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

Inclusion Criteria:

1. Those who voluntarily sign informed consent and can complete the experimentaccording to the plan;

2. Age 18-75 years old (including upper and lower limits), both male and female;

3. Rheumatoid arthritis (RA) diagnosed according to the 2010 American College ofRheumatology (ACR)/European League against Rheumatism (EULAR) classification, orSystemic sclerosis (SSc) according to the 2013 ACR/EULAR classification;

4. Interstitial lung disease (ILD) was confirmed by HRCT within 12 months beforescreening.

5. FVC≥ 40% of the expected value during the screening period;

6. DLCO (using hemoglobin correction) ≥ 40% of the expected value during the screeningperiod;

7. Patients may receive 1 immunosuppressant and must maintain a stable dose for 3months prior to the first dose and agree to maintain a stable dose for at least 6months after the first dose;

8. Subjects of childbearing age who do not plan to become pregnant or donate sperm/eggsand agree to use reliable contraception during the period of participation in thistrial and within 6 months after the last dosing.

Exclusion Criteria:

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

2. Airway obstruction (FEV1/FVC<0.7 before bronchodilator use) or other lungabnormalities deemed clinically significant by the investigator or a history ofasthma;

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

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

5. Receive azathioprine, colchicine, D-penicillamine, sulfasalazine within 8 weeksbefore randomization;

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

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

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

9. Previous clinical or echocardiographic evidence of significant right heartfailure;

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

11. Pulmonary hypertension requiring extraenteral treatment witheprostol/traprostacycline;

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

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

14. Have received live or attenuated vaccine within 3 months prior to screening, or planto receive live or attenuated vaccine during the study period; Vaccination againstCOVID-19 within 2 weeks prior to screening;

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

16. There is a history of serious immunodeficiency, or other acquired or congenitalimmunodeficiency diseases;

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

18. Recipients of kidney dialysis;

19. Presence of the following clinically significant heart diseases:

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

21. Myocardial infarction, acute coronary syndrome, viral myocarditis, andpulmonary embolism occurred within 3 months; Coronary revascularization wasperformed within 6 months.

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

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

24. There are the following abnormalities in the laboratory test values during thescreening period:

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

26. PLT<75×109/L;

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

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

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

30. hepatitis B surface antigen positive, or hepatitis B core antibody positive andHBV-DNA higher than the detection limit;

31. Hepatitis C virus (HCV) antibody positive;

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

33. Those who are positive for treponema pallidum antibodies and need treatment forsyphilis infection.

34. Received treatment with any investigational drug or medical device in a clinicaltrial within 3 months prior to screening;

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

36. The investigator assessed those who had other factors that made them unsuitable forparticipation in the trial