A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Crovalimab as Add-On Therapy in Patients with Antiphospholipid Syndrome and Recurrent Thrombosis

Introduction Antiphospholipid Syndrome (APS) is an autoimmune thrombo-inflammatory disorder characterized by thrombosis and/or pregnancy morbidity in patients with persistent antiphospholipid antibodies (aPL). Despite standard anticoagulant therapy, including warfarin/other vitamin K antagonists (VKAs), patients with a history of thromboses and the following aPL profiles remain at high risk for thrombosis: triple aPL-positive for anticardiolipin antibodies (aCL), anti-β2-glycoprotein 1 antibodies (aβ2GP1), and lupus anticoagulant (LAC); or double positive for two of the three criteria aPLs (aCL, aβ2GP1, LAC). Recurrent thromboses are the main cause of death and irreversible organ damage in APS patients and represent a significant unmet medical need. Crovalimab, a humanized anti-C5 monoclonal antibody, inhibits terminal complement activation, a key pathway implicated in APS pathogenesis. This study (BO46107) evaluates the efficacy, safety, and pharmacokinetics (PK) of crovalimab as an add-on therapy to VKA in patients with APS. Method This Phase II, international, multicenter, randomized, double-blind, placebo-controlled study sponsored and designed by Roche/Genentech will enroll adult patients (18-70 years) classified with APS, per the 2023 ACR/EULAR criteria with listed authors performing an advisory role. Eligible patients must have proven aPL persistence for triple or double aPL-positivity within 12 months prior to screening, and at least 2 prior thromboses. The latest thrombosis must have occurred>3 months and