Day 2 up to Day 12
measure: Panel B vs. Panel C: VL-AUC Determined by qRT-PCR
timeFrame: From Day 2 up to Day 12
measure: Panel B vs. Panel C: PVL Determined by qRT-PCR
timeFrame: From Day 2 up to Day 12
measure: Panel B vs. Panel C: Time to Negative Test by qRT-PCR
timeFrame: From Day 2 up to Day 12
measure: Panel B vs. Panel C: TSS-AUC
timeFrame: From Day -1 up to Day 12
measure: Panel B vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores Change From Baseline (TSS-AUC-CFB)
timeFrame: Baseline (Day -1) and up to Day 12
measure: Panel B vs. Panel C: Peak TSS
timeFrame: From Day -1 up to Day 12
measure: Panel B vs. Panel C: Peak Daily Symptom Score
timeFrame: From Day -1 up to Day 12
measure: Panel B vs. Panel C: Time to Symptom Resolution
timeFrame: From Day -1 up to Day 12
measure: Panels A & B: Maximum Plasma Concentration (Cmax) of N-Hydroxycytidine (NHC)
timeFrame: Day -1: Predose and 12 hours postdose; Days 2, 5, and 6: 12 hours postdose; Days 4 and 7: predose and 0.5, 1.5, 4, 8, and 12 hours postdose
measure: Panels A & B: Time to Maximum Plasma Concentration (Tmax) of NHC
timeFrame: Day -1: Predose and 12 hours postdose; Days 2, 5, and 6: 12 hours postdose; Days 4 and 7: predose and 0.5, 1.5, 4, 8, and 12 hours postdose
measure: Panels A & B: Area Under the Plasma Concentration Curve From 0 to 12 Hours Postdose (AUC0-12) of NHC
timeFrame: Day -1: Predose and 12 hours postdose; Days 2, 5, and 6: 12 hours postdose; Days 4 and 7: predose and 0.5, 1.5, 4, 8, and 12 hours postdose
measure: Panels A & B: Trough Concentration (Ctrough) of NHC
timeFrame: Day 2 at 12 hours predose (Panel A) or Day 6 at 12 hours predose (Panel B)
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: hVIVO Services ( Site 0001)
state: London, City Of
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: