Desidustat in the Treatment of Anemia in CKD on Dialysis Patients

Study Overview
=================
Brief Summary
-----------------
A phase 3, multicenter, open-label, randomized, active-controlled study to evaluate the efficacy and safety of Desidustat Tablet versus Epoetin alfa Injection for the treatment of anemia in patients with CKD on dialysis. (DREAM-D)

Official Title
-----------------
A Phase 3, Multicenter, Open-label, Randomized, Active-controlled Study to Evaluate the Efficacy and Safety of Desidustat Tablet Versus Epoetin Alfa Injection for the Treatment of Anemia in Patients With Chronic Kidney Disease (CKD) on Dialysis (DREAM-D)

Conditions
-----------------
Chronic Kidney Disease Stage 5 on Dialysis

Intervention / Treatment
-----------------
* Drug: Desidustat Oral Tablet
* Drug: Epoetin Alfa


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Ability to understand and give informed consent for participation. 2. Hemoglobin values during the screening period must be 8-11 g/dL (both inclusive). 3. Patients will be considered not treated with erythropoietin analogue (Epoetin and Darbepoeitin) if they have not received erythropoietin analogue for at least 4 weeks and Mircera® for at least 8 weeks prior to screening visit. OR Patients who are on ESA therapy must be on stable dose for 4 weeks prior to enrollment (≤30% of dose change). 4. Patients on hemodialysis (≥2 times in a week) for at least 12 weeks prior to screening visit and have access consisting of an arteriovenous fistula, AV graft, or catheter (permanent/temporary). 5. Patients with no planned change in dialysis modality and with no planned renal transplant during study period. 6. Left ventricular ejection fraction ≥40% by echocardiogram prior to randomization. 7. No iron, folate or Vitamin B12 deficiency. 8. 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: Red blood cell transfusion within 8 weeks prior to participating in the study. History of previous or concurrent cancer. Serologic status reflecting active hepatitis B or C infection or Human immunodeficiency virus (HIV) infection. Active infection at initiation of study. History of renal transplant. Uncontrolled hypertension (defined as SBP >180 mmHg or DBP >100 mmHg) at screening visit (before dialysis). Patient on high rhEPO dose at screening visit. [High dose defined as an epoetin dose of ≥450 IU/kg/week intravenous or ≥ 300 IU/kg/week subcutaneous or darbepoetin dose of ≥1.5 µg/kg/week subcutaneous]. 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; malabsorption 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 allergic reactions attributed to compounds of similar chemical or biologic composition to Desidustat or Epoetin alfa or to any erythropoieisis-stimulating agent. 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 clinically significant 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 electrocardiogram (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 entry in the study. Existing clinically active chronic inflammatory disease (RA, Celiac disease, UC, Crohns disease) In case of DM patients, HbA1c >9%. Female volunteers with following criteria will not be recruited: 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 anti-fertility measures Positive urine pregnancy test at Visit 2 Positive serum β-hCG level at the screening visit Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification or history of myocardial infarction prior to first dose with study drug.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 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>|
| Experimental: Epoetin Injection<br>Randomly assigned to receive Epoetin in a 1:1 ratio for 24 weeks. | Drug: Epoetin Alfa<br>* Epoetin Injection<br>|

What is the study measuring?
-----------------
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 |