Comparison of biosimilar CT-P10 and innovator rituximab in patients with rheumatoid arthritis: a randomized controlled Phase 3 trial. Issue 6 (18th August 2018)

• Record Type: Journal Article
• Authors: Park, Won; Božić-Majstorović, Ljubinka; Milakovic, Dragana; Berrocal Kasay, Alfredo; El-Khouri, Elias Chalouhi; Irazoque-Palazuelos, Fedra; Molina, Francisco Fidencio Cons; Shesternya, Pavel; Miranda, Pedro; Medina-Rodriguez, Francisco G.; Wiland, Piotr; Jeka, Slawomir; Chavez-Corrales, Jose; Garmish, Olena; Linde, Thomas; Rekalov, Dmytro; Hrycaj, Pawel; Krause, Andreas; Fomina, Natalia; Piura, Olena; Abello-Banfi, Mauricio; Suh, Chang-Hee; Shim, Seung Cheol; Lee, Sang Joon; Lee, Sung Young; Kim, Sung Hwan; Yoo, Dae Hyun
• Is Part Of: MAbs. Volume 10:Issue 6(2018)
• Page Start: 934
• Page End: 943
• Publication Date: 2018-08-18
• Subjects: Rituximab -- CT-P10 -- rheumatoid arthritis -- equivalence -- biosimilar; Monoclonal antibodies -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Periodicals; Antibodies, Monoclonal -- Periodicals; 616.0798
• DOI: 10.1080/19420862.2018.1487912
• Languages: English
• ISSNs: 1942-0862

Abstract

ABSTRACT: This multinational, randomized, double-blind trial, (ClinicalTrials.gov identifier NCT02149121) was designed to demonstrate equivalence in pharmacokinetics and efficacy between CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA). Adults with active RA were treated with CT-P10, United States-sourced RTX (US-RTX; Rituxan®), or European Union-sourced RTX (EU-RTX; MabThera®) at weeks 0 and 2. The co-primary pharmacokinetic endpoints were area under the serum concentration–time curve (AUC) from time zero to last measurable concentration (AUC0–last ), AUC from time zero to infinity (AUC0–∞ ), and maximum concentration (Cmax ) after two infusions. The primary efficacy endpoint was change from baseline to week 24 in Disease Activity Score using 28 joints-C-reactive protein (DAS28-CRP). Pharmacodynamics, immunogenicity, and safety were also assessed. 372 patients were randomly assigned to CT-P10 (n = 161) or RTX (n = 211 [US-RTX, n = 151; EU-RTX, n = 60]). For the co-primary pharmacokinetic endpoints, 90% confidence intervals (CI) for ratios of geometric means (CT-P10/US-RTX, CT-P10/EU-RTX or EU-RTX/US-RTX) all fell within the equivalence margin of 80–125%. Adjusted least squares (LS) mean (standard error) change from baseline in DAS28-CRP at week 24 was −2.13 (0.175) for CT-P10 and −2.09 (0.176) for RTX. The 95% CI (−0.29, 0.21) of the estimated treatment difference between CT-P10 and RTX (−0.04) was entirely within the efficacy equivalence margin of ±0.5. Pharmacodynamics, immunogenicity, and safety profiles were similar for CT-P10 and RTX. The pharmacokinetics of CT-P10, US-RTX, and EU-RTX were equivalent. CT-P10 and RTX were also equivalent in terms of efficacy and displayed similar pharmacodynamic, immunogenicity, and safety profiles up to week 24.