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

Respiratory Syncytial Virus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05559905
• Other study ID #: 4482-017
• Secondary ID: MK-4482-017
• Status: Completed
• Phase: Phase 2
• Start date: November 2, 2022
• Est. completion date: June 8, 2023

Study information

• Verified date: July 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 2A, double-blind, randomized, placebo-controlled 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 MK-4482 will reduce the peak viral load (PVL) compared to placebo when given either before (prophylactic) or after (treatment) RSV-A Memphis 37b inoculation. Participants arrive at the study center for check-in between Day -3 and Day -1. The assigned treatment sequence (consisting of a combination of molnupiravir or placebo) begins Day -1. Participants receive viral inoculation with RSV-A Memphis 37b on Day 0, and depart on Day 12. There is a follow-up visit on Day 28.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: June 8, 2023
• Est. primary completion date: April 18, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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, or any over-the-counter medications (eg, ibuprofen) within 7 days prior to Viral Challenge.
• 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.

Related Conditions & MeSH terms

• Respiratory Syncytial Virus
• Virus Diseases

Intervention

Drug:
• Molnupiravir
Four molnupiravir 200 mg capsules (800 mg total dose) taken twice daily by mouth.
• Placebo
Placebo capsule matched to molnupiravir taken twice daily by mouth.

Biological:
• 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).

Locations

Country	Name	City	State
United Kingdom	hVIVO Services ( Site 0001)	London	London, City Of

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Panel A: Peak Viral Load (PVL) Based on Viral Quantitative Culture	PVL is the maximum viral load determined by viral quantitative culture (plaque assay).	From Day 2 up to Day 12
Primary	Panel B: Area Under the Viral Load-time Curve (VL-AUC) Determined by Viral Quantitative Culture	VL-AUC is determined by viral quantitative culture (plaque assay).	Twice daily from Day -1 to Day 11; once on Day 12
Secondary	Panels A & B: Number of participants experiencing =1 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.	From Day -1 up to Day 28
Secondary	Panels A & B: Number of participants experiencing =1 serious AE (SAE)	An SAE is any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires hospitalization or prolongs existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly or birth defect; or is another important medical event such as invasive/malignant cancers or substance abuse/dependency.	From Day -1 up to Day 28
Secondary	Panels A & B: Number of participants experiencing =1 viral challenge-related 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.	From Day 0 up to Day 28
Secondary	Panels A & B: Number of participants experiencing =1 viral challenge-related SAE	An SAE is any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires hospitalization or prolongs existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly or birth defect; or is another important medical event such as invasive/malignant cancers or substance abuse/dependency.	From Day 0 up to Day 28
Secondary	Panel A: VL-AUC Determined by Viral Quantitative Culture	VL-AUC is determined by quantitative viral culture (plaque assay).	Twice daily from Day 2 to Day 11; once on Day 12
Secondary	Panel A: VL-AUC Determined by Real-time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR)	VL-AUC is determined by qRT-PCR.	Twice daily from Day 2 to Day 11; once on Day 12
Secondary	Panel A: PVL Determined by qRT-PCR	PVL is determined by maximum viral load defined by qRT-PCR.	From Day 2 up to Day 12
Secondary	Panel A: Area Under the Curve over Time of Total Clinical Symptoms (TSS-AUC)	TSS-AUC measured from 10 symptoms within the graded symptom scoring will be reported. Participants use a symptom diary card to record the severity of 10 symptoms on a scale ranging from 0 ("absence") to 3 ("bothersome and interferes with activities").	Three times daily from Day 2 to Day 11, once on Day 12
Secondary	Panel A: Area Under the Curve over Time of Total Clinical Symptoms Change from Baseline (TSS-AUC-CFB)	TSS-AUC-CFB measured from 10 symptoms within the graded symptom scoring will be reported. Participants use a symptom diary card to record the severity of 10 symptoms on a scale ranging from 0 ("absence") to 3 ("bothersome and interferes with activities").	Baseline and three times daily from Day 2 to Day 11, once on Day 12
Secondary	Panel A: Peak Total Clinical Symptoms (TSS)	Peak TSS measured from 10 symptoms within the graded symptom scoring will be reported. Participants use a symptom diary card to record the severity of 10 symptoms on a scale ranging from 0 ("absence") to 3 ("bothersome and interferes with activities").	From Day 2 up to Day 12
Secondary	Panel A: Peak Daily Symptom Score	Peak individual daily sum of symptom score measured from 10 symptoms within the graded symptom scoring will be reported. Participants use a symptom diary card to record the severity of 10 symptoms on a scale ranging from 0 ("absence") to 3 ("bothersome and interferes with activities").	From Day 2 up to Day 12
Secondary	Panel A: Incidence of Respiratory Syncytial Virus (RSV) Infection Based on qRT-PCR	RSV infection is defined as 2 quantifiable (> LLOQ) qRT-PCR measurements reported on 2 or more days.	From Day 2 up to Day 12
Secondary	Panel A: Incidence of A Nasal Swab Positive Test for RSV	The incidence of a positive (> LLOQ) cell culture measurement in nasal swab samples.	From Day 2 up to Day 12
Secondary	Panel A: Incidence of RT-PCR Confirmed Symptomatic RSV Infection	Incidence of symptomatic RSV infection is defined as 2 quantifiable (=LLOQ) qRT-PCR measurements reported on 2 or more days and a symptom of =2 at a single time point.	From Day 2 up to Day 12
Secondary	Panel A: Incidence of RT-PCR Confirmed Moderately Severe Symptomatic RSV Infection	Incidence of symptomatic RSV infection is defined as 2 quantifiable (=LLOQ) qRT-PCR measurements reported on 2 or more days and any symptoms of grade =2 at a single time point.	From Day 2 up to Day 12
Secondary	Panel A: Incidence of Culture Lab Confirmed Symptomatic RSV Infection	Incidence of culture lab confirmed RSV infection is defined by 1 quantifiable (=LLOQ) cell culture measurement from Day 2 up to Day 12, and symptom of =2 at a single time point.	From Day 2 up to Day 12
Secondary	Panel B: PVL Determined by Viral Quantitative Culture	VL-AUC is determined by quantitative viral culture (plaque assay).	From Day -1 up to Day 12
Secondary	Panel B: Time to Negative Test by Viral Quantitative Culture	The time to a negative test (result < low limit of quantification [LLOQ]) by viral quantitative culture (plaque assay) in days will be reported.	From Day -1 up to Day 12
Secondary	Panel B: VL-AUC Determined by qRT-PCR	VL-AUC is determined by qRT-PCR.	Twice daily from Day -1 to Day 11; once on Day 12
Secondary	Panel B: PVL Determined by qRT-PCR	PVL is determined by qRT-PCR.	From Day -1 up to Day 12
Secondary	Panel B: Time to Negative Test by qRT-PCR	The time in days to a negative test (result < LLOQ) by viral quantitative culture (plaque assay) will be reported.	From Day -1 up to Day 12
Secondary	Panel B: TSS-AUC	TSS-AUC measured from 10 symptoms within the graded symptom scoring will be reported. Participants use a symptom diary card to record the severity of 10 symptoms on a scale ranging from 0 ("absence") to 3 ("bothersome and interferes with activities").	Three times daily from Day 2 to Day 11, once on Day 12
Secondary	Panel B: TSS-AUC-CFB	TSS-AUC-CFB measured from 10 symptoms within the graded symptom scoring will be reported. Participants use a symptom diary card to record the severity of 10 symptoms on a scale ranging from 0 ("absence") to 3 ("bothersome and interferes with activities").	Baseline and three times daily from Day 2 to Day 11, once on Day 12
Secondary	Panel B: Peak TSS	Peak TSS measured from 10 symptoms within the graded symptom scoring will be reported. Participants use a symptom diary card to record the severity of 10 symptoms on a scale ranging from 0 ("absence") to 3 ("bothersome and interferes with activities").	From Day 2 up to Day 12
Secondary	Panel B: Peak Daily Symptom Score	Peak individual daily sum of symptom score measured from 10 symptoms within the graded symptom scoring will be reported. Participants use a symptom diary card to record the severity of 10 symptoms on a scale ranging from 0 ("absence") to 3 ("bothersome and interferes with activities").	From Day 2 up to Day 12
Secondary	Panel B: Time to Negative Test by Symptom Resolution	The time in days to symptom resolution, as measured from 10 symptoms within the graded daily symptom scoring system, will be reported.	From Day 2 up to Day 12
Secondary	Panels A & B: Maximum plasma concentration (Cmax) of N-hydroxycytidine (NHC)	The Cmax of NHC will be reported.	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
Secondary	Panels A & B: Time to maximum plasma concentration (Tmax) of NHC	The Tmax of NHC will be reported.	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
Secondary	Panels A & B: Area uncer the plasma concentration from 0 to 12 hours postdose (AUC0-12) of NHC	The AUC0-12 of NHC will be reported.	Day -1: Predose and 12 hours postdose; Days 2, 5,Day 7: predose and 0.5, 1.5, 4, 8, and 12 hours postdose
Secondary	Panels A & B: Trough concentration (Ctrough) of NHC	The Ctrough of NHC will be reported.	Day -1: Predose and 12 hours postdose; Days 2, 5,Day 7: predose and 0.5, 1.5, 4, 8, and 12 hours postdose

External Links

•   Merck Clinical Trials Information