Tocilizumab vs Azathioprine in Neuromyelitis Optica Spectrum Disorders

NCT03350633 | Completed Phase 2 DMC

• 1 other identifier: IRB2017-YX-009
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

In neuromyelitis optica spectrum disorder (NMOSD),interleukin-6 (IL-6) may play an important role in facilitating plasma cells to produce pathological aquaporin 4 (AQP4) autoantibody. Inhibition of IL-6 signaling pathway by Tocilizumab (ACTEMRA®), a humanized monoclonal antibody may have shown beneficial clinical effects in a few patients with NMOSD. Larger scale clincial trials may be needed to observe its efficacy and safety. Here, by choosing azathioprine, one of the most frequently used medication in case of relapses, the investigators compare the safety and efficacy of tocilizumab in preventing NMOSD attacks.

Conditions

Neuromyelitis Optica Spectrum Disorders; Neuromyelitis Optica

Outcome Measures

Primary Outcomes (1)

• Time to first relapse

  An acute attack was defined as a new neurological worsening lasting for at least 24 hours and occurring more than 30 days after the previous attack.

  From baseline to one year after

Secondary Outcomes (17)

• Proportion of patients who experience relapse-free

  From baseline to 60 weeks

• Worsening in EDSS

  Worsening from baseline in EDSS to 60 weeks

• Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks

  From baseline to 60 weeks

• Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks

  From baseline to 60 weeks

• Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks

  From baseline to 60 weeks

Study Arms (2)

Tocilizumab

EXPERIMENTAL

Tocilizumab Injection (ACTEMRA®) , a IL-6 receptor blockade

Drug: Tocilizumab Injection

Azathioprine

ACTIVE COMPARATOR

Imuran

Drug: Azathioprine

Interventions

Tocilizumab Injection DRUG

Tocilizumab Injection will be intravenously administered with a dose of 8 mg/kg every 4 weeks.

Also known as: ACTEMRA®

Tocilizumab

Azathioprine DRUG

Azathioprine will be orally given at a dose of 2-3 mg/kg/d

Also known as: Imuran

Azathioprine

Eligibility Criteria

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

You may qualify if:

• Male or female patients ≥ 18 years old
• Diagnosis of NMO or NMO spectrum disorder
• Clinical evidence of at least 2 relapses in last 12 months or 3 relapses in the last 24 months
• Able and willing to give written informed consent and comply with the requirements of the study protocol.
• EDSS \<= 7.5 (8 in special circumstances)
• Men and women of reproductive potential must agree to use a highly effective method of birth control from screening to 6 months after final dose of the investigational product.

You may not qualify if:

• Current evidence or known history of clinically significant infection (Herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus,human immunodeficiency virus, 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
• Participation in another interventional trial within the last 3 months
• Heart or kidney insufficiency
• Tumor disease currently or within last 5 years
• Clinically relevant liver, kidney or bone marrow function disorder
• Intolerance of azathioprine or previous relapses on azathioprine treatment
• Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal.

Sponsors & Collaborators

• Tianjin Medical University General Hospital: lead

Study Sites (1)

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300052, China

Location

Related Publications (1)

• Zhang C, Zhang M, Qiu W, Ma H, Zhang X, Zhu Z, Yang CS, Jia D, Zhang TX, Yuan M, Feng Y, Yang L, Lu W, Yu C, Bennett JL, Shi FD; TANGO Study Investigators. Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial. Lancet Neurol. 2020 May;19(5):391-401. doi: 10.1016/S1474-4422(20)30070-3.

  PMID: 32333897 DERIVED

MeSH Terms

Conditions

Neuromyelitis Optica

Interventions

tocilizumab; Azathioprine

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)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Fu-Dong Shi, MD,PhD

  Tianjin Medical University General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Neurology Department

Study Record Dates

• First Submitted: November 10, 2017
• First Posted: November 22, 2017
• Study Start: November 1, 2017
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: October 24, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)