Daniel E Furst1,2,3, Edward Keystone4, Jonathan Kay5, Janusz Jaworski6, Rafal Wojciechowski7, Piotr Wiland8, Anna Dudek9, Marek Krogulec10, Slawomir Jeka11, Agnieszka Zielinska12, Jakub Trefler13, Katarzyna Bartnicka-Maslowska14, Magdalena Krajewska-Wlodarczyk15, Piotr A Klimiuk16, Sang Joon Lee17, Yun Ju Bae17, Go Eun Yang17, Jae Kyoung Yoo17. 1. University of California, Los Angeles, CA, USA. 2. University of Washington, Seattle, WA, USA. 3. University of Florence, Florence, Italy. 4. University of Toronto, Toronto, Canada. edkeystone@rheumkey.com. 5. University of Massachusetts Medical School and UMass Memorial Medical, Worcester, MA, USA. 6. Reumatika-Centrum Reumatologii, Warsaw, Poland. 7. University Hospital No 2, Bydgoszcz, Poland. 8. Medical University, Wroclaw, Poland. 9. Centrum Medyczne AMED, Warsaw, Poland. 10. Rheumatology Clinic NZOZ Lecznica MAK-MED, Nadarzyn, Poland. 11. Nasz Lekarz Przychodnie Medyczne, Toruń, Poland. 12. Medycyna Kliniczna Marzena Waszczak-Jeka, Warsaw, Poland. 13. Reuma Centrum, Warsaw, Poland. 14. Centrum Medyczne AMED Oddzial w Lodzi, Łódź, Poland. 15. University of Warmia and Mazury, Olsztyn, Poland. 16. Medical University of Bialystok and Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk, Białystok, Poland. 17. Celltrion, Inc., Incheon, Republic of Korea.
Abstract
BACKGROUND: To demonstrate equivalent efficacy of the proposed high-concentration (100 mg/ml), citrate-free adalimumab biosimilar CT-P17 to European Union-approved adalimumab (EU-adalimumab) in subjects with active rheumatoid arthritis (RA). METHODS: This randomized, double-blind phase III study ( ClinicalTrials.gov , NCT03789292) randomized (1:1) subjects with active RA at 52 centers to receiveCT-P17 or EU-adalimumab 40 mg subcutaneously every 2 weeks until week 52. Results to week 24 are reported here. The primary endpoint was 20% improvement by American College of Rheumatology criteria (ACR20) response rate at week 24. Equivalence was concluded if the corresponding confidence intervals (CIs) for the estimate of treatment difference were within predefined equivalence margins: - 15 to 15% (95% CI; European Medicines Agency assumption); - 12 to 15% (90% CI; Food and Drug Administration assumption). Additional efficacy, pharmacokinetic, usability, safety, and immunogenicity endpoints were evaluated. RESULTS:648 subjects were randomized (324 CT-P17; 324 EU-adalimumab). The ACR20 response rate at week 24 was 82.7% (n = 268/324) in both groups (intention-to-treat population). The 95% CI (- 5.94 to 5.94) and 90% CI (- 4.98 to 4.98) were within predefined equivalence margins for both assumptions and equivalent efficacy was concluded. Additional endpoints and overall safety were comparable between groups. Mean trough serum concentrations of CT-P17 were slightly higher than those of EU-adalimumab. Immunogenicity was slightly lower numerically for the CT-P17 group than for the EU-adalimumab group. CONCLUSIONS:CT-P17 and EU-adalimumab have equivalent efficacy and comparable safety and immunogenicity in subjects with active RA. Overall safety of CT-P17 is consistent with the known safety profile of reference adalimumab. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03789292 . Registered 28 December 2018-retrospectively registered.
RCT Entities:
BACKGROUND: To demonstrate equivalent efficacy of the proposed high-concentration (100 mg/ml), citrate-free adalimumab biosimilar CT-P17 to European Union-approved adalimumab (EU-adalimumab) in subjects with active rheumatoid arthritis (RA). METHODS: This randomized, double-blind phase III study ( ClinicalTrials.gov , NCT03789292) randomized (1:1) subjects with active RA at 52 centers to receive CT-P17 or EU-adalimumab 40 mg subcutaneously every 2 weeks until week 52. Results to week 24 are reported here. The primary endpoint was 20% improvement by American College of Rheumatology criteria (ACR20) response rate at week 24. Equivalence was concluded if the corresponding confidence intervals (CIs) for the estimate of treatment difference were within predefined equivalence margins: - 15 to 15% (95% CI; European Medicines Agency assumption); - 12 to 15% (90% CI; Food and Drug Administration assumption). Additional efficacy, pharmacokinetic, usability, safety, and immunogenicity endpoints were evaluated. RESULTS: 648 subjects were randomized (324 CT-P17; 324 EU-adalimumab). The ACR20 response rate at week 24 was 82.7% (n = 268/324) in both groups (intention-to-treat population). The 95% CI (- 5.94 to 5.94) and 90% CI (- 4.98 to 4.98) were within predefined equivalence margins for both assumptions and equivalent efficacy was concluded. Additional endpoints and overall safety were comparable between groups. Mean trough serum concentrations of CT-P17 were slightly higher than those of EU-adalimumab. Immunogenicity was slightly lower numerically for the CT-P17 group than for the EU-adalimumab group. CONCLUSIONS:CT-P17 and EU-adalimumab have equivalent efficacy and comparable safety and immunogenicity in subjects with active RA. Overall safety of CT-P17 is consistent with the known safety profile of reference adalimumab. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03789292 . Registered 28 December 2018-retrospectively registered.
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