correction of anemia with enarodustat in non-dialysis dependent chronic kidney disease

Conditions: Chronic Kidney Disease Associated Anemia

Summary: the cannon trial is a prospective, open-label, randomized, multicenter study designed to investigate rational hemoglobin target value in patients with anemia of non-dialysis chronic kidney disease treated with enarodustat. eligible patients are randomly assigned 1:1 to the high-hemoglobin target group （hemoglobin of 13 g/dl）and low-hemoglobin target group （hemoglobin of 11 g/dl）and administered with enarodustat to achieve and maintain target hemoglobin over 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.


Eligibility criteria:
inclusion criteria: 1. aged 18-75 years at the time of consent to participate; 2. body weight ranged from 45 to 100 kg; 3. diagnosed with ckd stages 2-5 (10 ≤ egfr \< 90 ml/min/1.73m2) and were not dialysis dependent; 4. 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: 1. 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; 2. 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; 3. 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; 4. history of autoimmune diseases which could result in anemia such as systemic lupus erythematosus and anca vasculitis; 5. history of active bleeding within 4 weeks prior to screening; 6. 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; 7. severe heart failure (nyha class iv) at screening; 8. history of blood transfusion within 2 months prior to screening; 9. history of usage of immunosuppressants or other immune therapies within 6 months prior to screening; 10. patients who are estimated to require dialysis, kidney transplantation, or major surgery within 6 months; 11. 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; 12. receiving esa combined with roxadustat treatment at screening; 13. history of proliferative retinopathy or diabetic retinopathy requiring ophthalmological treatment; 14. severe hyperparathyroidism (ipth ≥ 500 pg/ml); 15. severe active infections (such as active tuberculosis, fungal infections, etc.); 16. patients who are bedridden or have difficulty walking, or have a history of atrial fibrillation or deep vein thrombosis of the lower limbs; 17. history of active tumors; 18. female patients who are pregnant or breastfeeding, or non-childbearing women who do not agree to effective contraception; 19. 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; 20. patients who are currently participating in any other interventional clinical trial; 21. other reasons determined by the investigator not suitable for participation in the study.

Keywords: hif-ph inhibitor anemia chronic kidney disease quality of life major adverse cardiovascular events enarodustat