A Trial to Evaluate Efficacy and Safety of Buloxibutid in People With Idiopathic Pulmonary Fibrosis.

Prior treatment

• Lower respiratory tract infection requiring antibiotics and not fully recovered according to investigator judgement within 4 weeks prior to visit 2.
• Confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring hospitalization and not fully recovered according to investigator judgement within 4 weeks prior to visit 2.
• 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.
• Acute IPF exacerbation within 3 months prior to visit 1 and/or during the screening period, as defined by Collard et al., 2016:
  • Acute worsening or development of dyspnea typically \<1 month duration.
  • Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern (if no previous computed tomography is available, the qualifier "new" can be dropped).
  • Deterioration not fully explained by cardiac failure or fluid overload.
• Treatment with pirfenidone within 8 weeks prior to visit 1 or anticipated need for pirfenidone during participation in the trial.
  • More exclusion criteria may apply.
  • Trial website: www.aspire-ipf.com

Other illness

• Concurrent serious medical condition that in the opinion of the investigator constitutes a risk or a contraindication for participation in the trial or that could interfere with the trial objectives, conduct or evaluation, including active or suspected malignancy or history of malignancy within 5 years prior to visit 1, except appropriately treated basal cell carcinoma of the skin, fully resected and cured squamous cell carcinoma of the skin, "under surveillance" prostate cancer or in situ carcinoma of uterine cervix.
• Known hypersensitivity or intolerance to buloxibutid or to any other components of the test product, including excipients.

Lab values

• 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.
• Severe renal impairment (i.e., estimated glomerular filtration rate (eGFR) ≤35 ml/min/1.73 m2 at visit 1 according to Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula).
• 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, as judged by the investigator. Patients with implantable cardiovascular devices (e.g. pacemaker) affecting the QT interval time may be enrolled in the trial based upon investigator judgement, following cardiologist consultation if deemed necessary, and only after discussion with the medical monitor.

Other

• Participants are excluded from the trial if any of the following criteria apply:
• Airways obstruction with a pre-bronchodilator forced expiratory volume in one second (FEV1)/FVC ratio \<0.7 at visit 1.
• Pregnant or breast-feeding female participants.
• Inability to generate a spirometry test at visit 1 meeting the standards of the ATS/ERS 2019 guideline (Graham et al., 2019).

• Age ≥ 40 years at the time of signing the informed consent.
• Diagnosed with IPF within 7 years prior to visit 1, as per applicable ATS/ERS/JRS/ALAT guidelines at the time of diagnosis.
• HRCT scan within 36 months prior to visit 1 with central reading confirming either a or b, and c
  • A pattern consistent with usual interstitial pneumonia (UIP) according to ATS/ERS/JRS/ALAT 2022 guideline (Raghu et al., 2022) UIP or probable UIP.
  • A pattern indeterminate for UIP according to ATS/ERS/JRS/ALAT 2022 guidelines (Raghu et al., 2022) and a historical biopsy (surgical lung biopsy or transbronchial lung cryobiopsy) consistent with IPF.
  • Extent of fibrosis \> extent of emphysema.
• FVC ≥50% predicted at visit 1.
• DLCO (corrected for hemoglobin) ≥30% predicted at visit 1.
• Either:
  • On a stable dose of licensed IPF therapy for at least 8 weeks prior to visit 1 and expected to remain on this background treatment after randomization. Due to the risk of DDIs, concomitant treatment with pirfenidone is not allowed in this trial.
  • Not currently receiving treatment for IPF with a licensed therapy for any reason, including prior intolerance, non-responsiveness, ineligibility, lack of access or voluntarily decline. Any such previous treatment must have been discontinued \>8 weeks prior to visit 1.
• 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).
• Contraceptive use by women of childbearing potential (WOCBP) which is highly effective and consistent with local regulations regarding the methods of contraception for those participating in clinical trials.
  • For UK and countries within the EU: Male participants, if heterosexually active with a female partner of childbearing potential, or a pregnant or breastfeeding partner, must agree to use barrier contraception (male condom) and abstain from sperm donation for the duration of the treatment period and for at least 2 weeks after the last dose of the trial drug.
• Written informed consent, consistent with ICH-GCP and local laws, obtained before the initiation of any trial-related procedure.