- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03745196
The Effect of PC945 on Aspergillus or Candida Lung Infections in Patients With Asthma or Chronic Respiratory Diseases
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
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
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
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Subject must be male or female, aged 18 years (inclusive) or older (at the time of consent).
- 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.
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.
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
- Subjects with other chronic respiratory disease (such as COPD or bronchiectasis) susceptible to fungal bronchitis.
- 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.
- Subject must be able to produce a spontaneous sputum sample.
Exclusion Criteria:
- 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.
- Subjects taking medication that could significantly increase the risks of AEs with triazoles.
- Subjects who are receiving antiretroviral protease inhibitors.
- Clinical or laboratory evidence of bacterial bronchitis at the point of screening.
- 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.
- 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.
- Positive test at screening for hepatitis B virus infection, or antibodies to hepatitis C virus.
- 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.
- 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.
- Any other reason that the Investigator considers makes the subject unsuitable to participate.
Study Plan
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
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Immune System Diseases
- Lung Diseases
- Hypersensitivity, Immediate
- Bronchial Diseases
- Bacterial Infections and Mycoses
- Lung Diseases, Obstructive
- Respiratory Hypersensitivity
- Hypersensitivity
- Mycoses
- Bronchiectasis
- Asthma
- Candidiasis
- Aspergillosis
- Respiration Disorders
- Respiratory Tract Diseases
Other Study ID Numbers
- PC_ASP_004
- 2018-000244-26 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
Clinical Trials on Bronchiectasis
-
Ruijin HospitalAstraZeneca Investment (China) Co., LtdNot yet recruitingBronchiectasis AdultChina
-
Fondazione IRCCS Ca' Granda, Ospedale Maggiore...Fondazione Policlinico Universitario Agostino Gemelli IRCCS; IRCCS Azienda... and other collaboratorsActive, not recruiting
-
University of Sao Paulo General HospitalEnrolling by invitation
-
University of Sao Paulo General HospitalFundação de Amparo à Pesquisa do Estado de São PauloCompletedBronchiectasis AdultBrazil
-
University of North Carolina, Chapel HillCompletedBronchiectasis AdultUnited States
-
Seoul National University Bundang HospitalUnknownSymptomatic BronchiectasisKorea, Republic of
-
Chang Gung Memorial HospitalNot yet recruitingBronchiectasis AdultTaiwan
-
Shanghai Pulmonary Hospital, Shanghai, ChinaNot yet recruitingBronchiectasis Adult
-
University of DundeeRecruitingBronchiectasis AdultUnited Kingdom
-
Papworth Hospital NHS Foundation TrustGlaxoSmithKlineCompletedBronchiectasis | Idiopathic BronchiectasisUnited Kingdom
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States