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

NCT ID: NCT05636891

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-19
• Study Completion Date: 2022-11-23

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.

Detailed Description

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).

Conditions

Chronic Kidney Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Stimus

Treatment: Nanogen's Darbepoetin alfa 10µg/0.4mL, 20µg/0.5mL, 40µg/0.4mL, 60µg/0.3mL, prefilled syringe

Group Type: EXPERIMENTAL

Stimus

Intervention Type: BIOLOGICAL

• 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)

Aranesp

Control: Amgen's Aranesp® 10µg/0.4mL, 20µg/0.5mL, 40µg/0.4mL, 60µg/0.3mL, prefilled syringe

Group Type: ACTIVE_COMPARATOR

Stimus

Intervention Type: BIOLOGICAL

• 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)

Interventions

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)

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vietstar Biomedical Research

INDUSTRY

Sponsor Role: collaborator

Clinical Research Consultants, Inc.

INDUSTRY

Sponsor Role: collaborator

Clinical Research Viet Nam Skill Training And Consultant Company Limited

UNKNOWN

Sponsor Role: collaborator

Nanogen Pharmaceutical Biotechnology Joint Stock Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

NANOGEN Pharmaceutical Biotechnology JSC

Ho Chi Minh City, , Vietnam

Countries

Vietnam

Other Identifiers

NNG06.1

Identifier Type: -

Identifier Source: org_study_id