None listed
Conditions
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)
Interventions
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
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.
Sponsors
Avalyn Pharma Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
40 Years to 90 No limit
Healthy volunteers
No
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
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
Outcome results
None listed