Clinical trial NCT03960606: Study in Adult Asthmatic Patients With Allergic Bronchopulmonary Aspergillosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Allergic Bronchopulmonary Aspergillosis
Keywords: Aspergillosis
Lead sponsor: Pulmatrix Inc.
Sponsor class: INDUSTRY
First posted: 2019-05-23
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
measure: Incidence of intraday FEV1 declines
timeFrame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
measure: Respiratory rate
timeFrame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
measure: Blood pressure
timeFrame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
measure: Heart rate
timeFrame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
measure: Oxygen saturation
timeFrame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
measure: Physical examination findings
timeFrame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
measure: Clinical laboratory test results
timeFrame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
measure: 12-Lead electrocardiogram findings
timeFrame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Secondary outcomes:
measure: Sputum concentrations of itraconazole and hydroxy-itraconazole
timeFrame: Day 2 to Day 28
measure: Sputum eosinophils
timeFrame: (Day -9 to Day -6) to Day 28
measure: To evaluate the effect of PUR1900 on pulmonary function following single- and multiple-dose administration of PUR1900
timeFrame: Day 1 to Day 28
measure: Asthma Control Questionnaire-6 (ACQ 6)
timeFrame: Day 1 to Day 28
measure: Change from baseline (Day 1) to Day 28 in A fumigatus burden in sputum
timeFrame: Day 1 to Day 28
measure: Cmax (maximum observed concentration in plasma)
timeFrame: Day 1 to Day 28
measure: Tmax (time to maximum concentration in plasma)
timeFrame: Day 1 to Day 28
measure: AUC (area under the concentration-time curve)
timeFrame: Day 1 to Day 28
measure: CL/F (clearance)
timeFrame: Day 1 to Day 28
measure: Vz/F (apparent volume of distribution)
timeFrame: Day 1 to Day 28
Other outcomes:
Locations:
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Hialeah
country: United States
facility: Integrity Clinical Research Center Inc.
state: Florida
city: Miami Lakes
country: United States
facility: Heuer M.D Research Inc.
state: Florida
city: Roswell
country: United States
facility: Infinite Clinical Trials
state: Georgia
city: Chicago
country: United States
facility: University Consultants In Allergy and Immunology
state: Illinois
city: Michigan City
country: United States
facility: Laporte County Institute for Clinical Research
state: Indiana
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Galveston
country: United States
facility: University of Texas Medical Branch at Galveston
state: Texas
city: New Lambton
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Mater Private Hospital Brisbane
state: Queensland
city: Hyderabad
country: India
facility: Yashoda Hospital
state: Andhra Pradesh
city: Nagpur
country: India
facility: Shree Hospital And Critical Care Centre
state: Maharashtra
city: Jaipur
country: India
facility: SMS Medical College and Hospital
state: Rajasthan
city: Bialystok
country: Poland
facility: Centrum Medycyny Oddechowej Mroz sp. j.
state: Podlaskie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne - PPDS
state: Pomorskie
city: Sosnowiec
country: Poland
facility: PULMAG Arkadiusz Brodowski, Grzegorz Gasior S. C.
state: Slaskie
city: Poznań
country: Poland
facility: Centrum Alergologii Teresa Hofman
state: Wielkopolskie
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: West Midlands
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital - PPDS
Study officials:
affiliation: University of Texas Medical Branch Galveston, TX 77555
name: William J. Calhoun, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Director, National Aspergillosis Centre Manchester, Wythenshawe M23 9LT, UK
name: David Denning, FRCP, FRC Path, FIDSA, FMedSci
role: PRINCIPAL_INVESTIGATOR
References: