Home > Publications Database > Generate-Boost: study protocol for a prospective, multicenter, randomized controlled, double-blinded phase II trial to evaluate efficacy and safety of bortezomib in patients with severe autoimmune encephalitis > print

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024 7 _ |a 10.1186/s13063-020-04516-7
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037 _ _ |a DZNE-2020-01276
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Wickel, Jonathan
|b 0
245 _ _ |a Generate-Boost: study protocol for a prospective, multicenter, randomized controlled, double-blinded phase II trial to evaluate efficacy and safety of bortezomib in patients with severe autoimmune encephalitis
260 _ _ |a London
|c 2020
|b BioMed Central
336 7 _ |a article
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520 _ _ |a BackgroundAutoimmune encephalitis is a new spectrum of autoimmune disorders of the central nervous system (CNS), which are characterized by pathogenic autoantibodies against neuronal surface antigens. Clinical presentations range from acute to subacute encephalopathy with neurological and psychiatric symptoms, and life-threatening autonomic dysfunction in severe cases. There exist no approved therapies nor is data available from controlled clinical trials. Patients are usually treated with diverse combinations of immunotherapy. However, effect of immunotherapy on antibody-producing cells and thus on levels of pathogenic autoantibodies is insufficient. Therefore, therapeutic response is sometimes prolonged with necessity of long-time intensive care treatment and also irreversible deficits occur in severe cases. This trial will investigate the efficacy and safety of bortezomib, a proteasome inhibitor known to selectively deplete plasma cells, in patients with severe autoimmune encephalitis who have been treated with rituximab with insufficient response.MethodsGenerate-Boost is an investigator-initiated, multicenter, double-blinded, randomized controlled phase II trial which will be conducted in specialized neurological hospitals within the GENERATE (GErman NEtwork for Research on AuToimmune Encephalitis) network in Germany. Adult patients with severe autoimmune encephalitis (modified Rankin scale, mRS ≥ 3), autoantibodies against neuronal surface antigens, and pretreatment with rituximab are eligible for study participation. Fifty patients will be randomized 1:1 and undergo up to 3 cycles (each 21 days with 4 s. c. applications) of bortezomib or placebo. All patients will receive concomitant medication with dexamethasone, acyclovir and co-trimoxazole. The primary efficacy endpoint is the mRS score 17 weeks after first treatment application. Secondary endpoints are neurocognitive function, antibody titers, markers of neuronal cell damage, length of ICU/hospital stay, and mRS and Glasgow coma scale scores throughout the trial up to week 17. General and bortezomib-specific adverse events are monitored continuously.DiscussionThe expected outcome of the study is to obtain first reliable data on a hypothesis-driven therapeutic option in severe and difficult-to-treat autoimmune encephalitis. If treatment with bortezomib is beneficial in these cases, this will be the basis for implementation in the current guidelines.
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650 _ 2 |a Acyclovir
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Autoantibodies: blood
|2 MeSH
650 _ 2 |a Bortezomib: adverse effects
|2 MeSH
650 _ 2 |a Bortezomib: therapeutic use
|2 MeSH
650 _ 2 |a Clinical Trials, Phase II as Topic
|2 MeSH
650 _ 2 |a Dexamethasone
|2 MeSH
650 _ 2 |a Double-Blind Method
|2 MeSH
650 _ 2 |a Drug Therapy, Combination
|2 MeSH
650 _ 2 |a Encephalitis: drug therapy
|2 MeSH
650 _ 2 |a Encephalitis: immunology
|2 MeSH
650 _ 2 |a Germany
|2 MeSH
650 _ 2 |a Glasgow Coma Scale
|2 MeSH
650 _ 2 |a Hashimoto Disease: drug therapy
|2 MeSH
650 _ 2 |a Hashimoto Disease: immunology
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Immunotherapy
|2 MeSH
650 _ 2 |a Multicenter Studies as Topic
|2 MeSH
650 _ 2 |a Prospective Studies
|2 MeSH
650 _ 2 |a Proteasome Inhibitors: adverse effects
|2 MeSH
650 _ 2 |a Proteasome Inhibitors: therapeutic use
|2 MeSH
650 _ 2 |a Randomized Controlled Trials as Topic
|2 MeSH
650 _ 2 |a Time Factors
|2 MeSH
650 _ 2 |a Treatment Outcome
|2 MeSH
650 _ 2 |a Trimethoprim, Sulfamethoxazole Drug Combination
|2 MeSH
700 1 _ |a Chung, Ha-Yeun
|b 1
700 1 _ |a Platzer, Stephanie
|b 2
700 1 _ |a Lehmann, Thomas
|b 3
700 1 _ |a Prüss, Harald
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700 1 _ |a Leypoldt, Frank
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700 1 _ |a Günther, Albrecht
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700 1 _ |a Scherag, André
|b 7
700 1 _ |a Geis, Christian
|0 0000-0002-9859-581X
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|e Corresponding author
773 _ _ |a 10.1186/s13063-020-04516-7
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856 4 _ |u https://link.springer.com/article/10.1186/s13063-020-04516-7
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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