Pharmacokinetic/Pharmacodynamic Parameters of NNG-DEPO (Stimus) With Aranesp® (Amgen) in Treatment of Anemia in CKD Patients on Dialysis

This is a double-blind, randomized, active-control study with 2-study arms-darbepoetin alfa biosimilar and Aranesp, noninferiority trial design in dialysis patients. Dialysis patients will be randomized into 1:1 ratio to receive either Darbepoetin alfa or Aranesp 0.75 µg/kg by subcutaneous injection every other week for 24 weeks.

Pharmacokinetic/pharmacodynamic parameters for evaluation are assessed as per study endpoints at defined time points on all patients.

During the treatment, dose adjustments will be made as necessary to achieve a hemoglobin response, defined as maintaining Hb in target range 10 - 12 g/dL.

PHASE OF TRIAL: I SAMPLE SIZE: 43 for pharmacokinetic/pharmacodynamic parameters TARGET POPULATION: Patients with chronic kidney disease undergoing dialysis

STUDY GROUPS:

1. Darbepoetin alfa (Nanogen) SC 0.75 µg/kg Q2W, for 24 weeks.
2. Aranesp® (Amgen) SC 0.75 µg/kg Q2W, for 24 weeks.

PK ASSESSMENT: Blood samples for PK assessments will be collected at:

* IV: time zero (predose) before injection of study drug and then after 0.25, 0.5, 4, 12, 24, 48, 96, 144, 240 and 336 hours post-dose.
* SC: time zero (predose) before injection of study drug and then after 4, 12, 24, 48, 96, 144, 240 and 336 hours post-dose.

PD ASSESSMENT: Blood samples for PD assessments will be collected at time zero (predose) before injection of study drug and then after 24, 48, 96, 144, 240 and 336 hours post-dose.

SAFETY AND TOLERABILITY ASSESSMENT:

Safety and tolerability assessments will be performed at each visit. Following variables will be considered to define the safety and tolerability of investigational drugs:

* Clinical adverse events (AEs): frequency of AEs, overall and by intensity.
* Severe clinical adverse events (SAEs): frequency of AEs, overall and by intensity.
* Symptoms directed physical examination including body weight, and vital signs during treatment period: mean change from baseline and the frequency of clinically relevant changes from baseline.
* Laboratory tests: frequency of clinically relevant changes from baseline.
* The frequency of any concomitant medication administered to treat any adverse events.
* Presence of anti-bodies to darbepoetin alfa (immunogenicity).

Eligibility Criteria:
Inclusion Criteria

* The patients signed the informe consent form and adhere to study visit schedule.
* Male or female patients aged from 18 to 65 years.
* Patients on hemodialysis or peritoneal dialysis for at least 3 months and have Hb baseline \<10 g/dL during the screening period.
* Have transferrin saturation ≥ 20%, serum ferritin ≥ 200 ng/mL, vitamin B12 and folate within the normal range.
* Have expected survival of at least 6 months from time of enrollment (by investigator's assessment).
* Women childbearing age must agree to use medically acceptable methods of contraception during the study and for 6 months after the last study treatment.
* The patient does not have any serious medical conditions that may affect to study treatment compliance.

Exclusion Criteria

* Uncontrolled hypertension over 2 weeks prior to and within the screening period (BP ≥ 160/90 mmHg).
* Patients treated with Darbepoetin alfa or r-HuEPO within 4 weeks prior to enrollment.
* Patients with Uncontrolled diabetes mellitus with HbA1C ≥ 10%.
* Congestive Heart Failure of grade 3 or 4 as New York Heart Association classification.
* History of unstable angina or myocardial infarction within 6 months.
* History of Grand mal seizures in last 2 years.
* Present with severe hyperparathyroidism (iPTH \>1500 pg/mL for Dialysis).
* History of major surgery within 12 weeks prior to screening.
* Systemic hematologic disorders including sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma and hemolytic anemia.
* Systemic infections, active inflammatory diseases and malignancies.
* Active liver disease or hepatic with liver enzymes AST and ALT raised \> 2-times of laboratory normal values, child B or child C cirrhosis.
* Are being treated with androgen therapy within the 8 weeks prior to the screening period.
* Pregnant or suspected pregnant women, breast-feeding women.
* Patients scheduled for any transplant procedure within 6 months of screening or with a previous history of kidney transplantation.
* Patients who are hypersensitive to any of substances of investigational product.
* Patients using drugs that can affect the concentration of Hb in the blood (except blood-forming drugs such as iron, folic acid).
* Patients with seropositivity to HIV, HBV or anti-HCV.
* Patients having acute tuberculosis or any acute bacterial infection within 1 month prior to the screening.
* Patient has occult blood in stool or any other known source of internal bleeding and confirmed gastrointestinal bleeding by endoscopy.
* Patients with blood transfusion due to acute bleeding within 12 weeks prior to screening period.
* Patients with a history of immunosuppressive therapy within 1 month.
* The patient is suffering from advanced cancer.
* Patients having participated in any other clinical trial within 1 month prior to the screening period.
* The patient had any medical condition that the investigator assessed as affecting the study.