| Eligibility |
Inclusion Criteria:
- Is a male or female, =18 years old at the time of signing the informed consent.
- BMI of =18.0 and <40.0 kg/m2 at screening.
- Has a diagnosis of asthma, as per the Global Initiative for Asthma (GINA) 2018 update
- Has a confirmed diagnosis of ABPA, based on the modified International Society for
human and Animal Mycology (ISHAM) ABPA working group 2013 and 2021 criteria including
a history of or documentation at screening of serum IgE = 500 IU/mL and A.
fumigatus-specific IgE>0.35KUA/L, or above normal IgE antibody to A. fumigatus, or a
positive immediate skin test and at least 2 of the 3 following supportive criteria:
eosinophil count >500 cells/µL; A. fumigatus-specific IgG >27 mgA/L or presence of
precipitating (or above normal immunoglobulin G [IgG]) antibody to A. fumigatus;
consistent radiographic opacities or bronchiectasis on chest CT.
- 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).
- At least 1 exacerbation requiring a systemic glucocorticosteroid(s) in the 12 months
prior to Screening. For patients on a biologic agent, at least one exacerbation
requiring a systemic glucocorticosteroid(s) must have occurred at least 3 months after
the initiation of the biologic agent.
- Has a serum IgE =500 IU/mL at screening.
- Has a documented stable asthma medication regimen during the 28 days prior to the
first dose of study drug ; applicable asthma medications can include but are not
limited to 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.
- 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.
- Can demonstrate the correct inhalation technique and achieve a minimum inspiratory
flow rate of 45 L/min for the use of the delivery device at screening and before
dosing on Day 1.
- 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.
- Subjects who are sexually active, male subjects able to father a child, and female
subjects of childbearing potential must agree to follow contraception requirements.
Exclusion Criteria:
- Currently requiring medications that are sensitive substrates for CYP3A4-mediated
metabolism or medications that are contraindicated with oral itraconazole.
- 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.
- Has used any systemic azole antifungal agent in the 6 weeks before first dose of study
drug.
- Has discontinued previously administered biologic agent(s) in the 3 months prior to
screening.
- 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.
Refer to Appendix 4 for definition of bronchiectasis exacerbations.
- 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 inhaled tobacco/nicotine 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 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.
- 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). Note that results that are positive for a drug of abuse or cotinine may
be acceptable for drugs that have been obtained by legal means or non-inhaled
tobacco/nicotine product use.
- 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 <1000 cells/L, platelet counts <100,000 to or >500,000 X
109/L, or hemoglobin <10 g/dL
- Is a female of childbearing potential who is pregnant or lactating or who plans to
become pregnant during the study. All female subjects must have a negative pregnancy
test at screening and pre dose on Day 1. A woman is of childbearing potential unless
she is either permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral
oophorectomy, bilateral tubal occlusion/ligation, endometrial ablation) or
postmenopausal (had no menses for 12 months without an alternative medical cause).
- Has a 12-lead ECG demonstrating a mean QT interval corrected by the Fridericia formula
(QTcF) >450 msec for a male subject or >470 msec for a female subject at screening. A
repeat triplicate ECG is allowed if a mean QTcF >450 msec for males and >470 msec for
females is recorded at Visit 1.
- Has a planned or elective surgery, hospitalizations, or participation in other
interventional studies any time during the study that may interfere with study
logistics or safety.
- Has donated or had a loss of greater than 400 mL of blood within the 3 months before
screening.
- Has other social, psychiatric, surgical, or medical conditions or screening laboratory
abnormalities that may increase the risk associated with study participation or may
interfere with the interpretation of study results and, in the judgement of the
Investigator, would make the subject inappropriate for entry into the study.
- Received any investigational medical product in a clinical research study within the
previous 3 months before first dose of study drug.
- Is a study site employee, an immediate family member of a study site employee, or a
Sponsor employee.
- Has previously received PUR1900.
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