• Tomohiro Koga, Naoko Hagimori, Sachiko Takemori, Shimpei Morimoto, Remi Sumiyoshi, Toshimasa Shimizu, Naoki Hosogaya, Chizu Fukushima, Hiroshi Yamamoto, and Atsushi Kawakami.
• aDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences bCenter for Bioinformatics and Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences cN... more agasaki University Hospital, Clinical Research Center, Nagasaki, Japan. less
• Medicine (Baltimore). 2020 Jul 24; 99 (30): e20710.

BackgroundIdiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder of unknown etiology with systemic symptoms that include fever, night sweats, weight loss, and fatigue. Although tocilizumab (TCZ), which is a recombinant, humanized, anti-human interleukin 6 receptor monoclonal antibody, has been recommended to treat patients with iMCD, 40% of patients with iMCD do not achieve complete remission with TCZ treatment.Methods/DesignIn this phase II, investigator-initiated, multicenter, double-blind, randomized, parallel-group trial, the efficacy and safety of sirolimus will be compared with placebo in patients with TCZ-resistant iMCD. The study will be conducted in 8 centers in Japan. Participants (n = 20) will be randomly assigned to receive 2 mg of oral sirolimus (n = 10) or placebo (n = 10) once daily for 16 weeks. The primary endpoint is a decrease in CHAP score by ≥1 from baseline at 16 weeks. Secondary endpoints include levels of hemoglobin, albumin, and C-reactive protein; change in CHAP score; SF-36 Health Survey Questionnaire; physician global assessment (100 mm visual analog scale); patient global assessment (100 mm visual analog scale) at 2, 4, 8, 12, and 16 weeks; change in lymphadenopathy at 16 weeks; and pharmacodynamic assessment, including the measurement of whole blood sirolimus level.DiscussionThis clinical trial will provide evidence of efficacy and safety of sirolimus as a potential new therapeutic agent for patients with TCZ-resistant iMCD.Trial RegistrationThis study was registered with the Japan Registry of Clinical Trials as jRCT2071190029 on October 8, 2019.

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