Русский
The first russian darbepoetin alfa bioanalogue: results of a double-blind, randomized clinical study of efficacy and safety for patients with nephrogenic anemia on programmed hemodialysis
DOI: https://dx.doi.org/10.18565/nephrology.2018.4.42-54
V.Yu. Shilo, V.P. Babich, G.V. Vasilieva, K.A. Vishnevsky, T.A. Gomova, V.P. Doru-Tovt, M.V. Dudarev, L.F. Yeremeeva, A.V. Zuev, L.I. Kotova, I.L. Novoseltsev, G.V. Rodoman, V.Yu. Ryasnyansky, A.B. Sabodash, A.V. Solovyova, O.M. Solovyova, V.N. Suchkov, A.G. Strokov, G.Yu. Timokhovskaya, V.M. Chistyakov, L.A. Shpagina, L.A. Fedotova, N.G. Khadikova, E.V. Khazova, M.A. Morozova, E.A. Dokukina, Yu.N. Lin’kov
1 FSBEI HE "A.I. Yedokimov Moscow State University of Medicine and Dentistry" of the Ministry of Health of the Russian Federation, Department of Nephrology; Moscow, Russia; 2 OOO Medical Center "NEPHROS"; Krasnodar, Russia; 3 OOO "St. Petersburg Dialysis Center"; Saint-Petersburg, Russia; 4 SPbSBHCI "City Hospital № 15"; Saint-Petersburg, Russia; 5 SHCI TR "Tula Regional Clinical Hospital"; Tula, Russia; 6 SI "St. Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine"; Saint-Petersburg, Russia; 7 OOO "Alliance Biomedical – Ural Group"; Izhevsk, Russia; 8 OOO "Fresenius Medical Care Kuban"; Krasnodar, Russia; 9 SBHCI RK "Republican Hospital.n.a. V.A. Baranov"; Petrozavodsk, Russia; 10 BHCI OR "Regional Clinical Hospital"; Omsk, Russia; 11 OOO "Dialysis Center"; Mytishchi, Russia; 12 SBHCI "City Clinical Hospital № 24 of the Moscow Healthcare Department"; Moscow, Russia; 13 FSBEI HE "North-Western State Medical University n.a. I.I. Mechnikov" of the Ministry of Health of the Russian Federation; Saint-Petersburg, Russia; 14 OOO "B. Braun Avitum Russland Clinics"; Saint-Petersburg, Russia; 15 FSBEI HE "Tver State Medical University" of the Ministry of Health of the Russian Federation; Tver, Russia; 16 SPbSBHCI "City Hospital of the Holy Reverend Martyr Elizabeth"; Saint-Petersburg, Russia; 17 SPbSBHCI "Mariinsky City Hospital"; Saint-Petersburg, Russia; 18 FSBI "Academician V.I. Shumakov Federal Scientific Center of Transplantology and Artificial Organs" of the Ministry of Health of the Russian Federation; Moscow, Russia; 19 SPbSBHCI "City Clinical Hospital № 31"; Saint-Petersburg, Russia; 20 OOO "New Clinic"; Pyatigorsk, Russia; 21 SBHCI NR "City Clinical Hospital № 2"; Novosibirsk, Russia; 22 OOO "Nephroline-Novosibirsk"; Novosibirsk, Russia; 23 SPbSBHCI "Nikolaev Hospital"; Saint-Petersburg, Russia; 24 FSBEI HE "Kazan State Medical University Ministry" of the Ministry of Health of the Russian Federation; Kazan, Russia; 25 ZAO "BIOCAD"; Saint-Petersburg, Russia; 26 OOO "B. Braun Avitum Russland Clinics"; Moscow, Russia
Objective. to prove the equivalent efficacy and safety of Darbestim (ZAO BIOCAD, Russia) and Aranesp (Amgen Europe B.V., The Netherlands) when used to maintain target hemoglobin levels in patients with end-stage chronic kidney disease (CKD) on hemodialysis.
Material and methods. A double-blind, randomized, parallel group comparative clinical study of the efficacy and safety of Darbestim and Aranesp included 196 patients with anemia against the background of end-stage CKD (CKD 5D) who were on program hemodialysis and regularly received recombinant human erythropoietin (rhEPO) preparations. Participants were randomly assigned to two groups of therapy: patients in the first group (n=98) received Darbestim, patients in the second group (n=98) – Aranesp. The main stage of the study lasted from the 1st to the 24th week of therapy inclusive; after it was completed, an analysis of the efficacy, safety and immunogenicity of the drugs was performed; the results of analysis are presented in this article. After the 24th week, all patients continued to receive therapy for up to one year in order to further assess the safety and efficacy of long-term therapy. The primary endpoint of effectiveness was a change in hemoglobin level.
Results. Efficacy analysis was conducted in the population of patients who completed 24 weeks of therapy (per protocol population (n=176): in group 1 (Darbestim) 86 patients were included in the analysis, in group 2 (Aranesp) – 90. Average value of change in hemoglobin level in the group 1 was 4.7±11.0 g/L, in the group 2 – 4.6±9.0 g/L (P=0.9717). The 95% confidence interval (CI) for the between-group difference of arithmetic mean values of the indicator "change in hemoglobin level during the evaluation period compared with the initial level" was [-3.04; 2.93]; the DI within the pre-defined boundaries of [-5.00; 5.00] indicate the equivalent efficacy of the two drugs being compared. Safety analysis between the test drug and the reference drug revealed no differences in both the spectrum and the frequency of the registered AEs and SAEs.
Conclusion. In the framework of this study, the equivalent efficacy and safety of Darbestim (ZAO BIOCAD, Russia) and Aranesp (Amgen Europe B.V., The Netherlands) were proved.
Material and methods. A double-blind, randomized, parallel group comparative clinical study of the efficacy and safety of Darbestim and Aranesp included 196 patients with anemia against the background of end-stage CKD (CKD 5D) who were on program hemodialysis and regularly received recombinant human erythropoietin (rhEPO) preparations. Participants were randomly assigned to two groups of therapy: patients in the first group (n=98) received Darbestim, patients in the second group (n=98) – Aranesp. The main stage of the study lasted from the 1st to the 24th week of therapy inclusive; after it was completed, an analysis of the efficacy, safety and immunogenicity of the drugs was performed; the results of analysis are presented in this article. After the 24th week, all patients continued to receive therapy for up to one year in order to further assess the safety and efficacy of long-term therapy. The primary endpoint of effectiveness was a change in hemoglobin level.
Results. Efficacy analysis was conducted in the population of patients who completed 24 weeks of therapy (per protocol population (n=176): in group 1 (Darbestim) 86 patients were included in the analysis, in group 2 (Aranesp) – 90. Average value of change in hemoglobin level in the group 1 was 4.7±11.0 g/L, in the group 2 – 4.6±9.0 g/L (P=0.9717). The 95% confidence interval (CI) for the between-group difference of arithmetic mean values of the indicator "change in hemoglobin level during the evaluation period compared with the initial level" was [-3.04; 2.93]; the DI within the pre-defined boundaries of [-5.00; 5.00] indicate the equivalent efficacy of the two drugs being compared. Safety analysis between the test drug and the reference drug revealed no differences in both the spectrum and the frequency of the registered AEs and SAEs.
Conclusion. In the framework of this study, the equivalent efficacy and safety of Darbestim (ZAO BIOCAD, Russia) and Aranesp (Amgen Europe B.V., The Netherlands) were proved.
Keywords: darbepoetin alfa, Aranesp, Darbestim, bioanalogue, anemia, chronic kidney disease, hemodialysis
About the Autors
Shilo V.Yu. – PhD in Medical Science, Associate Professor at the Department of Nephrology FPGPE SBEI HPE "MSMSU n.a. A.I. Evdokimov" of RMH, medical director of the network of B. Braun Avitum dialysis clinics in the Russian Federation; Moscow, Russia. E-mail: nephrolog@gmail.com
