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, multicenter, phase 4 study

Conditions: Chronic Kidney Disease

Summary: this open-label, multicenter, single-arm phase 4 clinical study aims to evaluate the efficacy and safety of once-monthly subcutaneous administration of darbepoetin alfa (darb) in maintaining hemoglobin (hb) concentration in patients with anemia due to advanced chronic kidney disease (ckd) not receiving dialysis. anemia in ckd is a major contributor to cardiovascular morbidity and mortality. although darb every-2-week dosing has been established as effective, studies suggest that once-monthly dosing may maintain hb levels while improving patient adherence and reducing healthcare burden. however, no clinical data exist for the korean population, which is rapidly aging and has increasing ckd prevalence.

serum creatinine, egfr (mdrd) c-reactive protein (crp) hepcidin (for iron regulation analysis) vitamin b12 and folate (screening only) parathyroid hormone (pth) (screening only) eligibility checkpoints informed consent: obtained prior to any study-related procedures. previous medications: documented for 1 month before consent. window periods: ±2 weeks for screening; ±1 week for each visit during the evaluation phase. criteria for early withdrawal subjects will be withdrawn if any of the following occur: kidney transplantation blood transfusion new diagnosis of malignancy or hematologic disorder use of other investigational drugs/devices inability to comply or investigator's judgment for discontinuation adverse event monitoring ae monitoring starts on the date of informed consent. ae assessments at every scheduled visit. serious or unresolved aes are followed until resolution or deemed clinically insignificant. events will be classified and coded according to severity and relationship to study drug. data handling and monitoring all subject data will be pseudonymized with study-specific codes. investigators will monitor data accuracy and completeness every 3 months. all data stored securely with restricted access. discontinuation criteria for study or site the study may be discontinued under the following conditions: inability to meet recruitment targets emerging safety concerns gcp or protocol violations administrative or sponsor-directed decisions statistical considerations primary outcome (proportion with hb ≥10.0 g/dl at week 25) modeled using binomial distribution. confidence intervals constructed assuming approximate normality due to sufficient sample size. full analysis set (fas): all enrolled participants who received ≥1 dose and had ≥1 post-baseline hb measurement. per-protocol (pp) set: fas participants without major protocol violations who completed the study. handling of missing data: missing values in fas will be imputed using next observation carried backward (nocb) as a conservative approach. data confidentiality patient identifiers (name, registration number) will not be collected. only study codes will be used. all research data stored in password-protected files and physically secured areas. access limited to investigators. data retained for 3 years post-study in accordance with the bioethics and safety act; thereafter, permanently deleted. biological samples and storage blood samples collected for biomarker analysis (not for genetic testing). stored with appropriate labeling at designated biorepository. use limited to this study only. discarded upon final report completion. participants may withdraw consent for biorepository use at any time.

Eligibility criteria:
inclusion criteria: 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 \ 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 exclusion criteria: * 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