New hope for lung scarring: HSK44459 enters final trial phase

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Age ≥40 years, regardless of gender; 2. Diagnosis of IPF confirmed prior to or during screening per the 2022 ATS/ERS/JRS/ALAT guidelines (Appendix 1); 3. Patients must meet one of the following criteria: 1. No treatment with nintedanib or pirfenidone for at least 8 weeks prior to screening (e.g., treatment-naïve or discontinued therapy), with no plans to initiate or resume antifibrotic treatment; 2. On a stable regimen of nintedanib or pirfenidone for at least 12 weeks prior to screening, without combination therapy with both drugs. \[Stable therapy is defined as maintaining a constant dosage with tolerable drug-specific adverse events\]; 4. Percentage predicted forced vital capacity (FVCpp) ≥45% at screening; 5. Percentage predicted diffusing capacity of the lungs for carbon monoxide (DLCOpp) ≥25% and \<90% at screening \[\*hemoglobin (Hb)-adjusted\]; 6. Willing to participate and voluntarily sign the informed consent form. Exclusion Criteria: 1. Clinically significant airway obstruction during screening \[pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) \<0.7\]; 2. Other clinically significant pulmonary abnormalities per investigator judgment (exceptions: conditions requiring no treatment during the trial, e.g., asymptomatic pulmonary nodules, emphysema); 3. Acute IPF exacerbation within 3 months before screening and/or during screening; 4. Receiving immunomodulators (excluding oral corticosteroids) for respiratory conditions, or prednisone \>15 mg/day (or equivalent); 5. History of vasculitis; 6. Any suicidal behavior within 2 years before screening (actual attempt, interrupted attempt, aborted attempt, or preparatory acts/behaviors); 7. Type 4 or 5 suicidal ideation per Columbia-Suicide Severity Rating Scale (C-SSRS) within 3 months before/during screening (active suicidal thoughts with method/intent but no plan, or with method/intent/plan); 8. Respiratory infection requiring antibiotics or other infections requiring treatment within 4 weeks before/during screening; 9. Major surgery within 3 months before screening or planned during the study (investigator-assessed; lung transplant listing excluded); 10. Malignancy within 5 years before screening (except treated basal cell carcinoma, squamous cell carcinoma in situ, or cervical carcinoma in situ); 11. Blood pressure ≥160/100 mmHg at screening; 12. Unstable/worsening cardiovascular/cerebrovascular disease within 6 months before screening (e.g., unstable angina, myocardial infarction, heart failure, thromboembolic events including stroke/TIA); 13. Aspartate transaminase (AST) or alanine transaminase (ALT) \>2.5×ULN or total bilirubin \>1.5×ULN at screening; 14. Estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m² at screening; 15. Gastrointestinal surgery/disease affecting pharmacokinetics (PK) (except appendectomy/hernia repair); 16. Active hepatitis B \[HBsAg-positive with HBV-DNA above ULN\], hepatitis C antibody-positive, syphilis (anti-TP-positive with TRUST above ULN), or HIV infection (anti-HIV-positive) at screening; 17. Current treated liver disease with Child-Pugh A/B/C impairment at screening; 18. Substance abuse, drug use, or excessive alcohol intake (\>2 units/day; 1 unit=360 mL beer \[5%\], 45 mL spirits \[40%\], or 150 mL wine) within 3 months before screening; 19. Tobacco/nicotine product use within 3 months before screening or unwillingness to abstain during the study; 20. Previous HSK44459 use or PDE1/3/4/10/non-selective PDE inhibitor treatment (excluding HSK44459, e.g., apremilast, roflumilast, ibudilast) within 8 weeks before screening; 21. Use of strong CYP3A4 inhibitors/inducers within 14 days or 5 half-lives (whichever longer) before first dose, or anticipated need during the study; 22. History of severe drug allergy or hypersensitivity to investigational product/excipients; 23. Participation in other clinical trials (receiving investigational drug/placebo) within 1 month before screening; 24. Pregnancy/lactation; participants of childbearing potential unwilling to use contraception during and for 3 months post-study (including male participants); 25. Any other investigator-determined factors making participation unsuitable.