Efficacy and Safety of CKD-11101 (Proposed Biosimilar of Darbepoetin-Alfa) Compared with Darbepoetin-Alfa in Patients on Hemodialysis: A Randomized, Double-Blinded, Parallel-Group Phase III Study
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Darbepoetin-alfa is an erythropoiesis-stimulating agent (ESA) with a long elimination half-life that achieves better hemoglobin (Hb) stability than short-acting ESAs.
We aimed to evaluate the efficacy and safety of intravenous CKD-11101 (a biosimilar of darbepoetin-alfa) compared with those of darbepoetin-alfa in hemodialysis patients.
The study was performed in 24 centers in Korea between June 2015 and June 2017. The study subjects were randomized in a double-blind manner. The follow-up duration was 24 weeks, which consisted of 20 weeks of maintenance and 4 weeks of evaluation period. All patients underwent a stabilization period to achieve a target baseline Hb of 10–12 g/dL before randomization. Following randomization, patients received darbepoetin-alfa or CKD-11101 weekly or biweekly.
A total of 403 patients were randomized into two groups, and a total of 325 patients (80.6%) completed the investigation. The differences between the two groups in terms of change in the average Hb level from baseline to evaluation were not significant. The average administered dose of ESA was similar between the groups. There was no difference in the proportion of patients who maintained the target Hb during the evaluation period [60.4% vs. 66.2% in the CKD-11101 and darbepoetin-alfa groups, respectively (p = 0.3038)]. In addition, the safety analysis, consisting of adverse events and adverse drug reactions, showed comparable results between the two groups.
The changes in the level of Hb, dose of erythropoietin, and achievement rate of the target Hb during the study period were comparable between the groups. CKD-11101 has an equivalent efficacy and safety compared with darbepoetin-alfa in patients undergoing hemodialysis.
All clinical data were provided from 24 different medical centers. We would like to thank the patients, caregivers, and investigators who contributed to the study. This research was supported by Chong Kun Dang Pharm with regard to the development of the protocol and performance of the clinical research and statistical analysis of the data.
All authors contributed to the acquisition, analysis, or interpretation of data, and to drafting or revising the manuscript. All authors approved the final version of the manuscript and are responsible for the overall work by properly investigating and resolving questions related to the accuracy or integrity of the work.
Compliance with Ethical Standards
This study was sponsored by Chong Kun Dang Pharm, Seoul, Republic of Korea.
Conflict of interest
The authors, Yaerim Kim, Su-Kil Park, Won Yong Cho, Kwon Wook Joo, Sug Kyun Shin, Dae Joong Kim, Yong-Lim Kim, Sung Hyun Son, Wookyung Chung, Kwang Young Lee, Sung Kwang Park, Joong Kyung Kim, Soo Wan Kim, Duk-Hee Kang, Jin Kuk Kim, Jin Seok Jeon, Kang Wook Lee, Chang Hwa Lee, Dong-Jin Oh, Won Suk An, Jong Soo Lee, Gun Woo Kang, Jun-young Do, Jung Pyo Lee, and Kyubok Jin, declare that they have no potential conflicts of interest that might be relevant to the contents of this article.
The study protocol was reviewed and approved by the health authorities of the Ministry of Food and Drug Safety of South Korea and the institutional review board of each medical center. Written informed consent was obtained from all subjects included in this study.
Asigned and dated informed consent document was required from each patient before any screening procedures were performed.
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