ClinicalTrials.gov record NCT03993262

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

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 17, 2026

A Multicenter Randomized, Controlled, Double-blinded Trial to Evaluate Efficacy and Safety of Bortezomib in Patients With Severe Autoimmune Encephalitis

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 2A study that tests whether a treatment has the intended effect and continues to check safety, usually in a larger group than phase 1.
Age18 years old and older
SexAll
LocationGermany
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

A randomized, quadruple-masked Phase 2 trial comparing bortezomib plus dexamethasone with placebo plus dexamethasone in people with severe autoimmune encephalitis. The study focuses on adults (≥18) with neuronal-surface autoantibodies and severe disability; prior treatment with rituximab is required. Key exclusions include pregnancy/breastfeeding, current chemotherapy for a malignancy, acute infiltrative pulmonary or pericardial disease, and continuing glucocorticoid or rituximab therapy during the study.

What it is studying. This trial tests whether adding bortezomib (given subcutaneously in 1–3 cycles, together with oral dexamethasone) changes clinical and safety outcomes compared with placebo plus dexamethasone in severe autoimmune encephalitis. The study also measures antibody levels, cellular immune responses, cognitive function, hospital/ICU length of stay, and several blood/CSF biomarkers of brain injury.

What the researchers hope to learn. Scientific goals: to evaluate the effect of bortezomib on functional outcome (mRS) at 17 weeks and to assess safety (including polyneuropathy, liver enzyme changes, infections, hematologic and gastrointestinal toxicity). The study also aims to describe changes in antibody titers, cellular immune markers, neurocognitive tests, hospital/ICU stay length, and neurologic biomarkers (UCH-L1, neurofilament light chain, GFAP, TAU).

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Bortezomib
  • Placebo

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

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)

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Detailed description from the registry

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.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants are randomized to receive 1–3 cycles of either subcutaneous bortezomib (1.3 mg/m2) plus oral dexamethasone or matching placebo (NaCl solution) plus dexamethasone, with dosing on days 1, 4, 8 and 11 of each cycle. Study visits include neurologic assessments (mRS, Glasgow Coma Scale), neurocognitive tests (MoCA, MMST, RAVLT, NPI), blood tests and cerebrospinal fluid sampling at baseline and about 17 weeks, and regular safety monitoring for neuropathy, liver tests, infections, hematologic and gastrointestinal toxicity. Lengths of hospital and ICU stay will be recorded. Participation requires following study restrictions (for example stopping ongoing glucocorticoids/rituximab before the first study dose) and providing informed consent.

How the study is structured. Phase 2, randomized, parallel-group, quadruple-masked trial. Participants are randomly assigned to receive either bortezomib (subcutaneous) plus oral dexamethasone or placebo (isotonic NaCl) plus oral dexamethasone for 1–3 treatment cycles. The main outcome is functional status measured by the modified Rankin Scale (mRS) at 17 weeks; participants have repeated clinical, cognitive, immune, and biomarker assessments during follow-up.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • Some participants receive a placebo. How is that decided, and what happens for placebo-group participants when the study ends?
  • The listed sites are in Germany. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on autoimmune encephalitis

Clinical trials40 trials listed for autoimmune encephalitisEvery trial the registry lists for autoimmune encephalitis, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in autoimmune encephalitis researchLatest monthly update: September 2026. Includes: Efgartigimod reports. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
May 13, 2020
Primary completion
Sep 30, 2026 (estimated)
Study completion
Dec 31, 2026 (estimated)
Target enrollment
50 participants (estimated)
Last updated on registry
Sep 4, 2025
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Jena University Hospital
Principal investigator
Christian Geis, Prof. Dr. med.
Jena University Hospital
Collaborators
  • Federal Ministry of Education and Reserach (BMBF)

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (17)

Terms used on this page · explanations by MedicalUpdates.ai

informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
Women of childbearing potential
Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
investigational product
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
glucocorticoids
Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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