Study in Adult Asthmatic Patients With Allergic Bronchopulmonary Aspergillosis

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety, Tolerability, & Pharmacokinetics of Itraconazole Administered as a Dry Powder for Inhalation (PUR1900) in Asthmatic Patients With ABPA

A Randomized, Double-Blind, Multicenter, Placebo-Controlled, Phase 2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Itraconazole Administered as a Dry Powder for Inhalation (PUR1900) in Adult Asthmatic Patients With Allergic Bronchopulmonary Aspergillosis

Study Overview

• Status: Terminated
• Conditions: Allergic Bronchopulmonary Aspergillosis
• Intervention / Treatment: Combination product: PUR1900; Combination product: Placebo

Detailed Description

This is a randomized, double-blind, multicenter, placebo controlled, multiple-arm study.

Following screening and confirmation of eligibility, subjects will be randomly assigned (1:1:1:1) into 4 arms of 16 subjects each and will receive 10 mg, 20 mg, or 35 mg of PUR1900 or placebo, administered via dry powder inhalation daily for 28 days. The doses of PUR1900 are stated in this protocol as the respective nominal doses of itraconazole.

Subject eligibility for the study will be determined within 28 days before the first dose of study drug (Day 1) and will be confirmed between 9 and 6 days before dosing and again on Day 1.

Eligible subjects will begin daily dosing with study drug (PUR1900 or placebo) on Day 1.

Subjects will return to the study site for visits on Days 2, 7, 14, and 28 and will be dosed at the study site. The remaining daily doses of study drug will be self-administered at home.

A follow-up visit will occur 7 to 10 days after the last dose of study drug.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • New Lambton, New South Wales, Australia, 2305
      • John Hunter Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4101
      • Mater Private Hospital Brisbane
• India
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500082
      • Yashoda Hospital
  • Maharashtra
    • Nagpur, Maharashtra, India, 440009
      • Shree Hospital And Critical Care Centre
  • Rajasthan
    • Jaipur, Rajasthan, India, 302016
      • SMS Medical College and Hospital
• Poland
  • Podlaskie
    • Bialystok, Podlaskie, Poland, 15-044
      • Centrum Medycyny Oddechowej Mroz sp. j.
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-952
      • Uniwersyteckie Centrum Kliniczne - PPDS
  • Slaskie
    • Sosnowiec, Slaskie, Poland, 41-200
      • PULMAG Arkadiusz Brodowski, Grzegorz Gasior S. C.
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 60-214
      • Centrum Alergologii Teresa Hofman
• United Kingdom
  • Manchester, United Kingdom, M23 9LT
    • Wythenshawe Hospital - PPDS
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B9 5SS
      • Birmingham Heartlands Hospital
• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Florida
    • Hialeah, Florida, United States, 33015
      • Integrity Clinical Research Center Inc.
    • Miami Lakes, Florida, United States, 32819
      • Heuer M.D Research Inc.
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Infinite Clinical Trials
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University Consultants in Allergy and Immunology
  • Indiana
    • Michigan City, Indiana, United States, 46360
      • LaPorte County Institute for Clinical Research
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch at Galveston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Is a male or female, 18 to 75 years old (inclusive) at the time of signing the informed consent.
• Has a body mass index of 18.0 to 35.0 kg/m2 (inclusive) at screening.
• Has a historical diagnosis of asthma, as per the Global Initiative for Asthma (GINA) 2018 update.
• Has a confirmed historical diagnosis of ABPA, as per the Modified International Society for Human and Animal Mycology (ISHAM) working group 2013 criteria.
• 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)
• Has a serum immunoglobulin (Ig) E ≥1000 IU/mL during screening (Visit 1 or Visit 2).
• Can perform a valid, reproducible spirometry test with demonstration of a prebronchodilator FEV1 ≥50% of predicted normal for age, sex, race, and height (Quanjer et al 2012) at a screening visit.
• Has a documented stable asthma medication regimen during screening (Day 28 to Day 1), including SABA, LABA, and LTRA use and inhaled and/or oral GCS.
• 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 of this protocol.
• Can demonstrate the correct inhalation technique for the use of the delivery device at screening and before dosing.

Exclusion Criteria:

• Is a female of childbearing potential who is pregnant or lactating or who plans to become pregnant during the study. A woman is considered to be of childbearing potential unless she is either permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion/ligation) or postmenopausal (had no menses for 12 months without an alternative medical cause).
• Has a history of life-threatening asthma within the last 5 years, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest, and/or hypoxic seizures.
• Had an occurrence of asthma or ABPA exacerbations within the 28 days before screening or during the 28-day period before Day 1.
• 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.
• Received any investigational medical product in a clinical research study within the previous 3 months before dosing in this study.
• Has previously received PUR1900.
• Has a history of any significant drug or alcohol abuse in the past 2 years before screening, as judged by the investigator.
• Has current tobacco or inhaled marijuana use or history of smoking tobacco or marijuana within the last 6 months before screening.
• Is a current user of e-cigarettes or has used these products within the last 6 months before screening.
• Has a positive urine test result for drugs of abuse, alcohol, or cotinine at screening
• Has a history of allergies to or hypersensitivity reactions after dosing of itraconazole or other antifungal azoles.
• Had a major trauma or surgery within the last 28 days before screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Combination product: Placebo; PUR1900 placebo
Experimental: 10 mg PUR1900; Study drug (PUR1900) will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)	Combination product: PUR1900; PUR1900 contains itraconazole as the active ingredient, and it is formulated as a dry powder for oral inhalation.
Experimental: 20 mg PUR1900; Study drug (PUR1900) will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)	Combination product: PUR1900; PUR1900 contains itraconazole as the active ingredient, and it is formulated as a dry powder for oral inhalation.
Experimental: 35 mg PUR1900; Study drug (PUR1900) will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)	Combination product: PUR1900; PUR1900 contains itraconazole as the active ingredient, and it is formulated as a dry powder for oral inhalation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events		From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Incidence of intraday FEV1 declines		From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Respiratory rate		From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Blood pressure	Systolic pressure over diastolic pressure	From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Heart rate	Beats per minute	From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Oxygen saturation	As a percentage	From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Physical examination findings	Physician's notes	From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Clinical laboratory test results	Lab reports with any out of range results flagged	From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
12-Lead electrocardiogram findings	ECG report and tracing	From Day 1 through Follow Up (which is 7 to 10 days after the last dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sputum concentrations of itraconazole and hydroxy-itraconazole		Day 2 to Day 28
Sputum eosinophils		(Day -9 to Day -6) to Day 28
To evaluate the effect of PUR1900 on pulmonary function following single- and multiple-dose administration of PUR1900		Day 1 to Day 28
Asthma Control Questionnaire-6 (ACQ 6)	Scores range between 0 (totally controlled) and 6 (severely uncontrolled).	Day 1 to Day 28
Change from baseline (Day 1) to Day 28 in A fumigatus burden in sputum	As assessed by quantitative PCR and sputum culture	Day 1 to Day 28
Cmax (maximum observed concentration in plasma)		Day 1 to Day 28
Tmax (time to maximum concentration in plasma)		Day 1 to Day 28
AUC (area under the concentration-time curve)		Day 1 to Day 28
CL/F (clearance)		Day 1 to Day 28
Vz/F (apparent volume of distribution)		Day 1 to Day 28

Collaborators and Investigators

• Sponsor: Pulmatrix Inc.
• Investigators: Principal Investigator: William J. Calhoun, MD, University of Texas Medical Branch Galveston, TX 77555; Principal Investigator: David Denning, FRCP, FRC Path, FIDSA, FMedSci, Director, National Aspergillosis Centre Manchester, Wythenshawe M23 9LT, UK

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2019
• Primary Completion (Actual): July 14, 2020
• Study Completion (Actual): July 14, 2020

Study Registration Dates

• First Submitted: May 14, 2019
• First Submitted That Met QC Criteria: May 20, 2019
• First Posted (Actual): May 23, 2019

Study Record Updates

• Last Update Posted (Actual): August 27, 2021
• Last Update Submitted That Met QC Criteria: August 25, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Aspergillosis
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bacterial Infections and Mycoses; Respiratory Hypersensitivity; Hypersensitivity; Mycoses; Lung Diseases, Fungal; Aspergillosis; Pulmonary Aspergillosis; Aspergillosis, Allergic Bronchopulmonary
• Other Study ID Numbers: 601-0014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No