S1057 A Randomized Phase I Study Comparing Pharmacokinetics, Safety and Immunogenicity of High Concentration Formulation (100 mg/mL) With GP2017 Formulation (50 mg/mL), an Adalimumab Biosimilar, in Healthy Male Subjects

Abstract

Introduction: GP2017 (adalimumab-adaz) is an approved biosimilar of adalimumab (ADL)1, with a concentration of 50 mg/mL. A high-concentration formulation (HCF) (100 mg/mL) can reduce the injection volume, and consequently decrease the number of injections required for patients who need to administer a higher dose. A phase I study (randomized, double-blind, parallel, 2-arm study with healthy male subjects) was conducted to demonstrate pharmacokinetics (PK) comparability between a newly developed GP2017 citrate-free -HCF and the currently approved GP2017. Methods: Healthy male subjects were randomized to receive a single 40 mg s.c. injection of either GP2017 or GP2017-HCF. PK, safety, and immunogenicity were assessed over 72 days post-injection. Primary endpoints were maximum serum concentration (Cmax), area under the concentration–time curve from time zero to infinity (AUC0–inf) and area under the concentration–time curve from time zero to 360 hours (AUC0-360); area under the concentration–time curve from time zero to the last quantifiable concentration (AUC0–last) was assessed as a secondary endpoint. PK comparability was concluded when the 90% confidence intervals (CIs) of the ratios of geometric means were within the predefined comparability margin of 0.80 to 1.25. Results: 331 subjects were randomized, of which 330 received study treatment (162 GP2017-HCF; 168 GP2017). The 90% CI of the ratios (GP2017-HCF / GP2017) of geometric means for the PK endpoints (Cmax, AUCinf, AUC0-360 and AUC0–last) were all contained within the pre-defined comparability limits of 0.80 to 1.25 (Figure). Safety was similar across groups (Table). The numbers and proportions of subjects with positive anti-drug antibodies (ADA) and with neutralizing antibodies (NAb) were comparable overall (up to day 72: GP2017-HCF 69.1% / 63%; GP2017 64.9% / 61.3%, respectively) and at all individual visits. Conclusion: PK comparability between GP2017-HCF and GP2017 was demonstrated, supporting the development of the new formulation of GP2017. Safety and immunogenicity profiles were comparable between treatment groups and consistent with previously reported adalimumab data.Figure 1.: Forest plot to compare primary and secondary PK endpoints between the treatment groups Table 1. - TEAEs by primary system organ class (at least 2% of subjects in any treatment group) Primary system organ classPreferred term GP2017-HCFN=162n (%) GP2017N=168n (%) Number of subjects with at least 1 event 80 (49.4) 95 (56.5) General disorders and administration site conditions 55 (34.0) 69 (41.1) Investigations 16 (9.9) 24 (14.3) Musculoskeletal and connective tissue disorders 8 (4.9) 14 (8.3) Nervous system disorders 8 (4.9) 6 (3.6) Skin and subcutaneous tissue disorders 10 (6.2) 4 (2.4) Gastrointestinal disorders 8 (4.9) 3 (1.8) Respiratory, thoracic and mediastinal disorders 2 (1.2) 6 (3.6) Eye disorders 1 (0.6) 4 (2.4) Injury, poisoning and procedural complications 4 (2.5) 1 (0.6)