Efficacy and safety of nipocalimab in adult patients with active systemic lupus erythematosus: design of a phase 2 study

Background Systemic lupus erythematosus (SLE) is a chronic, progressive, autoimmune disorder characterized by chronic inflammation of multiple organs and tissues; mediated by autoantibodies and immune complexes. Approved treatments are few and associated with limitations including suboptimal response. Nipocalimab is a novel high affinity, fully human, aglycosylated, immunoglobulin G1 (IgG1) monoclonal antibody that selectively blocks the neonatal Fc receptor (FcRn) and displays no effector function. Clinical studies conducted with nipocalimab in healthy volunteers ( NCT02828046 ) and in adult generalized myasthenia gravis patients ( NCT03896295 ) demonstrated rapid and durable serum IgG and pathogenic autoantibody reductions. Objectives To describe the protocol of a Phase 2 study evaluating the efficacy and safety of nipocalimab in patients with active SLE ( NCT04882878 ). Methods This is a phase 2, multicenter, randomized, placebo-controlled, double-blind, parallel-group study enrolling adults with active, autoantibody-positive SLE with an inadequate response to one or more standard of care treatments. The study consists of a ≤6-week screening period, a 52-week double-blind treatment period, and a 6-week follow-up period. A target of approximately 225 participants will be enrolled. Participants will be randomized in a 1:1:1 ratio to receive nipocalimab dose 1, dose 2 or placebo intravenously every 2 weeks through Week 50. Results The primary efficacy endpoint is the percentage of participants achieving an SLE Responder Index (SRI)-4 composite response at Week 24. Secondary efficacy endpoints assessed at Week 24 include the percentage of participants achieving: ≥50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity score (CLASI), ≥50% reduction in active joints, ≥4 points improvement in SLE Disease Activity Index 2000 (SLEDAI 2K), and British Isles Lupus Assessment Group Composite Lupus Assessment response (BICLA); time to first disease flare; and reduction in corticosteroid use. The percentage of participants achieving an SRI-4 composite response at Week 52 will also be assessed. Safety endpoints include adverse events (AEs), serious AEs, AEs of special interest (severe infections, Grade ≥3 hypoalbuminemia), and AEs leading to treatment discontinuation through Week 58. Additional assessments include pharmacokinetic, pharmacodynamic, and immunogenicity evaluations. Conclusion This ongoing phase 2 study will evaluate the safety and efficacy of nipocalimab in adults with active SLE, using multiple clinical outcome measures. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Fang Liu-Walsh Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson., Bart van Hartingsveldt Employee of: Janssen Biologics Europe, Leiden, Netherlands and may own stock or stock options in Johnson & Johnson., Qing Zuraw Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson., Robert W. Hoffman Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson., Terence Rooney Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson., Sheng Gao Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson., George Karpouzas Speakers bureau: Sanofi-Genzyme-Regeneron, Janssen, and Bristol-Meyer-Squibb, Consultant of: Sanofi-Genzyme-Regeneron, Janssen, and Bristol-Meyer-Squibb, Grant/research support from: Pfizer, Robert Gordon Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson., Jocelyn H Leu Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson., Cesar Calderon Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson., Federico Zazzetti Employee of: Janssen-Cilag Argentina and may own stock or stock options in Johnson & Johnson., Anne M. Stevens Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson., George Vratsanos Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson.