Pos1130 designing of a phase 2, multicenter, randomized, placebo-controlled, double-blind study to assess the efficacy and safety of nipocalimab, an fcrn inhibitor, in adults with primary sjögren’s syndrome

Background Dysregulated humoral immunity is a hallmark of primary Sjögren’s Syndrome (pSS). This dysregulation involves aberrant B-lymphocyte activity resulting in abnormally high immunoglobulin G (IgG) levels and the production of autoantibodies, particularly those reactive with Ro/La ribonuclear complexes. pSS can affect almost any organ system, and current evidence-based therapies only offer some symptom relief, but no licensed therapy has been shown to alter the disease course. Nipocalimab is a high-affinity, fully human monoclonal antibody that reduces circulating IgG levels by selectively blocking the interactions of IgG, including pSS autoantibodies, with the neonatal Fc receptor (FcRn). Nipocalimab has previously induced rapid, safe, and durable serum IgG reductions in healthy volunteers ( NCT02828046 ) [1] and in autoantibody-driven generalized myasthenia gravis (gMG) in adults (Vivacity-MG; NCT03896295 ) [2] , suggesting that nipocalimab may treat a broad range of autoimmune disorders associated with autoantibodies, immune complexes and B-lymphocyte hyperactivity, including pSS. Objectives Here, we describe the key data from Vivacity-MG that illustrate the therapeutic potential of nipocalimab in IgG autoantibody-driven conditions and review the design of a phase 2 study evaluating the efficacy and safety of nipocalimab in patients with pSS ( NCT04968912 ). Methods Study feasibility assessments involved evaluating results from the phase 2 placebo-controlled trial Vivacity-MG. Of the 68 patients enrolled, 54 patients were randomized 1:1:1:1:1 to 4 treatment groups or a placebo group. Results In Vivacity-MG, there were no discontinuations due to treatment-emergent adverse events (TEAEs), severe AEs, or related serious AEs with nipocalimab. The incidence of infections and headaches with nipocalimab were comparable to placebo ( Table 1 ). Treatment with nipocalimab resulted in rapid and dose-dependent reductions in serum total IgG levels and anti-AChR IgG autoantibodies ( Figure 1 ), as compared to placebo. The safety and pharmacodynamic data from Vivacity-MG support the hypothesis that nipocalimab has the potential to treat pSS through lowering pathogenic IgGs. As such, we developed a phase 2, multicenter, randomized, placebo-controlled, double-blind study enrolling adults with moderately-to-severely active pSS. The pSS study consists of a ≤6-week screening period, a 24-week double-blind treatment period, and a 6-week follow-up period. Participants are randomized 1:1:1 to treatment every 2 weeks with intravenous nipocalimab (low or high dose), or placebo, through Week 22. The primary efficacy endpoint is change from baseline in Clinical European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index (clinESSDAI) score at Week 24. Safety assessments include TEAEs, abnormal vital signs, and laboratory parameters. Conclusion Vivacity-MG demonstrated that nipocalimab has the potential to offer an important new and targeted treatment option for patients with IgG-mediated diseases. The ongoing phase 2 study evaluates the safety and efficacy of treatment with nipocalimab in patients with moderately-to-severely active pSS. References [1]Ling LE, et al. Clin Pharmacol Ther. 2019;105(4):1031-1039. [2]Ramchandren S, et al. MGFA 2022. Poster 90. Table 1. TEAE Overview Nipocalimab (n=54) Placebo (n=14) Patients with TEAE, n (%) 44 (81.5) 11 (78.6) Patients with grade ≥3 TEAE, n (%) 0 4 (28.6) Most frequent TEAEs, n (%) Exacerbation of MG 0 2 (14.3) Headache 6 (11.1) 1 (7.1) Nasopharyngitis 6 (11.1) 0 Diarrhea 6 (11.1) 1 (7.1) Patients who discontinued due to TEAEs, n (%) 0 2 (14.3) Patients with serious TEAE, n (%) 1 (1.9)* 2 (14.3)* Patients with TEAEs deemed related to study drug by investigator, n (%) 21 (38.9) 1 (7.1) MG, myasthenia gravis; TEAE, treatment-emergent adverse event. *Serious TEAE deemed unrelated to study drug. Acknowledgements: NIL. Disclosure of Interests Jonathan Hubbard Employee of: Janssen Research & Development, LLC and may own Johnson & Johnson stock or stock options, Kim Campbell Employee of: Janssen Research & Development, LLC and may own Johnson & Johnson stock or stock options, Kathy Sivils Employee of: Janssen Research & Development, LLC and may own Johnson & Johnson stock or stock options, Robert Hoffman Employee of: Janssen Research & Development, LLC and may own Johnson & Johnson stock or stock options, Kim Hung Lo Employee of: Janssen Research & Development, LLC and may own Johnson & Johnson stock or stock options, Jocelyn H Leu Employee of: Janssen Research & Development, LLC and may own Johnson & Johnson stock or stock options, Simon Bowman Consultant of: Abbvie, Astra Zeneca, Galapagos, and Novartis Pharmaceuticals, Sophia Liva Employee of: Janssen Research & Development, LLC and may own Johnson & Johnson stock or stock options, Qing Zuraw Employee of: Janssen Research & Development, LLC and may own Johnson & Johnson stock or stock options, Anne M. Stevens Employee of: Janssen Research & Development, LLC and may own Johnson & Johnson stock or stock options, Leona Ling Employee of: Janssen Research & Development, LLC and may own Johnson & Johnson stock or stock options, Keith Karcher Employee of: Janssen Research & Development, LLC and may own Johnson & Johnson stock or stock options, Sindhu Ramchandren Employee of: Janssen Research & Development, LLC and may own Johnson & Johnson stock or stock options, Hong Sun Employee of: Janssen Research & Development, LLC and may own Johnson & Johnson stock or stock options, R Hal Scofield: None declared, Raphaèle Seror Consultant of: GlaxoSmithKline, Boehringer, Janssen and Novartis; Grant/research support from: GlaxoSmithKline and Amgen, Daniel J. Wallace Consultant of: Amgen, Eli Lilly and Company, EMD Merck Serono, and Pfizer.