Pre-emptive treatment of Aspergillus fumigatus colonisation in lung transplant recipients MedDRA version: 20.0 Level: LLT Classification code 10059259 Term: Pulmonary aspergillosis System Organ Class: 100000004862
Conditions
Interventions
Product Name: PC945
Pharmaceutical Form: Nebuliser suspension
INN or Proposed INN: NA
Current Sponsor code: PC945
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentrat
Sponsors
Pulmocide Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Surveillance Phase: 1. Between the ages of 18 and 85 years. 2. Received a single or bilateral lung transplant. 3. Provided written informed consent prior to transplant. Pre-emptive treatment phase: 1. A positive test for A. fumigatus in BAL during the Surveillance Phase of the study 2. Provided written informed consent for participating in the Pre-Emptive Treatment Phase. Follow-up Phase: 1. 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. 2. Provided written informed consent for participating in the follow-up phase for SoC antifungal treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: Surveillance Phase: 1. Is precluded from participating in this study as a result of treatment with another investigational drug or participation in another clinical trial. 2. If female, the subject is pregnant, lactating or breast feeding. 3. 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). 4. 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. 5. Is receiving antiretroviral protease inhibitor therapy. 6. 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. 7. 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. Pre-emptive Treatment Phase: 1. Clinical, endobronchial and/or radiological features of fungal disease. 2. 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). Follow-up Phase: 1. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the safety and tolerability of PC945 in lung transplant recipients with A. fumigatus colonisation • To ascertain derived systemic pharmacokinetic parameters of PC945 and the potential circulating metabolite(s), if detectable, following single and repeat doses of PC945 ;Secondary Objective: • To ascertain airway/lung concentrations of PC945 during and after treatment. Lung concentrations of oral azoles will also be measured, if prescribed as SoC • To investigate the effect of PC945 on eradication of A. fumigatus from BAL • To investigate the effect of PC945 on the A. fumigatus fungal burden in BAL • To investigate the effect of PC945 on markers of fungal infection in BAL • To compare the tolerability and subject experience of inhaled amphotericin B (used as prophylaxis) and inhaled PC945 (used as pre-emptive treatment) • To assess the safety and tolerability of an additional 8 weeks of PC945 treatment in lung transplant recipients with persistent A. fumigatus colonisation following the initial 28 days of PC945 treatment • To measure the effect on lung function (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]) ;Primary end point(s): • Safety parameters: o Adverse events o 12-lead electrocardiogram (ECG) including QT interval corrected for Bazett’s formula (QTcB), QT interval, QRS interval, PR interval and ventricular rate o Vital signs (systolic and diastolic blood pressure, pulse rate [supine], respiratory rate and oxygen saturation) o Clinical laboratory evaluations (haematology, clinical chemistry and urinalysis); immunosuppressant levels o Spirometry • Derived pharmacokinetic parameters for systemic PC945 and the potential circulating metabolite(s), if detectable, including area under the concentration-time curve from 0 to 4 hours post-dose (AUC0-4h), maximum observed concentration (Cmax), concentration at the end of the dosage interval (Ctrough), time to maximum observed concentration (Tmax) and metaboli | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Lung concentrations of PC945. These will be measured in BAL and/or in endobronchial brushings or biopsy (if collected as SoC) during and post-PC945 treatment. Calculation of lung:plasma ratio of PC945 concentrations, corrected for procedure-related dilution where appropriate. Concentrations of oral azoles given as SoC may also be measured. • Results of markers of fungal infection at baseline, during and post pre-emptive PC945 treatment: In BAL: o Presence or absence of A. fumigatus on fungal culture o A. fumigatus concentration measured by quantitative polymerase chain reaction (qPCR) o The number of A. fumigatus colony forming units (CFU) on fungal culture o Galactomannan levels o Presence or absence of Aspergillus on an Aspergillus immunochromatographic lateral flow device (AspLFD) o Presence or absence of fungal hyphae or pseudohyphae on cytological examination (if performed as standard of care) •Tolerability and subject experience of inhaled PC945 • Tolerability and subject experience of inhaled amphotericin B • Lung function parameters at baseline, during treatment and post pre-emptive PC945 treatment: FEV1 and FVC ;Timepoint(s) of evaluation of this end point: Bronchoscopy: Surveillance phase (SP) - standard of care (SOC) bronchoscopy visits (BV); Pre-emptive treatment phase (PETP): Wk 2, 6, Wk 10 of extended treatment (ET) and BV during ET; Follow-up phase (FUP): SOC BV Questionnaires: SP: SOC BV; PETP: PD, D1, Wk2, 4, 6, 16, start of ET, Wk 4, 8, 10 of ET and BV during ET; FUP: SOC BV Spirometry: SP: D1, SOC BV; PETP: PD, D1, Wk2, 4, 6, 16, start of ET, Wk 4, 8, 10 of ET and BV during ET; FUP: SOC BV | — |
Countries
United Kingdom
Contacts
Public ContactDirector of Clinical Development
Pulmocide Ltd
Outcome results
None listed