Trial to Evaluate Efficacy and Safety of Bortezomib in Patients With Severe Autoimmune Encephalitis

NCT03993262 | Recruiting Phase 2 DMC

• 5 other identifiers: ZKSJ01202024-514494-21-002019-001423-12DRKS0001749701GM1908E
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 17

Brief Summary

Autoimmune Encephalitis is a disorder of the central nervous system caused by bodily substances, called antibodies. Antibodies normally help the body to prevent infections. However, in this disorder, the antibodies turn against the body itself and especially against cells in the brain and disturb the normal brain function. They are therefore called autoantibodies. There is no specific therapy for patients with autoimmune encephalitis so far. At the moment, the symptoms are treated with approved medications such as cortisone and immunotherapies also used in oncology. These therapies are unspecified and aim to reduce the number of autoantibodies and to contain the autoimmune process. In this trial we aim to test a new therapy option: in this therapy the body cells producing autoantibodies will be specifically targeted by a substance called bortezomib. The trial addresses patients with severe autoimmune encephalitis. The aim of the trial is to evaluate the efficacy and safety of bortezomib in patients with severe autoimmune encephalitis.

Conditions

Autoimmune Encephalitis

Keywords

autoimmune disease; autoimmune encephalitis; bortezomib; NMDAR; LGI1; encephalitis

Outcome Measures

Primary Outcomes (1)

• modified Rankin-Score (mRS)

  modified Rankin-Score from 0 = no symptoms to 6 = death

  17 weeks after first administration of the study drug

Secondary Outcomes (18)

• modified Rankin-Score (mRS)

  3, 6, 9 and 13 weeks after first administration of the study drug; GCS Score also 17 weeks after first administration of the study drug

• Length of in-hospital stay / length of ICU stay

  until 17 weeks after first administration of the study drug

• Immune response

  at study start and 17 weeks after first administration of the study drug

• neurocognitive function assessed by Montreal Cognitive Assessment

  at study start and 17 weeks after first administration of the study medication

• neurocognitive function assessed by Mini-Mental Status Test

  at study start and 17 weeks after first administration of the study medication

Study Arms (2)

Interventional

EXPERIMENTAL

1 to 3 cycles Bortezomib with 1,3mg/m2 body surface s.c. + 20mg dexamethasone p.o. on days 1, 4, 8 and 11 (= 1 cycle)

Drug: Bortezomib

Placebo

PLACEBO COMPARATOR

1 to 3 cycles placebo (NaCl solution) s.c. + 20mg dexamethasone p.o. on days 1, 4, 8 and 11 (= 1 cycle)

Drug: Placebo

Interventions

Bortezomib DRUG

1 to 3 cycles Bortezomib with 1,3mg/m2 body surface s.c. + 20mg dexamethasone p.o. on days 1, 4, 8 and 11 (= 1 cycle)

Interventional

Placebo DRUG

1 to 3 cycles placebo (NaCl solution) s.c. + 20mg dexamethasone p.o. on days 1, 4, 8 and 11 (= 1 cycle)

Also known as: isotonic NaCl solution

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinically diagnosed severe autoimmune encephalitis (defined as mRS ≥ 3) with autoantibodies to neuronal surface proteins in cerebrospinal fluid and / or serum
• Pretreatment with rituximab
• Age ≥18 years
• signed informed consent
• Women of childbearing potential (up to 2 years after menopause): negative pregnancy test

You may not qualify if:

• pregnancy/breast-feeding
• acute infiltrative pulmonary and pericardial disease
• malignant tumor under current chemotherapy
• Simultaneous participation in another intervention study
• Previous participation in this study
• Known hypersensitivity to an ingredient of the investigational product
• Continued therapy with glucocorticoids / rituximab during the study duration (last dose must be administered before the first dose of the investigational product)

Sponsors & Collaborators

• Jena University Hospital: lead
• Federal Ministry of Education and Reserach (BMBF): collaborator

Study Sites (17)

Ludwig-Maximilians-Universität München, Klinikum Großhadern

München, Bavaria, 81377, Germany

RECRUITING

Universitätsklinikum Würzburg

Würzburg, Bavaria, 97080, Germany

RECRUITING

Universitätsklinikum Jena, Sektion Translationale Neuroimmunologie, Klinik für Neurologie

Jena, Germany, 07747, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, Niedersachen, 30625, Germany

RECRUITING

Charité - Universitätsmedizin Berlin, Klinik für Neurologie mit Experimenteller Neurologie

Berlin, 10117, Germany

RECRUITING

Ruhr-Universität Bochum, St. Josef Hospital, Klinik für Neurologie

Bochum, 44791, Germany

RECRUITING

University Hospital Düsseldorf, Clinic for Neurology

Düsseldorf, 40225, Germany

RECRUITING

Universitätsklinikum Erlangen, Neurologische Klinik

Erlangen, 91054, Germany

RECRUITING

Universitätsklinikum Essen (AöR), Klinik für Neurologie

Essen, 45147, Germany

RECRUITING

University Hospital Frankfurt (Main), Clinic for Neurology

Frankfurt, 60528, Germany

RECRUITING

Universitätsmedizin Göttingen Georg-August-Universität, Klinik für Neurologie

Göttingen, 37075, Germany

RECRUITING

Universitätsmedizin Greifswald, Klinik und Poliklinik für Neurologie

Greifswald, 17475, Germany

RECRUITING

Klinik für Neurologie UKSH, Campus Kiel

Kiel, 24105, Germany

RECRUITING

Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurologie

Leipzig, 04103, Germany

RECRUITING

Universitätsmedizin Mainz, Klinik und Poliklinik für Neurologie

Mainz, 55131, Germany

RECRUITING

Universitätsklinikum Münster Klinik für Neurologie

Münster, 48149, Germany

RECRUITING

Universitätsklinikum Ulm, Klinik für Neurologie Neurologische Ambulanz

Ulm, 89081, Germany

RECRUITING

Related Publications (1)

• Wickel J, Chung HY, Platzer S, Lehmann T, Pruss H, Leypoldt F, Gunther A, Scherag A, Geis C; GENERATE Study Group. 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. Trials. 2020 Jul 8;21(1):625. doi: 10.1186/s13063-020-04516-7.

  PMID: 32641101 DERIVED

MeSH Terms

Conditions

Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Encephalitis

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Nervous System Diseases; Immune System Diseases; Brain Diseases; Central Nervous System Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Christian Geis, Prof.

  University Hospital Jena

  STUDY DIRECTOR

Central Study Contacts

Christian Geis, Prof.

CONTACT

+49 (0) 3641; Christian.Geis@med.uni-jena.de

Jonathan Wickel, Dr.

CONTACT

+49 (0) 3641; Jonathan.Wickel@med.uni-jena.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study drug will be provided blinded by the local pharmacy.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Model Details: 1:1 randomization will be done centrally and stratified by site. Block randomization of variable block sizes will be used.

Study Record Dates

• First Submitted: June 12, 2019
• First Posted: June 20, 2019
• Study Start: May 13, 2020
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 4, 2025

Record last verified: 2025-08

Locations

DE (17)