A Phase 3 Study of Efficacy and Safety of AK3280 in Patients With Idiopathic Pulmonary Fibrosis

Prior treatment

• Hospitalization due to acute IPF exacerbation within 8 weeks prior to screening or during screening
• Within 4 weeks prior to screening or during screening, local or systemic infection requiring: 1) Hospitalization ≥ 24 hours; or 2) Use of systemic antibiotics (IV, IM, oral, or inhaled)
• History of active tuberculosis within 12 months prior to screening
• Use of prohibited medications with potential effects on efficacy endpoints within 4 weeks or 5 half-lives (whichever is longer) prior to randomization

Other illness

• History of hypersensitivity to pirfenidone or AK3280
• History of other clinically significant lung diseases besides IPF (e.g., asthma, COPD, interstitial pneumonia of known cause, acute severe pulmonary infection, etc.), or planned lung transplantation within 6 months after signing informed consent
• History of heart disease meeting NYHA Class III-IV
• History of liver cirrhosis, severe hepatic impairment, or end-stage liver disease
• History of any clinically diagnosed autoimmune disease, including but not limited to scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis
• History of malignancy or possible malignancy upon evaluation (except treated localized basal cell carcinoma of the skin or cervical carcinoma in situ without recurrence)
• History of immunodeficiency, including but not limited to HIV infection
• History of any disease other than IPF with life expectancy \< 18 months; or requiring long-term medical care, or limited self-care ability; or conditions that the investigator believes may affect participant's ability to complete this clinical study, complete study-related assessments, or affect safety or efficacy assessments

Lab values

• Screening liver function abnormalities meeting any of the following:1) AST ≥ 2× ULN; 2) ALT ≥ 2× ULN; 3) ALP ≥ 2× ULN; 4) Total bilirubin ≥ 1.5× ULN
• Screening cystatin C-estimated eGFR \< 60 mL/min/1.73m²
• Screening coagulation test meeting any of the following: 1) INR \> 2; 2) Both PT and APTT prolonged \> 1.5× ULN
• Uncontrolled diabetes during screening (HbA1c \> 10%)

Other

• Known intolerance to pirfenidone single dose of 200 mg (total daily dose 600 mg)
• Post-bronchodilator FEV1/FVC \< 0.7 or positive bronchodilator response (defined as ≥ 12% relative increase in FEV1 and ≥ 200 mL absolute increase in FEV1 after bronchodilator use) during screening

• Age ≥ 40 years at enrolment
• Diagnosis of IPF per ATS/ERS/JRS/ALAT 2022 guidelines
• HRCT central review completed during screening or within 12 months prior to screening. If participant did not undergo lung surgical biopsy, HRCT imaging must be consistent with usual interstitial pneumonia (UIP) pattern for definitive IPF diagnosis.
• No prior anti-fibrotic treatment, or discontinued anti-fibrotic therapy for ≥4 weeks or 5 half-lives (whichever is longer) prior to randomization
• Screening assessments meeting all of the following: 1) Standardized %pFVC ≥ 50% and ≤ 90%；2) Hemoglobin-corrected %pDLco ≥ 30% and ≤ 90%；3) Resting SpO2 ≥ 88%