Journal Article

DZNE-2020-01276

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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

Wickel, J. ; Chung, H.-Y. ; Platzer, S. ; Lehmann, T. ; Prüss, H.DZNE* ; Leypoldt, F. ; Günther, A. ; Scherag, A. ; Geis, C. (Corresponding author)

2020
BioMed Central London

This record in other databases:    

Please use a persistent id in citations: doi:10.1186/s13063-020-04516-7

Abstract: 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.

Keyword(s): Acyclovir (MeSH) ; Adult (MeSH) ; Autoantibodies: blood (MeSH) ; Bortezomib: adverse effects (MeSH) ; Bortezomib: therapeutic use (MeSH) ; Clinical Trials, Phase II as Topic (MeSH) ; Dexamethasone (MeSH) ; Double-Blind Method (MeSH) ; Drug Therapy, Combination (MeSH) ; Encephalitis: drug therapy (MeSH) ; Encephalitis: immunology (MeSH) ; Germany (MeSH) ; Glasgow Coma Scale (MeSH) ; Hashimoto Disease: drug therapy (MeSH) ; Hashimoto Disease: immunology (MeSH) ; Humans (MeSH) ; Immunotherapy (MeSH) ; Multicenter Studies as Topic (MeSH) ; Prospective Studies (MeSH) ; Proteasome Inhibitors: adverse effects (MeSH) ; Proteasome Inhibitors: therapeutic use (MeSH) ; Randomized Controlled Trials as Topic (MeSH) ; Time Factors (MeSH) ; Treatment Outcome (MeSH) ; Trimethoprim, Sulfamethoxazole Drug Combination (MeSH)

---

Contributing Institute(s):

1. Autoimmune Encephalopathies (AG Prüß)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2020

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---