The efficacy and safety of caplacizumab in Japanese patients with immune-mediated thrombotic thrombocytopenic purpura: an open-label phase 2/3 study

• Published in: International journal of hematology 2023-03, Vol.117 (3), p.366-377
• Main Authors: Miyakawa, Yoshitaka, Imada, Kazunori, Ichikawa, Satoshi, Uchiyama, Hitoji, Ueda, Yasunori, Yonezawa, Akihito, Fujitani, Shigeki, Ogawa, Yoshiyuki, Matsushita, Tadashi, Asakura, Hidesaku, Nishio, Kenji, Suzuki, Kodai, Hashimoto, Yasuhiro, Murakami, Hidenori, Tahara, Sayaka, Tanaka, Tomoyuki, Matsumoto, Masanori
• Format: Article
• Language: English
• Subjects: ADAMTS13 Protein; Adult; Alanine; Alanine transaminase; Damage; East Asian People; Effectiveness; Gastrointestinal Hemorrhage; Hematology; Hemorrhage; Humans; International studies; Labels; Medicine; Medicine & Public Health; NCT; NCT04074187; Oncology; Original; Original Article; Patients; Plasma Exchange; Platelets; Prospective Studies; Purpura; Purpura, Thrombotic Thrombocytopenic; Safety; Single-Domain Antibodies - therapeutic use; Thrombocytopenia; Thrombocytopenic purpura; Thrombotic thrombocytopenic purpura; Von Willebrand factor
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-022-03495-6

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.