Study in Adult Asthmatic Patients With Allergic Bronchopulmonary Aspergillosis

NCT03960606 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 601-0014
• Study Type: interventional
• Target: 7
• Locations: 5 countries
• Sites: 20

Brief Summary

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

Conditions

Allergic Bronchopulmonary Aspergillosis

Keywords

Aspergillosis

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (10)

• 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)

  Day 1 to Day 28

• Change from baseline (Day 1) to Day 28 in A fumigatus burden in sputum

  Day 1 to Day 28

Study Arms (4)

10 mg PUR1900

EXPERIMENTAL

Study drug (PUR1900) will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)

Combination Product: PUR1900

20 mg PUR1900

EXPERIMENTAL

Study drug (PUR1900) will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)

Combination Product: PUR1900

35 mg PUR1900

EXPERIMENTAL

Study drug (PUR1900) will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)

Combination Product: PUR1900

Placebo

PLACEBO COMPARATOR

Placebo

Combination Product: Placebo

Interventions

PUR1900 COMBINATION_PRODUCT

PUR1900 contains itraconazole as the active ingredient, and it is formulated as a dry powder for oral inhalation.

10 mg PUR1900; 20 mg PUR1900; 35 mg PUR1900

Placebo COMBINATION_PRODUCT

PUR1900 placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pulmatrix Inc.: lead

Study Sites (20)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Integrity Clinical Research Center Inc.

Hialeah, Florida, 33015, United States

Location

Heuer M.D Research Inc.

Miami Lakes, Florida, 32819, United States

Location

Infinite Clinical Trials

Roswell, Georgia, 30076, United States

Location

University Consultants In Allergy and Immunology

Chicago, Illinois, 60612, United States

Location

Laporte County Institute for Clinical Research

Michigan City, Indiana, 46360, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

University of Texas Medical Branch at Galveston

Galveston, Texas, 77555, United States

Location

John Hunter Hospital

New Lambton, New South Wales, 2305, Australia

Location

Mater Private Hospital Brisbane

Brisbane, Queensland, 4101, Australia

Location

Yashoda Hospital

Hyderabad, Andhra Pradesh, 500082, India

Location

Shree Hospital And Critical Care Centre

Nagpur, Maharashtra, 440009, India

Location

SMS Medical College and Hospital

Jaipur, Rajasthan, 302016, India

Location

Centrum Alergologii Teresa Hofman

Poznan, Greater Poland Voivodeship, 60-214, Poland

Location

Centrum Medycyny Oddechowej Mroz sp. j.

Bialystok, Podlaskie Voivodeship, 15-044, Poland

Location

Uniwersyteckie Centrum Kliniczne - PPDS

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

PULMAG Arkadiusz Brodowski, Grzegorz Gasior S. C.

Sosnowiec, Silesian Voivodeship, 41-200, Poland

Location

Birmingham Heartlands Hospital

Birmingham, West Midlands, B9 5SS, United Kingdom

Location

Wythenshawe Hospital - PPDS

Manchester, M23 9LT, United Kingdom

Location

MeSH Terms

Conditions

Aspergillosis, Allergic Bronchopulmonary; Aspergillosis

Condition Hierarchy (Ancestors)

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

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study will be performed in a double-blind manner. All study drug will be supplied in identical packaging and will be similar in color, smell, taste, and appearance to enable double-blind conditions. All study personnel will remain blinded until after database lock, unless the nature of their activities in the study specifically requires them to be unblinded. Any study documents, supplies, and tools will be reviewed to identify components that have the potential to unblind the study, and blinding restrictions will be applied where appropriate.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: May 23, 2019
• Study Start: July 31, 2019
• Primary Completion: July 14, 2020
• Study Completion: July 14, 2020
• Last Updated: August 27, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); IN (3); PL (4); US (9); GB (2)