A Study to Compare Efficacy and Safety of Nanogen's Darbepoetin Alfa With Aranesp® (Amgen) in the Treatment of Anemia in Chronic Kidney Disease Patients on Dialysis (CKD)

Study Overview
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Brief Summary
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This is a double-blind, two-arm, randomized, multicenter to compare the efficacy and safety of NNG-DEPO and Aranesp in CKD on dialysis patients. Patients aged 18 to 65 years (inclusive), diagnosed with anemia due to CKD in dialysis, who meet all inclusion criteria, requiring treatment with Darbepoetin alfa. The study subjects (patients) will be randomized into a 1:1 ratio to NNG-DEPO and Aranesp treatment arms respectively. Patients will receive either NNG-DEPO or Aranesp 0.75 µg/kg by subcutaneous injection every other week for 24 weeks. During the treatment, dose adjustments will be made as necessary to achieve a hemoglobin response, defined as maintaining Hb in the target range of 10 - 12 g/dL.

Detailed Description
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The phase of the study: phase 3 Study sites: Nguyen Tri Phuong Hospital Thu Duc City Hospital An Sinh Hospital Thong Nhat General Hospital Dong Nai Sample size: 214 patients TARGET POPULATION: Patients with chronic kidney disease undergoing dialysis (aged 18 to 65 years) STUDY GROUPS: Darbepoetin alfa (Nanogen) SC/IV route 0.75 µg/kg Q2W, for 24 weeks. Aranesp® (Amgen) SC/IV route 0.75 µg/kg Q2W, for 24 weeks. Blood sample will be taken for Complete Blood Count (CBC) test at each visit (Week 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24) to monitor haemoglobin response. Study Procedures: This study was designed for 26 weeks (2 weeks for screening and 24 weeks for treatment) and there are total of 14 visits: Visit 1 is the screening visit. Visit 2: Randomization, initiate study treatment, assess the Hb baseline. Visit 3 - 7 is to monitor, evaluate the efficacy, safety. Visit 8 is to interim assess the efficacy, safety for each patient to make the decision continous/discontinous the study treatment. Vist 9 -13 is to monitor, evaluate the efficacy, safety. Visit 14 is termination visit. 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 darbepoetin alfa anti-bodies (immunogenicity).

Official Title
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A Multicenter, Double-blind, Randomized, Parallel Comparative Study of Efficacy and Safety of Nanogen's Darbepoetin Alfa With Aranesp® (Amgen) in the Treatment of Anemia in Chronic Kidney Disease Patients on Dialysis

Conditions
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Anemia, Chronic Kidney Disease Requiring Chronic Dialysis

Intervention / Treatment
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* Biological: Stimus (NNG-DEPO)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stimus<br>NNG-DEPO (Darbepoetin alfa 10 mcg/0.4 mL, 20 mcg/0.5 mL, 40 mcg/0.4 mL, 60 mcg/0.3 mL) is available as a prefilled syringe in a sterile, colorless, glass tube. Storage: 2-8ºC, not frozen. The process of transporting and storing the drug must ensure the temperature in the range of 2-8ºC. NNG-DEPO/Aranesp is administered subcutaneously (or intravenously) at a dose of 0.75 g/kg initially, every 2 weeks at the second visit. Study drug will be prepared according to standard procedure (SOP). Dosage adjustment guideline: Patients will have hemoglobin levels monitored every 2 weeks. The investigators will evaluate and adjust the dose of Darbepoetin alfa to maintain the Hb levels within the target range (10 - 12 g/dL) | Biological: Stimus (NNG-DEPO)<br>* Nanogen's Darbepoetin alfa 10µg/0.4mL, 20µg/0.5mL, 40µg/0.4mL, 60µg/0.3mL, prefilled syringe<br>|
| Active Comparator: Aranesp<br>Aranesp® (Darbepoetin alfa 10 mcg/ 0.4 mL, 20 mcg/ 0.5 mL, 40 mcg/ 0.4 mL, 60 mcg/ 0.3 mL) is manufactured by Amgen, as a pre-filled syringe in a sterile, glass tube, colourless. Storage: 2-8ºC, not frozen. The process of transporting and storing the drug must ensure the temperature in the range of 2-8ºC. NNG-DEPO/Aranesp is administered subcutaneously (or intravenously) at a dose of 0.75 g/kg initially, every 2 weeks at the second visit. Study drug will be prepared according to standard procedure (SOP). Dosage adjustment guideline: Patients will have hemoglobin levels monitored every 2 weeks. The investigators will evaluate and adjust the dose of Darbepoetin alfa to maintain the Hb levels within the target range (10 - 12 g/dL) | Biological: Stimus (NNG-DEPO)<br>* Nanogen's Darbepoetin alfa 10µg/0.4mL, 20µg/0.5mL, 40µg/0.4mL, 60µg/0.3mL, prefilled syringe<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The mean change Hemoglobin level from baseline to Week 24 |  | Week 0 (Assessed predose)- Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving 1 g/dL rise in Hb from baseline during 24 weeks after treatment |  | Week 0 (Assessed predose)- Week 24 | 
| Proportion of patients achieving Hb within the target range (10 - 12 g/dL) at week 24. |  | Week 24 | 
| Proportion of patients need for blood transfusion during 24 weeks after treatment. |  | Week 0 (Assessed predose)- Week 24 | 
| 4. The mean dose of NNG-DEPO/Aranesp administered for achievement of Hb in the target Hb levels (10 - 12 g/dL) during 24 weeks. |  | Week 0 (Assessed predose)- Week 24 | 
| Time to initial achievement of Hb ≥ 11 g/dL. |  | Week 0 (Assessed predose)- Week 24 | 
| Proportion of the adverse events (AE) including physical examinations, vital signs, and clinical laboratory investigations. |  | Week 0 (Assessed predose)- Week 24 | 
| Proportion of patients positive with anti-Darbepoetin alfa antibody after treatment. |  | Week 0 (Assessed predose)- Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CKD on dialysis, Nanogen, Anemia, Darbepoetin Alfa