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

NCT ID: NCT03993262

Last Updated: 2025-09-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-13

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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Autoimmune encephalitis is characterized by autoantibodies against neuronal surface antigens like the NMDA (N-methyl-D-aspartate) receptor or LGI1 (Leucin-rich glioma inactivated protein 1). So far, no specific therapy exists for this disease. Actual treatment includes combination therapies aiming for a reduction of pathogenic antibodies and containing the autoimmune process. In first line, patients are treated with plasmapheresis and cortisone. In second line, Rituximab and/or cyclophosphamide are administered. The response to these treatments are, however, often delayed and insufficient.

Therefore, we need a specific therapy aiming at the antibody-producing plasma cells.

Bortezomib is a proteasome inhibitor which interferes with NF-kB (nuclear factor kB) and the ubiquitin proteasome signaling pathway. Bortezomib acts preferably on cells with high protein synthesis - like plasma cells - and induces cell death in these cells. Bortezomib is used since more than a decade in chemotherapy of the multiple myeloma. Additionally, it is reported for systemic autoimmune diseases like lupus erythematodes that bortezomib leads to a depletion of plasma cells and therefore reduces the number of pathogenic antibodies and improves clinical outcome. The therapeutic potential of bortezomib for NMDAR encephalitis is described in a first case series with 5 patients.

Conditions

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Autoimmune Encephalitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

1:1 randomization will be done centrally and stratified by site. Block randomization of variable block sizes will be used.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The study drug will be provided blinded by the local pharmacy.

Study Groups

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Interventional

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)

Group Type EXPERIMENTAL

Bortezomib

Intervention Type 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)

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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Bortezomib

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)

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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isotonic NaCl solution

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Federal Ministry of Education and Reserach (BMBF)

UNKNOWN

Sponsor Role collaborator

Jena University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Christian Geis

Prof. Dr. med.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Christian Geis, Prof.

Role: STUDY_DIRECTOR

University Hospital Jena

Locations

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Ludwig-Maximilians-Universität München, Klinikum Großhadern

München, Bavaria, Germany

Site Status RECRUITING

Universitätsklinikum Würzburg

Würzburg, Bavaria, Germany

Site Status RECRUITING

Universitätsklinikum Jena, Sektion Translationale Neuroimmunologie, Klinik für Neurologie

Jena, Germany, Germany

Site Status RECRUITING

Medizinische Hochschule Hannover

Hanover, Niedersachen, Germany

Site Status RECRUITING

Charité - Universitätsmedizin Berlin, Klinik für Neurologie mit Experimenteller Neurologie

Berlin, , Germany

Site Status RECRUITING

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

Bochum, , Germany

Site Status RECRUITING

University Hospital Düsseldorf, Clinic for Neurology

Düsseldorf, , Germany

Site Status RECRUITING

Universitätsklinikum Erlangen, Neurologische Klinik

Erlangen, , Germany

Site Status RECRUITING

Universitätsklinikum Essen (AöR), Klinik für Neurologie

Essen, , Germany

Site Status RECRUITING

University Hospital Frankfurt (Main), Clinic for Neurology

Frankfurt, , Germany

Site Status RECRUITING

Universitätsmedizin Göttingen Georg-August-Universität, Klinik für Neurologie

Göttingen, , Germany

Site Status RECRUITING

Universitätsmedizin Greifswald, Klinik und Poliklinik für Neurologie

Greifswald, , Germany

Site Status RECRUITING

Klinik für Neurologie UKSH, Campus Kiel

Kiel, , Germany

Site Status RECRUITING

Universitätsklinikum Leipzig, Klinik und Poliklinik für Neurologie

Leipzig, , Germany

Site Status RECRUITING

Universitätsmedizin Mainz, Klinik und Poliklinik für Neurologie

Mainz, , Germany

Site Status RECRUITING

Universitätsklinikum Münster Klinik für Neurologie

Münster, , Germany

Site Status RECRUITING

Universitätsklinikum Ulm, Klinik für Neurologie Neurologische Ambulanz

Ulm, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Christian Geis, Prof.

Role: CONTACT

+49 (0) 3641 ext. 9323413

Jonathan Wickel, Dr.

Role: CONTACT

+49 (0) 3641 ext. 9323561

Facility Contacts

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Tania Kümpfel, Prof.

Role: primary

+49894400 ext. 74435

Joachim Havla, Dr.

Role: backup

+49894400 ext. 74435

Claudia Sommer, Prof.

Role: primary

+49931201 ext. 23763

Kathrin Doppler, PD Dr.

Role: backup

+49931201 ext. 23787

Christian Geis, Prof.

Role: primary

+49-3641 ext. -9323413

Jonathan Wickel, Dr.

Role: backup

+49 3641 ext. 9323561

Kurt-Wolfram Suehs, PD Dr.

Role: primary

+49511532 ext. 2495

Martin Stangel, Prof.

Role: backup

+49511532 ext. 6676

Harald Pruess, PD Dr.

Role: primary

+49 30 450560 ext. 560

Peter Koertvelyessy, Dr.

Role: backup

+49 30 450560 ext. 164

Ilya Ayzenberg, PD Dr.

Role: primary

+49 234 509 ext. 6423

Ruth Schneider, Dr.

Role: backup

+49 234 509 ext. 6433

Nico Melzer, PD Dr.

Role: primary

+4921181 ext. 18978

Sven G Meuth, Prof. Dr.

Role: backup

+4921181 ext. 17880

Veit Rothhammer, Prof. Dr.

Role: primary

Thanos Tsaktanis, Dr.

Role: backup

Carlos Quesada, Dr.

Role: primary

Refik Pul, Dr.

Role: backup

Felix Rosenow, Prof. Dr.

Role: primary

+49696301 ext. 84521

Adam P Strzelczyk, Prof. Dr.

Role: backup

+49696301 ext. 5852

Dirk Fitzner, Dr.

Role: primary

+49 551 39 ext. 65593

Bernadette Gaida, Dr.

Role: primary

Felix von Podewils, Prof. Dr.

Role: backup

Frank Leypoldt, PD Dr.

Role: primary

+49 431 500 ext. 16209

Klarissa Stuerner, Dr.

Role: backup

+49 431 500 ext. 23816

Florian Then Berg, Prof. Dr.

Role: primary

+49 341972 ext. 4320

Lars-Malte Teusser, Dr.

Role: backup

+49 341972 ext. 4320

Stefan Bittner, Prof.

Role: primary

+49 6131 17 ext. 2805

Felix Lüssi, PD Dr.

Role: backup

+49 6131 17 ext. 5278

Oliver M Grauer, PD Dr.

Role: primary

+49 251 8348 ext. 6814

Stjepana Kovac, PD Dr.

Role: backup

Jan Lewerenz, PD Dr.

Role: primary

+49 731 500 ext. 63146

Mabule Senel, Dr.

Role: backup

+49 731 077 ext. 5265

References

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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.

Reference Type DERIVED
PMID: 32641101 (View on PubMed)

Other Identifiers

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2024-514494-21-00

Identifier Type: CTIS

Identifier Source: secondary_id

2019-001423-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DRKS00017497

Identifier Type: REGISTRY

Identifier Source: secondary_id

01GM1908E

Identifier Type: REGISTRY

Identifier Source: secondary_id

ZKSJ0120

Identifier Type: -

Identifier Source: org_study_id

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