Background/Purpose Current SLE treatment options have limited efficacy and potential toxicities that impede an individual’s ability to remain on therapy. AMG 570 is a bispecific antibody inhibiting both ICOSL and BAFF that engages ICOSL on antigen-presenting cells (dendritic cells and B cells) and reduces circulating naïve B cells in healthy subjects. This phase 2 study will employ SLE drug screening and response-adaptive randomization (RAR) to optimize dose selection of AMG 570 in subjects with active SLE and inadequate response to standard of care (SOC) therapy (NCT04058028).
Methods In this adaptive, phase 2, placebo-controlled, dose-ranging study, subjects (N∼300, age 18–75 years) will be randomized to receive placebo or 1 of 3 doses of AMG 570 Q2W for 52 weeks, followed by 16 weeks of safety follow-up. The primary objective is to evaluate efficacy of AMG 570 compared with placebo at week 24 using the SLE Responder Index (SRI-4). Key secondary endpoints include SRI-4 at week 52 with oral corticosteroid (OCS) reduction (≥10 mg/day at baseline to ≤7.5 mg/day in weeks 44–52) and SRI-4 and Lupus Low Disease Activity State at week 52. Subjects will undergo 2 screening visits to fulfill criteria for active SLE and demonstrate adherence to prior SLE treatment including OCS, immunosuppressants, and/or immunomodulators. Blood screening tests will confirm detectable serum drug levels of baseline SOC medications. RAR aims to allocate more subjects to more efficacious doses while maintaining the placebo allocation constant; the randomization ratio could be adapted after interim analyses based on clinical efficacy. The trial includes interim analyses for futility using the Bayesian approach.
Results Study ongoing.
Conclusion This study will provide safety and efficacy data for AMG 570 compared with placebo, and its adaptive trial design aims to optimize development of a novel therapy for SLE patients with inadequate response to current SOC.
Acknowledgments Amgen Inc. sponsored this study.
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