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

  • STATUS
    Recruiting
  • End date
    Dec 31, 2022
  • participants needed
    50
  • sponsor
    Jena University Hospital
Updated on 19 February 2021

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.

Description

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.

Details
Condition Autoimmune Encephalitis, encephalitis autoimmune
Treatment Placebo, Bortezomib
Clinical Study IdentifierNCT03993262
SponsorJena University Hospital
Last Modified on19 February 2021

Eligibility

Yes No Not Sure

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)
Clear my responses

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Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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