A study to evaluate Safety, Tolerability and Potential Outcomesf Itraconazole Administered as a Dry Powder for Inhalation for Allergic bronchopulmonary aspergillosis (ABPA) in patients with asthma

Phase 1

• Conditions: Allergic bronchopulmonary aspergillosis (ABPA) in patients with asthma; MedDRA version: 20.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 20.1Level: LLTClassification code 10001707Term: Allergic bronchopulmonary aspergillosisSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2022-002289-33-FR
• Lead Sponsor: Pulmatrix, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-10-27
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

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 <40.0 kg/m2 at screening.
4) Meets the following criteria:
a) Has a diagnosis of asthma, as per the Global Initiative for Asthma (GINA) 2018 update
b) Has a confirmed diagnosis of ABPA, as per the Modified International Society
for Human and Animal Mycology (ISHAM) working group 2013 criteria, including
i) a history of serum IgE =1000 IU/mL and
ii) a positive immediate skin test or increased IgE antibody to A. fumigatus and
iii) at least 2 of the 3 following supportive criteria:
(1) eosinophils >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

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 <1000 cells/L, platelet counts <100,000 to >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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified