A Study of PC786 to Evaluate the Antiviral Activity, Safety and Pharmacokinetics of Multiple Doses in an RSV Challenge Study

Study Overview
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Brief Summary
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PC786 is a new medicine being developed for treatment of respiratory syncytial virus. The main purpose of this study is to evaluate the antiviral activity of PC786 in healthy adults infected with RSV virus in a viral challenge study.

Official Title
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A Single-blind, Placebo Controlled, Randomised Study to Evaluate Antiviral Activity and Safety and Pharmacokinetics of Inhaled PC786 Against Respiratory Syncytial Virus (RSV) in Healthy Adult Subjects in a Virus Challenge Model

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Drug: PC786
* Drug: Placebo/vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is in good health as determined by the Investigator based on medical history, physical examination, and routine laboratory tests at a screening evaluation. Male or female, aged between 18 and 55 years inclusive Body weight ≥ 50 kg and Body Mass Index (BMI) ≥ 18 kg/m2 and ≤ 30kg/m2 Subject must provide written informed consent Serosuitable to the challenge virus. Exclusion Criteria: History or evidence of any clinically significant or currently active major clinical illness. Any significant abnormality altering the anatomy of the nose or nasopharynx Any nasal or sinus surgery within six months of the study Abnormal lung function Positive human immunodeficiency virus (HIV), active hepatitis A (HAV), B (HBV), or C (HCV) test. Presence of cold like symptoms and/or fever on admission for the study History or currently active symptoms suggestive of upper or lower respiratory tract infection within 6 weeks of the study History of anaphylaxis-and/or a history of severe allergic reaction or significant intolerance to any food or drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PC786<br>Repeat dose | Drug: PC786<br>* Repeat doses<br>|
| Placebo Comparator: Placebo/vehicle<br>Repeat dose | Drug: Placebo/vehicle<br>* Repeat doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RSV viral load | AUC 0-t for RSV viral load measured in nasal washes by reverse transcription quantitative polymerase chain reaction (RT-qPCR) | Baseline to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants reporting one or more treatment-emergent adverse event (TEAE) |  | Screening to Day 28 | 
| Number of participants who discontinue due to an adverse event |  | Screening to Day 28 | 
| Number of participants who meet the markedly abnormal criteria for 12-lead ECG assessment at least once post dose |  | Screening to Day 28 | 
| Number of participants who meet the markedly abnormal criteria for vital signs assessments at least once post dose |  | Screening to Day 28 | 
| Number of participants who meet the markedly abnormal criteria for safety laboratory assessments at least once post dose |  | Screening to Day 28 | 
| Number of participants who meet the markedly abnormal criteria for spirometry (FEV1 & FVC measured together) assessments at least once post dose |  | Screening to Day 28 | 
| Area under the plasma concentration versus time curve (AUC) of PC786 measured in plasma |  | Pre-dose and at multiple time points to Day 12 | 
| Maximum observed concentration (Cmax) of PC786 measured in plasma |  | Pre-dose and at multiple time points to Day 12 | 
| Time maximum concentration observed (Tmax) of PC786 measured in plasma |  | Pre-dose and at multiple time points to Day 12 | 
| Apparent terminal half life (T1/2) of PC786 measured in plasma |  | Pre-dose and at multiple time points to Day 12 | 
| Determination of nasal concentrations of PC786 | PC786 concentrations in mucosal lining fluid collected using synthetic absorptive matrix | Pre-dose and at multiple time points to Day 28 | 
| Comparison of mucus production following treatment with PC786 or placebo post viral inoculation | Reduction in weight of mucus produced post viral infection | Baseline to Day 12 | 
| Comparison of the effect of treatment with PC786 or placebo on RSV symptoms | Composite score of self-reported symptoms on a symptom diary card. Nasal symptoms, sneezing, sore throat, cough, headache, wheezing, chest tightness, shortness of breath, joint aches, feverishness, malaise, earache are assessed using a score of 0 (no symptoms), 1 (just noticeable), 2 (bothersome but able to participate in activities), 3 (bothersome and not able to participate in activities) | Baseline to Day 12 | 
| Change in viral load measured in nasal wash | Change in viral load before first dose of PC786 to Day 12 | Baseline to Day 12 | 
| Time to non-detectability of virus measured in nasal wash |  | Baseline to Day 12 | 
| Peak viral load measured in nasal wash |  | Baseline to Day 12 | 
| Time peak viral load observed measured in nasal wash |  | Baseline to Day 12 |