Efficacy and Safety of Molnupiravir in Healthy Participants Inoculated With Experimental Influenza Virus (MK-4482-019)
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About
This is a phase 2a double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of molnupiravir (MK-4482) in healthy participants inoculated with experimental influenza virus. The primary hypotheses are that MK-4482 initiated 12 hours following intranasal inoculation of the influenza challenge virus reduces the peak viral load compared to placebo and that MK-4482 initiated 2 days following intranasal inoculation of the influenza challenge virus reduces the viral load area under the curve (AUC) compared to placebo.
Full description
This study has two parts. Part 1 is an open-label validation study, with a cohort of 20 untreated participants undergoing nasal inoculation with the A/France/759/21 [H1N1] strain on Day 0 to confirm viral infectivity and disease. Part 2 will be a randomized, double-blind placebo- and active-comparator-controlled study where participants will be inoculated on Day 0 with either the A/France/759/21 [H1N1] virus used in Part 1 or an alternative influenza virus. Part 2 will evaluate the antiviral efficacy, pharmacokinetics, and safety of MK-4482 in participants inoculated with the challenge virus.
Enrollment
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Inclusion criteria
- Is in good health based on medical history, physical examination, vital sign measurements, spirometry, and electrocardiograms performed before inoculation.
- Has a total body weight ≥50 kg and Body Mass Index (BMI) ≥18 kg/m^2 and ≤35 kg/m^2.
- For males: abstains from heterosexual intercourse as their preferred and usual lifestyle and agrees to remain abstinent OR uses contraception unless confirmed to be azoospermic.
- For participants assigned female sex at birth: is not pregnant or breastfeeding, AND is either not a person of childbearing potential (POCBP) or is a POCBP AND uses a contraceptive method that is highly effective (low user dependency method, OR a user dependent hormonal method in combination with barrier method), or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle, has a negative highly sensitive pregnancy test, abstains from breastfeeding, 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 has currently active, symptoms or signs suggestive of upper or lower respiratory tract infection within 4 weeks prior to admission to quarantine.
- Has a history of clinically significant endocrine, gastrointestinal (GI), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological abnormalities or diseases.
- Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy visit, or expected during the conduct of the study, or has a history of clinically significant psychiatric disorder of the last 5 years.
- Has a history of cancer.
- Has a history of rhinitis 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 prior to 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.
- Has a diagnosis of cluster headache/migraine or is receiving prophylaxis against migraine.
- Has a lifetime history of anaphylaxis and/or a lifetime history of severe allergic reaction. Significant intolerance to any food or drug in the last 12 months.
- Has had major surgery and/or donated or lost 1 unit of blood within 3 months prior to the prestudy visit.
- Uses or anticipates the use of concomitant medications, including vitamins or herbal and dietary supplements from approximately 2 weeks prior to the planned date of viral challenge until the poststudy visit.
- Has evidence of receipt of vaccine within the 4 weeks prior to the planned date of viral challenge.
- Intends to receive any vaccine(s) before the last day of follow-up.
- Has received any investigational drug within 3 months prior to the planned date of viral challenge.
- Has received 3 or more investigational drugs within the previous 12 months prior to the planned date of viral challenge.
- Has had prior inoculation with a virus from the same virus subtype as the challenge virus.
- Has had prior inoculation with a virus from the same virus-family as the challenge virus in the last 12 months.
- Has had prior participation in another human viral challenge study with a respiratory virus in the preceding 3 months, taken from the date of viral challenge in the previous study to the date of expected viral challenge in this study.
- Has smoked ≥10 pack-years at any time.
- Has a recent history or presence of alcohol addiction, or excessive use of alcohol.
- Consumes excessive amounts, defined as more than 6 servings of caffeinated beverages or xanthine-containing products.
- 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.
- Has had any nasal or sinus surgery within 3 months.
- Is a regular user of cannabis or any illicit drugs, or has a history of drug abuse within approximately 1 year.
Trial design
Primary purpose
Allocation
Interventional model
Masking
161 participants in 5 patient groups, including a placebo group
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Data sourced from clinicaltrials.gov
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