Strategies Using Darbepoetin alfa to Avoid Transfusions in Chronic Kidney Disease
This is a phase 3, 2 year, multicenter, randomized, double-blind, parallel group study. Anemic, ND-CKD subjects, without recent ESA use, will be randomized to 1 of 2 dosing strategies. In the Hb-based titration group, darbepoetin alfa doses will be titrated to maintain Hb >= 10.0 g/dL. In the other group, subjects will receive a fixed dose of
darbepoetin alfa. All subjects will receive investigational product (IP) as a subcutaneous injection Q4W. Treatment group, darbepoetin alfa doses, and protocol specified Hb concentrations will be blinded to the investigator, subjects and study team.
The study will be conducted in approximately 350 sites in North America with a total of 750 subjects. This site will enroll up to 30 subjects. At the conclusion of the screening period, eligible subjects will be randomized in a 1:1 ratio to 1 of 2 dosing strategies:
Hb-based titration group: Darbepoetin alfa titrated to maintain Hb >= 10.0 g/dL
Fixed dose group: Weight-based dose of darbepoetin alfa that will not be titrated
Randomization will be stratified by RBC transfusion received within 12 months prior to randomization (yes/no) and site practice setting (nephrology/non-nephrology).
The total duration on-study for an individual subject is approximately 2 years, which includes the following:
2- to 4-week screening period, 100-week on-study period including 96-week treatment period and 4-week follow-up period, after final dose of investigational product for collection of RBC transfusions and safety information (eg, adverse events).
The study drug (darbepoetin alfa or placebo) will be administered subcutaneously every
4 weeks. Darbepoetin alfa will be supplied as a clear, colorless, sterile protein solution in single
use prefilled syringes (PFS) at concentrations of 10, 20, 30, 40, 50, 60, 80, 100, 150, 200 and
300 [MICRO-SYMBOL]g. Placebo will be provided in similar PFS as a clear, colorless, sterile solution.
Every 4 weeks a protocol specified Hb will be measured using a Hb point of care device that is provided by the
sponsor and the results will be blinded. The codes provided by the point of care device will be entered into the
interactive voice response/interactive web response (IVR/IWR) system at each visit.
Extra visits may be required if the subject[AND]amp;apos;s blood pressure is high after starting the study drug, which could require changes in the subject[AND]amp;apos;s blood pressure medicines. These visits will be done between the routine study visits so that the study doctor can check the subject[AND]amp;apos;s blood pressure and to see if changes to their blood pressure medicines are needed. If the systolic blood pressure (top number) of their blood pressure measurement remains 160 mmHg or higher, the subject[AND]amp;apos;s dose of study drug will be stopped. They will begin taking the study drug again when the top number of their blood pressure measurement is below 140 mmHg.
Age 18 or older
Clinical history of advanced CKD not on dialysis with at least 1 historic
estimated glomerular filtration rate (eGFR) < 45.0 mL/min/1.73m2 at least
12 weeks prior to screening
eGFR >= 15.0 and < 45.0 mL/min/1.73m2, per the central laboratory during
Chronic anemia due to renal failure
Two Hb concentrations < 10.0 g/dL, at least 2 weeks apart during screening
using the Hb point of care 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
Clinically stable in the opinion of the investigator
Subject has provided written informed consent