Study in Adult Asthmatic Patients With Allergic Bronchopulmonary Aspergillosis

Allergic Bronchopulmonary Aspergillosis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03960606
• Other study ID #: 601-0014
• Status: Terminated
• Phase: Phase 2
• Start date: July 31, 2019
• Est. completion date: July 14, 2020

Study information

• Verified date: July 2021
• Source: Pulmatrix Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: July 14, 2020
• Est. primary completion date: July 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Allergic Bronchopulmonary Aspergillosis
• Aspergillosis
• Pulmonary Aspergillosis

Intervention

Combination Product:
• PUR1900
PUR1900 contains itraconazole as the active ingredient, and it is formulated as a dry powder for oral inhalation.
• Placebo
PUR1900 placebo

Locations

Country	Name	City	State
Australia	Mater Private Hospital Brisbane	Brisbane	Queensland
Australia	John Hunter Hospital	New Lambton	New South Wales
India	Yashoda Hospital	Hyderabad	Andhra Pradesh
India	SMS Medical College and Hospital	Jaipur	Rajasthan
India	Shree Hospital And Critical Care Centre	Nagpur	Maharashtra
Poland	Centrum Medycyny Oddechowej Mroz sp. j.	Bialystok	Podlaskie
Poland	Uniwersyteckie Centrum Kliniczne - PPDS	Gdansk	Pomorskie
Poland	Centrum Alergologii Teresa Hofman	Poznan	Wielkopolskie
Poland	PULMAG Arkadiusz Brodowski, Grzegorz Gasior S. C.	Sosnowiec	Slaskie
United Kingdom	Birmingham Heartlands Hospital	Birmingham	West Midlands
United Kingdom	Wythenshawe Hospital - PPDS	Manchester
United States	Montefiore Medical Center	Bronx	New York
United States	University Consultants In Allergy and Immunology	Chicago	Illinois
United States	National Jewish Health	Denver	Colorado
United States	University of Texas Medical Branch at Galveston	Galveston	Texas
United States	Integrity Clinical Research Center Inc.	Hialeah	Florida
United States	Heuer M.D Research Inc.	Miami Lakes	Florida
United States	Laporte County Institute for Clinical Research	Michigan City	Indiana
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Infinite Clinical Trials	Roswell	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Pulmatrix Inc.

Countries where clinical trial is conducted

United States,  Australia,  India,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events		From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Primary	Incidence of intraday FEV1 declines		From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Primary	Respiratory rate		From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Primary	Blood pressure	Systolic pressure over diastolic pressure	From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Primary	Heart rate	Beats per minute	From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Primary	Oxygen saturation	As a percentage	From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Primary	Physical examination findings	Physician's notes	From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Primary	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)
Primary	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	Sputum concentrations of itraconazole and hydroxy-itraconazole		Day 2 to Day 28
Secondary	Sputum eosinophils		(Day -9 to Day -6) to Day 28
Secondary	To evaluate the effect of PUR1900 on pulmonary function following single- and multiple-dose administration of PUR1900		Day 1 to Day 28
Secondary	Asthma Control Questionnaire-6 (ACQ 6)	Scores range between 0 (totally controlled) and 6 (severely uncontrolled).	Day 1 to Day 28
Secondary	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
Secondary	Cmax (maximum observed concentration in plasma)		Day 1 to Day 28
Secondary	Tmax (time to maximum concentration in plasma)		Day 1 to Day 28
Secondary	AUC (area under the concentration-time curve)		Day 1 to Day 28
Secondary	CL/F (clearance)		Day 1 to Day 28
Secondary	Vz/F (apparent volume of distribution)		Day 1 to Day 28