ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12618001838202

Ethics application status

Approved

Date submitted

6/11/2018

Date registered

12/11/2018

Date last updated

16/01/2023

Date data sharing statement initially provided

12/11/2018

Date results provided

13/04/2021

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]

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

Condition category

Condition code

Respiratory

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]

Treatment: Drugs

Comparator / control treatment

2 active arms

Control group

Dose comparison

Outcomes

Primary outcome [1]

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]

Week 24 post-first dose and Week 72 post first dose.

Primary outcome [2]

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]

Post first dose FEV % predicted at the baseline visit (Day 1)

Secondary outcome [1]

Change from baseline in FVC % predicted as measured by spirometry

Timepoint [1]

Week 24 post-first dose and Week 72 post-first dose

Secondary outcome [2]

Change from baseline in diffusing capacity of lungs for carbon monoxide (DLCO) as measured by pulmonary function tests

Timepoint [2]

Week 24 post-first dose and Week 72 post-first dose

Secondary outcome [3]

Change from baseline in Patient Reported Outcomes (Leicester Cough Questionnaire), which will be completed on paper by the patient at each visit

Timepoint [3]

Week 24 post-first dose and Week 72 post-first dose

Secondary outcome [4]

Change from baseline in cough frequency as measured by the Leicester Cough Monitor

Timepoint [4]

Week 24 post-first dose and Week 72 post-first dose

Secondary outcome [5]

Change from baseline in the extent of fibrosis as measured by High Resolution Computed Tomography (HRCT)

Timepoint [5]

Week 24 post first dose

Secondary outcome [6]

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]

Week 24 post-first dose and Week 72 post-first dose

Secondary outcome [7]

Change from baseline in lung volumes as measured by High Resolution Computed Tomography (HRCT)

Timepoint [7]

Week 24 post first dose

Eligibility

Key inclusion criteria

Population
1. Male and female patients, at least 40 years of age 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 60 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

No limit

Sex

Both males and females

Can healthy volunteers participate?

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

Completed

Date of first participant enrolment

Anticipated

21/01/2019

Actual

1/06/2019

Date of last participant enrolment

Anticipated

31/12/2019

Actual

29/04/2020

Date of last data collection

Anticipated

30/11/2021

Actual

20/10/2021

Sample size

Target

100

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,SA,WA,VIC

Recruitment hospital [1]

The Alfred - Melbourne

Recruitment hospital [2]

The Prince Charles Hospital - Chermside

Recruitment hospital [3]

Hunter Medical Research Institute - New Lambton Heights

Recruitment hospital [4]

St Vincent's Hospital (Darlinghurst) - Darlinghurst

Recruitment hospital [5]

Fiona Stanley Hospital - Murdoch

Recruitment hospital [6]

Royal Prince Alfred Hospital - Camperdown

Recruitment hospital [7]

Westmead Hospital - Westmead

Recruitment hospital [8]

Concord Repatriation Hospital - Concord

Recruitment hospital [9]

Nepean Hospital - Kingswood

Recruitment hospital [10]

The Queen Elizabeth Hospital - Woodville

Recruitment hospital [11]

Mater Private Hospital - South Brisbane

Recruitment hospital [12]

Institute for Respiratory Health - Nedlands

Recruitment postcode(s) [1]

2010 - Darlinghurst

Recruitment postcode(s) [2]

2050 - Camperdown

Recruitment postcode(s) [3]

2139 - Concord Repatriation Hospital

Recruitment postcode(s) [4]

2145 - Westmead

Recruitment postcode(s) [5]

2305 - New Lambton Heights

Recruitment postcode(s) [6]

2747 - Kingswood

Recruitment postcode(s) [7]

3001 - Melbourne

Recruitment postcode(s) [8]

3004 - Melbourne

Recruitment postcode(s) [9]

4032 - Chermside

Recruitment postcode(s) [10]

4101 - South Brisbane

Recruitment postcode(s) [11]

5011 - Woodville South

Recruitment postcode(s) [12]

5067 - Kent Town

Recruitment postcode(s) [13]

6150 - Murdoch

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Country [2]

Czech Republic

State/province [2]

Country [3]

Poland

State/province [3]

Country [4]

United Kingdom

State/province [4]

Country [5]

Netherlands

State/province [5]

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Avalyn Pharma Pty Ltd

Address [1]

Level 17 HWT Tower 40 City Road Southbank VIC 3006

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Avalyn Pharma Pty Ltd

Address

Level 17 HWT Tower 40 City Road Southbank VIC 3006

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry Limited

Ethics committee address [1]

129 Glen Osmond Road Eastwood Adelaide, South Australia 5063

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

31/10/2018

Approval date [1]

01/04/2019

Ethics approval number [1]

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

Dr Christopher Grainge

Address

Hunter Medical Research Institute
Lot 1 Kookaburra Circuit
New Lambton Heights
NSW 2305

Country

Australia

Phone

+61 2 4042 0000

Fax

Christopher.Grainge@hnehealth.nsw.gov.au

Contact person for public queries

Name

Felix Woodhead

Address

Avalyn Pharma Pty Ltd., Level 17 HWT Tower 40 City Road Southbank VIC 3006

Country

Australia

Phone

+61 3 9869 5922

Fax

fwoodhead@avalynpharma.com

Contact person for scientific queries

Name

Felix Woodhead

Address

Avalyn Pharma Pty Ltd., Level 17 HWT Tower 40 City Road Southbank VIC 3006

Country

Australia

Phone

+61 3 9869 5922

Fax

fwoodhead@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?

Type	Citation	Link	Email	Other Details	Attachment
Ethical approval			info@avalynpharma.com		376322-(Uploaded-17-08-2019-04-20-48)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Basic results	No			376322-(Uploaded-04-09-2022-05-09-11)-Basic results summary.pdf

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Inhaled pirfenidone solution (AP01) for IPF: A randomised, open-label, dose-response trial.	2023	https://dx.doi.org/10.1136/thorax-2022-219391
Dimensions AI	ERS International Congress 2023: highlights from the Interstitial Lung Diseases Assembly	2023	https://doi.org/10.1183/23120541.00839-2023
Dimensions AI	Natural Products-Based Inhaled Formulations for Treating Pulmonary Diseases	2024	https://doi.org/10.2147/ijn.s451206

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically