Back to resultsThe Effect of Early Treatment of PC945 on Aspergillus Fumigatus Lung Infection in Lung Transplant Patients.
Primary Purpose
Aspergillosis, Lung Transplant Infection
Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
PC945
Standard of Care
Sponsored by
About this trial
This is an interventional treatment trial for Aspergillosis
Eligibility Criteria
Inclusion Criteria (Surveillance Phase)
- Between the ages of 18 and 85 years.
- Received a single or bilateral lung transplant.
- Provided written informed consent prior to transplant
Exclusion Criteria (Surveillance Phase)
- Is precluded from participating in this study as a result of treatment with another investigational drug or participation in another clinical trial.
- If female, the subject is pregnant, lactating or breast feeding.
- Any other clinically significant disease or condition, which in the Investigator's medical opinion would preclude the subject's participation in a clinical trial (e.g., recent myocardial infarction).
- Is employed or is a first-degree relative of anyone employed by Pulmocide, a participating clinical trial site, or any contract research organisation involved in the study.
- Is receiving antiretroviral protease inhibitor therapy.
- Has human immunodeficiency virus or chronic, active hepatitis infection, or had a positive hepatitis B surface antigen or hepatitis C virus RNA test prior to transplant.
- Any known history or current evidence of alcohol or drug abuse that, in the Investigator's opinion, would exclude the subject from participation in the study
Inclusion Criteria (Pre-emptive Treatment Phase)
- A positive test for A. fumigatus in BAL during the Surveillance Phase of the study
- Provided written informed consent for participating in the Pre-Emptive Treatment Phase.
Exclusion Criteria (Pre-emptive Treatment Phase)
- Clinical, endobronchial and/or radiological features of fungal disease.*
- Any other disease or condition, which in the Investigator's medical opinion would preclude the subject's participation in the Pre-Emptive Treatment Phase of the study (e.g., recent myocardial infarction).
Inclusion Criteria (Follow-up Phase - SOC Antifungal Treatment)
- Subject is not eligible to receive pre-emptive PC945 treatment due to either clinical, endobronchial and/or radiological features of fungal disease OR a fungal infection other than A. fumigatus in BAL, that requires SoC antifungal treatment to be started during the Surveillance Phase of the study.
- Provided written informed consent for participating in the Follow-Up Phase for SoC antifungal treatment.
Exclusion Criteria (Follow-up Phase - SOC Antifungal Treatment)
- Any other disease or condition, which in the Investigator's medical opinion would preclude the subject's participation in the Follow-Up Phase for SoC antifungal treatment.
Sites / Locations
- Papworth Hospital
- Harefield Hospital
- Wythenshawe Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
PC945
Standard of Care
Arm Description
Standard of care anti-fungal medication
Outcomes
Primary Outcome Measures
Adverse events (AEs)
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for 12-lead ECG assessment at lease once post dose
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for vital signs assessment at lease once post dose
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for safety laboratory assessment at lease once post dose
Predicted post bronchodilator forced expiratory volume in 1 second (FEV1) values from participants receiving PC945
Forced vital capacity (FVC) values from participants receiving PC945
Area under the curve from time 0 to 2 h post-dose (AUC0-2)
Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable
Maximum plasma concentration
Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable
Concentration at the end of the dosage interval (Ctrough)
Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable
Secondary Outcome Measures
Lung Concentration of PC945
A. fumigatus fungal culture status (presence or absence) in subjects with a baseline A. fumigatus-positive bronchoalveolar lavage (BAL)
Change in BAL A. fumigatus measured by quantitative polymerase chain reaction (qPCR)
Change in the number of sputum A. fumigatus colony forming units (CFU) in cultured BAL.
Galactomannan levels in BAL
Aspergillus status (Presence or absence) of BAL using an Aspergillus immunochromatographic lateral flow device (AspLFD).
Status of fungal hyphae or pseudohyphae (presence or absence) on cytological examination
Subject experience of inhaled PC945
Assessed by a standardised study-specific questionnaire assessing participants' subjective experience across a number of domains including taste, smell and overall acceptability following inhalation of PC945.
Subject experience of inhaled amphotericin B
Assessed by a standardised study-specific questionnaire assessing participants' subjective experience across a number of domains including taste, smell and overall acceptability, following inhalation of amphotericin B.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03905447
Brief Title
The Effect of Early Treatment of PC945 on Aspergillus Fumigatus Lung Infection in Lung Transplant Patients.
Official Title
An Open-label, Pilot Study to Assess Safety, Tolerability, Pharmacokinetics and Effects of Inhaled PC945 in the Pre-emptive Treatment of Aspergillus Fumigatus Colonisation in Lung Transplant Recipients
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Terminated
Why Stopped
The study is being terminated early as a result of the coronavirus (COVID-19) outbreak.
Study Start Date
September 17, 2019 (Actual)
Primary Completion Date
June 1, 2020 (Actual)
Study Completion Date
June 1, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pulmocide Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study tests the effects of pre-emptive treatment with an experimental drug PC945 in lung transplant recipients whose lungs are infected by the fungus Aspergillus fumigatus.
PC945 may be useful in treating patients infected with Aspergillus fumigatus as, unlike the usual treatments, it is inhaled into the lung and has been designed to stay there and treat the infection. Participants will be monitored for up-to 12 weeks for the presence of Aspergillus in their lungs. Suitable participants will receive PC945 for an initial 28 days (Pre-emptive treatment phase) and, if needed, a further 8-weeks (Extended treatment phase).The amount of fungus in the patients' lungs will be measured over the course of the study. Participants with lung infections but not eligible for PC945 will be followed-up for 16-weeks on standard of care treatment. The study will take place at multiple sites in UK and 10 participants will receive PC945. The maximum study duration will be about 28 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aspergillosis, Lung Transplant Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Subjects in the surveillance phase with detectable Aspergillus fumigatus lung infections WITHOUT clinical symptoms will be eligible to receive PC945 for 28 days. Following 28 days on PC945, subjects with ongoing A. fumigatus lung infections may receive a further 56 days of PC945.
Subjects in the surveillance phase with EITHER detectable Aspergillus fumigatus lung infections WITH clinical symptoms, OR other fungal lung infection, will be eligible to be followed up for 16 weeks on Standard of Care.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PC945
Arm Type
Experimental
Arm Title
Standard of Care
Arm Type
Other
Arm Description
Standard of care anti-fungal medication
Intervention Type
Drug
Intervention Name(s)
PC945
Intervention Description
Nebulized PC945 5mg OD for 28 days with an optional extended treatment period of a further 56 days.
Intervention Type
Drug
Intervention Name(s)
Standard of Care
Intervention Description
Standard of Care antifungal medication
Primary Outcome Measure Information:
Title
Adverse events (AEs)
Time Frame
48 hours Post Transplant to Week 16 post treatment
Title
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for 12-lead ECG assessment at lease once post dose
Time Frame
Baseline to Week 16
Title
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for vital signs assessment at lease once post dose
Time Frame
Baseline to Week 16
Title
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for safety laboratory assessment at lease once post dose
Time Frame
Baseline to Week 16
Title
Predicted post bronchodilator forced expiratory volume in 1 second (FEV1) values from participants receiving PC945
Time Frame
Baseline to Week 16
Title
Forced vital capacity (FVC) values from participants receiving PC945
Time Frame
Baseline to Week 16
Title
Area under the curve from time 0 to 2 h post-dose (AUC0-2)
Description
Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable
Time Frame
Baseline to Week 16
Title
Maximum plasma concentration
Description
Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable
Time Frame
Baseline to Week 16
Title
Concentration at the end of the dosage interval (Ctrough)
Description
Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable
Time Frame
Baseline to Week 16
Secondary Outcome Measure Information:
Title
Lung Concentration of PC945
Time Frame
Baseline to Week 16
Title
A. fumigatus fungal culture status (presence or absence) in subjects with a baseline A. fumigatus-positive bronchoalveolar lavage (BAL)
Time Frame
Baseline to Week 16
Title
Change in BAL A. fumigatus measured by quantitative polymerase chain reaction (qPCR)
Time Frame
Baseline to Week 16
Title
Change in the number of sputum A. fumigatus colony forming units (CFU) in cultured BAL.
Time Frame
Baseline to Week 16
Title
Galactomannan levels in BAL
Time Frame
Baseline to Week 16
Title
Aspergillus status (Presence or absence) of BAL using an Aspergillus immunochromatographic lateral flow device (AspLFD).
Time Frame
Baseline to Week 16
Title
Status of fungal hyphae or pseudohyphae (presence or absence) on cytological examination
Time Frame
Baseline to Week 16
Title
Subject experience of inhaled PC945
Description
Assessed by a standardised study-specific questionnaire assessing participants' subjective experience across a number of domains including taste, smell and overall acceptability following inhalation of PC945.
Time Frame
Baseline to Week 16
Title
Subject experience of inhaled amphotericin B
Description
Assessed by a standardised study-specific questionnaire assessing participants' subjective experience across a number of domains including taste, smell and overall acceptability, following inhalation of amphotericin B.
Time Frame
Baseline to Week 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria (Surveillance Phase)
Between the ages of 18 and 85 years.
Received a single or bilateral lung transplant.
Provided written informed consent prior to transplant
Exclusion Criteria (Surveillance Phase)
Is precluded from participating in this study as a result of treatment with another investigational drug or participation in another clinical trial.
If female, the subject is pregnant, lactating or breast feeding.
Any other clinically significant disease or condition, which in the Investigator's medical opinion would preclude the subject's participation in a clinical trial (e.g., recent myocardial infarction).
Is employed or is a first-degree relative of anyone employed by Pulmocide, a participating clinical trial site, or any contract research organisation involved in the study.
Is receiving antiretroviral protease inhibitor therapy.
Has human immunodeficiency virus or chronic, active hepatitis infection, or had a positive hepatitis B surface antigen or hepatitis C virus RNA test prior to transplant.
Any known history or current evidence of alcohol or drug abuse that, in the Investigator's opinion, would exclude the subject from participation in the study
Inclusion Criteria (Pre-emptive Treatment Phase)
A positive test for A. fumigatus in BAL during the Surveillance Phase of the study
Provided written informed consent for participating in the Pre-Emptive Treatment Phase.
Exclusion Criteria (Pre-emptive Treatment Phase)
Clinical, endobronchial and/or radiological features of fungal disease.*
Any other disease or condition, which in the Investigator's medical opinion would preclude the subject's participation in the Pre-Emptive Treatment Phase of the study (e.g., recent myocardial infarction).
Inclusion Criteria (Follow-up Phase - SOC Antifungal Treatment)
Subject is not eligible to receive pre-emptive PC945 treatment due to either clinical, endobronchial and/or radiological features of fungal disease OR a fungal infection other than A. fumigatus in BAL, that requires SoC antifungal treatment to be started during the Surveillance Phase of the study.
Provided written informed consent for participating in the Follow-Up Phase for SoC antifungal treatment.
Exclusion Criteria (Follow-up Phase - SOC Antifungal Treatment)
Any other disease or condition, which in the Investigator's medical opinion would preclude the subject's participation in the Follow-Up Phase for SoC antifungal treatment.
Facility Information:
Facility Name
Papworth Hospital
City
Papworth Everard
State/Province
Cambridge
ZIP/Postal Code
CB23 3RE
Country
United Kingdom
Facility Name
Harefield Hospital
City
Harefield
State/Province
Uxbridge
ZIP/Postal Code
UB9 6JH
Country
United Kingdom
Facility Name
Wythenshawe Hospital
City
Manchester
ZIP/Postal Code
M23 9LT
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
The Effect of Early Treatment of PC945 on Aspergillus Fumigatus Lung Infection in Lung Transplant Patients.
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