Background Autoantibody-mediated diseases, such as systemic lupus erythematosus (SLE), are caused by pathogenic antibodies that can damage tissues or organs. Approved treatments are few and associated with limitations including suboptimal response. Nipocalimab is a novel high affinity, fully human, aglycosylated, effectorless IgG1 monoclonal antibody that selectively blocks the neonatal Fc receptor (FcRn). 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. Here we describe the protocol of a Phase 2 study evaluating the efficacy and safety of nipocalimab in patients with active SLE (NCT04882878).

Methods 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. 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.

Conclusions This ongoing phase 2 study will evaluate the safety and efficacy of nipocalimab in adults with active SLE, using multiple clinical outcome measures.