Strategies Using Darbepoetin Alfa to Avoid Transfusions in Chronic Kidney Disease
Condition: Anemia in Chronic Kidney Disease Patients Not on Dialysis
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Intervention: Darbepoetin alfa; Placebo
Intervention description: Darbepoetin alfa was presented as single use prefilled syringes (PFS). Investigational product was administered SC Q4W for the duration of the treatment period.; Placebo was presented as single use PFS. Participants received a SC placebo injection in place of darbepoetin alfa therapy when the dose of study drug was withheld per the dosing algorithm for the duration of the treatment period.
Intervention MeSH terms: Darbepoetin alfa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 756.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: anemia; chronic kidney disease; kidney disease; renal failure

Summary:

      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.
    

Eligibility criteria:

        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