Allergic bronchopulmonary aspergillosis (ABPA) in patients with asthma MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 20.1 Level: LLT Classification code 10001707 Term: Allergic bronchopulmonary aspergillosis System Organ Class: 100000004862
Conditions
Interventions
Product Name: PUR1900
Product Code: PUR1900
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Itraconazole
CAS Number: 84625-61-6
Current Sponsor code: PUR1900
Other descriptive name: PUR190
Sponsors
Pulmatrix, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each subject must meet all the following criteria to be enrolled in this study: 1) Can provide written informed consent before the performance of any study-specific procedures. 2) Is a male or female, =18 and =80 years old at the time of signing the informed consent. 3) Has a body mass index of =18.0 and 500 cells/µL, (2) presence of precipitating antibody (or increased immunoglobulin G [IgG]) to A. fumigatus, (3) consistent radiographic opacities at the time of diagnosis c) Is currently considered to be in one of the following stages of ABPA: Stage 2 (Response), Stage 4 (Remission), Stage 5a (Treatment-dependent ABPA), or Stage 5b (Glucocorticoid-dependent asthma) d) At least 1 exacerbation requiring an oral steroid(s) in the last 12 months. e) Has a serum IgE =500 IU/mL at screening. f) Has a documented stable asthma medication regimen during the screening period (i.e., Day -28 to Day -1); applicable asthma medications can include any or all of the following: inhaled short acting beta agonist (SABA), inhaled long-acting beta agonist (LABA), and leukotriene receptor antagonist (LTRA) use and inhaled and/or oral glucocorticosteroids. SABA use during this period should be mostly within a stable range (e.g., 2 puffs 2 to 4 times a day) and should not exceed 8 puffs a day on 2 out of 3 consecutive days. 5) Can perform a valid, reproducible spirometry test with demonstration of a prebronchodilator FEV1 =50% of predicted normal for age, sex, race, and height at a screening visit. 6) Can demonstrate the correct inhalation technique for the use of the delivery device at screening and before dosing on Day 1. 7) Is willing and able to comply with all study procedures and assessments, including scheduled visits, drug dosing plan, study procedures, laboratory tests, and study restrictions. 8) Subjects who are sexually active, male subjects able to father a child, and female subjects of childbearing potential must agree to follow the contraception requirements outlined in Section 5.8 of this protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: A subject who meets any of the following criteria will be excluded from the study: 1) Currently requiring medications that are metabolized via the CYP3A4 isoenzyme system. 2) Has evidence of ventricular dysfunction, such as congestive cardiac failure (New York Heart Association functional class III or IV), or a history of congestive cardiac failure. N-terminal pro B-type natriuretic peptide (NT pro BNP) will be checked at screening only. A subject with a confirmed value of >400 pg/mL will not be eligible to participate. 3) Has used any systemic azole antifungal agent in the 6 weeks before first dose of study drug. 4) Has a history or evidence of any of the following medical conditions: -Has a history of life-threatening asthma within the last 24 months, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest, and/or hypoxic seizures. -Has a current diagnosis of any chronic airway disease other than asthma, ABPA, or bronchiectasis believed to be related to ABPA, such as chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis, or Churg-Strauss syndrome. A subject whose predominating clinical disease burden is related to bronchiectasis (e.g., a subject with 2 or more infective exacerbations of bronchiectasis in the past 12 months or a subject with chronic colonization with Pseudomonas aeruginosa) will be excluded. -Had an occurrence of clinically significant bacterial, viral, or fungal infection that required systemic (oral or intravenous) antibiotics, antivirals, or antifungals within the 28 days before screening. Topical treatments, other than antifungals, are allowed. -Had an occurrence of asthma or ABPA exacerbations within the 28 days before screening. -Has the presence of hoarseness or oropharyngeal candidiasis at screening. -Had a major trauma or surgery within the last 28-days before screening. -Has a history of any clinically significant cardiovascular, renal, hepatic, or gastrointestinal disease or neurological or psychiatric disorder endocrine, immunological, or autoimmune disease or other medical condition that would affect the subject’s safety or confound the assessment of study endpoints as judged by the Investigator. -Has a history of any clinically significant drug or alcohol abuse in the past 6 months before screening, as judged by the Investigator. -Has current tobacco or inhaled marijuana use or history of smoking or vaping including tobacco or marijuana within the last 6 months before screening. -Has a history of allergic or hypersensitivity reaction or serious adverse reaction after dosing of itraconazole or other antifungal azoles. -Has a history of serious adverse reaction or known serious hypersensitivity to any of the formulation excipients. 5) Has a positive urine test result for drugs of abuse or cotinine at screening (unless, in the opinion of the Investigator, this can be explained by the subject’s current medications). 6) At screening, has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2x upper limit of normal (ULN), white blood cell (WBC) count > 20,000 X 109/L, absolute neutrophil count 500,000 X 109/L, or hemoglobin <10 g/dL 7)Has used omalizumab (Xolair®) in the 12 months prior to the first dose of study drug. 8) Is a female of childbearing potential who is pregnant or lactating or who plans to become pregnant during the study. All
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Primary: To evaluate the comparative safety and tolerability of 20 mg and 40 mg doses of PUR1900 in adults with asthma and ABPA ;Secondary Objective: • Secondary: To estimate the magnitude of effect of daily administration of PUR1900 on potential outcome measures in adults with asthma and ABPA;Primary end point(s): • Incidence of treatment-emergent adverse events (TEAEs) • Incidence of serious TEAEs • Safety assessments including: - Monitoring of FEV1 throughout the study - Vital sign measurements - Physical examination findings - Clinical laboratory test results - 2-lead electrocardiogram (ECG) findings ;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from baseline over time in FEV1 • Frequency of exacerbations • Change from baseline over time in Asthma Control Questionnaire-6 (ACQ-6) score • Change from baseline over time in Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ[S] 12+) score • Change from baseline over time in serum IgE levels ;Timepoint(s) of evaluation of this end point: From baseline over time | — |
Countries
Australia, France, United Kingdom, United States
Contacts
Public ContactPulmatrix Clinical Operations
Pulmatrix, Inc.
Outcome results
None listed