The Effect of Early Treatment of PC945 on Aspergillus Fumigatus Lung Infection in Lung Transplant Patients.

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

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.

Study Overview

• Status: Terminated
• Conditions: Aspergillosis; Lung Transplant Infection
• Intervention / Treatment: Drug: PC945; Drug: Standard of Care

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

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M23 9LT
    • Wythenshawe Hospital
  • Cambridge
    • Papworth Everard, Cambridge, United Kingdom, CB23 3RE
      • Papworth Hospital
  • Uxbridge
    • Harefield, Uxbridge, United Kingdom, UB9 6JH
      • Harefield Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PC945	Drug: PC945; Nebulized PC945 5mg OD for 28 days with an optional extended treatment period of a further 56 days.
Other: Standard of Care; Standard of care anti-fungal medication	Drug: Standard of Care; Standard of Care antifungal medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)		48 hours Post Transplant to Week 16 post treatment
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for 12-lead ECG assessment at lease once post dose		Baseline to Week 16
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for vital signs assessment at lease once post dose		Baseline to Week 16
Proportion of participants receiving PC945 who meet the markedly abnormal criteria for safety laboratory assessment at lease once post dose		Baseline to Week 16
Predicted post bronchodilator forced expiratory volume in 1 second (FEV1) values from participants receiving PC945		Baseline to Week 16
Forced vital capacity (FVC) values from participants receiving PC945		Baseline to Week 16
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	Baseline to Week 16
Maximum plasma concentration	Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable	Baseline to Week 16
Concentration at the end of the dosage interval (Ctrough)	Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable	Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung Concentration of PC945		Baseline to Week 16
A. fumigatus fungal culture status (presence or absence) in subjects with a baseline A. fumigatus-positive bronchoalveolar lavage (BAL)		Baseline to Week 16
Change in BAL A. fumigatus measured by quantitative polymerase chain reaction (qPCR)		Baseline to Week 16
Change in the number of sputum A. fumigatus colony forming units (CFU) in cultured BAL.		Baseline to Week 16
Galactomannan levels in BAL		Baseline to Week 16
Aspergillus status (Presence or absence) of BAL using an Aspergillus immunochromatographic lateral flow device (AspLFD).		Baseline to Week 16
Status of fungal hyphae or pseudohyphae (presence or absence) on cytological examination		Baseline to Week 16
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.	Baseline to Week 16
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.	Baseline to Week 16

Collaborators and Investigators

• Sponsor: Pulmocide Ltd

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2019
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: March 6, 2019
• First Submitted That Met QC Criteria: April 4, 2019
• First Posted (Actual): April 5, 2019

Study Record Updates

• Last Update Posted (Actual): July 16, 2021
• Last Update Submitted That Met QC Criteria: July 15, 2021
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bacterial Infections and Mycoses; Mycoses; Infections; Aspergillosis
• Other Study ID Numbers: PC_ASP_002; 2018-000240-26 (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