AB0402 PHARMACOKINETICS AND SAFETY OF CT-P47, A PROPOSED TOCILIZUMAB BIOSIMILAR, IN COMPARISON WITH EU-APPROVED TOCILIZUMAB; A PHASE 1, RANDOMIZED, DOUBLE-BLIND, TWO-ARM, SINGLE-DOSE STUDY IN HEALTHY SUBJECTS

• Published in: Annals of the rheumatic diseases Vol. 82; no. Suppl 1; pp. 1385 - 1386
• Main Authors: Yu, K. S., Kim, B., Shin, D., Park, M. K., Hwang, J. G., Kim, M., Chung, H., Ghim, J., Chung, J. Y., Smolen, J. S., Burmester, G. R., Kim, S. H., Bae, Y., Jeon, D., Yang, G., Yoo, J., Bae, J., Keystone, E.
• Format: Journal Article
• Language: English
• Published: Kidlington BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2023; Elsevier B.V; Elsevier Limited
• Subjects: Adverse events; Analysis of covariance; bDMARD; Biological products; Body weight; Clinical Trials; Double-blind studies; Drug dosages; Immunogenicity; Leukocytes (neutrophilic); Monoclonal antibodies; Pharmaceuticals; Pharmacokinetics; Rheumatoid arthritis; Safety; Scientific Abstracts; Statistical analysis; bDMARD; Clinical Trials; Rheumatoid arthritis
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2023-eular.268

BackgroundCT-P47 is a recombinant humanized monoclonal antibody that was developed as a proposed biosimilar of tocilizumab.ObjectivesThe purpose of this study was to compare the pharmacokinetics (PK), safety, and immunogenicity of CT-P47 and EU-approved tocilizumab (EU-tocilizumab) up to 42 days after a single subcutaneous injection of 162 mg of each product in healthy subjects.Methods289 healthy subjects aged 19 to 55 years were randomly assigned 1:1 to receive either CT-P47 or EU-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.ResultsDemographics and baseline characteristics were well balanced between groups. 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 (Tmax, t1/2, λz, CL/F, Vz/F, %AUCext) were also comparable between groups. Mean serum concentrations of tocilizumab observed through 42 days post-dose were comparable between groups (Figure 1).Overall, 55 (38.2%) and 72 (51.4%) subjects reported ≥1 treatment-emergent adverse event (TEAE) in the CT-P47 and EU-tocilizumab groups, respectively. Most of TEAEs were grade 1 or 2 in intensity and TEAEs considered to be related to study drug were reported by 47 (32.6%) and 61 (43.6%) subjects, respectively. Neutrophil count decreased was the most commonly reported TEAE overall (14 [9.7%] and 15 [10.7%] subjects, respectively). There were 3 treatment-emergent serious adverse events (2 [1.4%] and 1 [0.7%] subjects, respectively). Of these, only 1 case was considered to be related to study drug (EU-tocilizumab: headache).Overall, 20 (13.9%) and 29 (20.7%) subjects in the CT-P47 and EU-tocilizumab groups, respectively, had ≥1 post-treatment positive result for anti-drug antibodies (ADA) and 17 (11.8%) and 20 (14.3%) subjects, respectively, had ≥1 positive result post-treatment for neutralizing antibody. Primary PK parameters of AUC0-inf, AUC0-last, and Cmax were slightly lower in subjects with at least 1 ADA positive compared with those subjects with all ADA negative, at post-dose, among groups in the PK set.ConclusionThis study demonstrated PK equivalence of CT-P47 to EU-approved tocilizumab in healthy subjects. Safety profiles, including immunogenicity, were comparable between groups.ReferencesNIL.Table 1.Statistical Analysis of the Primary PK Endpoints (PK Set)Parameter (units)TreatmentgLSM (n)Ratio of gLSMs (90% CI)aAUC0-inf (day·μg/mL)CT-P47EU-tocilizumab79.37 (138)73.54 (136)107.92 (98.04, 118.80)AUC0-last (day·μg/mL)CT-P47EU-tocilizumab77.55 (144)72.52 (139)106.93 (97.36, 117.43)Cmax (μg/mL)CT-P47EU-tocilizumab8.89 (144)8.63 (140)103.00 (94.67, 112.06)Abbreviations: ANCOVA, analysis of covariance; AUC0-inf, area under the concentration–time curve from time zero to infinity; AUC0-last, area under the concentration-time curve from time zero to the last quantifiable concentration; CI, confidence interval; Cmax, maximum serum concentration; EU-tocilizumab, European Union-approved tocilizumab; gLSM, geometric least squares mean; PK, pharmacokinetic.aDetermined by ANCOVA performed with the natural log-transformed PK parameters as the dependent variable, treatment as a fixed effect and stratification factors (body weight at Day -1, gender [male versus female], and study center) as covariates.Figure 1.Mean (± SD) Serum Concentrations of Tocilizumab (PK Set)Abbreviations: EU-tocilizumab, European Union-approved tocilizumab; PK, pharmacokinetic; SD, standard deviation.Acknowledgements:NIL.Disclosure of InterestsKyung-Sang Yu: None declared, Byungwook Kim: None declared, Dongseong Shin: None declared, Min Kyu Park: None declared, Jun Gi Hwang: None declared, MinGul Kim: None declared, Hyewon Chung: None declared, JongLyul Ghim: None declared, Jae-Yong Chung: None declared, Josef S. Smolen Speakers bureau: AbbVie, AstraZeneca, Astro, BMS, Celltrion, Inc., Chugai, Gilead, Janssen, Lilly, Novartis- Sandoz, Pfizer, R-Pharm, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Astro, BMS, Celltrion, Inc., Chugai, Gilead, Janssen, Lilly, Novartis- Sandoz, Pfizer, R-Pharm, Samsung, Sanofi, Grant/research support from: Abbvie, AstraZeneca and Lilly, Gerd Rüdiger Burmester Consultant of: Celltrion, Inc., Chugai, Sanofi, Roche, Sung Hyun Kim Employee of: Celltrion, Inc., YunJu Bae Employee of: Celltrion, Inc., Dabee Jeon Employee of: Celltrion, Inc., GoEun Yang Employee of: Celltrion, Inc., JaeKyoung Yoo Employee of: Celltrion, Inc., JiHun Bae Employee of: Celltrion, Inc., Edward Keystone Speakers bureau: Amgen, AbbVie, Celltrion., Inc, F.Hoffmann-La Roche Inc., Janssen Inc., Merck, Pfizer Pharmaceuticals, Szndoz, Sanofi Genzyme, Consultant of: AbbVie, Amgen, Celltrion., Inc, Myriad Autoimmune, F.Hoffmann-La Roche Inc., Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepis, Grant/research support from: Amgen, Merck, Pfizer Pharmaceuticals.