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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03745196
Recruitment Status : Recruiting
First Posted : November 19, 2018
Last Update Posted : August 19, 2019
Sponsor:
Information provided by (Responsible Party):
Pulmocide Ltd

Brief 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.


Condition or disease Intervention/treatment Phase
Asthma Respiratory Candidiasis Respiratory Aspergillosis COPD Bronchiectasis Drug: PC945 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This is a double-blind study.
Primary Purpose: Treatment
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.
Actual Study Start Date : November 15, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : February 28, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: PC945
PC945 5mg once-daily, nebulized
Drug: PC945
Study drug under investigation

Placebo Comparator: Placebo
Placebo, nebulized
Drug: Placebo
Placebo control




Primary Outcome Measures :
  1. 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

  2. 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%


Secondary Outcome Measures :
  1. Predicted post bronchodilator forced expiratory volume in 1 second (FEV1) values [ Time Frame: Baseline to Day 84 ]
  2. Forced vital capacity (FVC) values [ Time Frame: Baseline to Day 84 ]
  3. The number of sputum A. fumigatus complex / A. niger complex CFUs in fungal culture [ Time Frame: Baseline to Day 84 ]
  4. Sputum A. fumigatus measured by quantitative polymerase chain reaction (qPCR) [ Time Frame: Baseline to Day 84 ]
  5. Spontaneous sputum weight (24-hour collection) [ Time Frame: Baseline to Day 84 ]
  6. The number of sputum Candida spp. CFUs in fungal culture [ Time Frame: Baseline to Day 84 ]
  7. C. albicans measured by qPCR in sputum [ Time Frame: Baseline to Day 84 ]
  8. The concentration of A. fumigatus-specific immunoglobulin G (IgG) as measured in serum [ Time Frame: Baseline to Day 84 ]
  9. Serum Total immunoglobulin E (IgE) levels [ Time Frame: Baseline to Day 84 ]
  10. A. fumigatus-specific IgE levels [ Time Frame: Baseline to Day 84 ]
  11. Change in Asthma control questionnaire - 6 item [ACQ6] (Total score) in asthma patients only [ Time Frame: Baseline to Day 84 ]
  12. Change in Asthma Quality of Life Questionnaire - Juniper [AQLQ-J] (Total score) in asthma patients only [ Time Frame: Baseline to Day 84 ]
  13. Change in St George's Respiratory Questionnaire [SGRQ] (Total score) [ Time Frame: Baseline to Day 84 ]
  14. Change in Leicester Cough Questionnaire (Total score) [ Time Frame: Baseline to Day 84 ]
  15. Breathlessness visual analogue scale rating, change over time [ Time Frame: Baseline to Day 84 ]
    Symptom severity rated from "Best ever" to "Worst possible"

  16. Correlation between A. fumigatus measured by qPCR and clinical response [ Time Frame: Baseline to Day 84 ]
  17. Correlation between Candida albicans measured by qPCR and clinical response [ Time Frame: Baseline to Day 84 ]
  18. 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

  19. Last quantifiable plasma concentration (Ct) [ Time Frame: Baseline to Day 84 ]
    Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable

  20. maximum observed concentration (Cmax) [ Time Frame: Baseline to Day 84 ]
    Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable

  21. 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

  22. Adverse events (AEs) incidence (safety and tolerability) [ Time Frame: Baseline to Day 84 ]
  23. 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).

  24. Proportion of participants who meet the markedly abnormal criteria for vital signs assessment at lease once post dose [ Time Frame: Baseline to Day 84 ]
  25. Proportion of participants who meet the markedly abnormal criteria for safety laboratory assessment at lease once post dose [ Time Frame: Baseline to Day 84 ]
  26. Change in peak expiratory flow rate [PEFR] [ Time Frame: Baseline to Day 84 ]
  27. Antibiotic use [ Time Frame: Baseline to Day 84 ]
  28. Sputum characteristics - consistency and presence of blood (fresh morning sputum samples) [ Time Frame: Baseline to Day 84 ]
  29. Sputum colour (fresh morning sputum samples) [ Time Frame: Baseline to Day 84 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03745196


Contacts
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Contact: Alison Murray, MBBCh +44(0)20 3763 9484 admin@pulmocide.com

Locations
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United Kingdom
Glenfield Hospital Recruiting
Leicester, United Kingdom, LE3 9QP
Contact: Andrew Wardlaw         
Principal Investigator: Andew Wardlaw         
Royal Liverpool University Hospital Recruiting
Liverpool, United Kingdom, L7 8XP
Contact: Chishimba Livingstone, BSc, MBChB, MRCP, PhD    01517063653      
Royal Brompton Hospital Recruiting
London, United Kingdom, SW3 6NP
Contact: Darius Armstrong-James         
Principal Investigator: Darius Armstrong-James         
Northwest Lung Research Centre Recruiting
Manchester, United Kingdom, M23 9LT
Contact: Robert Niven         
Principal Investigator: Robert Niven         
Sponsors and Collaborators
Pulmocide Ltd

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Responsible Party: Pulmocide Ltd
ClinicalTrials.gov Identifier: NCT03745196    
Other Study ID Numbers: PC_ASP_004
2018-000244-26 ( EudraCT Number )
First Posted: November 19, 2018    Key Record Dates
Last Update Posted: August 19, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Candidiasis
Aspergillosis
Asthma
Bronchiectasis
Respiration Disorders
Respiratory Tract Diseases
Bronchial Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Mycoses