Anti-viral Effect of PC786 on RSV Infection on HSCT Recipients (TreatRSV1)

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

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.

Study Overview

• Status: Terminated
• Conditions: Respiratory Syncytial Virus Infections
• Intervention / Treatment: Drug: PC786; Drug: SOC; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • Bristol, United Kingdom, BS2 8ED
    • Bristol Haematology and Oncology Centre
  • Liverpool, United Kingdom, L7 8XP
    • Clatterbridge Cancer Centre NHS Foundation Trust
  • London, United Kingdom, SW17 0QT
    • St Georges University Hospital
  • Manchester, United Kingdom, M13 9WL
    • Manchester University NHS Foundation Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospital NHS Trust
  • Sheffield, United Kingdom, S10 2JF
    • Sheffield Teaching Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Pulmocide Ltd
• Investigators: Study Director: Alison Murray, Pulmocide Ltd

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2018
• Primary Completion (Actual): February 19, 2019
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: October 17, 2018
• First Submitted That Met QC Criteria: October 19, 2018
• First Posted (Actual): October 22, 2018

Study Record Updates

• Last Update Posted (Actual): June 12, 2019
• Last Update Submitted That Met QC Criteria: June 10, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: RSV infection; Hematopoeitic stem cell transplant
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Disease Attributes; Paramyxoviridae Infections; Mononegavirales Infections; Pneumovirus Infections; Infections; Communicable Diseases; Respiratory Syncytial Virus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; PC-786
• Other Study ID Numbers: PC_RSV_004; 2018-001667-24 (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