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

Phase 2

Terminated

• Conditions: Myasthenia Gravis; Systemic Lupus Erythematosus; Rheumatoid Arthritis
• Interventions: Drug: Bortezomib

• Registration Number: NCT02102594
• Lead Sponsor: Charite University, Berlin, Germany

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-03-25
• Study First Submitted QC: 2014-04-02
• Study First Posted: 2014-04-03
• Study Start: 2014-10
• Primary Completion: 2019-08-30
• Study Completion: 2019-08-30
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-29
• Last Update Posted: 2019-12-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 11

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bortezomib (Velcade)	Bortezomib	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Change in quality of life (Qol score)	at regular intervals up to 30 weeks compared to baseline
need for hospitalisation	at regular intervals up to 30 weeks
change in dose of immunosuppressive co-medication	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 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 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
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

Trial Locations

Locations (2)

Charite - Universitätsmedizin Berlin, NeuroCure Clinical Research Center; 🇩🇪 Berlin, Germany

Charité - Universitätsmedizin Berlin, Internal Medicine / Rheumathology; 🇩🇪 Berlin, Germany