Comparison of the efficacy and safety of tocilizumab for colchicine-resistant or colchicine-intolerant familial Mediterranean fever: study protocol for an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial
Abstract Background Familial Mediterranean fever (FMF) is an inherited disorder caused by a number of mutations of the Mediterranean fever (MEFV) gene, coding a protein named pyrin that acts as a major regulatory component of the inflammasome. The first-line drug for FMF treatment is colchicine, but...
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| Format: | Article |
| Language: | English |
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BMC
2018-12-01
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| Series: | Trials |
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| Online Access: | http://link.springer.com/article/10.1186/s13063-018-3105-6 |
| _version_ | 1811220660010090496 |
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| author | Tomohiro Koga Shuntaro Sato Junya Miyamoto Naoko Hagimori Yurika Kawazoe Kumiko Arinaga Chizu Fukushima Hiroshi Yamamoto Atsushi Kawakami |
| author_facet | Tomohiro Koga Shuntaro Sato Junya Miyamoto Naoko Hagimori Yurika Kawazoe Kumiko Arinaga Chizu Fukushima Hiroshi Yamamoto Atsushi Kawakami |
| author_sort | Tomohiro Koga |
| collection | DOAJ |
| description | Abstract Background Familial Mediterranean fever (FMF) is an inherited disorder caused by a number of mutations of the Mediterranean fever (MEFV) gene, coding a protein named pyrin that acts as a major regulatory component of the inflammasome. The first-line drug for FMF treatment is colchicine, but 10% of patients with FMF do not respond well to colchicine. Although the efficacy of tocilizumab (TCZ), which is a recombinant, humanized, antihuman interleukin 6 (IL-6) receptor monoclonal antibody, has been reported to prevent FMF attacks, the effects of TCZ on individuals with colchicine-resistant or colchicine-intolerant FMF have not been evaluated in a randomized clinical trial. Methods/design In this phase III, investigator-initiated, multicenter, double-blind, randomized, parallel-group trial, the efficacy and safety of TCZ will be compared with placebo in patients with colchicine-resistant or colchicine-intolerant FMF. The study will be conducted in nine centers in Japan. Participants (n = 24) will be randomly assigned to receive 162 mg of TCZ (n = 12) or placebo (n = 12) administered subcutaneously once weekly for 24 weeks. Rescue treatment will be allowed if rescue criteria are met. A primary endpoint is the number of fever attacks until 24 weeks. Secondary endpoints include the number of occurrences of accompanying symptoms during attacks; the time until a fever attack occurs; the duration of fever attacks; serum C-reactive protein and serum amyloid A; 36-item Short Form Health Survey; general evaluation by a physician (100-mm visual analogue scale); body temperature; the percentage of subjects who achieve FMF 50 at 12 weeks and 24 weeks; and pharmacodynamic assessment, including the measurement of serum TCZ level and soluble IL-6 receptor. Discussion The study is expected to produce evidence regarding the efficacy of a potential new therapeutic agent, TCZ, in improving the clinical course and outcome for patients with colchicine-resistant or colchicine-intolerant FMF. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000028010. Registered on 7 July 2017. |
| first_indexed | 2024-04-12T07:45:40Z |
| format | Article |
| id | doaj.art-38864476973240ef8dc9ce3cde7be6e0 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-04-12T07:45:40Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-38864476973240ef8dc9ce3cde7be6e02022-12-22T03:41:43ZengBMCTrials1745-62152018-12-011911910.1186/s13063-018-3105-6Comparison of the efficacy and safety of tocilizumab for colchicine-resistant or colchicine-intolerant familial Mediterranean fever: study protocol for an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trialTomohiro Koga0Shuntaro Sato1Junya Miyamoto2Naoko Hagimori3Yurika Kawazoe4Kumiko Arinaga5Chizu Fukushima6Hiroshi Yamamoto7Atsushi Kawakami8Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical SciencesNagasaki University Hospital, Clinical Research CenterNagasaki University Hospital, Clinical Research CenterNagasaki University Hospital, Clinical Research CenterNagasaki University Hospital, Clinical Research CenterNagasaki University Hospital, Clinical Research CenterNagasaki University Hospital, Clinical Research CenterNagasaki University Hospital, Clinical Research CenterDepartment of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical SciencesAbstract Background Familial Mediterranean fever (FMF) is an inherited disorder caused by a number of mutations of the Mediterranean fever (MEFV) gene, coding a protein named pyrin that acts as a major regulatory component of the inflammasome. The first-line drug for FMF treatment is colchicine, but 10% of patients with FMF do not respond well to colchicine. Although the efficacy of tocilizumab (TCZ), which is a recombinant, humanized, antihuman interleukin 6 (IL-6) receptor monoclonal antibody, has been reported to prevent FMF attacks, the effects of TCZ on individuals with colchicine-resistant or colchicine-intolerant FMF have not been evaluated in a randomized clinical trial. Methods/design In this phase III, investigator-initiated, multicenter, double-blind, randomized, parallel-group trial, the efficacy and safety of TCZ will be compared with placebo in patients with colchicine-resistant or colchicine-intolerant FMF. The study will be conducted in nine centers in Japan. Participants (n = 24) will be randomly assigned to receive 162 mg of TCZ (n = 12) or placebo (n = 12) administered subcutaneously once weekly for 24 weeks. Rescue treatment will be allowed if rescue criteria are met. A primary endpoint is the number of fever attacks until 24 weeks. Secondary endpoints include the number of occurrences of accompanying symptoms during attacks; the time until a fever attack occurs; the duration of fever attacks; serum C-reactive protein and serum amyloid A; 36-item Short Form Health Survey; general evaluation by a physician (100-mm visual analogue scale); body temperature; the percentage of subjects who achieve FMF 50 at 12 weeks and 24 weeks; and pharmacodynamic assessment, including the measurement of serum TCZ level and soluble IL-6 receptor. Discussion The study is expected to produce evidence regarding the efficacy of a potential new therapeutic agent, TCZ, in improving the clinical course and outcome for patients with colchicine-resistant or colchicine-intolerant FMF. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000028010. Registered on 7 July 2017.http://link.springer.com/article/10.1186/s13063-018-3105-6IL-6PlaceboTocilizumabFMFColchicine-resistant |
| spellingShingle | Tomohiro Koga Shuntaro Sato Junya Miyamoto Naoko Hagimori Yurika Kawazoe Kumiko Arinaga Chizu Fukushima Hiroshi Yamamoto Atsushi Kawakami Comparison of the efficacy and safety of tocilizumab for colchicine-resistant or colchicine-intolerant familial Mediterranean fever: study protocol for an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial Trials IL-6 Placebo Tocilizumab FMF Colchicine-resistant |
| title | Comparison of the efficacy and safety of tocilizumab for colchicine-resistant or colchicine-intolerant familial Mediterranean fever: study protocol for an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial |
| title_full | Comparison of the efficacy and safety of tocilizumab for colchicine-resistant or colchicine-intolerant familial Mediterranean fever: study protocol for an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial |
| title_fullStr | Comparison of the efficacy and safety of tocilizumab for colchicine-resistant or colchicine-intolerant familial Mediterranean fever: study protocol for an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial |
| title_full_unstemmed | Comparison of the efficacy and safety of tocilizumab for colchicine-resistant or colchicine-intolerant familial Mediterranean fever: study protocol for an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial |
| title_short | Comparison of the efficacy and safety of tocilizumab for colchicine-resistant or colchicine-intolerant familial Mediterranean fever: study protocol for an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial |
| title_sort | comparison of the efficacy and safety of tocilizumab for colchicine resistant or colchicine intolerant familial mediterranean fever study protocol for an investigator initiated multicenter randomized double blind placebo controlled trial |
| topic | IL-6 Placebo Tocilizumab FMF Colchicine-resistant |
| url | http://link.springer.com/article/10.1186/s13063-018-3105-6 |
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