The efficacy and safety of caplacizumab in Japanese patients with immune-mediated thrombotic thrombocytopenic purpura: an open-label phase 2/3 study
Yoshitaka Miyakawa, Kazunori Imada, Satoshi Ichikawa, Hitoji Uchiyama, Yasunori Ueda, Akihito Yonezawa, Shigeki Fujitani, Yoshiyuki Ogawa, Tadashi Matsushita, Hidesaku Asakura, Kenji Nishio, Kodai Suzuki, Yasuhiro Hashimoto, Hidenori Murakami, Sayaka Tahara, Tomoyuki Tanaka, Masanori Matsumoto
Abstract
Caplacizumab is an anti-von Willebrand factor humanized single-variable-domain immunoglobulin fragment whose efficacy and safety in immune-mediated thrombotic thrombocytopenia purpura (iTTP) have been demonstrated in international studies. This prospective, open-label phase 2/3 study evaluated caplacizumab 10 mg administered daily during plasma exchange and for 30 days afterward, in combination with immunosuppressive treatment, in Japanese adults with a clinical diagnosis of iTTP (new or recurrent). The primary endpoint was prevention of iTTP recurrence; key secondary endpoints included time to platelet count response, time to organ damage normalization, and safety. Among 21 treated patients, 1 of 15 (6.7%) evaluable patients developed iTTP recurrence. Median time to normalization was 2.79 days for platelet count and 2.65 days for organ damage markers (n = 15). Treatment-emergent adverse events (TEAEs) were mostly mild to moderate in severity; the most frequently reported caplacizumab-related TEAEs were increased alanine aminotransferase, epistaxis, and gastrointestinal hemorrhage (all in 9.5% of patients). At least one bleeding event was reported in 7 of 21 patients (33%). Caplacizumab was effective in Japanese patients with iTTP, with a low rate of iTTP recurrence, rapid normalization of platelet counts and organ damage markers, and no unexpected TEAEs. Trial registration: ClinicalTrials.gov identifier, NCT04074187.