Ignite Creation Date:
2025-12-25 @ 2:06 AM
Ignite Modification Date:
2025-12-27 @ 10:55 PM
Study NCT ID:
NCT07025460
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-09-24
First Post:
2025-06-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
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
Organization:
Study Overview
Official Title:
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
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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.
Detailed Description:
Study Design and Procedures
This was a prospective, open-label, multicenter, single-arm phase 4 clinical trial designed to evaluate the efficacy and safety of once-monthly subcutaneous darbepoetin alfa (DARB) compared with the established biweekly dosing schedule in Korean patients with anemia secondary to non-dialysis chronic kidney disease (ND-CKD).
Study Flow Summary
Screening Phase (Week -12 to 0):
A total of 65 patients received DARB every 2 weeks for 12 weeks. Eligibility required stable Hb levels (≥9.5 g/dL) with \<25% dose variation during this period.
Enrollment (Week 0):
Forty patients who met all inclusion criteria and no exclusion criteria were enrolled into the evaluation phase and switched to once-monthly DARB dosing.
Evaluation Phase (Week 1 to 12):
Patients received once-monthly DARB for 12 weeks with predefined dose adjustments to maintain Hb within 10.0-11.0 g/dL.
Follow-up Visits:
Assessments were performed at Weeks 13, 17, 21, and 25.
Dosing Schedule
Initial monthly dose was based on the cumulative biweekly dose administered during the final month of the screening phase.
Dose titration rules:
Hb \<10.0 g/dL → increase to next higher dose
Hb 10.0-11.0 g/dL → maintain current dose
Hb \>11.0-12.0 g/dL → reduce to next lower dose
Hb \>12.0 g/dL → temporarily withhold, reinitiate at lower dose once Hb ≤12.0 g/dL
Available doses: 20, 30, 40, 60, and 120 mcg (prefilled syringes).
Laboratory and Clinical Assessments
Hemoglobin, serum iron, ferritin, transferrin saturation (TSAT), TIBC, creatinine, eGFR (MDRD), and blood pressure were measured at scheduled visits.
Safety assessments included adverse event monitoring, physical examinations, and routine laboratory tests.
Statistical Considerations
Primary endpoint: Proportion of patients maintaining Hb ≥10.0 g/dL at Week 25, analyzed for non-inferiority with a prespecified margin of 0.2 g/dL.
Secondary endpoints: Mean Hb, iron parameters, response frequency, total DARB dose, oral iron requirements, and safety outcomes including adverse events and blood pressure changes.
Analysis sets:
Full Analysis Set (FAS): All 40 enrolled patients who received ≥1 dose and had ≥1 post-baseline Hb measurement.
Per-Protocol (PP) Set: Patients in the FAS without major protocol deviations who completed the study.
Missing data were imputed using Next Observation Carried Backward (NOCB).
Study Completion
Of the 65 patients screened, 40 entered the evaluation phase and all 40 completed the study, allowing full assessment of efficacy and safety outcomes.
Significance
This trial demonstrates that once-monthly darbepoetin alfa is non-inferior to biweekly dosing for maintaining hemoglobin in Korean patients with ND-CKD. These findings support the feasibility of extending the dosing interval to monthly administration, potentially improving adherence and reducing treatment burden in real-world practice.
This was a prospective, open-label, multicenter, single-arm phase 4 clinical trial designed to evaluate the efficacy and safety of once-monthly subcutaneous darbepoetin alfa (DARB) compared with the established biweekly dosing schedule in Korean patients with anemia secondary to non-dialysis chronic kidney disease (ND-CKD).
Study Flow Summary
Screening Phase (Week -12 to 0):
A total of 65 patients received DARB every 2 weeks for 12 weeks. Eligibility required stable Hb levels (≥9.5 g/dL) with \<25% dose variation during this period.
Enrollment (Week 0):
Forty patients who met all inclusion criteria and no exclusion criteria were enrolled into the evaluation phase and switched to once-monthly DARB dosing.
Evaluation Phase (Week 1 to 12):
Patients received once-monthly DARB for 12 weeks with predefined dose adjustments to maintain Hb within 10.0-11.0 g/dL.
Follow-up Visits:
Assessments were performed at Weeks 13, 17, 21, and 25.
Dosing Schedule
Initial monthly dose was based on the cumulative biweekly dose administered during the final month of the screening phase.
Dose titration rules:
Hb \<10.0 g/dL → increase to next higher dose
Hb 10.0-11.0 g/dL → maintain current dose
Hb \>11.0-12.0 g/dL → reduce to next lower dose
Hb \>12.0 g/dL → temporarily withhold, reinitiate at lower dose once Hb ≤12.0 g/dL
Available doses: 20, 30, 40, 60, and 120 mcg (prefilled syringes).
Laboratory and Clinical Assessments
Hemoglobin, serum iron, ferritin, transferrin saturation (TSAT), TIBC, creatinine, eGFR (MDRD), and blood pressure were measured at scheduled visits.
Safety assessments included adverse event monitoring, physical examinations, and routine laboratory tests.
Statistical Considerations
Primary endpoint: Proportion of patients maintaining Hb ≥10.0 g/dL at Week 25, analyzed for non-inferiority with a prespecified margin of 0.2 g/dL.
Secondary endpoints: Mean Hb, iron parameters, response frequency, total DARB dose, oral iron requirements, and safety outcomes including adverse events and blood pressure changes.
Analysis sets:
Full Analysis Set (FAS): All 40 enrolled patients who received ≥1 dose and had ≥1 post-baseline Hb measurement.
Per-Protocol (PP) Set: Patients in the FAS without major protocol deviations who completed the study.
Missing data were imputed using Next Observation Carried Backward (NOCB).
Study Completion
Of the 65 patients screened, 40 entered the evaluation phase and all 40 completed the study, allowing full assessment of efficacy and safety outcomes.
Significance
This trial demonstrates that once-monthly darbepoetin alfa is non-inferior to biweekly dosing for maintaining hemoglobin in Korean patients with ND-CKD. These findings support the feasibility of extending the dosing interval to monthly administration, potentially improving adherence and reducing treatment burden in real-world practice.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: