ASPIRE Study

NSW 

• Concord Repatriation Hospital 
• St Vincent’s Hospital
• Royal Prince Alfred Hospital 

VIC

• Austin Health 
• Lung Research Victoria

SA

• Flinders Medical Centre
• Queen Elizabeth Hospital

QLD

• Prince Charles Hospital
• Townsville University Hospital

1. Age ≥ 40 years
2. Diagnosed with IPF within 7 years prior to visit 1
3. HRCT scan within 36 months confirming either a or b, and c:
   a. A pattern consistent with usual interstitial pneumonia (UIP)
   b. A pattern indeterminate for UIP and a historical biopsy (surgical lung biopsy or transbronchial lung cryobiopsy) consistent with IPF.
   c. Extent of fibrosis > extent of emphysema.
4. FVC ≥50% predicted at visit 1.
5. DLCO (corrected for hemoglobin) ≥30% predicted at visit 1.
6. Either:
   a. On a stable dose of IPF therapy for at least 8 weeks prior to visit 1 and expected to remain  on this background treatment after randomisation. Due to the risk of DDIs, concomitant treatment with pirfenidone is not allowed in this trial.  b. Not currently receiving treatment for IPF. Any previous treatment must have been discontinued >8 weeks prior to visit 1.
7. Anticipated life expectancy of at least 12 months at visit 1 and not anticipated to require a lung transplant during the trial period (being on a transplant list does not exclude a participant from the trial).
8. Contraceptive use by women of childbearing potential (WOCBP).
9. Written informed consent. 

1. Concurrent serious medical condition that in the opinion of the investigator constitutes a risk or contraindication for participation in the trial or that could interfere with the trial objectives, conduct or evaluation. 
2. Airways obstruction with a pre-bronchodilator forced expiratory volume in one second (FEV1)/FVC ratio <0.7 at visit 1.
3. Lower respiratory tract infection requiring antibiotics and not fully recovered according to investigator judgement within 4 weeks prior to visit 2.
4. Confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and not fully recovered within 4 weeks prior to visit 2.
5. Known impaired hepatic function or clinically significant liver disease (Child-Pugh B or C hepatic impairment), or aspartate aminotransferase (AST) or alanine aminotransferase (ALT)>3 times upper limit of normal (ULN) or total bilirubin>1.5 times ULN at visit 1. .
6. Severe renal impairment i.e. estimated glomerular filtration rate (eGFR) ≤35ml/min/1.73m2 at visit 1.  
7. Prolonged QTcF (QT interval with Fridericia’s correction) (>450 ms), AV-block II or III, uncontrolled arrhythmia, or other clinically significant abnormality in the resting ECG at visit 1.
8. Heart failure NYHA Class IV, acutely decompensated right heart failure, PH with syncopal episode, confirmed myocardial infarction, unstable angina or uncontrolled hypertension, within 6 months prior to visit 1.
9. Known hypersensitivity or intolerance to study drug or to any other components of the test product, including excipients.
10. Pregnant or breast-feeding female participants.
11. Acute IPF exacerbation within 3 months prior to visit 1 and/or during the screening period.
    1. Acute worsening or development of dyspnea typically <1 month duration.
    2. Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern.
    3. Any immunosuppressive therapies other than: inhaled, nasal and topical corticosteroids, corticosteroids for the treatment of acute exacerbations.
12. Inability to generate spirometry data at least twice at visit 1..
13. Treatment with pirfenidone (substrate of CYP1A2) within 8 weeks prior to visit 1 or anticipated need for pirfenidone during participation in the trial.
14. Treatment with the medications listed below within 2 weeks prior to visit 2 or anticipated need for such medication during participation in the trial:
    1. Sensitive or moderately sensitive substrates of CYP1A2 (e.g., theophylline, tizanidine), CYP2C9 (e.g., warfarin, tolbutamide, gliclazide, glibenclamide, acenocoumarol, phenprocoumon, phenytoin, siponimod), CYP2C19 (e.g., mephenytoin, valproic acid, escitalopram), or CYP2C8 (e.g., paclitaxel) with a narrow therapeutic index. 
    2. Fluvastatin or pitavastatin.
    3. Any immunosuppressive therapies other than: Inhaled, nasal and topical corticosteroids, corticosteroids for the treatment of acute exacerbations.
15. Current or previous participation in any other clinical trial where the participant has received a dose of IMP within 4 weeks or 5 half-lives of the IMP, whichever is longest, prior to visit 1.
16. Previous participation in a clinical trial with the study drug and received at least one dose of the study drug.