Therapy of Antibody-mediated Autoimmune Diseases by Bortezomib (TAVAB) (TAVAB)
Primary Purpose
Myasthenia Gravis, Systemic Lupus Erythematosus, Rheumatoid Arthritis
Status
Terminated
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Myasthenia Gravis focused on measuring Myasthenia Gravis, Systemic Lupus Erythematosus, Rheumatoid Arthritis, proteasome inhibitor, Bortezomib, Velcade, antibody-mediated autoimmune disease
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
Sites / Locations
- Charite - Universitätsmedizin Berlin, NeuroCure Clinical Research Center
- Charité - Universitätsmedizin Berlin, Internal Medicine / Rheumathology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Bortezomib (Velcade)
Arm Description
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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)
Change in quality of life (Qol score)
Change in Activities of Daily Living (Adl score)
change in dose of immunosuppressive co-medication
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
Change in number of antibody producing plasmablasts/cells
Change in number of antibody producing plasmablasts/cells in peripheral blood
Change in concentration of soluble mediators (e.g. IL-6)
Change in concentration of soluble mediators (e.g. IL-6) in peripheral blood
need for hospitalisation
Full Information
NCT ID
NCT02102594
First Posted
March 25, 2014
Last Updated
November 29, 2019
Sponsor
Charite University, Berlin, Germany
Collaborators
Prof. Dr. med. Falk Hiepe (Charité, Internal Medicine / Rheumathology), NeuroCure Clinical Research Center, Charite, Berlin
1. Study Identification
Unique Protocol Identification Number
NCT02102594
Brief Title
Therapy of Antibody-mediated Autoimmune Diseases by Bortezomib (TAVAB)
Acronym
TAVAB
Official Title
Therapy of Antibody-mediated Autoimmune Diseases by Bortezomib (TAVAB)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Terminated
Why Stopped
recruitment difficulties
Study Start Date
October 2014 (undefined)
Primary Completion Date
August 30, 2019 (Actual)
Study Completion Date
August 30, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Charite University, Berlin, Germany
Collaborators
Prof. Dr. med. Falk Hiepe (Charité, Internal Medicine / Rheumathology), NeuroCure Clinical Research Center, Charite, Berlin
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myasthenia Gravis, Systemic Lupus Erythematosus, Rheumatoid Arthritis
Keywords
Myasthenia Gravis, Systemic Lupus Erythematosus, Rheumatoid Arthritis, proteasome inhibitor, Bortezomib, Velcade, antibody-mediated autoimmune disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bortezomib (Velcade)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
Bortezomib will be subcutaneously applicated in 2 treatment cycles with 4 injections of 1.3 mg Bortezomib /m2 body surface per cycle.
Primary Outcome Measure Information:
Title
change in disease specific antibody titers after application of Bortezomib
Description
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).
Time Frame
6 months after end of therapy (6 weeks) compared to baseline (before therapy)
Secondary Outcome Measure Information:
Title
Change in disease specific antibody titer after Bortezomib application
Description
Change in disease specific antibody titer after Bortezomib application (except at time point 6 months after end of therapy = primary outcome measure)
Time Frame
at regular intervals up to 30 weeks compared to baseline
Title
Change in quality of life (Qol score)
Time Frame
at regular intervals up to 30 weeks compared to baseline
Title
Change in Activities of Daily Living (Adl score)
Time Frame
at regular intervals up to 30 weeks compared to baseline
Title
change in dose of immunosuppressive co-medication
Time Frame
at regular intervals up to 30 weeks compared to baseline
Title
Change in titers of protective antibodies (e.g. measles)
Description
Change in titers of protective antibodies against measles virus, rubella virus, varicella zoster virus, pneumococcus, cytomegalovirus
Time Frame
at regular intervals up to 30 weeks compared to baseline
Title
Change in number of antibody producing plasmablasts/cells
Description
Change in number of antibody producing plasmablasts/cells in peripheral blood
Time Frame
at regular intervals up to 30 weeks compared to baseline
Title
Change in concentration of soluble mediators (e.g. IL-6)
Description
Change in concentration of soluble mediators (e.g. IL-6) in peripheral blood
Time Frame
at regular intervals up to 30 weeks compared to baseline
Title
need for hospitalisation
Time Frame
at regular intervals up to 30 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas Meisel, Prof. Dr.
Organizational Affiliation
Charité - Universitätsmedizin Berlin, NeuroCure Clinical Research Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Falk Hiepe, Prof. Dr.
Organizational Affiliation
Charité - Universitätsmedizin Berlin, Internal Medicine / Rheumatology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Charite - Universitätsmedizin Berlin, NeuroCure Clinical Research Center
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Charité - Universitätsmedizin Berlin, Internal Medicine / Rheumathology
City
Berlin
ZIP/Postal Code
10117
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
26971655
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.
Results Reference
background
PubMed Identifier
30696682
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.
Results Reference
background
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Therapy of Antibody-mediated Autoimmune Diseases by Bortezomib (TAVAB)
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