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

Condition(s) studied

Investigational drug(s) / intervention(s)

darbepoetin alfa: 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.

Study 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.

Eligibility

Primary outcome measure(s)

• Proportion of participants maintaining hemoglobin (Hb) ≥10.0 g/dL at Week 25 — Week 25 (end of 12-week evaluation phase)
  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.

Trial sites (1)

More Gangnam Severance Hospital trials in South Korea

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