Clinical trial NCT07025460: 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
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, Multicenter, Phase 4 Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Chronic Kidney Disease
Lead sponsor: Gangnam Severance Hospital
Sponsor class: OTHER
First posted: 2025-06-17
Enrollment: 77
Sex: FEMALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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 \<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

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

Primary outcomes:
measure: Proportion of participants maintaining hemoglobin (Hb) ≥10.0 g/dL at Week 25
timeFrame: Week 25 (end of 12-week evaluation phase)
Secondary outcomes:
measure: Mean hemoglobin (Hb) concentration during the 12-week evaluation phase
timeFrame: Week 25 (end of 12-week evaluation phase)
measure: Change in iron parameters (serum ferritin, transferrin saturation) during the evaluation phase,
timeFrame: Week 25 (end of 12-week evaluation phase)
measure: Total dose of darbepoetin alfa administered during the evaluation phase,
timeFrame: Week 25 (end of 12-week evaluation phase)
measure: Use of oral iron supplementation
timeFrame: Week 25 (end of 12-week evaluation phase)
measure: Incidence of adverse events (AEs) and blood pressure changes
timeFrame: Week 25 (end of 12-week evaluation phase)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Institutional Review Board, Gangnam Severance Hospitial Yonsei University College of Medicine
Study officials:
References:
citation: 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.
citation: 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.