A Clinical Study to Evaluate the Efficacy and Safety of TQC2938 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetic Characteristics of TQC2938 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

The study is a Phase II, multicenter, double-blind, randomized, parallel, placebo-controlled clinical trial designed to evaluate the efficacy, safety, tolerability, and pharmacokinetic characteristics of TQC2938 in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD). It is anticipated that 256 subjects will be enrolled.

Inclusion Criteria:

• Understand and sign the written informed consent, and comply with the research process schedule during the study period.；
• Be aged 40-80 years inclusive at the time of signing the informed consent form；
• Have a record of COPD diagnosis for at least 12 months prior to screening；
• At screening or after bronchodilator use at the time of the first dose, FEV1 is ≥20% but <80% of the predicted value；
• The FEV1/forced vital capacity (FVC) ratio, measured after the use of bronchodilators at screening or at the time of the first dose, is less than 0.70；
• At screening, the Modified Medical Research Council (mMRC) score is ≥2；
• At screening, the CAT≥10；
• Current smokers or former smokers (who have quit smoking for at least 6 months before Visit 1) with a smoking history of ≥10 pack-years (for example: 20 cigarettes/day for 10 years). At screening, subjects who meet the definition of current smokers will be referred to a smoking cessation clinic；
• A chest X-ray or computed tomography (CT) scan within the 3 months prior to screening or during the screening period (before the first dose of study medication) confirms that there are no other clinically significant pulmonary diseases present apart from COPD.

Exclusion Criteria:

• History of severe allergic reactions or anaphylaxis to biologic agents, or known hypersensitivity to any component of the study drug, or a history of medications or other allergens that the investigator believes would prevent the subject from participating in the study;
• Current or past confirmed diagnosis of asthma;
• History of other clinically significant pulmonary diseases apart from COPD: such as lung cancer, bronchiectasis, sarcoidosis, pulmonary fibrosis, interstitial lung diseases, cystic fibrosis, constrictive bronchiolitis, tuberculosis, or other active pulmonary diseases;
• Evidence of cor pulmonale with right heart failure；
• Diagnosed with α-1-antitrypsin deficiency;
• History of long-term oxygen therapy with >4 L/min;
• When using respiratory assistive oxygen, the subject's oxygen saturation should be < 89%;
• Undergone lung volume reduction surgery or procedures within the 12 months prior to screening;
• Subjects participating or planning to participate in an intensive COPD rehabilitation program (subjects in the maintenance phase of a rehabilitation program are eligible for this study);
• History of lung transplantation;
• Any infection requiring hospitalization for ≥24 hours and/or treatment with oral, IV, or IM antibiotics within 4 weeks prior to screening or during the screening period;
• Upper or lower respiratory tract infections requiring antibiotic or antiviral medication within 4 weeks prior to screening or during the screening period;
• Moderate to severe COPD exacerbations within 4 weeks prior to screening or during the screening period.
• Received treatment with oral, IV, or intramuscular (IM) corticosteroids (>10 mg/day prednisone or equivalent dose) within 4 weeks prior to starting study medication;
• Received treatment with clinical trial medication, approved biologics (e.g., omalizumab, dupilumab, and/or anti-Interleukin 5 (IL-5) therapies) within 3 months prior to screening or within 5 half-lives of the drug (whichever is longer), or started or changed non-biologic immunomodulatory or immunosuppressive therapies;
• Receiving palliative care due to chronic respiratory disease, cardiovascular disease, endocrine and other systemic diseases, or cancer (e.g., for subjects with a life expectancy <12 months);
• Undergone major surgery within 8 weeks prior to screening or planning to undergo surgery that requires general anesthesia or hospitalization >1 day during the study period;
• Received or planning to receive live attenuated vaccine within 4 weeks prior to screening, during the screening period, or during the study period;
• Known immune deficiency, including but not limited to HIV infection;
• Elevated Aspartate Aminotransferase (AST), Alanine transaminase (ALT), or total bilirubin ≥2.0× the upper limit of normal (ULN) during the screening period;
• At screening, presence of any of the following: positive for hepatitis B surface antigen (HBsAg), positive for both hepatitis C virus antibody (HCV Ab) and hepatitis C virus RNA (HCV-RNA), positive for both specific and non-specific antibodies for syphilis (TP Ab);
• As determined by the investigator, history of illicit drug or drug abuse within the 12 months prior to screening;
• History of malignancy within 5 years prior to screening, except for those with negligible risk of metastasis or death (e.g., with a 5-year overall survival rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin cancer, localized prostate cancer, or ductal carcinoma in situ;
• Presence of any other serious disease or abnormal clinical laboratory test results that, in the opinion of the investigator, would prevent the subject from safely participating in or completing the study；
• Unstable cardiac disease, myocardial infarction, or New York Heart Association Class III or IV heart failure within 12 months prior to screening;
• History or current presence of clinically significant ECG abnormalities, as determined by the investigator, including but not limited to: (1) Atrial fibrillation (AF) with a rapid ventricular rate >120 bpm; (2) Sustained ventricular tachycardia (VT); (3) Bradycardia with a ventricular rate <45 bpm; (4) Mobitz Type II second-degree atrioventricular block and third-degree atrioventricular block (unless a pacemaker or defibrillator has been implanted);
• Corrected QT interval (QTcF) >450 ms for male subjects or >470 ms for female subjects; for subjects with Q wave, R wave, and S wave (QRS) >120 ms, QTcF >480 ms；
• History of ventricular arrhythmias or risk factors for ventricular arrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction, severe left ventricular hypertrophy with fibrosis), family history of unexplained sudden death or long QT syndrome, or history of sinus bradycardia (ventricular rate <45 beats/min);
• Pregnant or breastfeeding, or planning to become pregnant during the study period or within 12 weeks after the last dose of TQC2938, or female subjects with a positive pregnancy test at screening or randomization.