Phase II Clinical Study to Evaluate the Efficacy and Safety of XKH001 Injection

Exclusion Criteria

• •Trial participants with any of the following cannot be enrolled in this study:
• •1. Presence of any respiratory disorder other than COPD, including:
• •* Current diagnosis of asthma or a history of asthma according to the GINA or other recognized guidelines;
• •* Diagnosis of alpha-1 antitrypsin deficiency;
• •* Other concomitant active or clinically significant respiratory disorders that would significantly affect the study: such as active pulmonary tuberculosis, lung cancer (including suspected malignant pulmonary nodule \[Category 4\]), bronchiectasis, sarcoidosis, pulmonary fibrosis, interstitial lung disease, cystic fibrosis, obliterative bronchiolitis, pulmonary arterial hypertension, etc.;
• •2. AECOPD (including mild, moderate, and severe; for definitions of moderate and severe AECOPD, see Inclusion Criterion 4, item 3) and/or respiratory tract infection within 4 weeks prior to screening and before randomization;
• •3. Signs and/or symptoms of cor pulmonale and/or right ventricular failure;
• •4. Hypercapnia requiring the use of BiPAP;
• •5. Currently receiving or planning to start long-term oxygen therapy (\>15 hours of oxygen per day) or mechanical ventilation during the study;
• •6. Participation or planned participation in an intensive COPD rehabilitation program within 4 weeks prior to screening (trial participants in the maintenance phase of a rehabilitation program may be considered for enrollment);
• •7. Planned pulmonary resection or lung volume reduction surgery, or a history of such surgery;
• •8. Presence of any Grade ≥2 (NCI-CTCAE version 6.0) lipid profile abnormalities (the influence of physiological factors such as diet should be excluded);
• •9. Concomitant autoimmune disease requiring systemic immunosuppressant therapy (e.g., rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis);
• •10. Known or suspected history of an immunosuppressive disease, including a history of invasive opportunistic infections (e.g., TB, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis), even if the infection has resolved/subsided; or, in the investigator's judgment, a history of abnormally frequent, recurrent, or prolonged infections;
• •11. Confirmed active infection parasitic; suspected infection parasitic or high risk of infection, unless clinical assessment and (if necessary) laboratory assessment have ruled out active infection before randomization;
• •12. Confirmed acute or chronic infection requiring treatment with systemic antibiotics, antivirals, antifungals, antiparasitic, or antiprotozoals within 4 weeks prior to screening or during the screening period;
• •13. Undergone Grade III or IV surgery (as defined in the "Administrative Measures for the Grading of Medical Institution Surgeries", see Appendix 2: Surgical Grading Management for details) within 12 weeks prior to screening (excluding paracentesis biopsy); or planned surgery requiring general anesthesia or hospitalization \>1 day during the study;
• •14. Presence of other serious diseases that, in the investigator's judgment, may affect the patient's participation in this trial, including but not limited to: diseases that severely affect survival, uncontrolled diabetes mellitus, renal insufficiency requiring dialysis, Child-Pugh Class B/C liver function, demyelination diseases, neurological and psychological disorders, etc.;
• •15. Clinically significant cardiovascular disorder within 6 months prior to screening. Cardiovascular disorders include but are not limited to:
• •* Two-dimensional echocardiogram showing an LVEF \<50%;
• •* Acute myocardial infarction;
• •* Severe/unstable angina;
• •* History of arterial thromboembolism, including but not limited to cerebrovascular accident and transient ischemic attack;
• •* Cardiac failure congestive (NYHA functional class \>II);
• •* Any clinically significant abnormality in rhythm, conduction, or morphology on a resting ECG, complete bundle branch block left, third-degree heart block, second-degree heart block, PR interval \>250 msec;
• •* Mean resting QTc interval ≥500 msec obtained from 3 ECGs (corrected using Fridericia's formula, see Appendix 3: Calculation Formulas for QTcF and RR for details);
• •* Any factor that increases the risk of QTc interval prolongation or arrhythmic events, such as hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death in a first-degree relative under 40 years of age, or any concomitant medication known to prolong the QT interval;
• •* Hypertension not controlled by antihypertensive medication (blood pressure systolic \>160 mmHg and/or blood pressure diastolic \>100 mmHg);
• •16. Trial participants with a neoplasm malignant within 5 years prior to screening or currently (Note: ① Trial participants with carcinoma in situ of the cervix that has been resected, adequately treated, and currently has no evidence of disease recurrence may participate in this study; ② Trial participants with basal cell carcinoma or squamous cell carcinoma of the skin that has been completely resected, adequately treated, and currently has no evidence of disease recurrence may participate in this study);
• •17. Patients receiving the following drugs or treatments that are prohibited as concomitant therapy:
• •* Prior use of biologics with efficacy in treating COPD, such as Benralizumab, Mepolizumab, Omalizumab, Dupilumab, etc. (for Phase IIb, enrollment may be considered based on use and therapeutic effect, as assessed by the investigator);
• •* Received aminophylline, PDE-4 inhibitors, leukotriene receptor antagonists, and other systemic treatments for COPD within 2 weeks or 5 t1/2 (whichever is longer) before the first dose;
• •* Received systemic corticosteroids (excluding topical, ophthalmic, or intranasal use of corticosteroids) or systemic immunosuppressants/immunomodulators (e.g., Methotrexate) within 4 weeks before the first dose;
• •* Use of Chinese herbal medicines with therapeutic effects on COPD (excluding topical preparations) within 4 weeks before the first dose;
• •* Received IVIG therapy or allergen-SIT within 8 weeks or 5 t1/2 (whichever is longer) before the first dose;
• •* Received B- and/or T-cell targeted immunosuppressive therapy within 8 weeks or 5 t1/2 (whichever is longer) before the first dose;
• •* Planned vaccination with a live or live-attenuated vaccine within 12 weeks before the first dose or during the study;
• •* Received other biologics such as anti-TNF monoclonal antibody therapy within 16 weeks or 5 t1/2 (whichever is longer) before the first dose;
• •* Received macrolide antibiotic therapy within 6 weeks prior to screening (except for those who had been on a stable dose of macrolide antibiotics for ≥6 months prior to screening and had at least 1 AECOPD during this period).
• •18. Received blood products such as human blood albumin, hematopoietic growth factors (e.g., G-CSF), or platelet-increasing therapy within 2 weeks prior to screening;
• •19. Any of the following abnormalities in laboratory test results at screening:
• •* ANC \<1.5 × 109/L;
• •* TBIL \>1.5 × ULN;
• •* AST or ALT \>2 × ULN;
• •* Creatinine clearance \<50 mL/min (calculated by the Cockcroft-Gault formula);
• •* PLT \<90 × 109/L;
• •* HGB \<90 g/L;
• •* Other clinically significant laboratory test abnormalities that, in the investigator's judgment, make the participant unsuitable for enrollment; Note: If a laboratory test result exceeds the protocol-specified threshold but is suspected to be transient (due to physiological factors, test error, etc.), or is only slightly above the threshold, it may be re-tested once (and only once) during the screening period for clarification. If the re-test result still exceeds the threshold, the trial participant will be a screen failure;
• •20. Presence of any of the following infectious diseases:
• •* Positive for HBsAg, or negative for HBsAg but positive for HBcAb and positive for HBV-DNA; positive for HCV-Ab and positive for HCV-RNA;
• •* Positive for TP-Ab (unless negative on RPR or TRUST);
• •* Positive for HIV antibody;
• •21. History of severe allergic reaction or known allergy to XKH001 Injection or its excipients;
• •22. History of fainting at the sight of blood or from needles;
• •23. Pregnant or lactating females;
• •24. Blood donation or blood loss of ≥400 mL within 12 weeks prior to screening, or received a transfusion within 4 weeks prior to screening;
• •25. Participation in any other clinical study (including drug and device studies) and use of an investigational drug or medical device intervention within 12 weeks or 5 t1/2 (whichever is longer) prior to screening (calculated from the time of the last use of the investigational drug or medical device intervention);
• •26. History of alcohol abuse or various drug abuse within 2 years prior to signing the ICF;
• •27. Other factors that, in the investigator's opinion, make the participant unsuitable for the study.