Strategies Using Darbepoetin Alfa to Avoid Transfusions in Chronic Kidney Disease

20110226

A phase 3, multicenter, randomized, double-blind, parallel group study. Anemic subjects with chronic kidney disease (CKD) and not on dialysis will be randomized 1:1 to 1 of 2 dosing strategies to evaluate the proportion of subjects receiving at least one red blood cell (RBC) transfusion. In the haemoglobin (Hb)-based titration group, darbepoetin alfa doses will be titrated to maintain Hb ≥ 10.0 grams/deciliter (g/dL). In the fixed dose group, subjects will receive a fixed dose of darbepoetin alfa. Treatment group, darbepoetin alfa doses, and protocol specified Hb concentrations will be blinded. Subjects will be followed for approximately 2 years from the date of randomization.

2012-07-30

2017-10-19

2017-10-19

Completed

Early phase I

756

Key Inclusion Criteria: * 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 Key Exclusion Criteria: * 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

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2022-09-21