S305: PHASE 2 RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND, MULTICENTER STUDY OF RECOMBINANT ADAMTS13 IN PATIENTS WITH IMMUNE-MEDIATED THROMBOTIC THROMBOCYTOPENIC PURPURA

作者：Marie Scully, Jovanna Baptista, Indranil Bhattacharya, Spero R. Cataland, Paul Coppo, Loredana Cuccia, Tina Dutt, Shih‐Han S. Huang, Cristina Pascual, María Eva Mingot‐Castellano, Aric Parnes, Katerina Pavenski, Kavitha Rajavel, Isidro Jarque, Linda T. Wang, Miguel Fernández Zarzoso, Andy Z. X. Zhu, Björn Mellgård · 发表于：HemaSphere · 年份：2023 · DOI：10.1097/01.hs9.0000968132.86513.06 · 被引用次数：12 · 研究领域：Complement system in diseases、Iron Metabolism and Disorders、Blood groups and transfusion

Topic: 32. Platelet disorders Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disorder caused by a severe ADAMTS13 deficiency, due to anti-ADAMTS13 autoantibodies. iTTP treatment includes plasma exchange (PEX) and immunosuppressive therapy. A recombinant ADAMTS13 (rADAMTS13; TAK-755; Takeda Development Center Americas, Inc., Lexington, MA, USA) is under investigation as a therapeutic option for patients with iTTP. Aims: To assess the pharmacokinetic (PK) characteristics of ADAMTS13 in patients with iTTP receiving treatment for an acute TTP episode, the PK/pharmacodynamic (PD) relationship between ADAMTS13 activity levels and biomarkers, and safety. Methods: This phase 2, randomized, placebo-controlled, double-blind, multicenter study (NCT03922308) enrolled patients aged 18–75 years experiencing an acute TTP episode. Patients received up to 1 pre-study PEX. Eligible patients were randomized 1:1:1 into three treatment arms, all with daily PEX and immunosuppressants. Arm 1: placebo given post-PEX and 12 hours post-PEX; Arm 2: rADAMTS13 40 IU/kg intravenous (IV) given post-PEX and placebo 12 hours post-PEX; Arm 3: rADAMTS13 40 IU/kg IV given post-PEX and 12 hours post-PEX. Patients received treatment until clinical remission (platelet normalization [≥150 ×109/L] and lactate dehydrogenase levels <2 × upper limit of normal for ≥48 hours following initial platelet normalization). Post-remission follow-up was 3 months and included ADAMTS13 activity-dr...