A Study to Investigate VX-787 Given to Adult Volunteers Inoculated With Live Influenza Virus

Study Overview
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Brief Summary
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The purpose of this study is to determine the antiviral activity and safety of VX-787 given to healthy adult volunteers that have been inoculated with the influenza virus.

Official Title
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A Phase 2a, Randomized, Double-Blind,Placebo-Controlled Study to Investigate the Effects of VX-787 Administered to Adult Volunteers Experimentally Inoculated With Live Influenza Virus

Conditions
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Influenza Virus

Intervention / Treatment
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* Drug: VX-787
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Negative human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C(HCV) antibody screen Have not been vaccinated for influenza virus since 2006 or had a known influenza-like illness in the current season (as determined in the medical history), defined as in the last 12 months before Screening Exclusion Criteria: Subjects who are pregnant or nursing, or who are male and have a female partner who is pregnant, nursing, or is planning to become pregnant during the study period (from at least 14 days before the first dose until 90 days of the last dose of study drug) Presence of any significant acute or chronic, uncontrolled medical or psychiatric illness Abnormal pulmonary function as evidenced by clinically significant abnormalities in spirometry Health care workers (including doctors, nurses, medical students and allied healthcare professionals) anticipated to have patient contact within two weeks of viral inoculation Intending to travel(to countries for which vaccinations are recommended or where high risk of infections exists) Subjects with a history of asthma, COPD, pulmonary hypertension, reactive airway disease, or any chronic lung condition of any etiology; any history during adulthood of asthma of any etiology, COPD, or any use of a bronchodilator or other asthma medication during adulthood Regular daily smokers History or evidence of autoimmune disease or known impaired immune responsiveness History of heart failure or any other severe cardiac abnormality including clinically significant arrhythmia Receipt of any investigational drug within 3 months, or prior participation in a clinical trial of any influenza vaccine, medication, or experimental respiratory viral challenge delivered directly to the respiratory tract within 1 year before viral inoculation Previous exposure to study drug or similar substance(s)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 787 low dose<br>VX-787 low dose capsule, taken orally for 5 days | Drug: VX-787<br> <br> |
| Experimental: 787 high dose<br>VX-787 high dose capsule, taken orally for 5 days | Drug: VX-787<br> <br> |
| Experimental: Placebo low dose<br>Matching placebo low dose capsule, taken orally for 5 days | Drug: Placebo<br> <br> |
| Experimental: Placebo high dose<br>Matching placebo high dose capsule, taken orally for 5 days | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is viral AUC as calculated in cell culture of nasal swabs (quantitation of nasal swabs for viral infectivity by cell culture), from initiation of VX-787 treatment |  | up to 11 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability based on assessment of adverse events, clinical laboratory assessments, 12-lead electrocardiograms (ECGs), and vital signs. |  | up to 33 days | 
| Total tissue count and total mucus weight after viral inoculation |  | up to 10 days | 
| Sequence analysis of the relevant target region of influenza |  | up to 8 days | 
| Pharmacokinetic (PK) parameters of VX-787 | As measured by AUC, Cmax, tmax | 8 days | 
| Composite symptom score AUC |  | up to 8 days | 
| Viral AUC calculated by RT-PCR of nasal swabs, from initiation of VX-787 treatment |  | up to 8 days | 
| Duration of viral shedding by cell culture and/or RT-PCR |  | up to 8 days | 
| Peak viral shedding titer by cell culture and/or RT-PCR |  | up to 8 days | 
| Time to resolution from peak viral shedding by cell culture and/or RT-PCR |  | up to 8 days | 
| Time to peak of composite sympton score, duration, and time to resolution of composite score from peak |  | up to 8 days | 
| Peak severity of symptoms after viral inoculation |  | up to 8 days | 
| Duration of influenza-like illness after viral inoculation |  | up to 8 days |