Русский
Efficacy and safety of the first russian original long-acting erythropoiesis-stimulating agent for the treatment of anemia in patients with chronic renal failure. The results of the international multicenter randomized phase II clinical trial
DOI: https://dx.doi.org/10.18565/nephrology.2019.2.06-15
V.IU. Shilo, L.I. Alihanova, V.P. Babich, K.A. Vishnevskii, I.V. Zhdanova, A.V. Zuev, O.V. Kalachik, L.I. Kotova, A.B. Legotin, A.B. Sabodash, V.N. Suchkov, G.IU. Timokhovskaia, D.M. Toropilov, A.P. Tutin, S.V. Priluckij, L.A. Fedotova, N.G. Khadikova, M.A. Morozova, D.D. Bolsun, E.A. Dokukina, IU.N. Linkova, R.A. Ivanov
1) A.I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russian; 2) Republican Clinical Hospital Ministry of health Republic of Tatarstan, Kazan, Russian; 3) LLC Medical center "Nephros", Novorossiisk, Russian; 4) Saint-Petersburg State Budgetary Health Care Institution "City Hospital №15", St. Petersburg, Russian; 5) The Federal State Budgetary Institute "The Nikiforov Russian Center of Emergency and Radiation Medicine" The Ministry of Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters, St. Petersburg, Russian; 6) State Budgetary Health Care Institution of the Republic of Karelia "Republican Hospital named after V.A. Baranov", Petrozavodsk, Russian; 7) State institution "Minsk scientific and practical center of surgery, transplantology and hematology", Minsk, Russian; 8) Budgetary health care institution of Omsk, Omsk, Russian; 9) St. Petersburg State Budgetary Healthcare Institution "City Hospital of the Holy Martyr Elizabeth", St. Petersburg, Russian; 10) LLC "BBraun Avitum Russland Clinics", St. Petersburg, Russian; 11) St. Petersburg State Budgetary Healthcare Institution "City Mariinsky Hospital", St. Petersburg, Russian; 12) St. Petersburg State Health Care Institution "City Clinical Hospital №31", St. Petersburg, Russian; 13) 4-th City clinical hospital named after Mikalaj Sauchanka, Minsk, Russian; 14) LLC "Kupchinsky Center of outpatient dialysis", St. Petersburg, Russian; 15) Minsk Regional Clinical Hospital, Minsk region, AG Forest, Russian; 16) LLC "Nefroline-Novosibirsk", Novosibirsk, Russian; 17) St. Petersburg State Medical Academy "Nikolaev Hospital", St. Petersburg, Russian; 18) JSC BIOCAD, St. Petersburg, Russian
The purpose of the study was to determine the effective and safe therapeutic dose of the new original long-acting erythropoiesis-stimulating agent BCD-131 (pegylated darbepoetin) upon repeated administration for the treatment of anemia in patients with end-stage chronic kidney failure on dialysis.
Materials and methods. The international multicenter randomized open label comparative phase II clinical trial included 75 patients with anemia and end stage renal failure on dialysis, regularly receiving recombinant human erythropoietin. The trial consisted of two periods. During the first period it was planned to sequentially include patients in the three treatment groups of the investigational drug BCD-131 with the dose escalation: 1.05 µg/kg, 1.7 µg/kg and 2.75 µg/kg and parallel inclusion of participants in the group of active comparator Mircera. Drugs were administered once a month subcutaneously. During the first period of the trial we determined that two dose levels of BCD-131 1.05 µg/kg and 1.7 µg/kg produce the sufficient pharmacodynamic and clinical effect, therefore the dose 2.75 µg/kg of BCD-131 was not used in the further research. During the second period the initially included participants and newly recruited patients (until the number of 25 person in each of the three treatment groups) continued to receive therapy with the investigational drug BCD-131 1.05 µg/kg (group 1)
or 1.7 µg/kg (group 2) and the reference drug (group 3) up to the 21st week.
Results. During the 21 weeks treatment period the mean hemoglobin level was within the target range in all treatment groups (both doses of the investigational drug BCD-131 and Mircera). The calculated 95% CI for the difference in arithmetic mean values of the change in hemoglobin level between group 1 and group 3 was [-8.87; 4.47], does not exceed the predetermined equivalence limits 10,00 g/l and indicates the equivalent efficacy of the investigational drug BCD-131 1.05 µg/kg and Mircera. The safety analysis demonstrated the absence of statistically significant differences between the three treatment groups in the frequency and spectrum of registered adverse events (AEs), including treatment-emergent AEs and thrombotic complications. Throughout the study no binding antibodies were detected.
Conclusion. In this phase II clinical trial we determined the therapeutic dose of the new erythropoiesis-stimulating agent BCD-131 (pegylated darbepoetin). BCD-131 1.05 µg/kg and Mircera showed the equivalent efficacy. BCD-131 (both doses) and Mircera demonstrated the comparable and favorable safety profile, good tolerability and absence of the immunogenicity.
Materials and methods. The international multicenter randomized open label comparative phase II clinical trial included 75 patients with anemia and end stage renal failure on dialysis, regularly receiving recombinant human erythropoietin. The trial consisted of two periods. During the first period it was planned to sequentially include patients in the three treatment groups of the investigational drug BCD-131 with the dose escalation: 1.05 µg/kg, 1.7 µg/kg and 2.75 µg/kg and parallel inclusion of participants in the group of active comparator Mircera. Drugs were administered once a month subcutaneously. During the first period of the trial we determined that two dose levels of BCD-131 1.05 µg/kg and 1.7 µg/kg produce the sufficient pharmacodynamic and clinical effect, therefore the dose 2.75 µg/kg of BCD-131 was not used in the further research. During the second period the initially included participants and newly recruited patients (until the number of 25 person in each of the three treatment groups) continued to receive therapy with the investigational drug BCD-131 1.05 µg/kg (group 1)
or 1.7 µg/kg (group 2) and the reference drug (group 3) up to the 21st week.
Results. During the 21 weeks treatment period the mean hemoglobin level was within the target range in all treatment groups (both doses of the investigational drug BCD-131 and Mircera). The calculated 95% CI for the difference in arithmetic mean values of the change in hemoglobin level between group 1 and group 3 was [-8.87; 4.47], does not exceed the predetermined equivalence limits 10,00 g/l and indicates the equivalent efficacy of the investigational drug BCD-131 1.05 µg/kg and Mircera. The safety analysis demonstrated the absence of statistically significant differences between the three treatment groups in the frequency and spectrum of registered adverse events (AEs), including treatment-emergent AEs and thrombotic complications. Throughout the study no binding antibodies were detected.
Conclusion. In this phase II clinical trial we determined the therapeutic dose of the new erythropoiesis-stimulating agent BCD-131 (pegylated darbepoetin). BCD-131 1.05 µg/kg and Mircera showed the equivalent efficacy. BCD-131 (both doses) and Mircera demonstrated the comparable and favorable safety profile, good tolerability and absence of the immunogenicity.
About the Autors
Corresponding author:
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
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