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
ACTRN12621000170820
Ethics application status
Approved
Date submitted
15/12/2020
Date registered
18/02/2021
Date last updated
1/02/2023
Date data sharing statement initially provided
18/02/2021
Date results information initially provided
15/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Access to Pirfenidone Solution for Inhalation (AP01) for Treatment of Progressive, Fibrosing Interstitial Lung Diseases, including Idiopathic Pulmonary Fibrosis
Scientific title
Safety of Pirfenidone Solution for Inhalation (AP01) for Treatment of Progressive, Fibrosing Interstitial Lung Diseases, including Idiopathic Pulmonary Fibrosis in Adults with no Treatment Alternatives
Secondary ID [1] 302809 0
Sponsor protocol number: AP01-005
Universal Trial Number (UTN)
U1111-1261-2806
Trial acronym
Linked study record
ACTRN12618001838202 (ap01-002) is a parent study to this study. Patients that finish the study, wish to continue AP01 and in the opinion of the investigator will benefit from AP01 are able to enroll in the AP01-005 to continue treatment.

Health condition
Health condition(s) or problem(s) studied:
Progressive, fibrosing interstitial lung disease 319771 0
Idiopathic Pulmonary Fibrosis (IPF) 320344 0
Condition category
Condition code
Respiratory 317704 317704 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Drug: Pirfenidone solution for inhalation (AP01): each patient will receive 100 mg inhaled pirfenidone taken twice daily for up to 48 weeks, using the eFlow nebuliser for inhalation. The only barriers to completing the full 48 weeks is tolerability to AP01 and patient consent. If patients cannot tolerate 100 mg AP01 twice daily, the dose may be reduced to 50 mg twice daily and if not tolerable, additional reduction to 50 mg once daily is available.
Drug salbutamol: Patients who experience cough that limits their ability to complete dosing will administer 1 - 2 puffs (90-100 micrograms) of salbutamol using a metered dose inhaler in order to complete the in-clinic dose (new patients only). These patients, as well as patients with a history of asthma or smoking history of 20 pack years or greater will be required to administer 1 - 2 puffs (90-100 micrograms) 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.
New patients will be trained to use the nebuliser at the first treatment visit. All patients will use the eFlow nebuliser to administer AP01. Hands on training for use and cleaning of the eFlow nebuliser will be performed by site personnel with patients using the study specific instructions for use and quick reference guide provided.
The first treatment for new patients will be overseen by clinic personnel.
Eligible patients from the AP01-002 study will have the last AP01-002 study visit and their Baseline AP01-005 visit on the same day; there is no washout period for these patients. All patients rolling over from AP01-002 will be on the 100 mg twice daily dose unless the patient has tolerability issues. Patients will tolerability issues will stay on the dose being administered in the AP01-002 study. Compliance and tolerability will be assessed at clinic visits every 3 months. Overall study drug compliance will be assessed at clinic visits every 3 months for a total of 48 months or as long as the patient is on the study by calculating the amount of AP01 vials used versus the number of AP01 vials that were expected to be used during that study period.
A screening visit will be performed if the patient has not previously been on an Avalyn sponsored AP01 study. If a patient has been previously enrolled on an Avalyn sponsored AP01 study, a modified screening visit will occur.
If the patient stops treatment for any reason an end of treatment visit will take place.
Patients will have an in clinic visit every 12 weeks to collect any safety and lung function tests that are performed as standard care.
AP01 treatment within the realm of this study will continue if patient can tolerate the drug or regulatory approval is granted or the study is terminated. Study may be terminated by the sponsor at any time for any reason.
Intervention code [1] 319086 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 325744 0
The primary objective is to evaluate the safety outcomes of patients while on AP01 therapy by assessing treatment emergent adverse events during clinic visits every 12 weeks or as needed. AEs will be recorded throughout the study and at early termination and will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and will be graded by CTCAE. The investigator is responsible for the detection and documentation of AEs regardless of treatment group or suspected causal relationship to the investigational product. For all AEs, the investigator must pursue and obtain information adequate to determine the outcome of the AE and to assess whether the AE meets the criteria for classification as an SAE requiring immediate notification to Avalyn or its designated representative.
Timepoint [1] 325744 0
Daily adverse events will be assessed every 12 weeks for 48 weeks (end of study) or early termination date
Secondary outcome [1] 388975 0
The secondary objective is to evaluate the safety outcomes of patients while on AP01 therapy by monitoring treatment emergent deaths.
Timepoint [1] 388975 0
All secondary outcomes will be measured every 12 weeks up to 48 months (end of study) or early termination date
Secondary outcome [2] 390680 0
The secondary objective is to evaluate the safety outcomes of patients while on AP01 therapy by monitoring alanine transaminase (ALT) and aspartate aminotransferase (AST)
Timepoint [2] 390680 0
All secondary outcomes will be measured at every 12 weeks up to 48 months (end of study) or early termination date
Secondary outcome [3] 390681 0
The secondary objective is to evaluate the safety outcomes of patients while on AP01 therapy by monitoring Spirometry
Timepoint [3] 390681 0
All secondary outcomes will be measured every 12 weeks up to 48 months (end of study) or early termination date
Secondary outcome [4] 391996 0
The secondary objective is to evaluate the safety outcomes of patients while on AP01 therapy by monitoring saturated oxygen using a pulse oximeter.
Timepoint [4] 391996 0
All secondary outcomes will be measured every 12 weeks up to 48 months (end of study) or early termination date

Eligibility
Key inclusion criteria
1. Prior participant in an Avalyn AP01 study, excluding normal volunteers
Or
2. Patients with no other treatment options with Interstitial Lung Diseases, including but not limited to Idiopathic Pulmonary Fibrosis, fibrosing phenotype Interstitial Lung Disease, pulmonary involvement of scleroderma, rheumatoid lung and silicosis. Prior Sponsor approval of non-Avalyn study rollover patients is required.
3. Diagnosed chronic progressive fibrotic Interstitial Lung Disease, including Idiopathic Pulmonary Fibrosis, without treatment alternatives such as:
a. Not eligible for oral pirfenidone and nintedanib due to national formulary restrictions or lack of regulatory approval
b. Intolerant to oral pirfenidone and nintedanib, if previously offered
c. Not eligible for an ongoing clinical study of AP01 other than this study
4. Age greater than 18 years
5. Able to understand and sign a written informed consent form (ICF)
6. 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
7. Females of childbearing potential (FOCBP) must use a contraceptive method during the clinical study and 30 days after the last dose of pirfenidone solution for inhalation (AP01)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Disease-Related Exclusions
1. Significant clinical worsening of Interstitial Lung Disease/Idiopathic Pulmonary Fibrosis for AP01 naïve patients 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 Idiopathic Pulmonary Fibrosis exacerbation requiring hospitalization in the last 30 days
4. Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, sinusitis, urinary tract infection, or cellulitis
Medical Exclusions
5. Females with a positive pregnancy test at Screening (AP01 naïve patients) or Baseline (Rollover patients from previous study) or are currently breastfeeding
6. 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)
7. Any condition other than Interstitial Lung Disease/Idiopathic Pulmonary Fibrosis that, in the opinion of the investigator, is likely to result in the death of the patient within the next 6 months
8. History of severe hepatic impairment or end-stage liver disease or AST or ALT greater than 5 times the upper limit of normal at Screening (AP01 naïve patients)
9. History of end-stage renal disease requiring dialysis
10. Participation in a clinical study with administration of an investigational drug product within the previous 30 days, or five half-lives of the previously administered investigational product (IP) (AP01 naïve patients only)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
All safety parameters will be summarized overall and by timepoint using descriptive statistics. All safety parameters will be presented for individual patients in data listings.
The following safety parameters will be included:
• AEs
• AST and ALT blood levels
• Spirometry
• Oximetry
Treatment-emergent AEs (any AEs recorded during or following the study drug administration) will be summarized overall and categorized by severity and relationship to the study procedures and to the investigational drug. If a patient has more than 1 occurrence of the same AE, he/she will be counted only once within that preferred term in the summary tables. The most severe occurrence of an AE, as well as the most extreme relationship of the AE to the study procedures and investigational drug, will be indicated in cases of multiple occurrences of the same AE. SAEs and AEs of special interest also will be summarized separately. All AEs will be presented in a listing. Additionally, listings of SAEs and AEs leading to discontinuation will be generated. All SAEs will be evaluated to determine whether they are UARs or UADEs.

Recruitment
Recruitment status
Active, not 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 hospital [1] 18038 0
The Alfred - Melbourne
Recruitment hospital [2] 18039 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 18040 0
The Prince Charles Hospital - Chermside
Recruitment hospital [4] 18041 0
Hunter Medical Research Institute - New Lambton Heights
Recruitment hospital [5] 18043 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [6] 18044 0
Westmead Hospital - Westmead
Recruitment hospital [7] 18760 0
Institute for Respiratory Health - Nedlands
Recruitment hospital [8] 21974 0
Respiratory Clinical Trials - Kent Town
Recruitment postcode(s) [1] 32016 0
2050 - Camperdown
Recruitment postcode(s) [2] 32021 0
2145 - Westmead
Recruitment postcode(s) [3] 32018 0
2305 - New Lambton Heights
Recruitment postcode(s) [4] 32015 0
3004 - Melbourne
Recruitment postcode(s) [5] 32017 0
4032 - Chermside
Recruitment postcode(s) [6] 32020 0
5011 - Woodville
Recruitment postcode(s) [7] 33205 0
5067 - Kent Town
Recruitment postcode(s) [8] 33206 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 23103 0
New Zealand
State/province [1] 23103 0
Country [2] 23104 0
United Kingdom
State/province [2] 23104 0
Country [3] 23105 0
Netherlands
State/province [3] 23105 0
Country [4] 23106 0
Poland
State/province [4] 23106 0
Country [5] 23107 0
Czech Republic
State/province [5] 23107 0

Funding & Sponsors
Funding source category [1] 307235 0
Commercial sector/Industry
Name [1] 307235 0
Avalyn Pharma Pty Ltd
Country [1] 307235 0
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] 307840 0
None
Name [1] 307840 0
Address [1] 307840 0
Country [1] 307840 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307331 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 307331 0
Level 3, Pod, HMRI
Lot 1, Kookaburra Circuit, New Lambton Heights
NSW 2305

Ethics committee country [1] 307331 0
Australia
Date submitted for ethics approval [1] 307331 0
30/11/2020
Approval date [1] 307331 0
09/02/2021
Ethics approval number [1] 307331 0
2020/ETH02926
Ethics committee name [2] 307334 0
Bellberry Human Research Ethics Committee
Ethics committee address [2] 307334 0
Level 39, Rialto South Tower 525 Collins Street
Melbourne Victoria 3000
Postal: GPO Box 375 MELBOURNE VIC 3001


Ethics committee country [2] 307334 0
Australia
Date submitted for ethics approval [2] 307334 0
07/12/2020
Approval date [2] 307334 0
28/01/2021
Ethics approval number [2] 307334 0
2020-12-1245

Summary
Brief summary
The purpose of this protocol is to allow for patients on current AP01 studies to continue therapy and for patients with progressive, fibrosing ILD, including IPF without treatment options and who are unable to enroll in an AP01 study to be treated with AP01.
The primary objective is to allow patients to continue or start AP01 therapy.
A screening visit will be performed if the patient has not previously been on an Avalyn sponsored AP01 study. If a patient has been previously enrolled on an Avalyn sponsored AP01 study, a modified screening visit will occur.
If the patient stops treatment for any reason an end of treatment visit will take place. Patients will have an in clinic visit every 12 weeks to collect any safety and lung function tests that are performed as standard care.
AP01 treatment within the realm of this study will continue if patient can tolerate the drug or regulatory approval is granted or the study is terminated. Study may be terminated by the sponsor at any time for any reason. The data in this study will be used to assess the safety of patients on AP01 therapy.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 106862 0
Dr Christopher Grainge
Address 106862 0
Hunter Medical Research Institute
Lot 1 Kookaburra Circuit
New Lambton Heights
NSW 2305
Country 106862 0
Australia
Phone 106862 0
+61 02 4921 3542
Fax 106862 0
Email 106862 0
Christopher.Grainge@hnehealth.nsw.gov.au
Contact person for public queries
Name 106863 0
Dr Felix Woodhead
Address 106863 0
Avalyn Pharma Pty Ltd
Level 17 HWT Tower
40 City Road
Southbank VIC 3006
Country 106863 0
Australia
Phone 106863 0
+61 398695922
Fax 106863 0
Email 106863 0
fwoodhead@avalynpharma.com
Contact person for scientific queries
Name 106864 0
Dr Felix Woodhead
Address 106864 0
Avalyn Pharma Pty Ltd
Level 17 HWT Tower
40 City Road
Southbank VIC 3006
Country 106864 0
Australia
Phone 106864 0
+61 398695922
Fax 106864 0
Email 106864 0
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 via email to info@avalynpharma.com up to 36 months following article publication.


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.