Darbepoetin Alfa Once Monthly Dosing Schedule Maintains Hemoglobin Concentration Comparable to Every 2 Weeks Dosing Schedule in Advanced Chronic Kidney Disease Patients Not on Dialysis: A Multicenter, Phase 4 Study

NCT07025460 | Active Not Recruiting Phase 4

• 1 other identifier: 3-2019-0358
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label, multicenter, single-arm phase 4 trial evaluated the efficacy and safety of once-monthly subcutaneous administration of darbepoetin alfa (DARB) compared with biweekly dosing in Korean patients with non-dialysis chronic kidney disease (ND-CKD) and anemia. Anemia in CKD is a major contributor to cardiovascular morbidity and mortality. Although DARB every-2-week dosing has been established as effective, once-monthly dosing may maintain Hb levels while improving patient adherence and reducing healthcare burden. No clinical data were previously available for the Korean population, which is rapidly aging and has a high prevalence of CKD. Study Design: A total of 65 patients entered a 12-week screening period during which they received DARB every 2 weeks. Of these, 40 patients met eligibility criteria (stable Hb ≥9.5 g/dL, \<25% dose variation) and were enrolled into the 12-week evaluation phase with once-monthly DARB dosing. Dose adjustments were made based on Hb trends to maintain Hb within 10.0-11.0 g/dL. All 40 patients completed the study and were included in efficacy and safety analyses. Primary Endpoint: Proportion of participants maintaining Hb ≥10.0 g/dL at Week 25, assessed for non-inferiority with a prespecified margin of 0.2 g/dL. Secondary Endpoints: Mean Hb concentration during the evaluation phase (Weeks 13, 17, 21, and 25) Response frequency Proportion of patients with Hb \<10 g/dL or \>11 g/dL Change in iron parameters (serum ferritin, transferrin saturation) Total DARB dose administered Requirement for oral iron supplementation Incidence of adverse events and blood pressure changes Eligibility Criteria: Inclusion: Age ≥19 years Diagnosis of CKD not requiring dialysis eGFR ≤45 mL/min/1.73m² (MDRD formula) Mean Hb ≤11.5 g/dL during screening, with Hb ≥9.5 g/dL Stable DARB dosing during screening (\<25% variation) Ferritin ≥100 µg/L or transferrin saturation (TSAT) \>20% Exclusion: Non-CKD causes of anemia Acute myocardial infarction or hospitalization for heart failure within the past 12 weeks Hematologic diseases, active infection, or recent major surgery RBC transfusion within 8 weeks prior to screening, or DARB \>180 mcg in the month prior to enrollment Uncontrolled hypertension Active malignancy Sample Size: A total of 77 patients were planned for enrollment, accounting for an expected dropout rate of 20%. In practice, 65 patients entered screening, 40 patients were enrolled into the evaluation phase, and all 40 completed the study. Safety Considerations: No unexpected safety issues were identified. Blood pressure remained stable throughout the study. Potential risks such as cardiovascular complications and tumor progression were considered; patients with significant risk factors were excluded. All data were anonymized and securely protected. Significance: This study provides real-world evidence that once-monthly DARB is non-inferior to biweekly dosing for maintaining Hb in Korean patients with ND-CKD. Extending the dosing interval to monthly administration may improve patient adherence, reduce injection burden, and inform treatment strategies for anemia management in Korea's aging CKD population.

Conditions

Chronic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Proportion of participants maintaining hemoglobin (Hb) ≥10.0 g/dL at Week 25

  The primary endpoint is the proportion of participants whose hemoglobin (Hb) concentration is maintained at or above 10.0 g/dL at Week 25 following once-monthly subcutaneous administration of darbepoetin alfa. Non-inferiority was assessed using a prespecified margin of 0.2 g/dL.

  Week 25 (end of 12-week evaluation phase)

Secondary Outcomes (3)

• Hemoglobin profile during the evaluation phase

  Weeks 13, 17, 21, and 25

• Iron metabolism and treatment requirements

  Weeks 13-25

• Safety outcomes

  Weeks 1-25

Study Arms (1)

Once-monthly darbepoetin alfa group

EXPERIMENTAL

Participants receive darbepoetin alfa administered subcutaneously once every 4 weeks for 12 weeks. Initial dose is based on prior month's cumulative dose. Dose adjustments are made based on hemoglobin levels to maintain Hb within 10.0-11.0 g/dL.

Drug: darbepoetin alfa

Interventions

darbepoetin alfa DRUG

Participants receive darbepoetin alfa administered subcutaneously once every 4 weeks for 12 weeks during the evaluation phase. Dose adjustments are made to maintain hemoglobin levels within 10.0-11.0 g/dL.

Once-monthly darbepoetin alfa group

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 19 years
• Diagnosis of chronic kidney disease (CKD) not requiring dialysis
• Estimated glomerular filtration rate (eGFR) ≤ 45 mL/min/1.73 m² (calculated using the MDRD formula)
• Mean hemoglobin (Hb) concentration ≤ 11.5 g/dL during the screening period Hb concentration ≥ 9.5 g/dL during the screening period Stable DARB dosing during screening (defined as \<25% variation in dose)
• Serum ferritin ≥ 100 µg/L or transferrin saturation (TSAT) \> 20%
• Serum vitamin B12 and folate levels above the lower limit of normal (screening only) Provided written informed consent prior to any study-specific procedures

You may not qualify if:

• Planned kidney transplantation or prior kidney transplant
• Uncontrolled hypertension (systolic BP \> 180 mmHg or diastolic BP \> 110 mmHg) Acute myocardial infarction or hospitalization for heart failure within the past 12 weeks
• Serum parathyroid hormone (PTH) \> 1500 pg/mL (screening only) Active systemic infection
• Diagnosed hematologic diseases (e.g., sickle cell anemia, myelodysplastic syndrome, leukemia, multiple myeloma, hemolytic anemia)
• Major surgery within 12 weeks prior to screening (excluding vascular access surgery)
• Red blood cell transfusion within 8 weeks before screening or during the study period
• Use of any investigational drug or medical device within 30 days prior to screening or during the study
• Active malignancy not in remission
• Total darbepoetin alfa dose \> 180 mcg in the month prior to enrollment

Sponsors & Collaborators

• Gangnam Severance Hospital: lead

Study Sites (1)

Institutional Review Board, Gangnam Severance Hospitial Yonsei University College of Medicine

Seoul, South Korea

Location

Related Publications (2)

• Hertel J, Locay H, Scarlata D, Jackson L, Prathikanti R, Audhya P. Darbepoetin alfa administered every other week maintains hemoglobin levels over 52 weeks in patients with chronic kidney disease converting from once-weekly recombinant human erythropoietin: results from simplify the treatment of anemia with Aranesp (STAAR). Am J Nephrol. 2006;26(2):149-56. doi: 10.1159/000092852. Epub 2006 Apr 21.

  PMID: 16636531 BACKGROUND

• Roger SD, Kolmakova E, Fung M, Malecki R, Vinhas J, Dellanna F, Thomas M, Manamley N, Ferenczi S. Darbepoetin alfa once monthly corrects anaemia in patients with chronic kidney disease not on dialysis. Nephrology (Carlton). 2014 May;19(5):266-74. doi: 10.1111/nep.12214.

  PMID: 24506498 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Darbepoetin alfa

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: This study uses a single-group, open-label design in which all enrolled participants receive the investigational intervention-subcutaneous administration of darbepoetin alfa once monthly. After a 12-week screening phase with biweekly dosing to confirm hemoglobin stability and dosing consistency, eligible participants are transitioned to once-monthly dosing for a 12-week evaluation period. There is no comparator or randomization. All participants receive the same treatment protocol, and outcomes are assessed within this single cohort.

Study Record Dates

• First Submitted: June 9, 2025
• First Posted: June 17, 2025
• Study Start: December 19, 2019
• Primary Completion: October 17, 2024
• Study Completion: January 18, 2026
• Last Updated: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)