Pharmacokinetic/Pharmacodynamic Parameters of NNG-DEPO (Stimus) With Aranesp® (Amgen) in Treatment of Anemia in CKD Patients on Dialysis
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
PHASE OF TRIAL: I SAMPLE SIZE: 43 for pharmacokinetic/pharmacodynamic parameters TARGET POPULATION: Patients with chronic kidney disease undergoing dialysis
STUDY GROUPS:
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Darbepoetin alfa (Nanogen) SC 0.75 µg/kg Q2W, for 24 weeks.
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Aranesp® (Amgen) SC 0.75 µg/kg Q2W, for 24 weeks.
PK ASSESSMENT: Blood samples for PK assessments will be collected at:
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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.
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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:
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Clinical adverse events (AEs): frequency of AEs, overall and by intensity.
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Severe clinical adverse events (SAEs): frequency of AEs, overall and by intensity.
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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.
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Laboratory tests: frequency of clinically relevant changes from baseline.
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The frequency of any concomitant medication administered to treat any adverse events.
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Presence of anti-bodies to darbepoetin alfa (immunogenicity).
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Stimus Treatment: Nanogen's Darbepoetin alfa 10µg/0.4mL, 20µg/0.5mL, 40µg/0.4mL, 60µg/0.3mL, prefilled syringe |
Biological: Stimus
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.
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 for patients with PK-PD in the previous IV group), at a dose of 0.75 g/kg initially, every 2 weeks at the second visit.
IPs 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)
|
Active Comparator: Aranesp Control: Amgen's Aranesp® 10µg/0.4mL, 20µg/0.5mL, 40µg/0.4mL, 60µg/0.3mL, prefilled syringe |
Biological: Stimus
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.
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 for patients with PK-PD in the previous IV group), at a dose of 0.75 g/kg initially, every 2 weeks at the second visit.
IPs 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)
|
Outcome Measures
Primary Outcome Measures
- PK parameters comparison between NNG-DEPO and Aranesp®: Cmax [IV:Assessed predose and at 0.25; 0.5; 4;12;24;48;96;144;240;336 hours postdose/ SC: Assessed predose and at 4;12;24;48;96;144;240;336 hours postdose]
Serum peak concentrations (Cmax)
- PK parameters comparison between NNG-DEPO and Aranesp®: AUC(0, t) [IV:Assessed predose and at 0.25; 0.5; 4;12;24;48;96;144;240;336 hours postdose/ SC: Assessed predose and at 4;12;24;48;96;144;240;336 hours postdose]
Area under the curve from 0 to t (AUC 0-t)
Secondary Outcome Measures
- PD parameters comparison between NNG-DEPO and Aranesp®: Cmax of reticulocytes [Assessed predose and at and at 24;48;96;144;240;336 hours postdose]
Serum peak concentrations (Cmax) of reticulocytes
- PD parameters comparison between NNG-DEPO and Aranesp®: AUC(0, t) of reticulocytes [Assessed predose and at and at 24;48;96;144;240;336 hours postdose]
Area under the curve from 0 to t (AUC 0-t) of reticulocytes
- PD parameters comparison between NNG-DEPO and Aranesp®: Tmax of reticulocytes [Assessed predose and at and at 24;48;96;144;240;336 hours postdose]
Time for the drug to reach peak concentration (Tmax) of reticulocytes
- PK parameters comparison between NNG-DEPO and Aranesp®:Tmax [IV:Assessed predose and at 0.25; 0.5; 4;12;24;48;96;144;240;336 hours postdose/ SC: Assessed predose and at 4;12;24;48;96;144;240;336 hours postdose]
Time for the drug to reach peak concentration (Tmax)
- PK parameters comparison between NNG-DEPO and Aranesp®: AUC(0,∞) [IV:Assessed predose and at 0.25; 0.5; 4;12;24;48;96;144;240;336 hours postdose/ SC: Assessed predose and at 4;12;24;48;96;144;240;336 hours postdose]
Area under the curve from 0 to ∞ (AUC0-∞)
- PK parameters comparison between NNG-DEPO and Aranesp®:T1/2 [IV:Assessed predose and at 0.25; 0.5; 4;12;24;48;96;144;240;336 hours postdose/ SC: Assessed predose and at 4;12;24;48;96;144;240;336 hours postdose]
Half-life (T1/2)
- PK parameters comparison between NNG-DEPO and Aranesp®: CL/F [IV:Assessed predose and at 0.25; 0.5; 4;12;24;48;96;144;240;336 hours postdose/ SC: Assessed predose and at 4;12;24;48;96;144;240;336 hours postdose]
CL/F
- PK parameters comparison between NNG-DEPO and Aranesp®:Vz/F [IV:Assessed predose and at 0.25; 0.5; 4;12;24;48;96;144;240;336 hours postdose/ SC: Assessed predose and at 4;12;24;48;96;144;240;336 hours postdose]
Vz/F
- PK parameters comparison between NNG-DEPO and Aranesp®: λz. [IV:Assessed predose and at 0.25; 0.5; 4;12;24;48;96;144;240;336 hours postdose/ SC: Assessed predose and at 4;12;24;48;96;144;240;336 hours postdose]
λz.
- Proportion of the adverse events (AE) including physical examinations, vital signs, and clinical laboratory investigations. [Week 0 (Assessed predose)- Week 24]]
Rate of AE and SAE occurence
Eligibility Criteria
Criteria
Inclusion Criteria
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The patients signed the informe consent form and adhere to study visit schedule.
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Male or female patients aged from 18 to 65 years.
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Patients on hemodialysis or peritoneal dialysis for at least 3 months and have Hb baseline <10 g/dL during the screening period.
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Have transferrin saturation ≥ 20%, serum ferritin ≥ 200 ng/mL, vitamin B12 and folate within the normal range.
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Have expected survival of at least 6 months from time of enrollment (by investigator's assessment).
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Women childbearing age must agree to use medically acceptable methods of contraception during the study and for 6 months after the last study treatment.
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The patient does not have any serious medical conditions that may affect to study treatment compliance.
Exclusion Criteria
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Uncontrolled hypertension over 2 weeks prior to and within the screening period (BP ≥ 160/90 mmHg).
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Patients treated with Darbepoetin alfa or r-HuEPO within 4 weeks prior to enrollment.
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Patients with Uncontrolled diabetes mellitus with HbA1C ≥ 10%.
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Congestive Heart Failure of grade 3 or 4 as New York Heart Association classification.
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History of unstable angina or myocardial infarction within 6 months.
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History of Grand mal seizures in last 2 years.
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Present with severe hyperparathyroidism (iPTH >1500 pg/mL for Dialysis).
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History of major surgery within 12 weeks prior to screening.
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Systemic hematologic disorders including sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma and hemolytic anemia.
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Systemic infections, active inflammatory diseases and malignancies.
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Active liver disease or hepatic with liver enzymes AST and ALT raised > 2-times of laboratory normal values, child B or child C cirrhosis.
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Are being treated with androgen therapy within the 8 weeks prior to the screening period.
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Pregnant or suspected pregnant women, breast-feeding women.
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Patients scheduled for any transplant procedure within 6 months of screening or with a previous history of kidney transplantation.
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Patients who are hypersensitive to any of substances of investigational product.
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Patients using drugs that can affect the concentration of Hb in the blood (except blood-forming drugs such as iron, folic acid).
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Patients with seropositivity to HIV, HBV or anti-HCV.
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Patients having acute tuberculosis or any acute bacterial infection within 1 month prior to the screening.
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Patient has occult blood in stool or any other known source of internal bleeding and confirmed gastrointestinal bleeding by endoscopy.
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Patients with blood transfusion due to acute bleeding within 12 weeks prior to screening period.
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Patients with a history of immunosuppressive therapy within 1 month.
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The patient is suffering from advanced cancer.
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Patients having participated in any other clinical trial within 1 month prior to the screening period.
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The patient had any medical condition that the investigator assessed as affecting the study.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | NANOGEN Pharmaceutical Biotechnology JSC | Ho Chi Minh City | Vietnam |
Sponsors and Collaborators
- Nanogen Pharmaceutical Biotechnology Joint Stock Company
- Vietstar Biomedical Research
- Clinical Research Consultants, Inc.
- Clinical Research Viet Nam Skill Training And Consultant Company Limited
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NNG06.1