Study to Evaluate Itraconazole Administered as Inhaled Dry Powder in Adults With Asthma and ABPA

NCT05667662 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 601-0018
• Study Type: interventional
• Target: 8
• Locations: 4 countries
• Sites: 18

Brief Summary

The goal of this clinical trial is to learn about PUR1900 as an inhaled, antifungal therapeutic for the treatment of allergic bronchopulmonary aspergillosis (ABPA) in patients with asthma. The main questions it aims to answer are:

1. 1.Is PUR1900 safe and well tolerated in adults with asthma and ABPA?
2. 2.Is there an effect of daily administration of PUR1900 on potential outcome measures in adults with asthma and ABPA?
3. 3.Is there fungal resistance to A. fumigatus?

Conditions

ABPA

Keywords

Asthma; Allergic Bronchopulmonary Aspergillosis

Outcome Measures

Primary Outcomes (6)

• Incidence of Treatment Emergent Adverse Events (TEAEs)

  Review of TEAEs from time of consent to study completion.

  168 days

• Safety spirometry assessments

  FEV1 (the volume of air (in liters) exhaled in the first second during forced exhalation after maximal inspiration), FVC (liters), and PEFR (L/min) measurements compared to baseline.

  168 days

• Vital sign measurements

  Vital signs measurements collected before exposure, during and after treatment and compared to baseline. Vital sign measurements will include respiratory rate (bpm), blood pressure (mmHg), heart rate (bpm), oxygen saturation (by pulse oximetry), and oral or tympanic temperature (°C).

  168 days

• Physical examinations

  At screening, a complete physical examination will be performed which includes measurement of height (cm), weight (kg) and evaluation of appearance; skin; head and neck; eyes, ears, nose, and throat; chest and lungs; heart; abdomen; neurological system; and extremities.

  168 Days

• Clinical safety laboratory test results

  Hematology, serum chemistry, or urinalysis test results (normal, abnormal, clinical significance) compared to baseline.

  168 days

• Cardiac safety monitoring

  Electrocardiogram (ECG) recordings collected before exposure, during and after treatment. Electrocardiogram measurements will include heart rate and PR, RR, QRS, and QT intervals, as well as the QTcF and compared to baseline.

  168 days

Secondary Outcomes (4)

• Magnitude of effect of daily administration of PUR1900 - Spirometry

  168 days

• Magnitude of effect of daily administration of PUR1900 - Patient Reported Outcomes (ACQ)

  168 days

• Magnitude of effect of daily administration of PUR1900 - Patient Reported Outcomes (AQLQ(s) 12+)

  168 days

• Frequency of asthma exacerbations versus baseline

  168 days

Other Outcomes (1)

• Fungal resistance to Aspergillus fumigatus

  168 days

Study Arms (3)

PUR1900 40 mg

EXPERIMENTAL

4 PUR1900 (10 mg itraconazole) Capsules with 20 mg total powder (10 mg itraconazole plus 10 mg excipients) administered via oral inhalation, using the RS01 Monodose inhaler once daily for 112 days at approximately the same time each day.

Drug: Itraconazole Powder

PUR1900 20 mg

EXPERIMENTAL

2 PUR1900 (10 mg itraconazole) Capsules with 20 mg total powder (10 mg itraconazole plus 10 mg excipients) and 2 Placebo Capsules with with 11.8 mg total powder (excipients only) administered via oral inhalation, using the RS01 Monodose inhaler once daily for 112 days at approximately the same time each day.

Drug: Itraconazole Powder

Placebo

PLACEBO COMPARATOR

4 Placebo Capsules with with 11.8 mg total powder (excipients only) administered via oral inhalation, using the RS01 Monodose inhaler once daily for 112 days at approximately the same time each day.

Drug: Placebo

Interventions

Itraconazole Powder DRUG

Capsules with 20 mg total powder (10 mg itraconazole plus 10 mg excipients)

Also known as: PUR1900

PUR1900 20 mg; PUR1900 40 mg

Placebo DRUG

Capsules with 11.8 mg total powder (excipients only)

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pulmatrix Inc.: lead

Study Sites (18)

University of Alabama Medical Center at Birmingham

Birmingham, Alabama, 35233, United States

Location

Medical Research of Arizona

Scottsdale, Arizona, 85251, United States

Location

Jonathan Corren, MD

Santa Monica, California, 90025, United States

Location

Bensch Clinical Research

Stockton, California, 95207, United States

Location

Southern Illinois University Center for Clinical Research

Springfield, Illinois, 62702, United States

Location

University of Kansas Medical Center Research Institute

Kansas City, Kansas, 66160, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

UTMB Health

Galveston, Texas, 77555, United States

Location

Westmead Hospital

Westmead, New South Wales, NSW 2145, Australia

Location

Mater Hospital Brisbane, Respiratory Research Group

South Brisbane, Queensland, QLD 4101, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

CHU Pontchaillou

Rennes, Cedex 9, 35033, France

Location

Nouvel Hôpital Civil

Strasbourg, Strasbourg Cedex, 67091, France

Location

CHU de Marseille Hôpital Nord

Marseille, 13015, France

Location

University Hospitals Birmingham - Heartlands Hospital

Birmingham, West Midlands, B9 5SS, United Kingdom

Location

CPS Research Limited

Glasgow, G20 7BE, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6HP, United Kingdom

Location

University Hospital of South Manchester - Wythenshawe Hospital,

Manchester, M23 9LT, United Kingdom

Location

MeSH Terms

Conditions

Asthma; Aspergillosis, Allergic Bronchopulmonary

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pulmonary Aspergillosis; Aspergillosis; Mycoses; Bacterial Infections and Mycoses; Infections; Lung Diseases, Fungal; Respiratory Tract Infections

Study Officials

• Chris Cabell, MD

  Pulmatrix Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2022
• First Posted: December 28, 2022
• Study Start: February 1, 2023
• Primary Completion: February 27, 2024
• Study Completion: February 27, 2024
• Last Updated: April 2, 2024

Record last verified: 2024-04

Locations

US (8); FR (3); AU (3); GB (4)