Ab0027 Pharmacokinetics and Safety of Ct-P47, a Proposed Tocilizumab Biosimilar, in Comparison With Intravenous Eu-Approved Tocilizumab and Us-Licensed Tocilizumab; A Phase 1, Randomized, Double-Blind, Three-Arm, Single-Dose Study in Healthy Japanese Subjects

Background: CT-P47 which is recombinant humanized monoclonal antibody was developed as a candidate to the reference tocilizumab. Objectives: The purpose of this study was to compare the pharmacokinetics (PK), safety, and immunogenicity of CT-P47, EU-approved tocilizumab (EU-tocilizumab) and US-licensed tocilizumab (US-tocilizumab) up to 56 days after a single intravenous infusion of 8 mg/kg in healthy Japanese subjects. Methods: 133 subjects aged 18 to 54 years were randomized into 1:1:1 to receive either CT-P47, EU-tocilizumab or US-tocilizumab. The primary PK endpoints included area under the serum concentration-time curve (AUC) from time zero to infinity (AUC0-inf), AUC from time zero to the last quantifiable concentration (AUC0-last), and maximum serum concentration (Cmax). Secondary endpoints were additional PK, safety, and immunogenicity. Results: Of the 133 randomized subjects, 132 subjects received the study drug (CT-P47:45; EU-tocilizumab:43; US-tocilizumab:44). The 90% confidence intervals for the geometric least squares mean ratios of each of the primary PK parameters (AUC0-inf, AUC0-last, Cmax) were within the predefined equivalence margin of 80% to 125% (Table 1). Secondary PK variables and mean serum concentrations of tocilizumab were also comparable among all groups (Figure 1). Overall, 24 (53.3%), 24 (55.8%) and 24 (54.5%) subjects reported ≥1 treatment-emergent adverse event (TEAE) in the CT-P47, EU-tocilizumab and US-tocilizumab groups, respectively. Neutrophil count decreased was the most commonly reported TEAE overall (15 [33.3%], 13 [30.2%] and 12 [27.3%] subjects, respectively). No treatment-emergent serious adverse event was reported. Overall, 5 (11.1%), 1 (2.3%) and 2 (4.5%) subjects in the CT-P47, EU-tocilizumab and US-tocilizumab groups, respectively, had ≥1 post-treatment positive result for anti-drug antibodies (ADA) and 2 (4.4%), 0 and 1 (2.3%) subjects, respectively, had ≥1 positive result post-treatment for neutralizing antibody. Primary PK parameters were slightly lower in subjects with any type of ADA compared with ADA negative subjects, at post-dose. Conclusion: CT-P47, EU-tocilizumab, and US-tocilizumab were bioequivalent as measured by primary PK endpoints and CT-P47 was determined to be safe and well tolerated in healthy subjects as compared with the comparators. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Miwa Haranaka: None declared, Takashi Eto: None declared, Takanori Tanaka: None declared, Rie Yazawa: None declared, Gerd R. Burmester Chugai, Fresenius, Sanofi., Celltrion, Fresenius, Sanofi., Edward Keystone AbbVie, Celltrion, GSK Pharmaceuticals, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sandoz, AbbVie, Celltrion, GSK Pharmaceuticals, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sandoz, Samsung Bioepsis, Sung Hyun Kim Celltrion, Inc., YunJu Bae Celltrion, Inc., JeeHye Suh Celltrion, Inc., Yunah Kim Celltrion, Inc., JaeYong Lee Celltrion, Inc., Josef S. Smolen Abbvie, Amgen, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, Abbvie, Amgen, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, Abbvie, Astra-Zeneca, Janssen, Lilly, Novartis, Roche.