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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

Sponsor: Gangnam Severance Hospital

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.

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