Anti-viral Effect of PC786 on RSV Infection on HSCT Recipients

Study Overview
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Brief Summary
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This study tests the effects of an experimental drug PC786 in people infected with Respiratory Syncytial Virus (RSV). PC786 may be useful in treating patients infected with RSV as it works by interfering with the way the virus multiplies. PC786 is an inhaled medicine. Participants will be treated with SoC treatment (e.g. oral ribavirin and/or IV immunoglobulin), half of the participants will receive PC786 in addition and half will receive a placebo treatment. The study will take place at multiple sites in UK and will include approximately 30 participants. The maximum study duration will be about 4 weeks.

Official Title
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A Double Blind, Placebo-controlled Study to Assess the Anti-viral Effect, Safety and Tolerability of Inhaled PC786 for the Treatment of Acute Respiratory Syncytial Virus (RSV) Infection in Adult Hematopoietic Stem Cell Transplant Recipients

Conditions
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Respiratory Syncytial Virus Infections

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Received an allogeneic or autologous hematopoietic stem cell transplant (HSCT) using any conditioning regimen Experienced new onset of at least one of the following respiratory symptoms ≤5 days before study Day 1: Nasal congestion or stuffiness, runny nose (rhinorrhoea), cough, or sore throat OR Worsening of at least one of those symptoms, if symptoms are chronic OR Wheezing, sputum production, pleuritic chest pain, increased respiratory rate, signs on chest auscultation, hypoxia, increased supplemental oxygen requirement or new infiltrates on chest X-ray/CT A positive RSV diagnostic test Provided written informed consent Exclusion Criteria: Is intubated and requires invasive ventilation Has received any investigational RSV vaccine after HSCT, or has received any monoclonal anti-RSV antibodies within 4 months or 5 half-lives before participation Treatment with intravenous ribavirin Positive for test for influenza or parainfluenza Significant untreated bacteraemia or fungaemia Significant untreated bacterial, fungal, or viral pneumonia Precluded from participating as a result of treatment with another investigational drug or participation in another clinical trial Other disease or condition which would preclude the subject's participation in a clinical trial Is receiving an antiretroviral protease inhibitor Has chronic, active hepatitis infection Known alcohol or drug abuse

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active + SoC<br>Daily doses of PC786 for 3 days + SoC | Drug: PC786<br>* PC786 suspension for inhalation<br>Drug: SOC<br>* Standard treatment for RSV infection at study site<br>|
| Placebo Comparator: Placebo + SoC<br>Daily doses of Placebo for 3 days + SoC | Drug: Placebo<br>* Placebo solution for inhalation<br>Drug: SOC<br>* Standard treatment for RSV infection at study site<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RSV viral load measured in nasal secretions by reverse transcription quantitative PCR (RT-qPCR) |  | Day 1 to Day 3 | 
| Proportion of participants reporting one or more treatment-emergent adverse event (TEAE) |  | Baseline to Day 28 | 
| Proportion of participants who discontinue due to an adverse event |  | Baseline to Day 28 | 
| Proportion of participants who meet the markedly abnormal criteria for 12-lead ECG assessment at lease once post dose |  | Baseline to Day 28 | 
| Proportion of participants who meet the markedly abnormal criteria for vital signs assessment at lease once post dose |  | Baseline to Day 28 | 
| Proportion of participants who meet the markedly abnormal criteria for safety laboratory assessment at lease once post dose |  | Day 1 to Day 28 | 
| Proportion of participants who meet the markedly abnormal criteria for peak expiratory flow assessment at lease once post dose |  | Day 1 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average change in RSV load measured in nasal secretion |  | Day 1 to Day 7 | 
| Change in RSV load in nasal secretion |  | Baseline to Day 3 | 
| Change in RSV load in nasal secretion |  | Baseline to Day 7 | 
| Duration in viral shedding measured in nasal secretion |  | Day 1 to Day 28 | 
| Determination of nasal concentrations of PC786 |  | Days 1, 2, 3, 7, 14 and 28 | 
| Maximum observed concentration (Cmax) of PC786 measured in plasma |  | Day 1, Pre-dose to 4 hours | 
| Trough plasma concentration (Ctrough) of PC786 |  | Days 2 and 3, Pre-dose | 
| Area under the concentration versus time curve from time zero to time at 4 hours (AUC0-4) of PC786 in plasma |  | Day 1, Pre-dose to 4 hours | 
| Last quantifiable concentration (Ct last) of PC786 measured in plasma |  | Day 1, and multiple timepoints to Day 28 | 
| Changes in RSV symptoms measured using a symptom diary card |  | Days 1, 2, 3, 4, 5, 6, 7, 14 and 28 | 
| Proportion of participants developing lower respiratory tract infection (LRTI) or pneumonia |  | Day 1 to 28 | 
| Proportion of participants progressing to invasive ventilation |  | Day 1 to 28 | 
| Trends in oxygen saturation index |  | Day 1 to Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RSV infection, Hematopoeitic stem cell transplant