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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05667662




Registration number
NCT05667662
Ethics application status
Date submitted
1/12/2022
Date registered
28/12/2022
Date last updated
2/04/2024

Titles & IDs
Public title
Study to Evaluate Itraconazole Administered as Inhaled Dry Powder in Adults With Asthma and ABPA
Scientific title
Study to Evaluate the Effect of Dose and Duration of Treatment of Itraconazole Administered as a Dry Powder for Inhalation (PUR1900) on Safety, Tolerability, and Potential Outcomes in Adult Patients With ABPA
Secondary ID [1] 0 0
601-0018
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ABPA 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Itraconazole Powder
Treatment: Drugs - Placebo

Experimental: PUR1900 40 mg - 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.

Experimental: PUR1900 20 mg - 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.

Placebo Comparator: Placebo - 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.


Treatment: Drugs: Itraconazole Powder
Capsules with 20 mg total powder (10 mg itraconazole plus 10 mg excipients)

Treatment: Drugs: Placebo
Capsules with 11.8 mg total powder (excipients only)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Treatment Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
168 days
Primary outcome [2] 0 0
Safety spirometry assessments
Timepoint [2] 0 0
168 days
Primary outcome [3] 0 0
Vital sign measurements
Timepoint [3] 0 0
168 days
Primary outcome [4] 0 0
Physical examinations
Timepoint [4] 0 0
168 Days
Primary outcome [5] 0 0
Clinical safety laboratory test results
Timepoint [5] 0 0
168 days
Primary outcome [6] 0 0
Cardiac safety monitoring
Timepoint [6] 0 0
168 days
Secondary outcome [1] 0 0
Magnitude of effect of daily administration of PUR1900 - Spirometry
Timepoint [1] 0 0
168 days
Secondary outcome [2] 0 0
Magnitude of effect of daily administration of PUR1900 - Patient Reported Outcomes (ACQ)
Timepoint [2] 0 0
168 days
Secondary outcome [3] 0 0
Magnitude of effect of daily administration of PUR1900 - Patient Reported Outcomes (AQLQ(s) 12+)
Timepoint [3] 0 0
168 days
Secondary outcome [4] 0 0
Frequency of asthma exacerbations versus baseline
Timepoint [4] 0 0
168 days

Eligibility
Key inclusion criteria
- 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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.

- Has a history of allergic or hypersensitivity reaction or serious adverse reaction
after dosing of itraconazole or other antifungal azoles.

- Has a history of serious adverse reaction or known serious hypersensitivity to any of
the formulation excipients.

- Has a positive urine test result for drugs of abuse or cotinine at screening (unless,
in the opinion of the Investigator, this can be explained by the subject's current
medications). Note that results that are positive for a drug of abuse or cotinine may
be acceptable for drugs that have been obtained by legal means or non-inhaled
tobacco/nicotine product use.

- At screening, has alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
>2x upper limit of normal (ULN), white blood cell (WBC) count > 20,000 X 109/L,
absolute neutrophil count <1000 cells/L, platelet counts <100,000 to or >500,000 X
109/L, or hemoglobin <10 g/dL

- Is a female of childbearing potential who is pregnant or lactating or who plans to
become pregnant during the study. All female subjects must have a negative pregnancy
test at screening and pre dose on Day 1. A woman is of childbearing potential unless
she is either permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral
oophorectomy, bilateral tubal occlusion/ligation, endometrial ablation) or
postmenopausal (had no menses for 12 months without an alternative medical cause).

- Has a 12-lead ECG demonstrating a mean QT interval corrected by the Fridericia formula
(QTcF) >450 msec for a male subject or >470 msec for a female subject at screening. A
repeat triplicate ECG is allowed if a mean QTcF >450 msec for males and >470 msec for
females is recorded at Visit 1.

- Has a planned or elective surgery, hospitalizations, or participation in other
interventional studies any time during the study that may interfere with study
logistics or safety.

- Has donated or had a loss of greater than 400 mL of blood within the 3 months before
screening.

- Has other social, psychiatric, surgical, or medical conditions or screening laboratory
abnormalities that may increase the risk associated with study participation or may
interfere with the interpretation of study results and, in the judgement of the
Investigator, would make the subject inappropriate for entry into the study.

- Received any investigational medical product in a clinical research study within the
previous 3 months before first dose of study drug.

- Is a study site employee, an immediate family member of a study site employee, or a
Sponsor employee.

- Has previously received PUR1900.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/02/2024
Sample size
Target
Accrual to date
Final
8
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment hospital [2] 0 0
Mater Hospital Brisbane, Respiratory Research Group - South Brisbane
Recruitment hospital [3] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
NSW 2145 - Westmead
Recruitment postcode(s) [2] 0 0
QLD 4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
France
State/province [7] 0 0
Cedex 9
Country [8] 0 0
France
State/province [8] 0 0
Strasbourg Cedex
Country [9] 0 0
France
State/province [9] 0 0
Marseille
Country [10] 0 0
United Kingdom
State/province [10] 0 0
West Midlands
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Glasgow
Country [12] 0 0
United Kingdom
State/province [12] 0 0
London
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pulmatrix Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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. Is PUR1900 safe and well tolerated in adults with asthma and ABPA?

2. Is there an effect of daily administration of PUR1900 on potential outcome measures in
adults with asthma and ABPA?

3. Is there fungal resistance to A. fumigatus?

This study includes a 28-day screening period, a 112-day (16-week) treatment period, and a
56-day (8 week) observation period.

Participants will take either 40mg of PUR1900, 20 mg of PUR1900 or Placebo for 112 days and
complete an eDairy, answer questions about their asthma and complete peak respiratory flow
measurements at home. They will come to the clinic approximate once a month during the
treatment period and complete study assessments. At the end of the observation period
participants will complete one more clinic visit. Participants who complete this study may be
given the opportunity to continue on study drug in an open label extension study.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05667662
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Chris Cabell, MD
Address 0 0
Pulmatrix Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05667662