Study to Demonstrate Non-Inferior Efficacy and Safety of CinnoRA® Versus Humira® for Treatment of Active RA

Summary

The purpose of this study is to compare the efficacy and safety of adalimumab produced by CinnaGen company and AbbVie adalimumab in subjects with active Rheumatoid Arthritis. Patients with the diagnosis of active Rheumatoid arthritis according to EULAR criteria (European League Against Rheumatism) aged between 18 to 75 years will be included. This study is a Phase III, randomized, two arms, double-blind (patient and assessor blinded), parallel active-controlled non-inferiority clinical trial. The eligible patients are randomized in a 1:1 ratio to receive CinnoRA® or Humira®. Every two weeks, 40 mg of either of the drugs will be administered to each patient subcutaneously along with methotrexate (15 mg/week), folic acid (1 mg/day), and prednisolone (7.5 mg/day) over six months. The primary objective of the study is to compare the efficacy of test- adalimumab (CinnoRA®) and the reference adalimumab (Humira®) in patients with moderately to severely active rheumatoid arthritis regarding the evaluation of EULAR criteria based on Disease activity score (DAS). The secondary objectives of this study are: * To further compare the efficacy of test- adalimumab to reference adalimumab * To assess the safety of test- adalimumab compared to reference adalimumab

Timeline

Start

2015-11-18

Primary completion

2016-08-17

Completion

2017-01-04

Publications

• Background McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011 Dec 8;365(23):2205-19. doi: 10.1056/NEJMra1004965. No abstract available.
• Background den Broeder A, van de Putte L, Rau R, Schattenkirchner M, Van Riel P, Sander O, Binder C, Fenner H, Bankmann Y, Velagapudi R, Kempeni J, Kupper H. A single dose, placebo controlled study of the fully human anti-tumor necrosis factor-alpha antibody adalimumab (D2E7) in patients with rheumatoid arthritis. J Rheumatol. 2002 Nov;29(11):2288-98.
• Background Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, Moreland LW, O'Dell J, Winthrop KL, Beukelman T, Bridges SL Jr, Chatham WW, Paulus HE, Suarez-Almazor M, Bombardier C, Dougados M, Khanna D, King CM, Leong AL, Matteson EL, Schousboe JT, Moynihan E, Kolba KS, Jain A, Volkmann ER, Agrawal H, Bae S, Mudano AS, Patkar NM, Saag KG. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012 May;64(5):625-39. doi: 10.1002/acr.21641. No abstract available.
• Background Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS, Fischkoff SA, Chartash EK. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum. 2004 May;50(5):1400-11. doi: 10.1002/art.20217.
• Background Furst DE, Schiff MH, Fleischmann RM, Strand V, Birbara CA, Compagnone D, Fischkoff SA, Chartash EK. Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis). J Rheumatol. 2003 Dec;30(12):2563-71.
• Background Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, Teoh LA, Fischkoff SA, Chartash EK. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003 Jan;48(1):35-45. doi: 10.1002/art.10697.
• Background Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, Katz LM, Lightfoot R Jr, Paulus H, Strand V, et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995 Jun;38(6):727-35. doi: 10.1002/art.1780380602.
• Background Scallon B, Cai A, Solowski N, Rosenberg A, Song XY, Shealy D, Wagner C. Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther. 2002 May;301(2):418-26. doi: 10.1124/jpet.301.2.418.
• Background Khan MOA, Mohiuddin E, Usmanghani K, Hannan A, Akram M, Shah SA, et al. Clinical evaluation of herbal medicines for the treatment of rheumatoid arthritis. Pak J Nutr. 2011;10(1):51-3.
• Background Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J. Harrison's principles of internal medicine 18E Vol 2 EB: McGraw Hill Professional; 2012.
• Background Alamanos Y, Voulgari PV, Drosos AA. Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: a systematic review. Semin Arthritis Rheum. 2006 Dec;36(3):182-8. doi: 10.1016/j.semarthrit.2006.08.006. Epub 2006 Oct 11.
• Background Yood RA, Guidelines ACoRSoRA. Guidelines for the management of rheumatoid arthritis: 2002 update. 2002.
• Background Lee WY, Chen HY, Chen KC, Chen CY. Treatment of rheumatoid arthritis with traditional chinese medicine. Biomed Res Int. 2014;2014:528018. doi: 10.1155/2014/528018. Epub 2014 Jun 4.
• Background Weinblatt ME, Schiff M, Valente R, van der Heijde D, Citera G, Zhao C, Maldonado M, Fleischmann R. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum. 2013 Jan;65(1):28-38. doi: 10.1002/art.37711.
• Background Westhovens R, Kremer JM, Moreland LW, Emery P, Russell AS, Li T, Aranda R, Becker JC, Qi K, Dougados M. Safety and efficacy of the selective costimulation modulator abatacept in patients with rheumatoid arthritis receiving background methotrexate: a 5-year extended phase IIB study. J Rheumatol. 2009 Apr;36(4):736-42. doi: 10.3899/jrheum.080813. Epub 2009 Feb 27.
• Background Navarro Coy NC, Brown S, Bosworth A, Davies CT, Emery P, Everett CC, Fernandez C, Gray JC, Hartley S, Hulme C, Keenan AM, McCabe C, Redmond A, Reynolds C, Scott D, Sharples LD, Pavitt S, Buch MH. The 'Switch' study protocol: a randomised-controlled trial of switching to an alternative tumour-necrosis factor (TNF)-inhibitor drug or abatacept or rituximab in patients with rheumatoid arthritis who have failed an initial TNF-inhibitor drug. BMC Musculoskelet Disord. 2014 Dec 23;15:452. doi: 10.1186/1471-2474-15-452.
• Background Hallikainen A, Vartiainen T. Food control surveys of polychlorinated dibenzo-p-dioxins and dibenzofurans and intake estimates. Food Addit Contam. 1997 May-Jun;14(4):355-66. doi: 10.1080/02652039709374538.
• Background Blumenauer B, Judd M, Cranney A, Burls A, Coyle D, Hochberg M, Tugwell P, Wells G. Etanercept for the treatment of rheumatoid arthritis. Cochrane Database Syst Rev. 2003;(4):CD004525. doi: 10.1002/14651858.CD004525.
• Results Jamshidi A, Gharibdoost F, Vojdanian M, Soroosh SG, Soroush M, Ahmadzadeh A, Nazarinia MA, Mousavi M, Karimzadeh H, Shakibi MR, Rezaieyazdi Z, Sahebari M, Hajiabbasi A, Ebrahimi AA, Mahjourian N, Rashti AM. A phase III, randomized, two-armed, double-blind, parallel, active controlled, and non-inferiority clinical trial to compare efficacy and safety of biosimilar adalimumab (CinnoRA(R)) to the reference product (Humira(R)) in patients with active rheumatoid arthritis. Arthritis Res Ther. 2017 Jul 20;19(1):168. doi: 10.1186/s13075-017-1371-4.

Drugs

Indications