Safety, Tolerability and Efficacy of VUM02 Injection in Treatment of Idiopathic Pulmonary Fibrosis (IPF)

Prior treatment

• Suffering from interstitial lung diseases (ILD) other than IPF, including but not limited to: any other type of interstitial pneumonia; lung diseases related to exposure to fibrogenic agents or other environmental toxins or drugs (such as amiodarone, bleomycin, or methotrexate); other types of occupational lung diseases; granulomatous lung diseases; systemic diseases including vasculitis, infectious diseases (i.e., tuberculosis), and connective tissue diseases, or a history of prior pulmonary resection;
• Previously received stem cell therapy or intolerant to cell therapy;
• Used non-biological drugs with cell proliferation inhibition or immunosuppressive/immunomodulatory effects during the 3 months prior to screening, such as Mycophenolate Mofetil, cyclophosphamide, tacrolimus, and JAK inhibitors, as well as other Chinese herbal medicines with immunomodulatory effects; Patients who have used low-dose corticosteroids (≤10 mg/day prednisone or equivalent dose of similar drugs) are allowed to be enrolled.
• Used biologics such as rituximab, TNF-α monoclonal antibodies, and IFN-γ monoclonal antibodies within the 6 months prior to screening;
• Used anticoagulant drugs, sildenafil, bosentan, macitentan, imatinib, and other drugs for treating IPF within the 4 weeks prior to screening;
• Participated in interventional clinical studies within the 3 months or within the half-life of 5 drugs (whichever is longer) before screening;

Other illness

• Allergic to any ingredient of the product;
• During the screening period, having any of the following pulmonary diseases: asthma, pulmonary embolism, pneumothorax; lung cancer, obstructive bronchitis, or other active lung diseases; a known history of immune system diseases (such as thymic diseases, systemic lupus erythematosus); acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
• Had a lung infection within the past month;
• Had a history of invasive or non-invasive mechanical ventilation, or currently require oxygen therapy (oxygen therapy time \>15 h/d);
• Evidence suggests that the subject currently has digestive system, urinary system, cardiovascular system, hematological system, nervous system, psychiatric, or metabolic diseases that may affect safety, such as severe kidney disease requiring blood dialysis or peritoneal dialysis; advanced hepatitis or cirrhosis; severe heart failure (NYHA Grade III and IV); poorly controlled hypertension (≥180/100 mmHg); severe pulmonary heart disease or pulmonary arterial hypertension considered by the investigators to affect the evaluation of the trial results;
• Have various malignant tumors or a history of malignant tumors;
• 12-lead electrocardiogram shows severe arrhythmias (such as ventricular tachycardia, frequent supraventricular tachycardia, atrial fibrillation, and atrial flutter) or degree II and above atrioventricular block;
• Positive results in serological tests (HBsAg, HCV antibodies, HIV antibodies, syphilis spirochete antibodies), among which carriers of hepatitis B virus, stable patients with hepatitis B (DNA titer ≤2000 IU/mL or copy number \<1000 copies/mL) after drug treatment, and cured patients with hepatitis C (negative HCV RNA) can be enrolled after being judged eligible by the investigator;

Lab values

• Laboratory tests meet any of the following criteria: white blood cell count less than 3.5×109/L or neutrophils less than 1.5×109/L for any reason; hemoglobin (HGB) ≤90 g/L; fibrinogen (FIB) ≤0.5×LLN; alanine aminotransferase (ALT) \>2×ULN, aspartate aminotransferase (AST) \>2×ULN, total bilirubin (TBIL) \>1.5×ULN, direct bilirubin (DBIL) \>1.5×ULN, blood creatinine (Cr) \>1.5×ULN;

Age

• Pregnant or lactating women, or those with a positive result in the screening period for beta-human chorionic gonadotropin (β-HCG) testing; or male subjects of childbearing potential and female subjects of childbearing age who are unable and unwilling to take effective non-drug contraceptive measures during the study and 6 months after the end of the study;

Other

• Patients meeting any of the following criteria are not eligible for this trial:
• Chest HRCT during the screening period shows emphysema area \> fibrosis area;
• Hospitalized 2 or more times in the past year due to acute exacerbation of IPF;
• Smoked within the past 3 months or cannot quit smoking during the trial;
• The expected survival period may be less than 1 year judged by investigator;
• Subjects deemed inappropriate for entry into this study by the investigator.

• Patients must meet all of the following criteria to be eligible for this trial:
• Gender unrestricted, aged between 40 and 80 years old (inclusive);
• Diagnosed with IPF according to the 2022 Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.
• In the 3 months prior to administration, determined by the investigator to have stable disease, with diffusing capacity of the lung for carbon monoxide (DLCO) ≥ 30% of the predicted value (adjusted for Hb), FVC/predicted ≥50%, and forced expiratory volume in one second (FEV1)/FVC ≥0.70;
• Newly diagnosed IPF patients (who may receive both the investigational drug and stable background antifibrotic therapy after enrollment), or IPF patients whose disease has been stable for at least 4 weeks at screening (a. no nintedanib and/or pirfenidone treatment for at least 4 weeks prior to screening; or b. receiving stable doses of nintedanib and/or pirfenidone for at least 4 weeks at screening, with planned continuation of this stable background therapy after entering the study; stable background therapy is defined as an individual patient being generally able to tolerate pirfenidone or nintedanib treatment).
• Good compliance, able to understand and cooperate with pulmonary function test procedures, willing to participate voluntarily in the trial according to the protocol requirements, and understand and sign the informed consent form voluntarily.