The Effect of PC945 on Aspergillus Fumigatus Lung Infection in Patients With Cystic Fibrosis

NCT03870841 | Terminated Phase 2

• 2 other identifiers: PC_ASP_0032018-000243-87
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

Brief Summary

This study tests the effects of an experimental drug PC945 in people with cystic fibrosis whose lungs are infected by the fungus Aspergillus fumigatus. PC945 may be useful in treating patients infected with Aspergillus fumigatus 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 be treated with their usual cystic fibrosis treatment and will also receive PC945. The amount of fungus 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 18 participants. The maximum study duration will be about 16 weeks.

Conditions

Aspergillosis; Cystic Fibrosis

Outcome Measures

Primary Outcomes (13)

• Adverse events (AEs)

  Baseline to Day 84

• Proportion of participants who meet the markedly abnormal criteria for 12-lead ECG assessment at lease once post dose

  Baseline to Day 84

• Proportion of participants who meet the markedly abnormal criteria for safety laboratory assessment at lease once post dose

  Baseline to Day 84

• Proportion of participants who meet the markedly abnormal criteria for vital signs assessment at lease once post dose

  Baseline to Day 84

• Predicted post bronchodilator forced expiratory volume in 1 second (FEV1) values

  Baseline to Day 84

• Forced vital capacity (FVC) values

  Baseline to Day 84

• Peak expiratory flow rate values (PEFR)

  Baseline to Day 84

• Maximum expiratory flow values (MEF25-75)

  Baseline to Day 84

• Breathlessness visual analogue scale rating, change over time

  Symptom severity rated from "Best ever" to "Worst possible"

  Baseline to Day 84

• Cough visual analogue scale rating, change over time

  Symptom severity rated from "Best ever" to "Worst possible"

  Baseline to Day 84

• Area under the curve from time 0 to 2 h post-dose (AUC0-2)

  Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable

  Baseline to Day 84

• Maximum plasma concentration

  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)

  Derived pharmacokinetic parameters for PC945 and the potential circulating metabolite(s), if detectable

  Baseline to Day 84

Secondary Outcomes (10)

• Change in the number of sputum A. fumigatus colony forming units (CFU)

  Baseline to Day 84

• A. fumigatus status (presence or absence) in subjects with a baseline A. fumigatus-positive sputum culture

  Day 1 to Day 84

• Change in sputum A. fumigatus measured by quantitative polymerase chain reaction (qPCR)

  Baseline to Day 84

• Change in the serum concentration of A. fumigatus-specific immunoglobulins G (IgG)

  Baseline to Day 84

• Change in serum Total immunoglobulin E (IgE) levels

  Baseline to Day 84

Study Arms (1)

PC945

EXPERIMENTAL

PC945 5mg once daily

Drug: PC945

Interventions

PC945 DRUG

PC945, nebulized

PC945

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be male or female, aged 18 years inclusive or older (at the time of consent).
• Subject must be willing and able to adhere to the restrictions and prohibitions required by this protocol.
• Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose and requirements of the study and that they are willing to participate.
• A confirmed diagnosis of CF by standard criteria.
• Subject is able to produce sputum.
• A history of persistently positive A. fumigatus sputum cultures from at least 2 sputum samples in the last year, the most recent of which must have been within the last 6 months.
• Subject must have a positive sputum fungal culture at screening with one or more colonies of A. fumigatus detected using a modified standard approach.

You may not qualify if:

• Any other disease or condition, which in the Investigator's medical opinion would preclude the subject's participation in a clinical trial.
• Is taking inhaled amphotericin B or has taken it within 7 weeks of Day 1.
• Is taking systemic steroid treatment or has taken it within 4 weeks of Day 1. Subjects considered to be stable on a systemic steroid dose of \<15 mg for at least a month will not be excluded.
• Is taking systemic antifungal treatment (intravenous, oral or inhaled) or has received antifungal therapy (intravenous, oral or inhaled) within 6 weeks of Day 1.
• If female, the subject is pregnant (e.g., has a positive serum β human chorionic gonadotropin (β-hCG) at screening or a positive urinary pregnancy test pre-dose on Day 1), lactating or breast feeding.
• Any respiratory exacerbation within 2 weeks of the start of the study.
• Any upper respiratory tract infection or signs or symptoms thereof within 2 weeks prior to dosing.
• Positive culture for Mycobacterium abscessus within 12 months before screening or between screening and baseline, or currently receiving treatment for Mycobacterium abscessus.
• Has chronic, active hepatitis or a positive hepatitis B surface antigen or positive hepatitis C antibody result at screening.
• Is taking antiretroviral protease inhibitor therapy.
• Allergy to any of the active or inactive ingredients in the study medication.
• History of drug (or other) allergy or intolerance that, in the opinion of the Investigator or Pulmocide Medical Monitor, would contraindicate their participation.
• Clinically significant haemoptysis (\>200 mL per episode) within 90 days before screening.
• Subject is mentally or legally incapacitated. 19 July 2018 CONFIDENTIAL Page 27 of 58 Pulmocide Ltd Clinical Protocol PC\_ASP\_003
• Subject is employed or is a first-degree relative of anyone employed by Pulmocide, a participating clinical trial site, or any contract research organisation involved in the study.

Sponsors & Collaborators

• Pulmocide Ltd: lead

Study Sites (2)

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Northwest Lung Research Centre

Manchester, M23 9LT, United Kingdom

Location

MeSH Terms

Conditions

Aspergillosis; Cystic Fibrosis

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2018
• First Posted: March 12, 2019
• Study Start: April 3, 2019
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: July 16, 2021

Record last verified: 2021-07

Locations

GB (2)