The Effect of PC945 on Aspergillus or Candida Lung Infections in Patients With Asthma or Chronic Respiratory Diseases

Asthma Clinical Trial

Official title:

A Double-blind, Placebo-controlled Study to Assess the Effects of Inhaled PC945 in the Treatment of Culture-positive Aspergillus or Candida Fungal Bronchitis in Subjects With Moderate to Severe Asthma or Other Chronic Respiratory Diseases.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03745196
• Other study ID #: PC_ASP_004
• Secondary ID: 2018-000244-26
• Status: Terminated
• Phase: Phase 2
• Start date: November 15, 2018
• Est. completion date: June 1, 2020

Study information

• Verified date: June 2020
• Source: Pulmocide Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study tests the effects of an experimental drug PC945 in people with asthma or other chronic respiratory diseases whose lungs are infected by Aspergillus fungi and Candida yeasts.

PC945 may be useful in treating patients infected with Aspergillus as, unlike the usual treatments, it is inhaled into the lung and has been designed to stay there and treat the infection. Participants will continue to receive their usual treatment for their chronic respiratory disease. Half of the participants will receive PC945 and half will receive a placebo. The amount of fungus and yeast in the patients' phlegm will be measured over the course of the study. The study will take place at multiple sites in UK and will include approximately 46 participants. The maximum study duration will be about 16 weeks.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: June 1, 2020
• Est. primary completion date: June 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. Subject's diagnosis of moderate to severe asthma (GINA Step 3 or 4) made by a respiratory physician and treated with an inhaled steroid or other chronic respiratory disease.

1. For subjects with asthma, the diagnosis of asthma must be supported either by:

• i. Historical evidence of:

• 1. Increased airway hyper-responsiveness (methacholine PC20 <8 mg/ml).

• or

• 2. Airflow obstruction (FEV1/FVC ratio of less than 70%) and short-term variations in FEV1 (>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

2. 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.

Exclusion Criteria:

1. Subjects who have received more than 2 weeks of intravenous (IV), oral or inhaled antifungal therapy within 6 months prior to Visit 3 or any antifungal therapy (IV, oral or inhaled) 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. Clinical or laboratory evidence of bacterial bronchitis at the point of screening.

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.

Related Conditions & MeSH terms

• Aspergillosis
• Asthma
• Bronchiectasis
• Candidiasis
• COPD
• Respiration Disorders
• Respiratory Aspergillosis
• Respiratory Candidiasis
• Respiratory Tract Diseases

Intervention

Drug:
• PC945
Study drug under investigation
• Placebo
Placebo control

Locations

Country	Name	City	State
United Kingdom	Glenfield Hospital	Leicester
United Kingdom	Royal Liverpool University Hospital	Liverpool
United Kingdom	Royal Brompton Hospital	London
United Kingdom	Northwest Lung Research Centre	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Pulmocide Ltd

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence or absence of Aspergillus fumigatus (A. fumigatus) complex / Aspergillus niger (A. niger) complex colonies on sputum culture	This is a binary endpoint	Baseline to Day 32-35
Primary	Reduction in the numbed of colonies of Candida species (spp) on sputum culture	Substantial reduction in colony forming unit (CFU) count by at least 50%	Baseline to Day 32-35
Secondary	Predicted post bronchodilator forced expiratory volume in 1 second (FEV1) values		Baseline to Day 84
Secondary	Forced vital capacity (FVC) values		Baseline to Day 84
Secondary	The number of sputum A. fumigatus complex / A. niger complex CFUs in fungal culture		Baseline to Day 84
Secondary	Sputum A. fumigatus measured by quantitative polymerase chain reaction (qPCR)		Baseline to Day 84
Secondary	Spontaneous sputum weight (24-hour collection)		Baseline to Day 84
Secondary	The number of sputum Candida spp. CFUs in fungal culture		Baseline to Day 84
Secondary	C. albicans measured by qPCR in sputum		Baseline to Day 84
Secondary	The concentration of A. fumigatus-specific immunoglobulin G (IgG) as measured in serum		Baseline to Day 84
Secondary	Serum Total immunoglobulin E (IgE) levels		Baseline to Day 84
Secondary	A. fumigatus-specific IgE levels		Baseline to Day 84
Secondary	Change in Asthma control questionnaire - 6 item [ACQ6] (Total score) in asthma patients only		Baseline to Day 84
Secondary	Change in Asthma Quality of Life Questionnaire - Juniper [AQLQ-J] (Total score) in asthma patients only		Baseline to Day 84
Secondary	Change in St George's Respiratory Questionnaire [SGRQ] (Total score)		Baseline to Day 84
Secondary	Change in Leicester Cough Questionnaire (Total score)		Baseline to Day 84
Secondary	Breathlessness visual analogue scale rating, change over time	Symptom severity rated from "Best ever" to "Worst possible"	Baseline to Day 84
Secondary	Correlation between A. fumigatus measured by qPCR and clinical response		Baseline to Day 84
Secondary	Correlation between Candida albicans measured by qPCR and clinical response		Baseline to Day 84
Secondary	Area undertake curve from time 0 to 2h post dose (AUC(0-2))	Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable	Baseline to Day 84
Secondary	Last quantifiable plasma concentration (Ct)	Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable	Baseline to Day 84
Secondary	maximum observed concentration (Cmax)	Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable	Baseline to Day 84
Secondary	concentration at the end of the dosage interval (Ctrough)	Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable	Baseline to Day 84
Secondary	Adverse events (AEs) incidence (safety and tolerability)		Baseline to Day 84
Secondary	Twelve-lead electrocardiogram (ECG) (Safety parameter)	including QT interval corrected for Bazetts formula, QT interval, QRS Interval, PR Interval and ventricular rate).	Baseline to Day 84
Secondary	Proportion of participants who meet the markedly abnormal criteria for vital signs assessment at lease once post dose		Baseline to Day 84
Secondary	Proportion of participants who meet the markedly abnormal criteria for safety laboratory assessment at lease once post dose		Baseline to Day 84
Secondary	Change in peak expiratory flow rate [PEFR]		Baseline to Day 84
Secondary	Antibiotic use		Baseline to Day 84
Secondary	Sputum characteristics - consistency and presence of blood (fresh morning sputum samples)		Baseline to Day 84
Secondary	Sputum colour (fresh morning sputum samples)		Baseline to Day 84