A Randomized, Double-blind, Placebo-controlled Phase II Clinical Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetic Profile of Genakumab Injection in Patients With Connective Tissue Disease-associated Interstitial Lung Disease

1. Allergic to experimental drugs or biological agents; People who have previously known other severe allergic reactions;

2. Airway obstruction (FEV1/FVC\<0.7 before bronchodilator use) or other lung abnormalities deemed clinically significant by the investigator or a history of asthma;

3. Those who have received any of the following drugs or treatments :

1. Receiving prednisone \>15mg/ day or equivalent dose of glucocorticoid within 2 weeks prior to randomization;

2. Receive azathioprine, colchicine, D-penicillamine, sulfasalazine within 8 weeks before randomization;

3. received rituximab, tolizumab, nidanib, pirfenidone and other treatments within 6 months before randomization; Abacil, TNF inhibitors and other biologic agents were received within 3 months before randomization; Tofaciib, tacrolimus, cyclosporin A, and potassium para-aminobenzoate were used 30 days or 5 half-lives prior to screening, whichever was older.

4. Combined with other rheumatic diseases, such as idiopathic inflammatory myopathy, systemic lupus erythematosus, Sjogren's syndrome, mixed connective tissue disease, systemic vasculitis;

5. Significant pulmonary hypertension, meeting one of the following conditions:

1. Previous clinical or echocardiographic evidence of significant right heart failure;

2. Right cardiac catheterization showed cardiac index ≤ 2 l/min/m2;

3. Pulmonary hypertension requiring extraenteral treatment with eprostol/traprostacycline;

6. There are active bleeding diseases of internal organs, or have a serious bleeding tendency (such as hemophilia, etc.), or are undergoing anticoagulant treatment;

7. There are infections requiring systemic drug control within 7 days prior to screening; Diagnosed with active tuberculosis infection;

8. Have received live or attenuated vaccine within 3 months prior to screening, or plan to receive live or attenuated vaccine during the study period; Vaccination against COVID-19 within 2 weeks prior to screening;

9. Previous stem cell therapy or any type of bone marrow transplant; Previous solid organ transplants; Long-term systemic use of glucocorticoids for other diseases;

10. There is a history of serious immunodeficiency, or other acquired or congenital immunodeficiency diseases;

11. History of malignant tumor within 5 years before screening;

12. Recipients of kidney dialysis;

13. Presence of the following clinically significant heart diseases:

1. A history of chronic congestive heart failure, NYHA level IV; History of cardiac ejection fraction (EF) \< 30% by echocardiography;

2. Myocardial infarction, acute coronary syndrome, viral myocarditis, and pulmonary embolism occurred within 3 months; Coronary revascularization was performed within 6 months.

3. There are severe arrhythmias that require Class Ia or III antiarrhythmic drugs; Arrhythmias with diseased sinus syndrome, grade II type II or grade III atrioventricular block, and no pacemaker implanted;

4. During the screening period, electrocardiogram indicated QTcF interval ≥ 480 ms (according to Fridericia correction formula, where QTcF=QT/RR\^0.33), or a history of prolonged QTc interval;

14. There are the following abnormalities in the laboratory test values during the screening period:

1. White blood cell count \<3×109/L, neutrophil count \<1.5×109/L;

2. PLT\<75×109/L;

3. Total bilirubin \>1.5×ULN, alanine aminotransferase (ALT) \>3×ULN, aspartate aminotransferase (AST) \>3×ULN;

4. Estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73m2;

15. History or current positive results of serum virology tests:

1. hepatitis B surface antigen positive, or hepatitis B core antibody positive and HBV-DNA higher than the detection limit;

2. Hepatitis C virus (HCV) antibody positive;

3. Positive for human immunodeficiency virus (HIV) antibodies;

4. Those who are positive for treponema pallidum antibodies and need treatment for syphilis infection.

16. Received treatment with any investigational drug or medical device in a clinical trial within 3 months prior to screening;

17. Pregnancy test positive during screening period; Lactating women;

18. The investigator assessed those who had other factors that made them unsuitable for participation in the trial

What this study is about