Phase 2
N=116
Respiratory Syncytial Virus (RSV) Human Challenge Study of Molnupiravir in Healthy Participants (MK-4482-017)
Respiratory Syncytial Virus
Bottom Line
View on ClinicalTrials.gov: NCT05559905 ↗Enrolled (actual)
116
Serious AEs
0.0%
Results posted
May 2024
Primary outcome: Primary: Panel A vs Panel C: Peak Viral Load (PVL) Determined by Viral Quantitative Culture — 2.55; 2.84 log10 plaque forming units (PFU)/mL — p=0.578
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Molnupiravir (Drug); Placebo (Drug); RSV A Memphis 37b (Biological)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Apr 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Panel A vs Panel C: Peak Viral Load (PVL) Determined by Viral Quantitative Culture |
2.55; 2.84 | 0.578 |
| PRIMARY Panel B vs. Panel C: Area Under the Viral Load-time Curve (VL-AUC) Determined by Viral Quantitative Culture |
7.02; 9.72 | 0.201 |
| SECONDARY All Panels: Number of Participants Who Experienced ≥1 Adverse Event (AE) |
13; 15; 13 | — |
| SECONDARY All Panels: Number of Participants Who Experienced ≥1 Serious AE (SAE) |
0; 0; 0 | — |
| SECONDARY All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related AE |
1; 1; 1 | — |
| SECONDARY All Panels: Number of Participants Who Experienced ≥1 Viral Challenge-Related SAE |
0; 0; 0 | — |
| SECONDARY All Panels: Number of Participants Using Concomitant Medications From Viral Challenge Through Day 28 |
6; 7; 7 | — |
| SECONDARY Panel A vs. Panel C: VL-AUC Determined by Viral Quantitative Culture |
7.56; 8.17 | 0.736 |
| SECONDARY Panel A vs. Panel C: VL-AUC Determined by Real-time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) |
17.62; 19.54 | 0.646 |
| SECONDARY Panel A vs. Panel C: PVL Determined by qRT-PCR |
4.66; 4.80 | 0.849 |
| SECONDARY Panel A vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores (TSS-AUC) |
7.5; 9.59 | 0.371 |
| SECONDARY Panel A vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores Change From Baseline (TSS-AUC-CFB) |
6.84; 8.66 | 0.360 |
| SECONDARY Panel A vs. Panel C: Peak Total Symptom Scores |
2.74; 3.20 | 0.459 |
| SECONDARY Panel A vs. Panel C: Peak Daily Symptom Score |
0.8; 1.1; 0.6; 0.9; 0.7; 1.0 | — |
| SECONDARY Panel A vs. Panel C: Percentage of Participants With Respiratory Syncytial Virus (RSV) Infection Based on qRT-PCR |
68.42; 65.00 | — |
| SECONDARY Panel A vs. Panel C: Percentage of Participants With RSV Infection Based on Cell Culture Measurement of Nasal Sample |
57.89; 55.00 | — |
| SECONDARY Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Symptomatic RSV Infection |
47.37; 50.00 | — |
| SECONDARY Panel A vs. Panel C: Percentage of Participants With qRT-PCR Confirmed Moderately Severe Symptomatic RSV Infection |
26.32; 42.50 | — |
| SECONDARY Panel A vs. Panel C: Percentage of Participants With Culture-Confirmed Symptomatic RSV Infection |
42.11; 45.00 | — |
| SECONDARY Panel B vs. Panel C: PVL Determined by Viral Quantitative Culture |
2.85; 3.53 | 0.253 |
| SECONDARY Panel B vs. Panel C: Time to Negative Test by Viral Quantitative Culture |
5.0; 5.0 | 0.1708 |
| SECONDARY Panel B vs. Panel C: VL-AUC Determined by qRT-PCR |
20.58; 26.51 | 0.257 |
| SECONDARY Panel B vs. Panel C: PVL Determined by qRT-PCR |
5.43; 6.02 | 0.453 |
| SECONDARY Panel B vs. Panel C: Time to Negative Test by qRT-PCR |
NA; 9.0 | 0.9121 |
| SECONDARY Panel B vs. Panel C: TSS-AUC |
4.74; 6.57 | 0.377 |
| SECONDARY Panel B vs. Panel C: Area Under the Curve Over Time of Total Symptom Scores Change From Baseline (TSS-AUC-CFB) |
2.60; 2.74 | 0.958 |
| SECONDARY Panel B vs. Panel C: Peak TSS |
3.00; 3.62 | 0.520 |
| SECONDARY Panel B vs. Panel C: Peak Daily Symptom Score |
0.6; 1.4; 1.3; 2.0; 1.5; 2.3 | — |
| SECONDARY Panel B vs. Panel C: Time to Symptom Resolution |
6.0; 8.5 | 0.0459 sig |
| SECONDARY Panels A & B: Maximum Plasma Concentration (Cmax) of N-Hydroxycytidine (NHC) |
3640; 3010 | — |
| SECONDARY Panels A & B: Time to Maximum Plasma Concentration (Tmax) of NHC |
1.47; 1.48 | — |
| SECONDARY Panels A & B: Area Under the Plasma Concentration Curve From 0 to 12 Hours Postdose (AUC0-12) of NHC |
9270; 8100 | — |
| SECONDARY Panels A & B: Trough Concentration (Ctrough) of NHC |
25.1; 19.8 | — |
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.
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
Data sourced from ClinicalTrials.gov (NCT05559905). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.