Clinical Trial Results:
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
Summary
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EudraCT number |
2018-001667-24 |
Trial protocol |
GB |
Global end of trial date |
19 Feb 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
17 May 2020
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First version publication date |
17 May 2020
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
PC_RSV_004
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03715023 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Pulmocide Ltd.
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Sponsor organisation address |
Pulmocide Ltd, 52 Princes Gate, London, United Kingdom, SW7 2PG
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Public contact |
Director of Clinical Development, Pulmocide Ltd, +44 7766250133, Lindsey@pulmocide.com
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Scientific contact |
Director of Clinical Development, Pulmocide Ltd, +44 7766250133, Lindsey@pulmocide.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Interim
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Date of interim/final analysis |
27 Feb 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Feb 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Feb 2019
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
•To evaluate the anti-viral effect of inhaled PC786 compared with placebo when added to standard of care (SoC) RSV treatment in
haematopoietic stem cell transplant (HSCT) recipients with acute RSV infection
•To assess the safety and tolerability of 3 days of inhaled PC786 in HSCT subjects with acute RSV infection
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practice and applicable regulatory requirements. Known instances of non-conformance were documented and are not considered to have had an impact on the overall conclusions of the study.
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Background therapy |
Subjects received SoC for treatment of RSV at the study site. All medications taken were recorded. Oral ribavirin was permitted at all times on the study. Intravenous ribavirin treatment as SoC may be administered if required, only if a subject was already enrolled in the study. Treatment with intravenous immunoglobulins was permitted throughout the study. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 Dec 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 5
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Worldwide total number of subjects |
5
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EEA total number of subjects |
5
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
5
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Six subjects met all of the eligibility criteria and were randomised to receive treatment at 3 sites in the UK between 11 Dec 2018 and 19 Feb 2019. One subject was withdrawn from the study without being dosed. Five subjects who received 3 doses of PC786 or placebo were therefore included in the safety population. | |||||||||
Pre-assignment
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Screening details |
It was planned to recruit 30 subjects, with a minimum of 15 subjects to conduct an interim analysis after the winter 18/19 season. A total of six subjects were screened to take part in the study, of which, five subjects were randomised and completed the study. | |||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Assessor | |||||||||
Blinding implementation details |
Due to a difference in appearance of the active and placebo treatments, the investigational
product was prepared and dosed by independent staff team members who did not undertake any other study duties.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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PC786 | |||||||||
Arm description |
Once daily doses of PC786 10mg administered by inhalation via a face mask for a total of 3 doses | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
PC786 powder for reconstitution 30mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nebuliser suspension
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Routes of administration |
Inhalation use
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Dosage and administration details |
Nebulised PC786 was administered by inhalation via a facemask at the study site at a dose of 10 mg once daily for three days. In addition to the study drug, subjects were treated according to the SoC at the study site.
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Arm title
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Placebo | |||||||||
Arm description |
Once daily doses of placebo administered by inhalation via a face mask for a total of 3 doses | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nebuliser solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
Nebulised placebo was administered by oral inhalation via a face mask once daily for 3 doses. In addition to the study drug, subjects were treated according to the SoC at the study site.
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Baseline characteristics reporting groups
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Reporting group title |
PC786
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Reporting group description |
Once daily doses of PC786 10mg administered by inhalation via a face mask for a total of 3 doses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Once daily doses of placebo administered by inhalation via a face mask for a total of 3 doses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
PC786
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Reporting group description |
Once daily doses of PC786 10mg administered by inhalation via a face mask for a total of 3 doses | ||
Reporting group title |
Placebo
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Reporting group description |
Once daily doses of placebo administered by inhalation via a face mask for a total of 3 doses | ||
Subject analysis set title |
PC786
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Pharmacokinetic Parameters for PC786
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End point title |
Slope of RSV viral load [1] | ||||||||||||
End point description |
Slope of the RSV load over Days 1–3 measured in nasal secretions by reverse transcription quantitative polymerase chain reaction (RT-qPCR)
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End point type |
Primary
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End point timeframe |
Baseline to day 3
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no treatment comparisons in this study due to the small sample size (N=5). |
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No statistical analyses for this end point |
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End point title |
Change in Viral load to Day 7 | ||||||||||||
End point description |
Change in RSV load from baseline to day 7 measured in nasal secretions by reverse transcription quantitative polymerase chain reaction (RT-qPCR)
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End point type |
Secondary
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End point timeframe |
Days 1 to 7
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No statistical analyses for this end point |
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End point title |
Duration of Viral Shedding | ||||||||||||
End point description |
Duration of viral shedding
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End point type |
Secondary
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End point timeframe |
Day 1 to day 28
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No statistical analyses for this end point |
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End point title |
Change in viral load to day 4 | ||||||||||||
End point description |
Change in RSV load from baseline (before first dose of PC786 or placebo) to Day 4
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End point type |
Secondary
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End point timeframe |
Baseline to day 4 am
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No statistical analyses for this end point |
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End point title |
Cmax | ||||||||
End point description |
Maximum plasma concentration
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End point type |
Secondary
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End point timeframe |
Time 0h to day 28
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No statistical analyses for this end point |
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End point title |
Tmax | ||||||||
End point description |
time to maximum concentration
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End point type |
Secondary
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End point timeframe |
time 0h to day 28
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No statistical analyses for this end point |
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End point title |
Lower Respiratory Tract Infection/Pneumonia and Oxygen Requirements and Ventilation | |||||||||||||||||||||
End point description |
Development of LRTI or pneumonia (due to RSV or secondary [bacterial or fungal] infection), Oxygen Requirements and Invasive Ventilation
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End point type |
Secondary
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End point timeframe |
Baseline to Day 28
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Consent until completion of the subject's last study-related procedure (which may include contact for follow-up of safety).
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Adverse event reporting additional description |
All clinically relevant changes (including laboratory safety testing), with the exception of expected signs and symptoms of RSV-related illness, observed during the study were recorded as an AE.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.1
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Reporting groups
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Reporting group title |
PC786
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Reporting group description |
Once daily doses of PC786 10mg administered by inhalation via a face mask for a total of 3 doses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Once daily doses of placebo administered by inhalation via a face mask for a total of 3 doses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Poor recruitment during the 2018/19 RSV season meant that an interim analysis to adjust the sample size was not possible. The chances of completing enrolment in the study in the 2019/20 RSV season were low and the study was terminated prematurely. |