OP0210 EFFICACY AND SAFETY OF SM03, A RECOMBINANT ANTI-HUMAN CD22 MONOCLONAL ANTIBODY IN CHINESE PATIENTS WITH RHEUMATOID ARTHRITIS: A PHASE II RANDOMIZED, DOUBLE-BLIND, MULTI-DOSE, PLACEBO-CONTROLLED STUDY

Abstract

Background:Rheumatoid arthritis (RA) is a common chronic inflammatory rheumatic disease in China. SM03 is a novel chimeric monoclonal antibody (mAb) specific to the B cell restricted antigen CD22 developed for the treatment of rheumatoid arthritis (RA) and other B cell related immunological diseases.Objectives:We aim to evaluate the efficacy and safety of SM03 in patients with moderately-to-severely active RA in China.Methods:In this 24-week Phase II randomized, double-blind, multi-dose, placebo-controlled study, 156 patients were randomized with ratio of 1:1:1 to receive 3600mg cumulative dose of SM03 (group A, 600mg * 6 infusions at 0, 2, 4, 12, 14, and 16 week), 2400mg cumulative dose of SM03 (group B, 600mg*4 infusions at 0, 2, 12, and 14 week) and placebo (group C). All patients remained on background treatment of MTX. Efficacy and safety were assessed at weeks 4, 8, 12,16 and 24.The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 24.Safety profile was also assessed.Results:ACR20 response rates at 24-week were significant for group A (65.3%, p=0.002) and B (56.9 %, p=0.024) versus group C (34.0%). There is no significant difference in ACR20 between group A and B(Table 1 & Fig 1). We did not observe significant difference in any adverse event (AE) among group A (35.3%), B (51.9%) and C (34.6%)(Table 2). In groups A and B, 13 (12.6%) patients reported treatment-related infection, and 5 (6.8%) patients were positive in anti-drug antibodies analysis. In group A (higher dose), 3.9% patient had AE of treatment-related infections. No patients reported treatment-related severe infection or any malignancies caused by treatment in groups A and B.Table 1.Summary of ACR/DAS EULAR Responses of Patients with RA to SM03 at Week 24ResponseGroup CPlacebo+MTX(n=47)Group A SM03600mg*6+MTX(n=49)Group B SM03600mg*4 +MTX(n=51)ACR 2034.0%65.3% *56.9% *ACR 5017.0%44.9%**29.4%ACR 704.3%18.4%***9.8%EULAR response good & moderate40.4%75.5%^70.6%^EULAR response good12.8%30.6%^^15.7%Change of DAS28 from baseline-0.70-1.65^^^-1.38^^^DAS28≤3.214.9%30.6%19.6%DAS28<2.68.5%18.4%5.9%Compared with group C(Placebo), results of group A and B were shown respectively*P=0.002, P=0.024; **P= 0.003; ***P= 0.03;^ P<0.001, P=0.003; ^^ P=0.034; ^^^P=0.008, P=0.047Table 2.Profile of Adverse EventsAdverse event, N (%)Group C(N=52)Group A(N=51)Group B(N=52)Any AE18(34.6)18(35.3)27(51.9)AE-drug related7(13.5)5(9.8)8(15.4)AE-mild16 (30.8)15(29.4)24(46.2)AE-moderate2(3.8)2(3.9)3(5.8)AE-severe-1(2.0)-AE-leading to discontinuation-2(3.9)-Serious adverse event, SAE1(1.9)1(2.0)-AE-1stcycle(week 0-12)151322AE-2ndcycle(week 12-24)9914Fig 1.Percent of Patients Achieving ACR 20 Response by VisitConclusion:In Chinese patients with active RA, both 2400mg and 3600mg cumulative doseof SM03,in combination with MTX were efficacious and well tolerated. throughout the 24 weeks of treatment.Moreover, SM03 has demonstrated a good safety profile, especially in terms of treatment-related infection, malignancy and immunogenicity.