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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

Tracking Information
First Submitted Date  ICMJE March 6, 2019
First Posted Date  ICMJE April 5, 2019
Last Update Posted Date June 12, 2020
Actual Study Start Date  ICMJE September 17, 2019
Actual Primary Completion Date June 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 4, 2019)
  • Adverse events (AEs) [ Time Frame: 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 [ Time Frame: Baseline to Week 16 ]
  • 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 ]
  • 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 ]
  • Predicted post bronchodilator forced expiratory volume in 1 second (FEV1) values from participants receiving PC945 [ Time Frame: Baseline to Week 16 ]
  • Forced vital capacity (FVC) values from participants receiving PC945 [ Time Frame: Baseline to Week 16 ]
  • 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
  • Maximum plasma concentration [ Time Frame: Baseline to Week 16 ]
    Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2019)
  • Lung Concentration of PC945 [ Time Frame: Baseline to Week 16 ]
  • 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 ]
  • Change in BAL A. fumigatus measured by quantitative polymerase chain reaction (qPCR) [ Time Frame: Baseline to Week 16 ]
  • Change in the number of sputum A. fumigatus colony forming units (CFU) in cultured BAL. [ Time Frame: Baseline to Week 16 ]
  • Galactomannan levels in BAL [ Time Frame: Baseline to Week 16 ]
  • Aspergillus status (Presence or absence) of BAL using an Aspergillus immunochromatographic lateral flow device (AspLFD). [ Time Frame: Baseline to Week 16 ]
  • Status of fungal hyphae or pseudohyphae (presence or absence) on cytological examination [ Time Frame: Baseline to Week 16 ]
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2019)
  • Lung Concentration of PC945 [ Time Frame: Baseline to Week 16 ]
  • 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 ]
  • Change in BAL A. fumigatus measured by quantitative polymerase chain reaction (qPCR) [ Time Frame: Baseline to Week 16 ]
  • Change in the number of sputum A. fumigatus colony forming units (CFU) in cultured BAL. [ Time Frame: Baseline to Week 16 ]
  • Galactomannan levels in BAL [ Time Frame: Baseline to Week 16 ]
  • Aspergillus status (Presence or absence) of BAL using an Aspergillus immunochromatographic lateral flow device (AspLFD). [ Time Frame: Baseline to Week 16 ]
  • Status of fungal hypae or pseudohypahe (presence or absence) on cytological examination [ Time Frame: Baseline to Week 16 ]
  • Subject experience of inhaled PC945 [ Time Frame: Baseline to Week 16 ]
    Assessed by a standardised study-specific questionnaire.
  • Subject experience of inhaled amphotericin B [ Time Frame: Baseline to Week 16 ]
    Assessed by a standardised study-specific questionnaire.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Early Treatment of PC945 on Aspergillus Fumigatus Lung Infection in Lung Transplant Patients.
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Aspergillosis
  • Lung Transplant Infection
Intervention  ICMJE
  • Drug: PC945
    Nebulized PC945 5mg OD for 28 days with an optional extended treatment period of a further 56 days.
  • Drug: Standard of Care
    Standard of Care antifungal medication
Study Arms  ICMJE
  • Experimental: PC945
    Intervention: Drug: PC945
  • Standard of Care
    Standard of care anti-fungal medication
    Intervention: Drug: Standard of Care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 10, 2020)
2
Original Estimated Enrollment  ICMJE
 (submitted: April 4, 2019)
10
Actual Study Completion Date  ICMJE June 1, 2020
Actual Primary Completion Date June 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03905447
Other Study ID Numbers  ICMJE PC_ASP_002
2018-000240-26 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pulmocide Ltd
Study Sponsor  ICMJE Pulmocide Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Pulmocide Ltd
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP