A Phase II Clinical Trial of the Safety and Efficacy of SAL0120 in Patients With Chronic Kidney Disease (CKD)

Inclusion criteria

• On the day of signing the informed consent, the age is 18-75 years old (including the boundary value), regardless of gender;
• at a stable dose within 12 weeks before screening;
• During screening, the patient is diagnosed with chronic kidney disease, and the estimated glomerular filtration rate eGFR calculated based on the CKD-EPI formula (see Appendix 1 for details) is ≥20 mL/min/1.73 m2;
• At screening visit 1, the urine albumin/creatinine ratio (UACR) measured twice on different days within ≤7 days must meet ≥300 and <5000 mg/g at the same time;
• Body mass index (BMI) ≤40 kg/m2;
• All male subjects and female subjects of childbearing potential agree to use highly effective contraceptive methods for contraception from the date of signing the ICF until 1 month after the last dose of the investigational drug (see Appendix 2 for details).
• Be able to understand the procedures and methods of this study, and be willing to strictly abide by the clinical trial protocol and complete this trial.

Exclusion criteria

• Patients suspected or diagnosed with polycystic kidney disease (autosomal dominant and recessive), rapidly progressive glomerulonephritis; patients with acute kidney injury or receiving peritoneal dialysis or hemodialysis treatment within 6 months before the screening period;
• Known history of heart failure or disease related to fluid overload (such as pulmonary edema, uncontrolled peripheral edema, pleural effusion, or ascites).
• Cardiovascular diseases that are not suitable for participation in the study: ① Primary heart valve disease, severe mitral/tricuspid regurgitation; patients planning to undergo heart valve repair or replacement; ② Patients with stroke, myocardial infarction, cerebral infarction (except asymptomatic cerebral infarction), and transient ischemic attack within 6 months before screening; ③ Carotid artery surgery or carotid artery angioplasty within 3 months before screening. ④Acute coronary syndrome (ACS)-related events within 3 months before screening; ⑤Congenital QT prolongation syndrome, history of other drug-related QT interval prolongation, prolongation of QT interval on electrocardiogram at screening visit 1 or at randomization (visit 2) (male QTcF>470 ms; female QTcF>480 ms); ⑥ The electrocardiogram results at screening visit 1 show clinically significant abnormalities, such as supraventricular tachycardia, atrial fibrillation, atrial flutter, second or third degree atrioventricular block, etc.;
• Have used systemic steroid glucocorticoids or immunosuppressants within 3 months before screening, excluding topical or intra-articular, intranasal and inhaled glucocorticoids; have used rituximab and cytotoxic drugs within 6 months before screening;
• Have received strong inhibitors or inducers of P-gp within 2 weeks before screening (for example: ranolazine, verapamil, itraconazole, clarithromycin, quinidine, ritonavir, tipranavir, saquinavir, etc.); have received strong inhibitors or inducers of CYP3A within 2 weeks before screening (for example: rifampicin, phenytoin, carbamazepine, ketoconazole, etc.);
• Concomitant with the following clinically significant, unstable or uncontrolled diseases within 6 months before screening, including but not limited to respiratory system, digestive system, cardiovascular and cerebrovascular, endocrine, immune, urinary, adrenal, blood, neurological, psychiatric and other diseases or other medical diseases that may confuse the research results and bring additional risks to the subjects.
• Acute complications of diabetes such as diabetic ketoacidosis, hyperosmolar nonketotic diabetic coma, lactic acidosis, and hypoglycemic coma occurred within 6 months before the screening period; and there were complications requiring acute treatment at screening visit 1, including but not limited to: proliferative vitreoretinopathy, maculopathy, painful diabetic peripheral neuropathy, and diabetic foot (ulcer, infection);
• Patients with poorly controlled hypertension (for example, screening visit 1 and random blood pressure show systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg), or systolic blood pressure <90mmHg;
• Nt-proBNP ≥ 600pg/mL at screening visit 1;
• Glycated hemoglobin (HbA1c) ≥9% at screening visit 1;
• Patients with type 1 diabetes;
• Hemoglobin <90g/L at screening visit 1, or a history of blood transfusion to treat anemia within 3 months of screening.
• Have a history of pulmonary hypertension (WHO group 1), idiopathic pulmonary fibrosis or any lung disease requiring oxygen therapy (for example: chronic obstructive pulmonary disease, emphysema, pulmonary edema, etc.);
• Patients with a history of organ transplantation (except patients with a history of corneal transplantation) or patients who plan to have a kidney transplant during the study period;
• Known or suspected allergy to the study drug or its components or excipients;
• Patients with malignant tumors (including hematological malignancies), except for the following circumstances: tumors determined to be cured or in remission for 5 years, basal cell or squamous cell carcinoma of the skin that has been radically removed, or carcinoma in situ at any location;
• Patients with severe hepatobiliary system diseases (for example, AST or ALT >2 times the upper limit of normal value at Screening Visit 1, or patients with liver cirrhosis, or total bilirubin >2 times the upper limit of normal value at Screening Visit 1);
• Have a history of alcohol or drug abuse within 1 year before screening. Alcohol abuse is defined as: drinking more than 14 units of alcohol per week (1 unit of alcohol = 360ml of beer or 45ml of spirits with an alcohol content of 40% or 150ml of wine);
• People with serious mental illness, including but not limited to: schizophrenia, bipolar disorder, depression, mania, etc.;
• Patients with active hepatitis B (if hepatitis B surface antigen is positive, HBV DNA testing is required. If hepatitis B surface antigen is positive and the HBV DNA test is >500 copies/mL or >100 IU/mL, patients with active hepatitis B must be excluded). Hepatitis C (if the HCV antibody test is positive, HCV RNA testing is required. If the HCV antibody test is positive and the HCV RNA result is positive, hepatitis C patients must be excluded); patients with active syphilis (if the Treponema pallidum antibody test is positive, antibody titer testing is required, and patients with active syphilis are excluded according to the center's testing standards); HIV-positive patients, whose condition is in a stable stage, can be included by the researcher based on the comprehensive performance of the subjects;
• Patients who are pregnant, lactating, or have the possibility of pregnancy (based on the pregnancy test results of screening visit 1, the researcher cannot rule out the possibility of pregnancy);
• Patients who have been treated with other experimental drugs (or investigational drugs) or treated with experimental medical devices (or research devices) within 3 months before screening and before randomization, or who are participating in interventional clinical research (a medical behavior that exceeds routine diagnosis and treatment, performed for research purposes) and receiving treatment;
• Any other medical condition that, in the opinion of the investigator, may pose a safety risk to the subjects in this study, may confound the evaluation of efficacy or safety, or may interfere with the subject's participation in the study.