Neuromyelitis Optica Spectrum DisordersPhase 2/3TANGONCT03350633
Tocilizumab vs Azathioprine in Neuromyelitis Optica Spectrum Disorders
A Phase 2/3 study testing Tocilizumab Injection and Azathioprine in people with Neuromyelitis Optica Spectrum Disorders and Neuromyelitis Optica, run by Tianjin Medical University General Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuromyelitis Optica Spectrum Disorders, Neuromyelitis Optica
- What is being tested?
- Tocilizumab Injection and Azathioprine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2017to 1 Sep 2019
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Tianjin Medical University General Hospital
Tianjin, Tianjin Municipality, 300052
About this study
Official title: Safety and Efficacy of Tocilizumab Versus Azathioprine in Neuromyelitis Optica Spectrum Disorders: a Randomized, Controlled, Open-label, Phase 2 Trial
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.
Read the 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.
- Being tested
- Tocilizumab Injection, Azathioprine
- Medical subject headings
- Neuromyelitis Optica
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tocilizumab InjectionDrug
Also called ACTEMRA®
Tocilizumab Injection will be intravenously administered with a dose of 8 mg/kg every 4 weeks.
AzathioprineDrug
Also called Imuran
Azathioprine will be orally given at a dose of 2-3 mg/kg/d
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab | Experimental | Tocilizumab Injection (ACTEMRA®) , a IL-6 receptor blockade Receives: Drug: Tocilizumab Injection |
| Azathioprine | Active comparator | Imuran Receives: Drug: Azathioprine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to one year after
Secondary outcomes (17)
Proportion of patients who experience relapse-free
To record whether the patients had no relapses in the follow-ups
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: From baseline to 60 weeks
Overall safety and tolerability of tocilizumab or azathioprine
Adverse events related to tocilizumab or azathioprine are recorded.
Measured: 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
Measured: From baseline to 60 weeks
Counts of peripheral blood B cell subsets
Compare peripheral blood plasma cells before and one year after initial intervention
Measured: From baseline to 60 weeks
Determination of serum immunoglobulins
Compare immunoglobulins before and one year after initial intervention
Measured: From baseline to 60 weeks
Determination of serum AQP4 antibodies
Compare serum AQP4-ab titers before and one year after initial intervention
Measured: From baseline to 60 weeks
Determination of serum cytokines
Compare serum cytokines before and one year after initial intervention
Measured: From baseline to 60 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2017
- Study start1 Nov 2017
- Primary completion1 Sep 2019
- Study completion1 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuromyelitis Optica Spectrum DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tianjin Medical University General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fu-Dong Shi, Tianjin Medical University General Hospital
- Investigators
- Fu-Dong Shi, MD,PhD, Principal investigator, Tianjin Medical University General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03350633
- Sponsor's protocol ID
- IRB2017-YX-009
- Acronym
- TANGO
- Status last verified
- Oct 2019
- First submitted
- 10 Nov 2017
- Last updated
- 24 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32333897
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Tocilizumab Versus Azathioprine in Neuromyelitis Optica Spectrum Disorders: a Randomized, Controlled, Open-label, Phase 2 Trial
- ClinicalTrials.gov ID
- NCT03350633
- Acronym / sponsor ID
- TANGO / IRB2017-YX-009
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Tianjin Medical University General HospitalUniversity, hospital or other
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 1 Sep 2019 (actual)
- Study completion
- 1 Sep 2019 (actual)
- First posted
- 22 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab | Experimental | Drug: Tocilizumab InjectionTocilizumab Injection (ACTEMRA®) , a IL-6 receptor blockade |
| Azathioprine | Active comparator | Drug: AzathioprineImuran |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tocilizumab InjectionAlso: ACTEMRA®Tocilizumab Injection will be intravenously administered with a dose of 8 mg/kg every 4 weeks. | Drug | Tocilizumab |
| AzathioprineAlso: ImuranAzathioprine will be orally given at a dose of 2-3 mg/kg/d | Drug | Azathioprine |
Primary outcome
Time to first relapse
Time frame: From baseline to one year after
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.
17 secondary outcomes
Proportion of patients who experience relapse-free
Time frame: From baseline to 60 weeks
Worsening in EDSS
Time frame: Worsening from baseline in EDSS to 60 weeks
Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks
Time frame: From baseline to 60 weeks
Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks
Time frame: From baseline to 60 weeks
Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks
Time frame: From baseline to 60 weeks
Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 24 Weeks
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
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
Time frame: From baseline to 60 weeks
Change in Low-contrast Letter Acuity (LCLA) at Week 60
Time frame: From baseline to 60 weeks
Change in High-contrast Letter Acuity (HCLA) at Week 60
Time frame: From baseline to 60 weeks
Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI)
Time frame: From baseline to 60 weeks
Overall safety and tolerability of tocilizumab or azathioprine
Time frame: From baseline to 60 weeks
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: From baseline to 60 weeks
Counts of peripheral blood B cell subsets
Time frame: From baseline to 60 weeks
Determination of serum immunoglobulins
Time frame: From baseline to 60 weeks
Determination of serum AQP4 antibodies
Time frame: From baseline to 60 weeks
Determination of serum cytokines
Time frame: From baseline to 60 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2019.
- Derived from this study: PubMed 32333897Zhang 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fu-Dong Shi, MD,PhD principal investigator
Tianjin Medical University General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Tocilizumab Injection and Azathioprine in people with Neuromyelitis Optica Spectrum Disorders and Neuromyelitis Optica, run by Tianjin Medical University General Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to first relapse (time frame: From baseline to one year after). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03350633, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2019.