Efficacy and Safety of Bortezomib as add-on Treatment in Relapsing Neuromyelitis Optica Spectrum Disorder

NCT02893111 | Completed Phase 2 DMC

• 1 other identifier: IRB2016-YX-021
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Neuromyelitis Optica Spectrum Disorders (NMOSD) is characterized by the pathogenic anti-AQP4 antibody, which can be produced by specific plasma cells. The patients who are not responsive to rituximab treatment may be due to the presence of short-lived and long-lived plasma cells. Previous studies confirmed that the proteasome inhibitor bortezomib (Velcade®, approved for therapy of multiple myeloma) eliminated both plasmablasts and plasma cells by activation of the terminal unfolded protein response. Treatment with bortezomib may help deplete plasma cells producing auto-antibodies. Therefore, the rationale for using bortezomib in NMOSD is in that bortezomib may help eliminate autoreactive plasma cells and reduce anti-AQP4 antibodies titers. It is noted that bortezomib may protect astrocytes from NFκB-dependent inflammatory damage in early events in NMOSD pathogenesis. The purpose of this study is to determine if the drug bortezomib contributes to reduce the average relapsing rates (ARRs) and alleviate neurological disability in NMOSD patients.

Conditions

Neuromyelitis Optica Spectrum Disorder

Keywords

neuromyelitis optica spectrum disorders; Bortezomib; Velcade; Proteasome inhibitor

Outcome Measures

Primary Outcomes (1)

• Annual relapse rate (ARR) of NMOSD Attacks

  Compare annual relapse rate before and one year after initial Bortezomib administration

  Baseline, after 12 months of initial treatment

Secondary Outcomes (8)

• Number of Participants with Adverse Events

  Baseline, 12 months

• Change in Expanded Disability Status Scale (EDDS) Score

  Baseline, 12 months

• Timed 25-foot Walk

  Baseline, 12 months

• Number of Subjects With Change in Visual Acuity in at Least One Eye by at Least One Point

  Baseline, 12 months

• MRI brain and spine

  Baseline, 12 months

Study Arms (1)

Bortezomib (Velcade)

EXPERIMENTAL

A proteasome inhibitor

Drug: Bortezomib

Interventions

Bortezomib DRUG

Bortezomib will be subcutaneously applicated in 4 treatment cycles with 4 injections of 1 mg Bortezomib /m2 body surface per cycle

Also known as: Velcade

Bortezomib (Velcade)

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Diagnosis of NMOSD, as defined by 2015 criteria OR NMOSD seropositive spectrum disorder (Recurrent ON or longitudinally extensive transverse myelitis (LETM)). All patients must be NMO-IgG seropositive.
• Clinical evidence of at least 2 relapses in last 6 months or 3 relapses in the last 12 months (with at least 1 relapse occurring in the preceding 6 months)
• The B cell count must be normal (5-20% of total lymphocytes) in subjects before administration of bortezomib
• Provision of written informed consent to participate in the study
• Corrected visual acuity 20/100 or better in at least one eye; otherwise, last attack was myelitis and only attacks of myelitis are outcomes
• Ambulatory (with or without walker); otherwise, last attack was optic neuritis and only attacks of optic neuritis are outcomes

You may not qualify if:

• Current evidence or known history of clinically significant infection (HSV, VZV, CMV, EBV, HIV, Hepatitis viruses, Syphilis, etc)
• Pregnant, breastfeeding, or child-bearing potential during the course of the study
• Patients will not participate in any other clinical therapeutic study or will not have participated in any other experimental treatment study within 30 days of screening
• Patients with a history of splenectomy, because of a potential increased risk of developing meningococcal infection
• Participation in another interventional trial within the last 3 months
• Pre-existent sensory or motor polyneuropathy ≥ degree 2 (NCI CTC AE criteria), within 14 days before screening
• Heart or kidney insufficiency
• Tumor disease currently or within last 5 years
• Clinically relevant liver, kidney or bone marrow function disorder

Sponsors & Collaborators

• Tianjin Medical University General Hospital: lead

Study Sites (1)

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300052, China

Location

MeSH Terms

Conditions

Neuromyelitis Optica

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

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: Director of Neurology

Study Record Dates

• First Submitted: August 27, 2016
• First Posted: September 8, 2016
• Study Start: December 1, 2015
• Primary Completion: December 25, 2016
• Study Completion: January 31, 2017
• Last Updated: April 11, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)