A Phase 2/3 interventional study of Tocilizumab Injection and Azathioprine in Neuromyelitis Optica Spectrum Disorders and Neuromyelitis Optica, sponsored by Tianjin Medical University General Hospital. Completed at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-10-24.
Sponsored by Tianjin Medical University General Hospital · Phase 2/3, Interventional, and Treatment
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.
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.
Exclusion Criteria:
Tocilizumab Injection (ACTEMRA®) , a IL-6 receptor blockade
Drug: Tocilizumab Injection
Imuran
Drug: Azathioprine
Tocilizumab Injection will be intravenously administered with a dose of 8 mg/kg every 4 weeks.
Also known as: ACTEMRA®
Azathioprine will be orally given at a dose of 2-3 mg/kg/d
Also known as: Imuran
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.
Time frame: From baseline to one year after
Proportion of patients who experience relapse-free
To record whether the patients had no relapses in the follow-ups
Time frame: From baseline to 60 weeks
Worsening in EDSS
The Expanded Disability Status Scale (EDSS) is a rating system that is frequently used for classifying and standardizing the severity and progression. EDSS ranges from 0 to 10.
Time frame: Worsening from baseline in EDSS to 60 weeks
Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks
Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) \>=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (\<=) 5.5 B) \>=0.5 point from the baseline EDSS score when the baseline score was \>5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. Participants who had initial disability progression with no confirmatory EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment.
Time frame: From baseline to 60 weeks
Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks
Disability improvement was assessed only for the subgroup of participants with a baseline EDSS score of \>= 2.0. It was defined as a reduction in EDSS score of: A) \>=1.0 from the baseline EDSS score when the baseline score was \>=2 and \<=5.5 B) \>= 0.5 when the baseline EDSS score \> 5.5. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death).
Time frame: From baseline to 60 weeks
Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks
Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) \>=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (\<=) 5.5 B) \>=0.5 point from the baseline EDSS score when the baseline score was \>5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death). Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 24 weeks after the initial documentation of neurological worsening. Participants who had initial disability progression with no confirmatory EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment.
Time frame: From baseline to 60 weeks
Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 24 Weeks
Disability improvement was assessed only for the subgroup of participants with a baseline EDSS score of \>= 2.0. It was defined as a reduction in EDSS score of: A) \>=1.0 from the baseline EDSS score when the baseline score was \>=2 and \<=5.5 B) \>= 0.5 when the baseline EDSS score \> 5.5. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death).
Time frame: From baseline to 60 weeks
Percentage Change in Spectral-domain Optical Coherence Tomography (SD-OCT) Average Retinal Nerve Fiber Layer (RNFL) Thickness at Week 60
Adjusted mean percentage change in thickness of the RNFL at Week 60 for the affected eye from the baseline as determined by SD-OCT.
Time frame: From baseline to 60 weeks
Percentage change in SD-OCT Average Retinal Ganglion Cell Layer/Inner Plexiform Retinal Layer (RGCL/IPL) at Week 60
Adjusted mean change in thicknesses of the RGCL/IPL at Week 60 for the affected eye from the baseline as determined by segmentation of SD-OCT.
Time frame: From baseline to 60 weeks
Change in Low-contrast Letter Acuity (LCLA) at Week 60
Adjusted mean change in LCLA at Week 60 from baseline as determined by 2.5% low contrast Sloan letter charts, adjusted for the baseline LCLA value.
Time frame: From baseline to 60 weeks
Change in High-contrast Letter Acuity (HCLA) at Week 60
Adjusted mean change in HCLA at Week 60 from baseline as determined by 100% high contrast Sloan letter charts, adjusted for the baseline HCLA value.
Time frame: From baseline to 60 weeks
Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI)
The total number of new and/or enlarging T2 lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 12, 36, and 60
Time frame: From baseline to 60 weeks
Overall safety and tolerability of tocilizumab or azathioprine
Adverse events related to tocilizumab or azathioprine are recorded.
Time frame: From baseline to 60 weeks
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Treatment-emergent adverse events, treatment-emergent serious adverse events (TESAEs), including laboratory measurements as well as their changes or shift from baseline over time
Time frame: From baseline to 60 weeks
Counts of peripheral blood B cell subsets
Compare peripheral blood plasma cells before and one year after initial intervention
Time frame: From baseline to 60 weeks
Determination of serum immunoglobulins
Compare immunoglobulins before and one year after initial intervention
Time frame: From baseline to 60 weeks
Determination of serum AQP4 antibodies
Compare serum AQP4-ab titers before and one year after initial intervention
Time frame: From baseline to 60 weeks
Determination of serum cytokines
Compare serum cytokines before and one year after initial intervention
Time frame: From baseline to 60 weeks
Plan to share: No
This study is completed, as verified in Oct 2019. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Tianjin Medical University General Hospital