Phase II Clinical Study of BC006 in Patients With Idiopathic Pulmonary Fibrosis

Prior treatment

• Acute exacerbation of IPF within 3 months prior to screening or during the screening period, as judged by the investigator.
• Sustained improvement in IPF severity within 12 months prior to screening or during the screening period, as judged by the investigator based on changes in FVC, DLCO, and/or chest HRCT scan.
• History of smoking within 3 months prior to screening or during the screening period, or inability to refrain from smoking (including cigarettes, cigars, pipes, and e-cigarettes) for the duration of the study.
• Completed a cardiopulmonary rehabilitation program focusing on exercise training within 8 weeks prior to screening, or planning to initiate such a program during the study.
• Major surgery within 4 weeks prior to screening or during the screening period, or planning major surgery during the study (assessed as major surgery by the investigator).
• Acute respiratory or systemic bacterial, viral, or fungal infection requiring antimicrobial therapy within 4 weeks prior to screening or during the screening period.
• Positive interferon-γ release assay for tuberculosis during the screening period (testing is not required for patients who completed treatment for active or latent tuberculosis within 6 months prior to screening with no evidence of recurrent disease).
• Prior treatment with a highly selective small-molecule CSF-1R inhibitor (excluding nintedanib), or anti-CSF-1/CSF-1R antibody.
• Known allergy or contraindication to the investigational product components or excipients, or history of hypersensitivity or severe infusion reaction to antibody-based products.
• Received an investigational drug within 4 weeks prior to screening or within 5 half-lives (whichever is longer) or during the screening period.
• Received other newly approved anti-fibrotic therapies other than nintedanib and pirfenidone within 4 weeks prior to screening or during the screening period, or planning to receive such therapies during the study.
• Received combination therapy with nintedanib and pirfenidone within 8 weeks prior to screening or during the screening period.
• Received cytotoxic, immunosuppressive, cytokine-modulating agents, or receptor antagonists (including but not limited to methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, everolimus) within 4 weeks prior to screening or during the screening period.
• Received systemic corticosteroid therapy with prednisone \> 15 mg/day or equivalent within 4 weeks prior to screening or during the screening period.
  • Patients taking nintedanib: using or planning to use strong P-glycoprotein (P-gp) inhibitors (e.g., ketoconazole, erythromycin) or inducers (e.g., rifampicin, carbamazepine, phenytoin, St. John's Wort) during screening or the study.
  • Patients taking pirfenidone: using or planning to use strong CYP1A2 inhibitors (e.g., fluvoxamine, enoxacin) or inducers (e.g., rifampicin) during screening or the study.
• Unable to avoid use of the following medications: Short-acting bronchodilators within 4 hours prior to spirometry and DLCO measurements; Once-daily long-acting bronchodilators within 24 hours prior to spirometry and DLCO measurements; Twice-daily long-acting bronchodilators within 12 hours prior to spirometry and DLCO measurements.
• Known or suspected history of alcohol or drug abuse within 2 years prior to screening or during the screening period.

Other illness

• Interstitial lung disease of known etiology (e.g., domestic and occupational environmental exposures, connective tissue disease, drug toxicity, etc.).
• Other pulmonary diseases considered clinically significant by the investigator (e.g., asthma, chronic obstructive pulmonary disease, cavitary or pleural disease, etc.).
• Presence of pulmonary hypertension or cor pulmonale that, in the investigator's opinion, would significantly limit compliance with study requirements or may affect assessment of study safety or efficacy.
• History of lung volume reduction surgery or lung transplantation, or planning to undergo lung volume reduction surgery or lung transplantation during the study (patients on a lung transplant waiting list are permitted).
• Current or suspected malignancy, or history of malignancy within 5 years prior to screening (excluding basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, or other carcinoma in situ that has received curative treatment with no recurrence).
• Active autoimmune disease, or history of autoimmune disease that may relapse (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc., including but not limited to these diseases or syndromes).
• History of immunodeficiency, including positive human immunodeficiency virus (HIV) antibody test.

Lab values

• History of severe cardiovascular or cerebrovascular disease, including but not limited to: ventricular arrhythmia requiring clinical intervention; uncontrolled atrial arrhythmia; congestive heart failure meeting New York Heart Association (NYHA) functional Class ≥ III; previous evidence of left ventricular ejection fraction (LVEF) \< 35%; uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg) or poor compliance with antihypertensive medications; acute coronary syndrome, stroke, or transient ischemic attack within 6 months prior to screening.
• Active hepatitis B or hepatitis C. Active hepatitis B is defined as positive hepatitis B surface antigen (HBsAg) and HBV DNA \> upper limit of normal (ULN). Active hepatitis C is defined as positive hepatitis C antibody (HCV-Ab) and HCV RNA \> ULN.
• Presence of any of the following laboratory abnormalities during the screening period: AST or ALT \> 1.5 × ULN; Total bilirubin \> 1.5 × ULN; Creatinine (Cr) \> 1.5 × ULN
• Pregnant (female patients of childbearing potential confirmed by serum pregnancy test within 7 days prior to first dose of study drug) or lactating female.
• Any disease, treatment, or abnormal laboratory finding that, in the investigator's opinion, may affect the patient's participation in the entire study, increase patient risk, or confound study results; or participation in the study is not in the patient's best interest, in the investigator's judgment.

Other

• Emphysema ≥ 50%, or emphysema greater than fibrosis, as determined by independent central imaging review of HRCT.
• Pre-bronchodilator forced expiratory volume in 1 second (FEV1)/FVC \< 0.70 during the screening period.
• Known increase in FEV1 and/or FVC ≥ 12% and ≥ 200 mL post-bronchodilator.

• Must provide written informed consent form (ICF) indicating understanding of the study and voluntary participation.
• Aged ≥40 years at the time of signing the ICF, with no gender restriction.
• Diagnosis of idiopathic pulmonary fibrosis (IPF) according to the 2022 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Society (ATS/ERS/JRS/ALAT) clinical practice guideline.
• HRCT pattern consistent with usual interstitial pneumonia (UIP) or probable UIP for IPF confirmed by independent central imaging review (acceptable-quality HRCT obtained within 12 months prior to screening or during the screening period). If HRCT shows indeterminate UIP, the diagnosis of IPF must be confirmed by histopathology from a prior lung biopsy (surgical/video-assisted thoracoscopic lung biopsy or bronchoscopic cryobiopsy) recognized by the investigator, if available.
• Forced vital capacity percent predicted (FVC% predicted) ≥45% during the screening period.
• Diffusing capacity of the lung for carbon monoxide percent predicted (DLCO% predicted), corrected for hemoglobin (Hb), ≥30% and ≤90% during the screening period.
• Meets either of the following:
  • The patient has been on a stable dose of nintedanib or pirfenidone for at least 8 weeks prior to screening and during screening (nintedanib ≥100 mg BID, pirfenidone ≥400 mg TID, no dose changes), tolerates the treatment, and plans to continue this background therapy during the study.
  • The patient has not received nintedanib or pirfenidone for at least 4 weeks prior to screening and during screening (previous treatment discontinued or treatment-naïve), and does not plan to initiate or re-initiate nintedanib or pirfenidone during the study. No patient should discontinue approved therapy to participate in this study. Treatment-naïve patients must decline after full discussion with the investigator regarding the risks/benefits of such therapy.
• Patients of reproductive potential (male and female) must agree to use highly effective contraceptive methods (hormonal, barrier, or abstinence) from signing the ICF until at least 6 months after the last dose of study drug.