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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03905447
Recruitment Status : Terminated (The study is being terminated early as a result of the coronavirus (COVID-19) outbreak.)
First Posted : April 5, 2019
Last Update Posted : June 12, 2020
Sponsor:
Information provided by (Responsible Party):
Pulmocide Ltd

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.


Condition or disease Intervention/treatment Phase
Aspergillosis Lung Transplant Infection Drug: PC945 Drug: Standard of Care Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
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
Actual Study Start Date : September 17, 2019
Actual Primary Completion Date : June 1, 2020
Actual Study Completion Date : June 1, 2020

Resource links provided by the National Library of Medicine


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.

Standard of Care
Standard of care anti-fungal medication
Drug: Standard of Care
Standard of Care antifungal medication




Primary Outcome Measures :
  1. Adverse events (AEs) [ Time Frame: 48 hours Post Transplant to Week 16 post treatment ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Predicted post bronchodilator forced expiratory volume in 1 second (FEV1) values from participants receiving PC945 [ Time Frame: Baseline to Week 16 ]
  6. Forced vital capacity (FVC) values from participants receiving PC945 [ Time Frame: Baseline to Week 16 ]
  7. Area under the curve from time 0 to 2 h post-dose (AUC0-2) [ Time Frame: Baseline to Week 16 ]
    Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable

  8. Maximum plasma concentration [ Time Frame: Baseline to Week 16 ]
    Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable

  9. Concentration at the end of the dosage interval (Ctrough) [ Time Frame: Baseline to Week 16 ]
    Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable


Secondary Outcome Measures :
  1. Lung Concentration of PC945 [ Time Frame: Baseline to Week 16 ]
  2. 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 ]
  3. Change in BAL A. fumigatus measured by quantitative polymerase chain reaction (qPCR) [ Time Frame: Baseline to Week 16 ]
  4. Change in the number of sputum A. fumigatus colony forming units (CFU) in cultured BAL. [ Time Frame: Baseline to Week 16 ]
  5. Galactomannan levels in BAL [ Time Frame: Baseline to Week 16 ]
  6. Aspergillus status (Presence or absence) of BAL using an Aspergillus immunochromatographic lateral flow device (AspLFD). [ Time Frame: Baseline to Week 16 ]
  7. Status of fungal hyphae or pseudohyphae (presence or absence) on cytological examination [ Time Frame: Baseline to Week 16 ]
  8. Subject experience of inhaled PC945 [ Time Frame: Baseline to Week 16 ]
    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.

  9. Subject experience of inhaled amphotericin B [ Time Frame: Baseline to Week 16 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03905447


Locations
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United Kingdom
Papworth Hospital
Papworth Everard, Cambridge, United Kingdom, CB23 3RE
Harefield Hospital
Harefield, Uxbridge, United Kingdom, UB9 6JH
Wythenshawe Hospital
Manchester, United Kingdom, M23 9LT
Sponsors and Collaborators
Pulmocide Ltd
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Responsible Party: Pulmocide Ltd
ClinicalTrials.gov Identifier: NCT03905447    
Other Study ID Numbers: PC_ASP_002
2018-000240-26 ( EudraCT Number )
First Posted: April 5, 2019    Key Record Dates
Last Update Posted: June 12, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection
Aspergillosis
Mycoses