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

June 10, 2020 updated by: Pulmocide Ltd

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.

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Leicester, United Kingdom, LE3 9QP
        • Glenfield Hospital
      • Liverpool, United Kingdom, L7 8XP
        • Royal Liverpool University Hospital
      • London, United Kingdom, SW3 6NP
        • Royal Brompton Hospital
      • Manchester, United Kingdom, M23 9LT
        • Northwest Lung Research Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 β 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PC945
PC945 5mg once-daily, nebulized
Study drug under investigation
Placebo Comparator: Placebo
Placebo, nebulized
Placebo control

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence or absence of Aspergillus fumigatus (A. fumigatus) complex / Aspergillus niger (A. niger) complex colonies on sputum culture
Time Frame: Baseline to Day 32-35
This is a binary endpoint
Baseline to Day 32-35
Reduction in the numbed of colonies of Candida species (spp) on sputum culture
Time Frame: Baseline to Day 32-35
Substantial reduction in colony forming unit (CFU) count by at least 50%
Baseline to Day 32-35

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 15, 2018

Primary Completion (Actual)

June 1, 2020

Study Completion (Actual)

June 1, 2020

Study Registration Dates

First Submitted

October 24, 2018

First Submitted That Met QC Criteria

November 14, 2018

First Posted (Actual)

November 19, 2018

Study Record Updates

Last Update Posted (Actual)

June 12, 2020

Last Update Submitted That Met QC Criteria

June 10, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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