C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial

Abstract

Background and objectives: This study examined the efficacy of C.E.R.A., a continuous erythropoietin receptor activator, for correcting anemia in patients who had chronic kidney disease (CKD) and were not on dialysis.

Design, setting, participants, & measurements: In this open-label, randomized, parallel-group, Phase III study, 324 adult patients with CKD not on dialysis nor receiving treatment with erythropoiesis-stimulating agents (ESAs) were randomly assigned (1:1) to receive subcutaneous C.E.R.A. once every 2 wk or darbepoetin alfa once weekly during an 18-wk correction period and a 10-wk evaluation period. Thereafter, patients receiving C.E.R.A. were randomly assigned to C.E.R.A. once every 2 wk or once monthly, and patients receiving darbepoetin alfa could receive darbepoetin alfa once weekly or once every 2 wk for a 24-wk extension period. Dosage was adjusted to achieve a hemoglobin (Hb) response and to maintain Hb +/-1 g/dl of the response level and 11 to 13 g/dl. Primary end points were Hb response rate during correction and evaluation and change in Hb concentration between baseline and evaluation.

Results: Hb response rates were 97.5% for C.E.R.A. and 96.3% for darbepoetin alfa. Adjusted mean changes in Hb from baseline to evaluation were 2.15 g/dl (C.E.R.A.) and 2.00 g/dl (darbepoetin alfa). Analysis showed that C.E.R.A. once every 2 wk was as effective as darbepoetin alfa once weekly for correcting anemia. Hb levels remained stable in all groups during the extension period. C.E.R.A. and darbepoetin alfa were well tolerated.

Conclusions: Subcutaneous C.E.R.A. once every 2 wk corrects anemia in ESA-naïve patients who are not on dialysis.

Figure 1.

Study design. QW, once weekly; Q2W, once every 2 wk; Q4W, once every 4 wk.

Figure 2.

Patient populations and disposition. AE, adverse event; ITT, intent-to-treat; PP, per-protocol.

Figure 3.

Response rates to C.E.R.A. and darbepoetin alfa during the correction and evaluation periods (ITT and PP populations). CI, confidence interval.

Figure 4.

Difference in change in mean adjusted Hb with C.E.R.A. and darbepoetin alfa between baseline and evaluation (ITT and PP populations).

Figure 5.

Mean Hb values during the correction and evaluation periods with C.E.R.A. and darbepoetin alfa (ITT population).

Figure 6.

Kaplan-Meier plot of responders over time (ITT population).

Figure 7.

Mean Hb values during the extension period with C.E.R.A. and darbepoetin alfa (ITT population).

Figure 8.

Changes in quality of life from baseline to weeks 13 and 29 measured by the Short Form-36 (SF-36) questionnaire. A clinically meaningful change is defined as a change of ≥5 points versus baseline.