Clinical trial NCT02102594: Therapy of Antibody-mediated Autoimmune Diseases by Bortezomib (TAVAB)
Official title: Therapy of Antibody-mediated Autoimmune Diseases by Bortezomib (TAVAB)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myasthenia Gravis
Systemic Lupus Erythematosus
Rheumatoid Arthritis
Keywords: Myasthenia Gravis
Systemic Lupus Erythematosus
Rheumatoid Arthritis
proteasome inhibitor
Bortezomib
Velcade
antibody-mediated autoimmune disease
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Prof. Dr. med. Falk Hiepe (Charité, Internal Medicine / Rheumathology)
name: NeuroCure Clinical Research Center, Charite, Berlin
First posted: 2014-04-03
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: change in disease specific antibody titers after application of Bortezomib
timeFrame: 6 months after end of therapy (6 weeks) compared to baseline (before therapy)
Secondary outcomes:
measure: Change in disease specific antibody titer after Bortezomib application
timeFrame: at regular intervals up to 30 weeks compared to baseline
measure: Change in quality of life (Qol score)
timeFrame: at regular intervals up to 30 weeks compared to baseline
measure: Change in Activities of Daily Living (Adl score)
timeFrame: at regular intervals up to 30 weeks compared to baseline
measure: change in dose of immunosuppressive co-medication
timeFrame: at regular intervals up to 30 weeks compared to baseline
measure: Change in titers of protective antibodies (e.g. measles)
timeFrame: at regular intervals up to 30 weeks compared to baseline
measure: Change in number of antibody producing plasmablasts/cells
timeFrame: at regular intervals up to 30 weeks compared to baseline
measure: Change in concentration of soluble mediators (e.g. IL-6)
timeFrame: at regular intervals up to 30 weeks compared to baseline
measure: need for hospitalisation
timeFrame: at regular intervals up to 30 weeks
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite - Universitätsmedizin Berlin, NeuroCure Clinical Research Center
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Internal Medicine / Rheumathology
Study officials:
affiliation: Charité - Universitätsmedizin Berlin, NeuroCure Clinical Research Center
name: Andreas Meisel, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Charité - Universitätsmedizin Berlin, Internal Medicine / Rheumatology
name: Falk Hiepe, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kohler S, Losen M, Alexander T, Hiepe F, Meisel A. Myasthenia gravis: subgroup classifications. Lancet Neurol. 2016 Apr;15(4):356-7. doi: 10.1016/S1474-4422(16)00033-8. No abstract available.
citation: Kohler S, Marschenz S, Grittner U, Alexander T, Hiepe F, Meisel A. Bortezomib in antibody-mediated autoimmune diseases (TAVAB): study protocol for a unicentric, non-randomised, non-placebo controlled trial. BMJ Open. 2019 Jan 28;9(1):e024523. doi: 10.1136/bmjopen-2018-024523.