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

NCT03905447 | Terminated Phase 2

• 2 other identifiers: PC_ASP_0022018-000240-26
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 3

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.

Conditions

Aspergillosis; Lung Transplant Infection

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (9)

• 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

Study Arms (2)

PC945

EXPERIMENTAL

Drug: PC945

Standard of Care

OTHER

Standard of care anti-fungal medication

Drug: Standard of Care

Interventions

PC945 DRUG

Nebulized PC945 5mg OD for 28 days with an optional extended treatment period of a further 56 days.

PC945

Standard of Care DRUG

Standard of Care antifungal medication

Standard of Care

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between the ages of 18 and 85 years.
• Received a single or bilateral lung transplant.
• Provided written informed consent prior to transplant

You may not qualify if:

• 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
• 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.
• 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).
• 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.
• 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.

Sponsors & Collaborators

• Pulmocide Ltd: lead

Study Sites (3)

Papworth Hospital

Papworth Everard, Cambridge, CB23 3RE, United Kingdom

Location

Harefield Hospital

Harefield, Uxbridge, UB9 6JH, United Kingdom

Location

Wythenshawe Hospital

Manchester, M23 9LT, United Kingdom

Location

MeSH Terms

Conditions

Aspergillosis

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 6, 2019
• First Posted: April 5, 2019
• Study Start: September 17, 2019
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: July 16, 2021

Record last verified: 2020-06

Locations

GB (3)