What is the safety and efficacy of desidustat over darbepoetin injection on the haemoglobin levels in anaemic patients with CKD who are not on dialysis?

Study Sites • Colombo North Teaching Hospital • National Hospital of Sri-Lanka Subjects will be randomly assigned to receive Desidustat 100 mg Tablet or Darbepoetin Injection in a 1:1 ratio. The randomization schedule will be generated Using SAS® software (Version: 9.4 or higher; SAS Institute Inc., USA). The study will be conducted over a period of up to 30 weeks. Subjects will be evaluated at study sites for 10 scheduled visits: at screening visit (Visit 1: Week -4); randomization visit (Visit 2: Week 0); (Visit 3: Week 2); Visit 4 (Week 4); Visit 5 (Week 6); Visit 6 (Week 8); Visit 7 (Week 12); Visit 8 (Week 16); Visit 9 (Week 20) and end-of-treatment (EOT) (Visit 10: Week 24). Desidustat 100 mg tablet will be orally administered thrice in a week in anemic patients with CKD who are not on dialysis for a period of 24 weeks. Darbepoetin Alfa (Cresp®) dose and dose regimen: Initial dose will be 0.75 mcg/kg. Dose regimen throughout the study will be every 2 weeks till target Hb is achieved and stabilized.

1. Current clinical diagnosis of anemia due to CKD with baseline hemoglobin concentrations between 7.0-10.0 g/dL (both inclusive) before the enrollment.
2. Ability to understand and give informed consent for participation.
3. Male or female patients diagnosed with CKD (stage III to V, not receiving dialysis) defined by estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
4. Male or female, 18 to 80 years of age.
5. Body weight > 40 kg.
6. Subjects not on dialysis and not expected to start dialysis during the study period.
7. Patients must not be treated with erythropoiesis-stimulating agent (ESA) therapy within 6 weeks prior to enrollment.
8. Estimated GFR >10 mL/min/1.73 m2.
9. Serum ferritin >100 ng/mL and/or TSAT >20%.
10. No iron, folate or Vitamin B12 deficiency.
11. Females of childbearing potential, must agree to use one of the approved contraception methods, from screening until completion of the follow-up visit.

1. Prior chronic hemodialysis or chronic peritoneal dialysis treatment.

2. Intravenous iron within 14 days prior to enrollment.

3. Prior exposure of rhEPO analogues less than 04 weeks.

4. Red blood cell transfusion within 8 weeks prior to enrollment.

5. History of previous or concurrent cancer.

6. Serologic status reflecting active hepatitis B or C infection or Human immunodeficiency virus (HIV) infection.

7. Active infection prior to enrollment.

8. History of renal transplant.

9. Major surgery within 90 days of the first day of study drug dosing, and minor surgery within 30 days of the first day of study drug dosing.

10. Unable to swallow tablets or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption such as; mal-absorption syndrome, resection of the small bowel or poorly controlled inflammatory bowel disease affecting the small intestine.

11. History of uncontrolled autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (ITP) or thalassemia.

12. Presence or a history of bleeding disorders or clinical conditions (e.g. gastrointestinal [GI] bleeding or constitutional disorders) that may increase risk of life-threatening bleeding.

13. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.

14. History of severe allergic or hypersensitivity to investigational products and its excipients.

15. Requires or is receiving anticoagulation with warfarin or equivalent vitamin K antagonists or other medications within 28 days of the first dose of study drug that in the investigator’s opinion, could compromise patient safety.

16. Pregnant and breastfeeding women.

17. Current life-threatening illness, medical condition or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety.

18. Other laboratory abnormalities that, in the opinion of the investigator, would compromise the patient's safety or interfere with data interpretation.

19. Presence of other systemic disorders or diseases (e.g., respiratory, gastrointestinal, endocrine, immunological, dermatological, neurological, psychiatric disease or any other body system involvement) which, in the Investigator's opinion, could compromise the patient's safety.

20. History of significant alcoholism or drug abuse within the past 1 year. History or presence of significant smoking (more than 10 cigarettes per day) or consumption of tobacco/nicotine products (more than 10 times per day).

21. History of difficulty with donating blood.

22. History or presence of any clinically significant ECG abnormalities during screening.

23. Participants who have participated in any drug research study other than the present trial within past 3 months.

24. Participants who have donated one unit (350 ml) of blood in the past 3 months or history of whole blood transfusion in last 120 days prior to enrollment.

25. History of chronic inflammatory disease (RA, Celiac disease, UC, Crohns disease, Systemic Lupus Erythematosus [SLE]).

26. In case of DM patients, glycosylated haemoglobin (HbA1c) >9 %.

27. In case of hypertensive patients, systolic and diastolic BP is > 160 and 100 mm of Hg respectively or uncontrolled blood pressure.

28. Female volunteers with following criteria will not be eligible: • History of pregnancy or lactation in the past 3 months. • Fertile female volunteers not protected against pregnancy by adequate long-term anti-fertility measures • History of less than 1 year of menopause and not using adequate long-term antifertility measures • Oral hormone replacement therapy • Positive serum -hCG level at the screening visit

29. Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any class 3 or 4 cardiac disease as defined by the NYHA (New York Heart Association) classification.

30. History of myocardial infarction in the past 6 months.

31. Abnormal baseline laboratory investigations as follows: • WBC count <3 x 103 /uL • Platelets count <100 x 103 /uL • Bilirubin >2.0 mg/dL • ALT and/or AST >2.5 times of the ULN