Clinical trial NCT03350633: Tocilizumab vs Azathioprine in Neuromyelitis Optica Spectrum Disorders
Official title: Safety and Efficacy of Tocilizumab Versus Azathioprine in Neuromyelitis Optica Spectrum Disorders: a Randomized, Controlled, Open-label, Phase 2 Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Neuromyelitis Optica Spectrum Disorders
Neuromyelitis Optica
Lead sponsor: Tianjin Medical University General Hospital
Sponsor class: OTHER
First posted: 2017-11-22
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The investigators primarily aim to observe the time to first relapse from initiation of tocilizumab or azathioprine treatment. The proportion of participants who experience relapse-free in one year follow-up will be compared.

The secondary outcomes are to determine: The safety profile of tocilizumab and azathioprine in participants with NMO and whether tocilizumab improves visual function, Expanded Disability Status Scale (EDSS), et al.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients ≥ 18 years old
2. Diagnosis of NMO or NMO spectrum disorder
3. Clinical evidence of at least 2 relapses in last 12 months or 3 relapses in the last 24 months
4. Able and willing to give written informed consent and comply with the requirements of the study protocol.
5. EDSS \<= 7.5 (8 in special circumstances)
6. 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.

Exclusion Criteria:

1. 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)
2. Pregnant, breastfeeding, or child-bearing potential during the course of the study
3. 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
4. Participation in another interventional trial within the last 3 months
5. Heart or kidney insufficiency
6. Tumor disease currently or within last 5 years
7. Clinically relevant liver, kidney or bone marrow function disorder
8. Intolerance of azathioprine or previous relapses on azathioprine treatment
9. Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal.

Primary outcomes:
measure: Time to first relapse
timeFrame: From baseline to one year after
Secondary outcomes:
measure: Proportion of patients who experience relapse-free
timeFrame: From baseline to 60 weeks
measure: Worsening in EDSS
timeFrame: Worsening from baseline in EDSS to 60 weeks
measure: Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks
timeFrame: From baseline to 60 weeks
measure: Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks
timeFrame: From baseline to 60 weeks
measure: Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks
timeFrame: From baseline to 60 weeks
measure: Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 24 Weeks
timeFrame: From baseline to 60 weeks
measure: Percentage Change in Spectral-domain Optical Coherence Tomography (SD-OCT) Average Retinal Nerve Fiber Layer (RNFL) Thickness at Week 60
timeFrame: From baseline to 60 weeks
measure: Percentage change in SD-OCT Average Retinal Ganglion Cell Layer/Inner Plexiform Retinal Layer (RGCL/IPL) at Week 60
timeFrame: From baseline to 60 weeks
measure: Change in Low-contrast Letter Acuity (LCLA) at Week 60
timeFrame: From baseline to 60 weeks
measure: Change in High-contrast Letter Acuity (HCLA) at Week 60
timeFrame: From baseline to 60 weeks
measure: Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI)
timeFrame: From baseline to 60 weeks
measure: Overall safety and tolerability of tocilizumab or azathioprine
timeFrame: From baseline to 60 weeks
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: From baseline to 60 weeks
measure: Counts of peripheral blood B cell subsets
timeFrame: From baseline to 60 weeks
measure: Determination of serum immunoglobulins
timeFrame: From baseline to 60 weeks
measure: Determination of serum AQP4 antibodies
timeFrame: From baseline to 60 weeks
measure: Determination of serum cytokines
timeFrame: From baseline to 60 weeks
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University General Hospital
name: Fu-Dong Shi, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.