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

NCT02102594 | Terminated Phase 2

• 2 other identifiers: TAVAB2013-005362-19
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

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.

Conditions

Myasthenia Gravis; Systemic Lupus Erythematosus; Rheumatoid Arthritis

Keywords

Myasthenia Gravis; Systemic Lupus Erythematosus; Rheumatoid Arthritis; proteasome inhibitor; Bortezomib; Velcade; antibody-mediated autoimmune disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Change in disease specific antibody titer after Bortezomib application

  at regular intervals up to 30 weeks compared to baseline

• 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 titers of protective antibodies (e.g. measles)

  at regular intervals up to 30 weeks compared to baseline

Study Arms (1)

Bortezomib (Velcade)

EXPERIMENTAL

Drug: Bortezomib

Interventions

Bortezomib DRUG

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

Also known as: Velcade

Bortezomib (Velcade)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Prof. Dr. med. Falk Hiepe (Charité, Internal Medicine / Rheumathology): collaborator
• NeuroCure Clinical Research Center, Charite, Berlin: collaborator

Study Sites (2)

Charite - Universitätsmedizin Berlin, NeuroCure Clinical Research Center

Berlin, 10117, Germany

Location

Charité - Universitätsmedizin Berlin, Internal Medicine / Rheumathology

Berlin, 10117, Germany

Location

Related 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. No abstract available.

  PMID: 26971655 BACKGROUND

• 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.

  PMID: 30696682 BACKGROUND

MeSH Terms

Conditions

Myasthenia Gravis; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Andreas Meisel, Prof. Dr.

  Charité - Universitätsmedizin Berlin, NeuroCure Clinical Research Center

  PRINCIPAL INVESTIGATOR

• Falk Hiepe, Prof. Dr.

  Charité - Universitätsmedizin Berlin, Internal Medicine / Rheumatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: March 25, 2014
• First Posted: April 3, 2014
• Study Start: October 1, 2014
• Primary Completion: August 30, 2019
• Study Completion: August 30, 2019
• Last Updated: December 3, 2019

Record last verified: 2019-11

Locations

DE (2)