Strategies Using Darbepoetin alfa to Avoid Transfusions in Chronic Kidney DiseaseSTART-CKD

- Clinical history of advanced CKD not on dialysis with at least 1 historic estimated glomerular filtration rate (eGFR) < 45.0 mL/mi)/1.73 m2 at least 12 weeks prior to screening - Not currently receiving dialysis with an eGFR < 45.0 mL/min/1.73m2, per the central laboratory during screening - Chronic anemia due to renal failure - Two Hb concentrations < 10.0 g/dL, at least 2 weeks apart during screening using the modified Hb point of care (POC) device - Iron replete, defined as a transferrin saturation (TSAT) ≥ 20% and a ferritin ≥ 100 ng/mL, per the central laboratory during screening - Vitamin B12 and folate replete, defined as a vitamin B12 level > 180 pg/mL and a folate concentration > 7 nmol/L, per the central laboratory during screening - Clinically stable in the opinion of the investigator - Subject has provided written informed consent

- Systemic hematologic disease (eg, sickle cell anemia, myelodysplastic syndrome, hematologic malignancy) - Current or prior malignancy within 5 years of screening, with the exception of non-melanoma skin cancers and cervical intraepithelial neoplasia - Treatment for any malignancy (eg, radiation, chemotherapy, hormone therapy, or biologics) within 5 years of screening, with the exception of locally excised non-melanoma skin cancer or cervical intraepithelial neoplasia - Female subject not willing to use highly effective methods of birth control during treatment and for 4 weeks after the end of treatment - Subject is pregnant or breast feeding, or might become pregnant during the study or within 4 weeks after the end of treatment - Currently receiving intravenous (IV) antibiotics for treatment of an active infection - Known Human Immunodeficiency Virus (HIV) positive - Currently receiving systemic immunosuppressive therapy with the exception of prednis(ol)one ≤ 10 mg per day (or the steroid equivalent) - History of any organ transplant - Currently enrolled in another interventional study (eg, studies which require medical device use or drug therapy or with protocol required procedures), or less than 4 weeks since ending another interventional study(s) or receiving investigational agent(s) - Known neutralizing anti-erythropoietic protein antibodies - Known sensitivity to any of the products to be administered during dosing - Previously enrolled in this study - Not expected to be available for protocol required study visits or procedures to the best of the subject and investigator’s knowledge -Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or comply with all required study procedures - Occurrence of stroke or myocardial infarction (MI) within 24 weeks of screening - Receipt of RBC transfusion within 8 weeks of screening - Occurrence of seizure, clinically relevant active bleeding (eg, gastrointestinal [GI] bleed) or any hospitalization within 8 weeks of screening - Receipt of any IV iron therapy within 4 weeks of screening - Changes in oral iron therapy within 4 weeks of screening - Receipt of ESA therapy within 4 weeks of screening - Diagnosis or treatment of malignancy, with the exception of non-melanoma skin cancers and cervical intraepithelial neoplasia during screening - Receipt of ESA therapy, RBC transfusions, IV iron therapy during screening - Changes in oral iron therapy during screening - Occurrence of stroke, MI, seizure, clinically relevant active bleeding (eg, GI bleed), any hospitalization or outpatient surgery during screening - Uncontrolled hypertension during screening. Defined in this study, as a mean systolic blood pressure > 140 mmHg at both screening visits, or a mean systolic blood pressure >/= 160 mmHg at any screening visit, or a mean diastolic blood pressure >/= 90 mmHg at any screening visit. - Expected or scheduled change in oral iron therapy or receipt of IV iron therapy within 4 weeks after randomization - Expected or scheduled receipt of a RBC transfusion within 8 weeks after randomization - Expected or scheduled organ transplant within 24 weeks after randomization - Expected or scheduled initiation of dialysis within 24 weeks after randomization