The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12618001838202p
Ethics application status
Submitted, not yet approved
Date submitted
6/11/2018
Date registered
12/11/2018
Date last updated
12/11/2018
Date data sharing statement initially provided
12/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomized Open-Label, Phase 1b Study of the Safety of Pirfenidone Solution for Inhalation (AP01) in Patients with Idiopathic Pulmonary Fibrosis (ATLAS Study)
Scientific title
A Randomized Open-Label, Phase 1b Study of the Safety of Pirfenidone Solution for Inhalation (AP01) in Patients with Idiopathic Pulmonary Fibrosis (ATLAS Study)
Secondary ID [1] 296524 0
Sponsor protocol number: AP01-002
Universal Trial Number (UTN)
Trial acronym
ATLAS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Pulmonary Fibrosis 310306 0
Condition category
Condition code
Respiratory 309040 309040 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Drug: Inhaled Pirfenidone: Each patient will be randomized to either 50 mg inhaled pirfenidone taken once per day or 100 mg inhaled pirfenidone taken twice per day for 72 weeks, using the eFlow nebulizer.
Drug: Salbutamol: Patients who experience cough that limits their ability to complete dosing will administer 1 - 2 puffs (90 - 100 microgram (µg)) of salbutamol using a metered dose inhaler in order to complete the in-clinic dose. These patients, as well as patients with a history of asthma or smoking history of 20 pack years or greater, or patients that have a greater than or equal to 15% drop in FEV1 percent predicted in their pre-dose and post-dose readings will be required to administer 1 - 2 puffs (90 - 100 µg) of salbutamol using a metered dose inhaler prior to dosing throughout the study unless these patients are currently taking a long-acting beta-2-agonist therapy.
Patients will be trained to use the nebulizer at the first treatment visit. The first treatment will be overseen by clinic personnel. Compliance and tolerability to study drug will be assessed during a telephone call one week after the first dose, as well as at monthly visits during the first 24 weeks. During Part B of the study (Week 25 - Week 72), compliance and tolerability will be assessed during a monthly phone call, as well as at clinic visits every 3 months. Overall study drug compliance will be assessed by calculating the amount of vials used at each clinic visit.
Intervention code [1] 312835 0
Treatment: Drugs
Comparator / control treatment
2 active arms
Control group
Dose comparison

Outcomes
Primary outcome [1] 307999 0
The primary objective is to evaluate safety and tolerability of treatment with AP01 by monitoring AEs and post-dose spirometry.
Adverse events will be assessed during scheduled phone calls to the patients and at clinic visits. Adverse events will be recorded in the electronic CRFs. In the AP01-001 single ascending dose study, the drug was well tolerated in both normal volunteers and IPF patients. The most commonly reported event was cough, which was noted in 7 of 38 volunteers and 1 of 6 IPF patients in the Phase 1 study. Cough was mild, self-limited, and did not prevent the full administration of aerosol dose in any subject. No serious adverse events were reported in the study and all subjects completed the trial.
Timepoint [1] 307999 0
Week 24 post-first dose and Week 72 post first dose.
Primary outcome [2] 308033 0
The primary objective is to evaluate safety and tolerability of treatment with AP01 by monitoring AEs and post-dose spirometry.
Change from pre dose FVC % predicted as measured by spirometry. A drop of greater than or equal to 15% from the pre-first dose FEV1 value accompanied by clinical symptoms will be considered a bronchospasm.
Timepoint [2] 308033 0
Post first dose FEV % predicted at the baseline visit (Day 1)
Secondary outcome [1] 353619 0
Change from baseline in FVC % predicted as measured by spirometry
Timepoint [1] 353619 0
Week 24 post-first dose and Week 72 post-first dose
Secondary outcome [2] 353743 0
Change from baseline in diffusing capacity of lungs for carbon monoxide (DLCO) as measured by pulmonary function tests
Timepoint [2] 353743 0
Week 24 post-first dose and Week 72 post-first dose
Secondary outcome [3] 353744 0
Change from baseline in Patient Reported Outcomes (Leicester Cough Questionnaire), which will be completed on paper by the patient at each visit
Timepoint [3] 353744 0
Week 24 post-first dose and Week 72 post-first dose
Secondary outcome [4] 353745 0
Change from baseline in cough frequency as measured by the Leicester Cough Monitor
Timepoint [4] 353745 0
Week 24 post-first dose and Week 72 post-first dose
Secondary outcome [5] 353746 0
Change from baseline in the extent of fibrosis as measured by High Resolution Computed Tomography (HRCT)
Timepoint [5] 353746 0
Week 24 post first dose
Secondary outcome [6] 353851 0
Change from baseline in Patient Reported Outcomes (King's Brief Interstitial Lung Disease (KBILD) Questionnaire), which will be completed on paper by the patient at each visit
Timepoint [6] 353851 0
Week 24 post-first dose and Week 72 post-first dose
Secondary outcome [7] 353852 0
Change from baseline in lung volumes as measured by High Resolution Computed Tomography (HRCT)
Timepoint [7] 353852 0
Week 24 post first dose

Eligibility
Key inclusion criteria
Population
1. Male and female patients, ages 40 through 90 years (inclusive) at Screening
2. Not eligible for oral pirfenidone and nintedanib due to national formulary restrictions OR intolerant to or unwilling to start oral pirfenidone and nintedanib, if previously offered
Diagnosis of IPF
3. Clinical symptoms consistent with IPF of greater than or equal to 12 months duration (with or without IPF diagnosis)
4. Diagnosis of IPF, defined as the first instance in which a patient was informed of having IPF, no more than 48 months before randomization
5. Extent of fibrotic changes (honeycombing, reticular changes) greater than the extent of emphysema on HRCT scan
6. No features supporting an alternative diagnosis on transbronchial biopsy, BAL, or surgical lung biopsy, if performed
7. FVC % predicted greater than or equal to 40% and less than or equal to 90% at Screening based on Global Lung Initiative equations. The first 20 patients randomized must have FVC greater than or equal to 50% predicted. After the first 20 patients have randomized, patients with FVC greater than 40% and less than 50% predicted at Screening will be allowed to be randomized in the study but randomization for these patients will be capped at 20 patients
8. Change in FVC (measured in liters) between Screening and Day 1 (pre-dose measurement) must be less than 10% relative difference
9. DLCO greater than or equal to 30% and less than or equal to 90% at Screening
10. In the investigator’s opinion, no evidence of improvement in measure of IPF disease severity over the preceding year
11. FEV1/FVC greater than or equal to 70%
12. Able to understand and sign a written informed consent form
13. Able to understand the importance of adherence to study treatment and the study protocol and willing to follow all study requirements, including the concomitant medication restrictions, throughout the study

Minimum age
40 Years
Maximum age
90 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Significant clinical worsening of IPF between Screening and Day 1, in the opinion of the investigator
2. Not a suitable candidate for enrollment or unlikely to comply with the requirements of this study, in the opinion of the investigator
3. History of acute IPF exacerbation requiring hospitalization in the last 3 months
4. History of clinically significant environmental exposure known to cause pulmonary fibrosis, including but not limited to drugs (such as amiodarone), asbestos, beryllium, radiation, and domestic birds
5. Known explanation for interstitial lung disease, including but not limited to radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans organizing pneumonia, human immunodeficiency virus, viral hepatitis, and cancer
6. Clinical diagnosis of any connective tissue disease, including but not limited to scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis
7. Current diagnosis of asthma or chronic obstructive pulmonary disease
8. Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, sinusitis, urinary tract infection, or cellulitis
9. Females with a positive pregnancy test at Screening or are currently breastfeeding
10. Any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next 6 months. This does not include minor surgical procedures for localized cancer (e.g., basal cell carcinoma)
11. Any condition other than IPF that, in the opinion of the investigator, is likely to result in the death of the patient within the next 6 months
12. History of severe hepatic impairment or end-stage liver disease or ALT or AST greater than 5 times the upper limit of normal at Screening
13. History of end-stage renal disease requiring dialysis

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment outside Australia
Country [1] 20990 0
New Zealand
State/province [1] 20990 0
Country [2] 20991 0
Czech Republic
State/province [2] 20991 0
Country [3] 20992 0
Poland
State/province [3] 20992 0
Country [4] 20993 0
United Kingdom
State/province [4] 20993 0
Country [5] 20994 0
Netherlands
State/province [5] 20994 0
Country [6] 20996 0
France
State/province [6] 20996 0

Funding & Sponsors
Funding source category [1] 301109 0
Commercial sector/Industry
Name [1] 301109 0
Avalyn Pharma Pty Ltd
Address [1] 301109 0
Level 19 HWT Tower 40 City Road Southbank VIC 3006
Country [1] 301109 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Avalyn Pharma Pty Ltd
Address
Level 19 HWT Tower 40 City Road Southbank VIC 3006
Country
Australia
Secondary sponsor category [1] 300721 0
None
Name [1] 300721 0
Address [1] 300721 0
Country [1] 300721 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 301859 0
Bellberry Limited
Ethics committee address [1] 301859 0
129 Glen Osmond Road Eastwood Adelaide, South Australia 5063
Ethics committee country [1] 301859 0
Australia
Date submitted for ethics approval [1] 301859 0
31/10/2018
Approval date [1] 301859 0
Ethics approval number [1] 301859 0

Summary
Brief summary
A Randomized Open-Label, Phase 1b Study of the Safety of Pirfenidone Solution for Inhalation (AP01) in Patients with Idiopathic Pulmonary Fibrosis (ATLAS Study)
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88346 0
Dr Christopher Grainge
Address 88346 0
Hunter Medical Research Institute
Lot 1 Kookaburra Circuit
New Lambton Heights
NSW 2305
Country 88346 0
Australia
Phone 88346 0
+61 2 4042 0000
Fax 88346 0
Email 88346 0
Christopher.Grainge@hnehealth.nsw.gov.au
Contact person for public queries
Name 88347 0
Dr Bruce Montgomery
Address 88347 0
Avalyn Pharma Pty Ltd., Level 19 HWT Tower 40 City Road Southbank VIC 3006
Country 88347 0
Australia
Phone 88347 0
+61 3 9869 5922
Fax 88347 0
Email 88347 0
bmontgomery@avalynpharma.com
Contact person for scientific queries
Name 88348 0
Dr Bruce Montgomery
Address 88348 0
Avalyn Pharma Pty Ltd., Level 19 HWT Tower 40 City Road Southbank VIC 3006
Country 88348 0
Australia
Phone 88348 0
+61 3 9869 5922
Fax 88348 0
Email 88348 0
bmontgomery@avalynpharma.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in this article after deidentification
When will data be available (start and end dates)?
Beginning 9 months and ending 36 months following article publication.
Available to whom?
Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose
Available for what types of analyses?
For individual participant data meta-analyses
How or where can data be obtained?
Proposals may be submitted up to 36 months following article publication.
What supporting documents are/will be available?
Study protocol
Summary results
No Results