Correction of Anemia With Enarodustat in Non-dialysis Dependent Chronic Kidney Disease

This study is a prospective, open-label, randomized controlled, multicenter investigation conducted among adult patients with ND-CKD anemia in China, with the aim of exploring the rational hemoglobin target value for the treatment of patients with ND-CKD anemia using enarodustat.

This study plans to enrol 1,670 patients with non-dialysis chronic kidney disease (ND-CKD) anemia. After screening, patients who meet the inclusion criteria and do not meet the exclusion criteria will be randomly assigned at a 1:1 ratio to: the low Hb target value group: with a Hb target value of 11 g/dL; the high Hb target value group: with a Hb target value of 13 g/dL. The initial dose of enarodustat tablets in both groups is 4 mg once daily. The dose will be adjusted in accordance with the instructions and the requirements of different Hb value groups.

The follow-up period will last for 96 weeks. The first primary endpoint was the difference of mean change in 36-Item Short Form Health Survey at week 24. The second primary endpoint was safety endpoints included time to major adverse cardiovascular + event (MACE+; all-cause mortality, myocardial infarction, stroke, and congestive heart failure requiring hospitalization) during 96 weeks.

Inclusion criteria

• Aged 18-75 years at the time of consent to participate;
• Body weight ranged from 45 to 100 kg;
• Diagnosed with CKD stages 2-5 (10 ≤ eGFR < 90 mL/min/1.73m2) and were not dialysis dependent;
• Diagnosed with renal anemia:

1)Hemoglobin level of 6 - 10 g/dL for those who have not received ESA or HIF-PHI treatment within 6 weeks at screening; 2)Hemoglobin level of 8 - 12 g/dL for those who are currently receiving ESA (ESA dosage ≤ 10,000 IU/week) or HIF-PHI (roxadustat dosage≤ 100 mg TIW) at screening; 5. Serum ferritin > 100 μg/L or transferrin saturation > 20% at screening; 6. Voluntary participation in the trial and signing of the informed consent form.

Exclusion criteria

• Uncontrolled hypertension identified as systolic blood pressure >160mmHg or diastolic blood pressure >100mmHg after 4 weeks of regular and adequate drug therapy prior to screening;
• Uncontrolled proteinuria identified as UACR >3000mg/g or 24-hour urine protein >3.5g in non-diabetic patients and UACR of >5000mg/g or 24-hour urine protein >5.5g in diabetic patients;
• Anemia due to other reasons except CKD including systemic hematological disorders (such as myelodysplastic syndrome, aplastic anemia, etc.), hemolytic anemia, hemorrhagic anemia or cancer-related anemia;
• History of autoimmune diseases which could result in anemia such as systemic lupus erythematosus and ANCA vasculitis;
• History of active bleeding within 4 weeks prior to screening;
• History of serious thrombotic event such as a myocardial infarction, cerebral infarction, pulmonary embolism, unstable angina, or PCI or cardiac surgery within 6 months prior to screening;
• Severe heart failure (NYHA class IV) at screening;
• History of blood transfusion within 2 months prior to screening;
• History of usage of immunosuppressants or other immune therapies within 6 months prior to screening;
• Patients who are estimated to require dialysis, kidney transplantation, or major surgery within 6 months;
• Severe liver and biliary system complications (AST or ALT >3 times the upper limit of normal, total bilirubin >2 times the upper limit of normal) at screening;
• Receiving ESA combined with roxadustat treatment at screening;
• History of proliferative retinopathy or diabetic retinopathy requiring ophthalmological treatment;
• Severe hyperparathyroidism (iPTH ≥ 500 pg/mL);
• Severe active infections (such as active tuberculosis, fungal infections, etc.);
• Patients who are bedridden or have difficulty walking, or have a history of atrial fibrillation or deep vein thrombosis of the lower limbs;
• History of active tumors;
• Female patients who are pregnant or breastfeeding, or non-childbearing women who do not agree to effective contraception;
• Patients with a history of severe drug allergies (such as anaphylactic shock), or known allergies to any of the active ingredients or excipients of enarodostat;
• Patients who are currently participating in any other interventional clinical trial;
• Other reasons determined by the investigator not suitable for participation in the study.