Myasthenia Gravis, Rheumatoid Arthritis, Systemic Lupus Erythematosus
Conditions
Keywords
Myasthenia Gravis, Systemic Lupus Erythematosus, Rheumatoid Arthritis, proteasome inhibitor, Bortezomib, Velcade, antibody-mediated autoimmune disease
Brief summary
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.
Interventions
DRUGBortezomib
Bortezomib will be subcutaneously applicated in 2 treatment cycles with 4 injections of 1.3 mg Bortezomib /m2 body surface per cycle.
Sponsors
Prof. Dr. med. Falk Hiepe (Charité, Internal Medicine / Rheumathology)
NeuroCure Clinical Research Center, Charite, Berlin
Charite University, Berlin, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
(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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| change in disease specific antibody titers after application of Bortezomib | 6 months after end of therapy (6 weeks) compared to baseline (before therapy) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 disease specific antibody titer after Bortezomib application | at regular intervals up to 30 weeks compared to baseline | Change in disease specific antibody titer after Bortezomib application (except at time point 6 months after end of therapy = primary outcome measure) |
| Change in number of antibody producing plasmablasts/cells | at regular intervals up to 30 weeks compared to baseline | Change in number of antibody producing plasmablasts/cells in peripheral blood |
| Change in concentration of soluble mediators (e.g. IL-6) | at regular intervals up to 30 weeks compared to baseline | Change in concentration of soluble mediators (e.g. IL-6) in peripheral blood |
| need for hospitalisation | at regular intervals up to 30 weeks | — |
| Change in titers of protective antibodies (e.g. measles) | at regular intervals up to 30 weeks compared to baseline | Change in titers of protective antibodies against measles virus, rubella virus, varicella zoster virus, pneumococcus, cytomegalovirus |
Countries
Germany
Outcome results
None listed