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

Conditions: Systemic Sclerosis Associated Interstitial Lung Disease; Rheumatoid Arthritis Associated Interstitial Lung Disease (RA-ILD); Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD)

Summary: this study was conducted in a randomized, double-blind, placebo-controlled design to evaluate the efficacy and safety of genakumab injection in the treatment of ctd-ild including rheumatoid arthritis associated interstitial lung disease (ra-ild) and systemic sclerosis associated interstitial lung disease (ssc-ild)


Eligibility criteria:
inclusion criteria: 1. those who voluntarily sign informed consent and can complete the experiment according 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 of rheumatology (acr)/european league against rheumatism (eular) classification, or systemic sclerosis (ssc) according to the 2013 acr/eular classification; 4. interstitial lung disease (ild) was confirmed by hrct within 12 months before screening. 5. fvc≥ 40% of the expected value during the screening period; 6. dlco (using hemoglobin correction) ≥ 40% of the expected value during the screening period; 7. patients may receive 1 immunosuppressant and must maintain a stable dose for 3 months prior to the first dose and agree to maintain a stable dose for at least 6 months after the first dose; 8. subjects of childbearing age who do not plan to become pregnant or donate sperm/eggs and agree to use reliable contraception during the period of participation in this trial and within 6 months after the last dosing. exclusion criteria: 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

Keywords: connective tissue disease-associated interstitial lung disease rheumatoid arthritis associated interstitial lung disease (ra-ild) systemic sclerosis associated interstitial lung disease (ssc-ild)