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 V2.
• Confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring hospitalization not fully recovered according to investigator judgement within 4 weeks prior to V2.
• Heart failure NYHA Class IV, acutely decompensated right heart failure, pulmonary hypertension with syncopal episode, confirmed myocardial infarction, unstable angina or uncontrolled hypertension, within 6 months prior to V1.
• Acute IPF exacerbation within 3 months prior to V1 and/or during the screening period, as defined by Collard et al, 2016: a. Acute worsening or development of dyspnoea typically <1 month duration. b. 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). c. Deterioration not fully explained by cardiac failure or fluid overload.
• Treatment with pirfenidone (substrate of CYP1A2) within 8 weeks prior to V1 or anticipated need for pirfenidone during the participation in the trial.
• Treatment with the specific medications listed as per protocol within 2 weeks prior to V2 or anticipated need for such medication during the participation in this trial.
• 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 V1.
• Previous participation in a clinical trial with buloxibutid and received at least one dose of buloxibutid.

Other illness

• Concurrent serious medical condition which in the opinion of the investigator constitutes a risk or a contraindication for the 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 V1, 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.
• Know 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 V1. Retesting is allowed once.
• Severe renal impairment (i.e., estimated glomerular filtration rate (eGFR) ≤35 ml/min/1.73 m2 at V 1 according to Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula). Retesting is allowed once.
• 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 V1, 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.
• Abnormal laboratory value at V1 indicating a potential risk for the participant if enrolled in the trial as evaluated by the investigator. Retesting is allowed once.

Other

• Inability to refrain from smoking (including e-cigarettes and cannabis) on days of site visits until completion of trial procedures.
• Where applicable per country regulation, the participant must not currently be committed to an institution by virtue of an order issued either by judicial or administrative authorities.
• Airways obstruction with a pre-bronchodilator forced expiratory volume in one second (FEV1)/FVC ratio <0.7 at V1.
• The investigator considers the participant unlikely to comply with trial procedures, restrictions and requirements.
• Pregnant or breast-feeding female participants
• Resting oxygen saturation of < 89% using up to 4 L/min of supplemental oxygen at sea level and up to 6 L/min at altitude (≥ 5000 feet [1524 meters] above sea level) during screening.
• Inability to generate a spirometry test at V1 meeting the standards of the ATS/ERS 2019 guideline.

• Age ≥ 40 years at the time of signing the informed consent
• Diagnosed of IPF within 7 years prior to V1, as per applicable ATS/ERS/JRS/ALAT at the time of diagnosis.
• HRCT scan within 36 months prior to V1 with central reading confirming either a or b, and c: a. A pattern consistent with usual interstitial pneumonia (UIP) according to ATS/ERS/JRS/ALAT 2022 guideline: UIP or probable UIP. b. A pattern indeterminate for UIP according to ATS/ERS/JRS/ALAT 2022 guideline and a historical biopsy (surgical lung biopsy or transbronchial lung cryobiopsy) consistent with IPF. c. Extent of fibrosis > extent of emphysema.
• FVC ≥50% predicted at V1.
• DLCO (corrected for hemoglobin) ≥30% predicted at V1
• Either: a. On a stable dose of licensed IPF therapy for at least 8 weeks prior to V1 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. b. 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 V1.
• Anticipated life expectancy of at least 12 months at V1 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. 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 study drug.
• Written informed consent, consistent with ICH-GCP and local laws, obtained before the initiation of any trial-related procedure.