Open AccessAn open-label continuation trial of sirolimus for tocilizumab-refractory idiopathic multicentric Castleman disease
Author(s) -
Tomohiro Koga,
Sachiko Takemori,
Naoko Hagimori,
Shimpei Morimoto,
Remi Sumiyoshi,
Toshimasa Shimizu,
Naoki Hosogaya,
Chizu Fukushima,
Hiroshi Yamamoto,
Atsushi Kawakami
Publication year - 2020
Publication title -
medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 148
eISSN - 1536-5964
pISSN - 0025-7974
DOI - 10.1097/md.0000000000023291
Subject(s) - medicine , sirolimus , clinical endpoint , tocilizumab , adverse effect , placebo , clinical trial , visual analogue scale , randomized controlled trial , gastroenterology , surgery , disease , pathology , alternative medicine
Background: Interleukin 6 (IL-6) inhibitors are the first-line treatment for idiopathic multicentric Castleman disease (iMCD); however, there is no established treatment for cases that are resistant to IL-6 inhibitors. Although sirolimus, a mammalian target of rapamycin inhibitor, has been suggested to be effective in patients with iMCD, the long-term safety and efficacy of sirolimus on individuals with IL-6 inhibitor-resistant iMCD have not been evaluated. Methods/Design: In this investigator-initiated, multicenter, open-label trial, the long-term safety of sirolimus will be evaluated in patients participating in a placebo-controlled, randomized, double-blind, parallel-group trial on tocilizumab (TCZ)-resistant iMCD. The study will be conducted in 7 centers in Japan. This trial will be promptly started after the evaluation and examination for 16 weeks in the preceding study. The trial will be completed by the time the drug is approved for iMCD treatment in Japan. The primary endpoint is the incidence of adverse events. The secondary endpoints include the following: the levels of hemoglobin, albumin, and C-reactive protein; change in CHAP score; physician global assessment (100-mm visual analog scale); patient global assessment (100-mm visual analog scale); and lymph node changes in subjects with lymphadenopathy. Discussion: This clinical trial will provide evidence regarding the long-term safety of sirolimus as a potential novel therapeutic agent for patients with tocilizumab-resistant iMCD. Trial Registration number: jRCT2051200050