Ab0339 efficacy, Pharmacokinetics and Safety Between Ct-P13 and China-Approved Infliximab: 54 Week Result From a Phase Iii Randomized Controlled Trial in Chinese Patients With Active Rheumatoid Arthritis

Abstract

BackgroundCT-P13 is an approved biosimilar to EU-approved and US-licensed Infliximab (INX) for the indications of rheumatoid arthritis (RA), adult and paediatric Crohn’s disease, adult and paediatric ulcerative colitis, ankylosing spondylitis, psoriatic arthritis and psoriasis.ObjectivesThe purpose of this study was to demonstrate equivalence of efficacy and compare PK and safety profiles of CT-P13 and China-approved INX.MethodsIn this randomized, double blinded, multicenter, parallel-group, phase III study, patients with active RA who had been responding inadequately to methotrexate for at least 3 months, were randomized to receive either CT-P13 or China-approved INX. Patients were treated with doses of 3 mg/kg at Weeks 0, 2, 6, then every 8 weeks up to Week 54. Prior to dosing at Week 30, patients randomized to China-approved INX underwent a second randomization either to continue China-approved INX or to switch to CT-P13 at Week 30. Results of patients who underwent transition to CT-P13 were included in the China-approved INX group. The primary efficacy endpoint was change in DAS28 (CRP) from baseline to Week 14, which was analyzed using an analysis of covariance. Equivalence was determined if the 90% CI for the estimate of treatment difference was entirely contained within the predefined equivalence margin of -0.6 to 0.6.Results270 patients were randomly assigned to 2 treatment groups in a 1:1 ratio (136 and 134 patients in the CT-P13 and China-approved INX groups, respectively) and 184 patients completed the study. The least square mean change (standard error) of DAS28 (CRP) from baseline to Week 14, -1.566 [0.1419] and -1.547 [0.1491], was similar between the CT-P13 and China-approved INX groups, respectively. The 90% CI for the estimate of treatment difference (-0.29, 0.25) was contained within the predefined equivalence margin, which demonstrated therapeutic equivalence between the groups. The mean actual values for DAS28 (CRP) decreased from baseline to Week 54 and were similar between the groups (Figure 1). Additional efficacy endpoints, including ACR responses (ACR20 at Week 14; 60.6%, 54.8% and at Week 54; 65.1%, 60.6% in the CT-P13 and China-approved INX groups, respectively), EULAR responses, CDAI, and SDAI, were similar between the groups, even after switching at Week 30. During the study, mean serum INX concentrations were similar between the groups. Between Weeks 14 and 22, mean (percent coefficient of variation) AUCτ were 11156333.615 (44.796) ng·h/mL and 11462884.280 (51.057) ng·h/mL, and Cmax,ss were 66577.2 (31.4) ng/mL and 66356.1 (21.0) ng/mL in the CT-P13 and China-approved INX groups, respectively, which were similar between the groups. Most treatment-emergent AEs were grade 1 or 2 in intensity. One malignancy was reported in the CT-P13 group and no deaths were reported. The proportions of patients with anti-drug antibodies were similar between the groups, even after switching at Week 30. The overall safety profile of CT-P13 was comparable to that of China-approved INX and no new safety issues were observed (Table 1).Table 1.Summary of Safety ResultsNumber of patients (%)CT-P13 (N=136)China-approved Infliximab (N=133)Treatment-emergent AEsTotal115 (84.6%)107 (80.5%)Related97 (71.3%)86 (64.7%)Treatment-emergent serious AEsTotal17 (12.5%)12 (9.0%)Related10 (7.4%)6 (4.5%)Infusion related reaction/ hypersensitivity/anaphylactic reactionsTotal(=Related)20 (14.7%)19 (14.3%)InfectionsTotal45 (33.1%)43 (32.3%)Related36 (26.5%)40 (30.1%)Note: Summary is presented for the safety population who received at least 1 dose (full or partial) of study drug.ConclusionThe study demonstrated that efficacy of CT-P13 is equivalent to that of China-approved INX. Also, the PK and safety profiles of CT-P13 were comparable to those of China-approved INX. No loss of efficacy or difference in safety or immunogenicity was observed after switching from China-approved INX to CT-P13 at Week 30.Disclosure of InterestsJonathan Kay Consultant of: Boehringer Ingelheim GmbH; Pfizer Inc.; Samsung Bioepis; Sandoz Inc., Grant/research support from: Pfizer Inc. (paid to UMass Chan Medical School), Xiaofeng Zeng Grant/research support from: Celltrion, Inc, Lin Chen Grant/research support from: Celltrion, Inc, Kaijiang Tang Grant/research support from: Celltrion, Inc, guixiu shi Grant/research support from: Celltrion, Inc, Lin Liu Grant/research support from: Celltrion, Inc, Lijun Wu Grant/research support from: Celltrion, Inc, Yi Liu Grant/research support from: Celltrion, Inc, Jiankang Hu Grant/research support from: Celltrion, Inc, Shengyun Liu Grant/research support from: Celltrion, Inc, Zheng Yi Grant/research support from: Celltrion, Inc, Sung Hyun Kim Employee of: Celltrion, Inc, YunJu Bae Employee of: Celltrion, Inc, JeeHye Suh Employee of: Celltrion, Inc, Seungjin Rhee Employee of: Celltrion, Inc, SeulGi Lee Employee of: Celltrion, Inc, Chankyoung Hwang Employee of: Celltrion, Inc