Study Evaluation Rentosertib (INS018_055) Administered Orally in Patients With Idiopathic Pulmonary Fibrosis (IPF)

Prior treatment

• Concurrent participation in another interventional drug, device, or biological investigational research study, or use of an investigational agent within 5 half-lives of the agent (or within 8 weeks when half-life is unknown) prior to screening is not allowed.
• Unstable cardiovascular or other disease within 6 months prior to the screening visit or during the screening period.
• Presence of other clinically significant airway disease that may, in the opinion of the investigator, impact the study safety or efficacy objectives, such as asthma, bronchiectasis, cystic fibrosis, active aspergillosis, active tuberculosis, or other serious concomitant respiratory disorder other than pulmonary fibrosis.
• Acute exacerbation of IPF within 6 months prior to screening visit and/or during the screening period.
• Major surgery performed within 3 months prior to screening visit, during the screening period, or have major surgery planned during the study period.
• Use of any of the following therapies within 4 weeks prior to screening visit and during the screening period or planned during the study: warfarin and immunosuppressive medications.
• Patients currently taking endothelin receptor antagonists,phosphodiesterase type 5 inhibitors, soluble guanylate cyclase modulators, prostacyclin analogues and prostanoids, or activin signaling inhibitor.
• Patients currently on a treatment with nerandomilast within 8 weeks prior to screening visit and during the screening period.
• Patients (female) who used hormone replacement therapy in the 4 weeks prior to randomization. No hormone replacement therapy use is allowed during the study (for female)

Other illness

• Interstitial lung disease associated with known primary diseases (eg, autoimmune disease-related interstitial lung diseases, sarcoidosis and amyloidosis), exposures (eg, radiation, silica, asbestos, and coal dust), or drugs (eg, amiodarone).
• Pulmonary hypertension that is clinically relevant or severe as deemed by the investigator, or other clinically significant pulmonary abnormalities.
• Patients with underlying chronic liver disease (Child Pugh A, B, or C hepatic impairment), and patients with non-alcoholic steatohepatitis.
• Patients with hyperbilirubinemia or Gilbert's syndrome.
• Relevant chronic or acute infections including human immunodeficiency virus (HIV) and clinically significant viral hepatitis.
• Patient with a history of lung volume reduction surgery or lung transplant.
• History of drug abuse, drug use, or alcohol abuse within the past 3 months.
• Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening visit.
• Patients with known hypersensitivity or contraindications to serine/threonine kinase inhibitors.
• Any condition that would interfere with the interpretation of study assessments or impair study participation.
• Any physical or psychological conditions or circumstance that, in the opinion of the investigator, may make a patient unsuitable for inclusion or unlikely or unable to complete the study or comply with study procedures and requirements.

Lab values

• Aspartate aminotransferase or alanine aminotransferase ≥1.5 × upper limit of normal (ULN), and/or total bilirubin ≥1.0 × ULN, and/or gamma glutamyl transferase ≥3 × ULN, and/or alkaline phosphatase ≥1.5 × ULN at screening.
• Patient with 12-lead ECG demonstrating corrected QT interval by Fridericia (QTcF) \>450 ms for males and \>470 ms for females at screening (Visit 1).
• Use of any of the following drugs within 2 weeks prior to Visit 1/screening or planned during the duration of the study
  • Strong and moderate cytochrome P450 3A4 or 1A2 inhibitors/inducers
  • Medications associated with substantial risk for prolongation of corrected QT interval.

Other

• Estimated glomerular filtration rate \<60 mL/min/1.73m2 at screening.
• Current smoker and/or cotinine (smoking) test positive.
• Patients who have consumed grapefruit or grapefruit juice, pomelo, Seville orange or Seville orange-containing products within 48 hours before Day 1.

• An informed consent form (ICF) signed and dated at screening (Visit 1), prior to initiation of any study related procedures, and in accordance with ICH-GCP and local legislation.
• Patients aged ≥40 years at time of signing the ICF.
• Diagnosis of IPF based on the 2022 ATS/ERS/JRS/ALAT Clinical Practice Guideline, confirmed by an HRCT chest scan within 3 months prior to screening visit.
• UIP or probable UIP with fibrosis extent \>10% at HRCT.
• Meet all the following criteria during the screening period:
  • FVC ≥45% predicted of normal
  • FEV1/FVC ≥0.7
  • DLCO (corrected for hemoglobin) ≥25% and \<80% predicted of normal.
• Background antifibrotic therapies are allowed, patients may be either:
  • on monotherapy with nintedanib or pirfenidone must have been on a stable therapy for at least 12 weeks prior to randomization.
  • not on a treatment with nintedanib or pirfenidone for at least 8 weeks prior to screening visit and during the screening period and do not plan to start or restart antifibrotic therapy.
• Male patients and female patients of childbearing potential agree to use highly effective contraception/preventive exposure measures from the time of the first dose of the study drug (for the male patient) or the signing of the ICF (for the female patient) until 90 days after the last dose of the study drug.