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

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Syncytial Virus Infections
• Intervention / Treatment: Drug: PC786; Drug: Placebo/vehicle

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, E1 2AX
    • hVIVO Services Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PC786; Repeat dose	Drug: PC786; Repeat doses
Placebo Comparator: Placebo/vehicle; Repeat dose	Drug: Placebo/vehicle; Repeat doses

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pulmocide Ltd
• Investigators: Principal Investigator: Bryan J Murray, MBBS, hVIVO Services Ltd

Publications and helpful links

General Publications

• DeVincenzo J, Cass L, Murray A, Woodward K, Meals E, Coates M, Daly L, Wheeler V, Mori J, Brindley C, Davis A, McCurdy M, Ito K, Murray B, Strong P, Rapeport G. Safety and Antiviral Effects of Nebulized PC786 in a Respiratory Syncytial Virus Challenge Study. J Infect Dis. 2022 Jun 15;225(12):2087-2096. doi: 10.1093/infdis/jiaa716.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2017
• Primary Completion (Actual): May 9, 2018
• Study Completion (Actual): May 9, 2018

Study Registration Dates

• First Submitted: December 8, 2017
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (Actual): December 22, 2017

Study Record Updates

• Last Update Posted (Actual): May 16, 2018
• Last Update Submitted That Met QC Criteria: May 15, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Respiratory Syncytial Virus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; PC-786
• Other Study ID Numbers: PC_RSV_003; 2017-002563-18 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No