Desidustat in the Treatment of Anemia in CKD

Study Overview
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Brief Summary
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This is a phase III, multicenter, multi-country, open-label, randomized, active-controlled clinical trial to evaluate the efficacy and safety of Desidustat versus Darbepoetin for the treatment of anemia in patients with CKD who are not on dialysis. The study will be conducted over a period of up to 30 weeks.

Official Title
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A Phase 3, Multicenter, Multi-country, Open-label, Randomized, Active-controlled Clinical Trial to Evaluate the Efficacy and Safety of Desidustat Versus Darbepoetin for the Treatment of Anemia in Patients With Chronic Kidney Disease (CKD) Who Are Not on Dialysis

Conditions
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Anemia, Chronic Kidney Disease Stage 3, Chronic Kidney Disease Stage 4, Chronic Kidney Disease Stage 5

Intervention / Treatment
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* Drug: Desidustat Oral Tablet
* Drug: Darbepoetin Alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current clinical diagnosis of anemia due to CKD, baseline hemoglobin concentrations must be 7.0-10.0 g/dL (both inclusive) before the enrollment. Ability to understand and give informed consent for participation. 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. Male or female, 18 to 80 years of age. Body weight > 40 kg. Subjects not on dialysis and not expected to start dialysis during the study period. Patients must not be treated with erythropoiesis-stimulating agent (ESA) therapy within 6 weeks prior to enrollment. Estimated GFR ≥10 mL/min/1.73 m2. Serum ferritin ≥100 ng/mL and/or Transferrin Saturation >20%. No iron, folate or Vitamin B12 deficiency. Females of childbearing potential, must agree to use one of the approved contraception methods, from screening until completion of the follow-up visit. Exclusion Criteria: Prior chronic hemodialysis or chronic peritoneal dialysis treatment. Intravenous iron within 14 days prior to enrollment. Prior exposure of rhEPO analogues less than 04 weeks. Red blood cell transfusion within 8 weeks prior to enrollment. History of previous or concurrent cancer. Serologic status reflecting active hepatitis B or C infection or Human immunodeficiency virus (HIV) infection. Active infection prior to enrollment. History of renal transplant. 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. 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. History of uncontrolled autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (ITP) or thalassemia. 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. History of stroke or intracranial hemorrhage within 6 months prior to enrollment. History of severe allergic or hypersensitivity to investigational products and its excipients. 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. Pregnant and breastfeeding women. Current life-threatening illness, medical condition or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety. Other laboratory abnormalities that, in the opinion of the investigator, would compromise the patient's safety or interfere with data interpretation. 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. 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). History of difficulty with donating blood. History or presence of any clinically significant ECG abnormalities during screening. Participants who have participated in any drug research study other than the present trial within past 3 months. 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. History of chronic inflammatory disease (RA, Celiac disease, UC, Crohns disease, Systemic Lupus Erythematosus [SLE]). In case of Diabetes mellitus patients, glycosylated haemoglobin (HbA1c) >9 %.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Darbepoetin Alfa Injection<br>Randomly assigned to receive Darbepoetin in a 1:1 ratio for 24 weeks. | Drug: Darbepoetin Alfa<br>* Darbepoetin injection<br>|
| Active Comparator: Desidustat oral tablet<br>Randomly assigned to receive Desidustat 100 mg in a 1:1 ratio for 24 weeks. | Drug: Desidustat Oral Tablet<br>* Desidustat tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin level | Change in Hb levels from baseline | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin Response | No. of subjects with Hb response | 24 weeks | 
| Hemoglobin target range | Time to achieve target range Hb level | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DREAM-ND