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

Rheumatoid Arthritis Clinical Trial

— TAVAB  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02102594
• Other study ID #: TAVAB
• Secondary ID: 2013-005362-19
• Status: Terminated
• Phase: Phase 2
• Start date: October 2014
• Est. completion date: August 30, 2019

Study information

• Verified date: November 2019
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: August 30, 2019
• Est. primary completion date: August 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

(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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Autoimmune Diseases
• Lupus Erythematosus, Systemic
• Myasthenia Gravis
• Rheumatoid Arthritis
• Systemic Lupus Erythematosus

Intervention

Drug:
• Bortezomib
Bortezomib will be subcutaneously applicated in 2 treatment cycles with 4 injections of 1.3 mg Bortezomib /m2 body surface per cycle.

Locations

Country	Name	City	State
Germany	Charité - Universitätsmedizin Berlin, Internal Medicine / Rheumathology	Berlin
Germany	Charite - Universitätsmedizin Berlin, NeuroCure Clinical Research Center	Berlin

Sponsors (3)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	NeuroCure Clinical Research Center, Charite, Berlin, Prof. Dr. med. Falk Hiepe (Charité, Internal Medicine / Rheumathology)

Country where clinical trial is conducted

Germany, 

References & Publications (2)

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. — View Citation

Kohler S, Märschenz 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Change in quality of life (Qol score)		at regular intervals up to 30 weeks compared to baseline
Secondary	Change in Activities of Daily Living (Adl score)		at regular intervals up to 30 weeks compared to baseline
Secondary	change in dose of immunosuppressive co-medication		at regular intervals up to 30 weeks compared to baseline
Secondary	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
Secondary	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
Secondary	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
Secondary	need for hospitalisation		at regular intervals up to 30 weeks

External Links

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