Pulmonary aspergillosis and candidiasis of lung MedDRA version: 20.0 Level: LLT Classification code 10059259 Term: Pulmonary aspergillosis System Organ Class: 100000004862 MedDRA version: 20.0 Level: LLT Classification code 10007155 Term: Candidiasis of lung System Organ Class: 100000004862
Conditions
Interventions
Product Code: PC945
Pharmaceutical Form: Nebuliser suspension
INN or Proposed INN: Not applicable
Current Sponsor code: PC945
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equa
Sponsors
Pulmocide Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject must be male or female, aged 18 years (inclusive) or older (at the time of consent). 2. Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose and requirements of the study and is willing to participate. 3. Subjects with a diagnosis of moderate to severe asthma (GINA Step 3, 4 or 5) made by a respiratory physician and treated with an inhaled steroid or other chronic respiratory disease. a. For subjects with asthma this must have a diagnosis shown either by: i. Historical evidence of: 1. Increased airway hyper-responsiveness (methacholine PC20 12%). or ii. Bronchodilator reversibility =12% or =200 mL improvement in FEV1 post bronchodilator after administration of a short-acting beta agonist at screening. OR b. Subjects with other chronic respiratory disease (such as COPD or bronchiectasis) susceptible to fungal bronchitis. 4. Subject must have a positive sputum fungal culture with one or more colonies of A. fumigatus complex/A. niger complex or 200 or more colonies of yeast measured using a modified standard approach on one occasion obtained within the 28-day screening period. 5. Subject must be able to produce a spontaneous sputum sample. 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Subjects who have received more than 2 weeks of intravenous (IV), oral or inhaled antifungal therapy within 2 months of Visit 3. 2. Subjects taking medication that could significantly increase the risks of AEs with triazoles. 3. Subjects who are receiving antiretroviral protease inhibitors. 4. At screening, has a clinically significant bacterial chest infection that has not been adequately treated. 5. Subjects who have used an experimental medical device or received an experimental drug within 3 months or within a period less than five times the experimental drug’s half-life, whichever is longer, before the first dose of the study drug is scheduled. 6. Clinically significant screening abnormalities (including, but not limited to, vital signs, ECG, laboratory tests, physical examination and spirometry) that, in the Investigator’s opinion, exclude the subject from participation in the study. 7. Positive test at screening for hepatitis B virus infection, or antibodies to hepatitis C virus. 8. If female, the subject is pregnant (e.g. has a positive serum ß human chorionic gonadotropin at screening or a positive urinary pregnancy test pre-dose on Day 1), lactating or breast feeding. 9. Subject is an employee or a first-degree relative of anyone employed by Pulmocide, a participating clinical trial site, or any contract research organisation involved in the study. 10. Any other reason that the Investigator considers makes the subject unsuitable to participate.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the antifungal effect of PC945 on A. fumigatus complex/A. niger complex or Candida spp. in sputum;Secondary Objective: To measure the effect PC945 on lung function(FEV1 and FVC) To investigate the effect of PC945 on: -the Aspergillus burden in sputum, measured by the number of colony forming units (CFU) on fungal culture and quantitative polymerase chain reaction (qPCR) -the weight of spontaneous sputum production -the number of colonies of Candida in sputum culture -Candida albicans burden in sputum measured by qPCR -circulating fungal markers in particular A. fumigatus-specific IgG, markers of A. fumigatus sensitisation,clinically relevant outcome measures and quality of life (QoL) To obtain estimates of derived systemic pharmacokinetic parameters of PC945 and the potential circulating metabolite(s), if detectable, following single and repeat doses of inhaled PC945 To investigate the safety of daily, inhaled doses of PC945 in subjects with moderate to severe asthma. To investigate the correlation between sputum Aspergillus and Candida levels measured by qPCR and clinical variables;Primary end point(s): Absence of A. fumigatus complex/A. niger complex on sputum culture at Visit 5 in subjects with an A. fumigatus complex/A. niger complex-positive sputum culture at baseline or a substantial (at least 50%) reduction in Candida spp. CFUs between baseline and Visit 5 in patients who were A. fumigatus complex/ A. niger complex negative at baseline.;Timepoint(s) of evaluation of this end point: Baseline and Visit 5 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Predicted post bronchodilator FEV1 values at baseline, Visit 3, Visit 4, Visit 5 and at follow-up at Visit 6. • Forced vital capacity values at baseline, Visit 3, Visit 4, Visit 5 and at follow-up at Visit 6. • The number of sputum A. fumigatus complex/A. niger complex CFUs in fungal culture at baseline, Visit 5 and at follow-up at Visit 6. • Number of colonies of Candida spp. in sputum measured by the number of CFUs at baseline, Visit 5 and at follow-up at Visit 6. • Sputum A. fumigatus measured by qPCR at baseline, Visit 5 and at follow-up at Visit 6. • Spontaneous sputum weight (24-hour collection) at baseline, Visit 5 and at follow-up at Visit 6. • C. albicans measured by qPCR in sputum at baseline, Visit 5 and at follow-up at Visit 6. • The concentration of A. fumigatus-specific IgG as measured in serum at baseline, Visit 4, Visit 5 and at follow-up at Visit 6. • Serum Total IgE levels at baseline, Visit 4, Visit 5 and at follow-up at Visit 6. • A. fumigatus-specific IgE levels at baseline, Visit 4, Visit 5 and at follow-up at Visit 6. • St George’s Respiratory Questionnaire (SGRQ), cough (Leicester Cough Questionnaire), breathlessness (visual analogue scale [VAS]) and sputum characteristics (fresh morning sputum samples) at baseline, Visit 4, Visit 5 and at follow-up (Visit 6). • Asthma control questionnaire (ACQ6), Juniper Asthma QoL Questionnaire (AQLQ-J) scores at baseline, Visit 4, Visit 5 and at follow-up (Visit 6) in subjects with asthma. • Correlation between A. fumigatus measured by qPCR and clinical response: e.g. culture, QoL questionnaire scores, sputum weight, FVC, FEV1 and to investigate if change in sputum A. fumigatus measured by qPCR predicts clinical response. • Correlation between Candida albicans measured by qPCR and clinical response: e.g. culture, QoL questionnaire scores, sputum weight, FVC, FEV1 and to investigate if change in sputum Candida albicans measured by qPCR predicts clinical response. • Derived | — |
Countries
United Kingdom
Contacts
Public ContactDirector of Clinical Development
Pulmocide Ltd
Outcome results
None listed