A Randomized, Double-Blind, Phase III Study to Compare the Efficacy and Safety of GB242 and Infliximab When Administered with Methotrexate in Patients with Active Moderate to Severe Rheumatoid Arthritis

Abstract

Objectives: This double-blind, active-controlled, randomized, multicenter phase III study evaluated the efficacy, safety and immunogenicity of GB242 , an infliximab biosimilar, vs infliximab (Remicade®) reference product in patients with moderate to severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy. Methods: Patients randomised in a 1:1 ratio to receive either GB242 or INF (3 mg/kg intravenous at weeks 0, 2, 6, 14 and 22). MTX was given as an oral weekly dose of 10–25 mg/week with folic acid of 5–10 mg/week, 30 times totally. The primary end point was the American College of Rheumatology 20% (ACR20) response rate at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was declared if the two-sided 95% CI for the treatment difference was within ±14%. Statistical analysis was also performed with a two-sided 95% CI using ±14% margin. Secondary endpoints included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity of GB242.Results: 570 subjects were randomized into GB242 (N=285) or INF (N=285). Finally, 283 subjects in each group were analysed. The primary endpoint was the ACR20 response. In the full analysis population, 177 (62.54%) of 283 patients in the GB242 group (95% CI 56.62% – 68.20%) and 161 (56.89%) of 283 patients in the INF group (95% CI 50.90% – 62.74%) reached ACR20 at week 30. The difference between the two groups was 5.65% with a 95% CI of -2.48 to 13.74, which was within the predefined equivalence margin. The second endpoints outcomes such as ACR50 response rate, ACR70 response rate and DAS28 were similar between GB242 and INF. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs 59.4% in INF) was comparable. Conclusions: GB242 demonstrated equivalent efficacy to INF at week 30, with a similar immunogenicity. GB242 was well tolerated, with a safety profile comparable to INF. Trial Registration: ClinicalTrials.gov NCT04178850 Funding: This study was funded by Genor Biopharma Co., Ltd., China. Declaration of Interest: None to declare. Ethical Approval: The study was conducted according to the Declaration of Helsinki and the International Committee on Harmonisation good clinical practice and all applicable regulatory requirements. The study protocol was reviewed and approved by independent ethics committees of each study site. All patients provided written informed consent.