Comparing Efficacy and Safety of CinnaGen Beta Erythropoietin (CinnaPoietin®) Versus Eprex® on the Treatment of Anemia in ESRD Hemodialysis Patients

Summary

This Phase III, randomized, two-armed, parallel, double-blind, active-controlled clinical trial is designed to compare efficacy and safety of CinnaPoietin® (Beta erythropoietin) and Eprex® (epoetin alpha) on the treatment of anemia in 156 End-Stage Renal Disease hemodialysis patients. 156 patients have been planned to randomize and assign to receive CinnaPoietin® or Eprex® for a 26-week period. Administration dose for patients who are treated with erythropoietin is the similar dose of the previously administered amount (IV or SC without any change). After then, dose adjustment will be made based on patients' response. The primary objective of this study is to compare the efficacy of CinnaPoietin® with Eprex®. The secondary objectives of this study are further comparison and evaluation of efficacy along with safety between CinnaPoietin® and Eprex®.

Timeline

Start

2016-06-22

Primary completion

2017-07-19

Completion

2017-07-19

Publications

• Background Astor BC, Muntner P, Levin A, Eustace JA, Coresh J. Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988-1994). Arch Intern Med. 2002 Jun 24;162(12):1401-8. doi: 10.1001/archinte.162.12.1401.
• Background McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr. 2009 Apr;12(4):444-54. doi: 10.1017/S1368980008002401. Epub 2008 May 23.
• Background Brittin GM, Brecher G, Johnson CA, Elashoff RM. Stability of blood in commonly used anticoagulants. Use of refrigerated blood for quality control of the Coulter Counter Model S. Am J Clin Pathol. 1969 Dec;52(6):690-4. doi: 10.1093/ajcp/52.6.690. No abstract available.
• Background Locatelli F, Aljama P, Barany P, Canaud B, Carrera F, Eckardt KU, Horl WH, Macdougal IC, Macleod A, Wiecek A, Cameron S; European Best Practice Guidelines Working Group. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant. 2004 May;19 Suppl 2:ii1-47. doi: 10.1093/ndt/gfh1032. No abstract available.
• Background Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005 Mar 10;352(10):1011-23. doi: 10.1056/NEJMra041809. No abstract available.
• Background Fehr T, Ammann P, Garzoni D, Korte W, Fierz W, Rickli H, Wuthrich RP. Interpretation of erythropoietin levels in patients with various degrees of renal insufficiency and anemia. Kidney Int. 2004 Sep;66(3):1206-11. doi: 10.1111/j.1523-1755.2004.00880.x.
• Background Ross RP, McCrea JB, Besarab A. Erythropoietin response to blood loss in hemodialysis patients in blunted but preserved. ASAIO J. 1994 Jul-Sep;40(3):M880-5. doi: 10.1097/00002480-199407000-00122.
• Background Lipschitz DA, Cook JD, Finch CA. A clinical evaluation of serum ferritin as an index of iron stores. N Engl J Med. 1974 May 30;290(22):1213-6. doi: 10.1056/NEJM197405302902201. No abstract available.
• Background Rambod M, Kovesdy CP, Kalantar-Zadeh K. Combined high serum ferritin and low iron saturation in hemodialysis patients: the role of inflammation. Clin J Am Soc Nephrol. 2008 Nov;3(6):1691-701. doi: 10.2215/CJN.01070308. Epub 2008 Oct 15.
• Background Fernandez-Rodriguez AM, Guindeo-Casasus MC, Molero-Labarta T, Dominguez-Cabrera C, Hortal-Casc n L, Perez-Borges P, Vega-Diaz N, Saavedra-Santana P, Palop-Cubillo L. Diagnosis of iron deficiency in chronic renal failure. Am J Kidney Dis. 1999 Sep;34(3):508-13. doi: 10.1016/s0272-6386(99)70079-x.
• Background Kalantar-Zadeh K, Hoffken B, Wunsch H, Fink H, Kleiner M, Luft FC. Diagnosis of iron deficiency anemia in renal failure patients during the post-erythropoietin era. Am J Kidney Dis. 1995 Aug;26(2):292-9. doi: 10.1016/0272-6386(95)90649-5.
• Background Aljama P, Ward MK, Pierides AM, Eastham EJ, Ellis HA, Feest TG, Conceicao S, Kerr DN. Serum ferritin concentration: a reliable guide to iron overload in uremic and hemodialyzed patients. Clin Nephrol. 1978 Sep;10(3):101-4.
• Background Barany P, Eriksson LC, Hultcrantz R, Pettersson E, Bergstrom J. Serum ferritin and tissue iron in anemic dialysis patients. Miner Electrolyte Metab. 1997;23(3-6):273-6.
• Background Blumberg AB, Marti HR, Graber CG. Serum ferritin and bone marrow iron in patients undergoing continuous ambulatory peritoneal dialysis. JAMA. 1983 Dec 23-30;250(24):3317-9.
• Background Hussein S, Prieto J, O'Shea M, Hoffbrand AV, Baillod RA, Moorhead JF. Serum ferritin assay and iron status in chronic renal failure and haemodialysis. Br Med J. 1975 Mar 8;1(5957):546-8. doi: 10.1136/bmj.1.5957.546.
• Background Mirahmadi KS, Paul WL, Winer RL, Dabir-Vaziri N, Byer B, Gorman JT, Rosen SM. Serum ferritin level. Determinant of iron requirement in hemodialysis patients. JAMA. 1977 Aug 15;238(7):601-3. doi: 10.1001/jama.238.7.601.
• Background Spinowitz BS, Kausz AT, Baptista J, Noble SD, Sothinathan R, Bernardo MV, Brenner L, Pereira BJ. Ferumoxytol for treating iron deficiency anemia in CKD. J Am Soc Nephrol. 2008 Aug;19(8):1599-605. doi: 10.1681/ASN.2007101156. Epub 2008 Jun 4.
• Background Silverberg DS, Blum M, Agbaria Z, Deutsch V, Irony M, Schwartz D, Baruch R, Yachnin T, Steinbruch S, Iaina A. The effect of i.v. iron alone or in combination with low-dose erythropoietin in the rapid correction of anemia of chronic renal failure in the predialysis period. Clin Nephrol. 2001 Mar;55(3):212-9.
• Background Stancu S, Barsan L, Stanciu A, Mircescu G. Can the response to iron therapy be predicted in anemic nondialysis patients with chronic kidney disease? Clin J Am Soc Nephrol. 2010 Mar;5(3):409-16. doi: 10.2215/CJN.04280609. Epub 2009 Dec 17.
• Background Fishbane S, Frei GL, Maesaka J. Reduction in recombinant human erythropoietin doses by the use of chronic intravenous iron supplementation. Am J Kidney Dis. 1995 Jul;26(1):41-6. doi: 10.1016/0272-6386(95)90151-5.
• Background Sunder-Plassmann G, Horl WH. Importance of iron supply for erythropoietin therapy. Nephrol Dial Transplant. 1995 Nov;10(11):2070-6.
• Background Macdougall IC, Tucker B, Thompson J, Tomson CR, Baker LR, Raine AE. A randomized controlled study of iron supplementation in patients treated with erythropoietin. Kidney Int. 1996 Nov;50(5):1694-9. doi: 10.1038/ki.1996.487.
• Background Chang CH, Chang CC, Chiang SS. Reduction in erythropoietin doses by the use of chronic intravenous iron supplementation in iron-replete hemodialysis patients. Clin Nephrol. 2002 Feb;57(2):136-41. doi: 10.5414/cnp57136.
• Background DeVita MV, Frumkin D, Mittal S, Kamran A, Fishbane S, Michelis MF. Targeting higher ferritin concentrations with intravenous iron dextran lowers erythropoietin requirement in hemodialysis patients. Clin Nephrol. 2003 Nov;60(5):335-40. doi: 10.5414/cnp60335.
• Background Rozen-Zvi B, Gafter-Gvili A, Paul M, Leibovici L, Shpilberg O, Gafter U. Intravenous versus oral iron supplementation for the treatment of anemia in CKD: systematic review and meta-analysis. Am J Kidney Dis. 2008 Nov;52(5):897-906. doi: 10.1053/j.ajkd.2008.05.033. Epub 2008 Oct 8.
• Background Senger JM, Weiss RJ. Hematologic and erythropoietin responses to iron dextran in the hemodialysis environment. ANNA J. 1996 Jun;23(3):319-23; discussion 324-5.
• Background Navarro JF, Teruel JL, Liano F, Marcen R, Ortuno J. Effectiveness of intravenous administration of Fe-gluconate-Na complex to maintain adequate body iron stores in hemodialysis patients. Am J Nephrol. 1996;16(4):268-72. doi: 10.1159/000169008.
• Background Tessitore N, Solero GP, Lippi G, Bassi A, Faccini GB, Bedogna V, Gammaro L, Brocco G, Restivo G, Bernich P, Lupo A, Maschio G. The role of iron status markers in predicting response to intravenous iron in haemodialysis patients on maintenance erythropoietin. Nephrol Dial Transplant. 2001 Jul;16(7):1416-23. doi: 10.1093/ndt/16.7.1416.
• Background Van Wyck DB, Roppolo M, Martinez CO, Mazey RM, McMurray S; United States Iron Sucrose (Venofer) Clinical Trials Group. A randomized, controlled trial comparing IV iron sucrose to oral iron in anemic patients with nondialysis-dependent CKD. Kidney Int. 2005 Dec;68(6):2846-56. doi: 10.1111/j.1523-1755.2005.00758.x.
• Background Allegra V, Mengozzi G, Vasile A. Iron deficiency in maintenance hemodialysis patients: assessment of diagnosis criteria and of three different iron treatments. Nephron. 1991;57(2):175-82. doi: 10.1159/000186246.
• Background Li H, Wang SX. Intravenous iron sucrose in Chinese hemodialysis patients with renal anemia. Blood Purif. 2008;26(2):151-6. doi: 10.1159/000113529. Epub 2008 Jan 22.
• Background Palmer SC, Navaneethan SD, Craig JC, Johnson DW, Tonelli M, Garg AX, Pellegrini F, Ravani P, Jardine M, Perkovic V, Graziano G, McGee R, Nicolucci A, Tognoni G, Strippoli GF. Meta-analysis: erythropoiesis-stimulating agents in patients with chronic kidney disease. Ann Intern Med. 2010 Jul 6;153(1):23-33. doi: 10.7326/0003-4819-153-1-201007060-00252. Epub 2010 Jun 24.
• Background Parfrey PS, Wish T. Quality of life in CKD patients treated with erythropoiesis-stimulating agents. Am J Kidney Dis. 2010 Mar;55(3):423-5. doi: 10.1053/j.ajkd.2009.12.014. No abstract available.
• Background Gandra SR, Finkelstein FO, Bennett AV, Lewis EF, Brazg T, Martin ML. Impact of erythropoiesis-stimulating agents on energy and physical function in nondialysis CKD patients with anemia: a systematic review. Am J Kidney Dis. 2010 Mar;55(3):519-34. doi: 10.1053/j.ajkd.2009.09.019. Epub 2009 Dec 23.
• Background Johansen KL, Finkelstein FO, Revicki DA, Gitlin M, Evans C, Mayne TJ. Systematic review and meta-analysis of exercise tolerance and physical functioning in dialysis patients treated with erythropoiesis-stimulating agents. Am J Kidney Dis. 2010 Mar;55(3):535-48. doi: 10.1053/j.ajkd.2009.12.018. Epub 2010 Feb 4.
• Background Solomon SD, Uno H, Lewis EF, Eckardt KU, Lin J, Burdmann EA, de Zeeuw D, Ivanovich P, Levey AS, Parfrey P, Remuzzi G, Singh AK, Toto R, Huang F, Rossert J, McMurray JJ, Pfeffer MA; Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) Investigators. Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med. 2010 Sep 16;363(12):1146-55. doi: 10.1056/NEJMoa1005109.
• Azmandian J, Abbasi MR, Pourfarziani V, Nasiri AA, Ossareh S, Ezzatzadegan Jahromi S, Sanadgol H, Amini S, Shahvaroughi Farahani A. Comparing Therapeutic Efficacy and Safety of Epoetin Beta and Epoetin Alfa in the Treatment of Anemia in End-Stage Renal Disease Hemodialysis Patients. Am J Nephrol. 2018;48(4):251-259. doi: 10.1159/000493097. Epub 2018 Sep 25.

Drugs

Indications