Therapy of Antibody-mediated Autoimmune Diseases by Bortezomib (TAVAB)

Study Overview
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Brief Summary
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The aim of this pilot study is to investigate the application of proteasome inhibitor Bortezomib (Velcade®, approved for therapy of multiple myeloma) in patients with therapy-refractory antibody-mediated autoimmune diseases. The investigators hypothesis is that the proteasome inhibition will lead to reduced antibody titers and improved clinical outcome.

Official Title
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Therapy of Antibody-mediated Autoimmune Diseases by Bortezomib (TAVAB)

Conditions
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Myasthenia Gravis, Systemic Lupus Erythematosus, Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Bortezomib


Participation Criteria
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Eligibility Criteria
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(main) Inclusion Criteria: age 18 - 75 years at screening ability to give written consent, informed written consent negative pregnancy test at screening therapy-refractory Myasthenia Gravis (generalized) or Systemic Lupus Erythematosus or Rheumatoid Arthritis (main) Exclusion Criteria: Belimumab therapy within the last 6 months B-cell-depletion therapy within the last 9 months heart or kidney insufficiency known intolerability to Bortezomib participation in another interventional trial within the last 3 months liver cirrhosis preexistent sensory or motor polyneuropathy ≥ degree 2 (NCI CTC AE criteria), within 14 days before screening hints on clinically apparent herpes zoster reactivation active systemic infection, or viral infection (CMV, EBV) within last 6 month before screening serologically active hepatitis B and /or C, known HIV infection tumor disease currently or within last 5 years clinically relevant liver, kidney or bone marrow function disorder pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bortezomib (Velcade)<br> | Drug: Bortezomib<br>* Bortezomib will be subcutaneously applicated in 2 treatment cycles with 4 injections of 1.3 mg Bortezomib /m2 body surface per cycle.<br>* Other names: Velcade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in disease specific antibody titers after application of Bortezomib | Change in disease specific antibody titers (anti-ACh for myasthenia gravis, anti-dsDNA for systemic lupus erythematosus, anti-ACPA for rheumatoid arthritis) 6 months after end of Bortezomib therapy (duration 6 weeks) compared to baseline (before therapy). | 6 months after end of therapy (6 weeks) compared to baseline (before therapy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in disease specific antibody titer after Bortezomib application | Change in disease specific antibody titer after Bortezomib application (except at time point 6 months after end of therapy = primary outcome measure) | at regular intervals up to 30 weeks compared to baseline | 
| Change in quality of life (Qol score) |  | at regular intervals up to 30 weeks compared to baseline | 
| Change in Activities of Daily Living (Adl score) |  | at regular intervals up to 30 weeks compared to baseline | 
| change in dose of immunosuppressive co-medication |  | at regular intervals up to 30 weeks compared to baseline | 
| Change in titers of protective antibodies (e.g. measles) | Change in titers of protective antibodies against measles virus, rubella virus, varicella zoster virus, pneumococcus, cytomegalovirus | at regular intervals up to 30 weeks compared to baseline | 
| Change in number of antibody producing plasmablasts/cells | Change in number of antibody producing plasmablasts/cells in peripheral blood | at regular intervals up to 30 weeks compared to baseline | 
| Change in concentration of soluble mediators (e.g. IL-6) | Change in concentration of soluble mediators (e.g. IL-6) in peripheral blood | at regular intervals up to 30 weeks compared to baseline | 
| need for hospitalisation |  | at regular intervals up to 30 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, proteasome inhibitor, Bortezomib, Velcade, antibody-mediated autoimmune disease, Myasthenia Gravis, Systemic Lupus Erythematosus