Neuromyelitis Optica Spectrum DisordersPhase 1/2NCT03062579
A Longitudinal Study of ACTEMRA® (Tocilizumab) as Monotherapy in Highly Active NMOSD
A Phase 1/2 study testing Tocilizumab in people with Neuromyelitis Optica Spectrum Disorders and Neuromyelitis Optica, run by Fu-Dong Shi at 1 site in China.
Trial summary
Neuromyelitis Optica Spectrum Disorder (NMOSD) is a severe inflammatory disease of the central nervous system characterized by relapsing optic neuritis and longitudinal extensive transverse myelitis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Neuromyelitis Optica Spectrum Disorders, Neuromyelitis Optica, Devic's Disease
- What is being tested?
- Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 1 Feb 2017to 15 May 2018
- Phase
- Phase 1/2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of NMOSD, as defined by 2015 criteria.
- NMOSD patients with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years.
- Provision of written informed consent to participate in the study.
- Peripheral blood B cell count must be normal (5-20% of total lymphocytes) in subjects before administration of tocilizumab.
- EDSS <= 7.5 (8 in special circumstances).
Who cannot join
- 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
- Participation in another interventional trial within the last 3 months
- Heart or kidney insufficiency
- Tumor disease currently or within last 5 years
Show all 10Show fewer
- Clinically relevant liver, kidney or bone marrow function disorder
- Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal.
- Receipt of IVIG within 1 month prior to randomization.
- Receipt of any other concomitant immunosuppressive therapies including corticosteroids, azathioprine, mycophenolate mofetil.
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: Single-center, Open Label Trial of ACTEMRA® (Tocilizumab) as Monotherapy in Highly Active Neuromyelitis Optica Spectrum Disorders (NMOSD)
Neuromyelitis Optica Spectrum Disorder (NMOSD) is a severe inflammatory disease of the central nervous system characterized by relapsing optic neuritis and longitudinal extensive transverse myelitis. The specific autoantibody against aquaporin 4 (AQP4-ab) has been suggested to contribute to the pathogenesis of the disease. Peripheral blood plasma cells are a major source of AQP4-ab. Previous studies have observed increased IL-6 levels in serum and cerebrospinal fluid of patients with NMOSD, particularly during relapses. Exogenous interleukin (IL)-6 promotes the survival of plasma cells and their production of AQP4-ab in vitro. And blockade of IL-6 receptor signaling by an anti-IL-6 receptor antibody reduces the survival of plasma cells in vitro. Tocilizumab (ACTEMRA®), a humanized monoclonal antibody against the IL-6 receptor, has shown beneficial clinical effects in some patients with NMOSD when concomitant immunosuppressive medications were administered. However, the long-lasting biological effects of preceding immunotherapies such as rituximab might overlap with the subsequent tocilizumab therapy. To reduce the side effects of concomitant treatments to large extent and verify the beneficial effects of tocilizumab, we evaluate the safety and efficacy of tocilizumab as monotherapy in patients with NMOSD.
Read the detailed description
The purpose of this study is to determine if the drug tocilizumab as monotherapy contributes to reduce the average relapsing rate (ARR) and improve neurological disability in NMOSD patients, who still have experienced relapses when common immunosuppressive medications including rituximab had been used.
The primary (most important) objectives of this study are to determine: Whether bortezomib reduces relapse frequency in patients with relapsing NMO. The number of attacks during the one year treatment period will be compared to the number of attacks that occurred prior to initiation of tocilizumab treatment.
The secondary objectives are to determine:
The safety profile of tocilizumab in patients with NMO and whether tocilizumab improves walking, visual function and quality of life as measured by a variety of established disability scales.
- Being tested
- Tocilizumab
- Medical subject headings
- Neuromyelitis Optica
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called ACTEMRA®
Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, 6 weeks if possible, without concurrent other immunosuppressive treatments.
| Study group | Role | What they receive |
|---|---|---|
| ACTEMRA® (Tocilizumab) | Experimental | Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, 6 weeks if possible. Receives: Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Number of Neuromyelitis Optica Spectrum Disorder (NMOSD) Attacks Per Year
Compare annual relapses rate before and one year after initial tocilizumab administration
Measured: Baseline, 12 months
Secondary outcomes (10)
Number of Participants with Adverse Events
All adverse events and side effects related to this drug will be recorded.
Measured: Baseline, 12 months
Neurological Disability - Expanded Disability Scale Score (EDSS)
The EDSS provides a total score on a scale that ranges from 0 to 10. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death.
Measured: Baseline, 12 months
Timed 25-foot Walk
The Timed 25-Foot Walk test is a quantitative measure of lower extremity function. If required, the subject may use an appropriate assistive device to walk as quickly as he/she can from one end to the other end of a clearly marked, unobstructed, 25-foot course.
Measured: Baseline, 12 months
Change in Visual Acuity in eyes involved in NMOSD
100% visual acuity and 2.5% contrast visual acuity are examined with high-contrast Sloan letter charts, which are readily available and provide a practical, quantitative, and standardized assessment of visual function. Each chart consists of rows of black letters (decreasing in size from top to bottom) on a white background.
Measured: Baseline, 12 months
Retinal Nerve Fiber Layer (RNFL) Thickness Determination
Compared RNFL by use of Optical Coherence Tomography (OCT) before and one year after initial tocilizumab administration
Measured: Baseline, 12 months
Ganglion Cell Complex (GCC) Thickness Determination
Compared GCC by use of Optical Coherence Tomography (OCT) before and one year after initial tocilizumab administration
Measured: Baseline, 12 months
Full Field Visual Evoked Response (VEP) P100 waves
To determine the latency and amplitude of full field visual evoked response.
Measured: Baseline, 12 months
Number of new lesions by T2 hyperintensity in the spinal cord and brain MRI
MRIs will be performed for standard of care purposes and will be used to evaluate imaging relapses. For this trial, the MRIs will be analyzed for counting the number of new lesions by T2 hyperintensity in the spinal cord and brain.
Measured: Baseline, 12 months
Counts of peripheral blood plasma cells
Compare peripheral blood plasma cells before and one year after initial tocilizumab administration
Measured: Baseline, 12 months
Determination of serum immunoglobulins
Compare immunoglobulins before and one year after initial tocilizumab administration
Measured: Baseline, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2017
- Study start1 Feb 2017
- Primary completion15 Feb 2018
- Study completion15 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fu-Dong Shi
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-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
- NCT03062579
- Sponsor's protocol ID
- IRB2017-YX-006
- Status last verified
- Apr 2024
- First submitted
- 13 Feb 2017
- Last updated
- 11 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-center, Open Label Trial of ACTEMRA® (Tocilizumab) as Monotherapy in Highly Active Neuromyelitis Optica Spectrum Disorders (NMOSD)
- ClinicalTrials.gov ID
- NCT03062579
- Acronym / sponsor ID
- IRB2017-YX-006
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Fu-Dong ShiUniversity, hospital or other
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 15 Feb 2018 (actual)
- Study completion
- 15 May 2018 (actual)
- First posted
- 23 Feb 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.
Neuromyelitis Optica Spectrum Disorder (NMOSD) is a severe inflammatory disease of the central nervous system characterized by relapsing optic neuritis and longitudinal extensive transverse myelitis. The specific autoantibody against aquaporin 4 (AQP4-ab) has been suggested to contribute to the pathogenesis of the disease. Peripheral blood plasma cells are a major source of AQP4-ab. Previous studies have observed increased IL-6 levels in serum and cerebrospinal fluid of patients with NMOSD, particularly during relapses. Exogenous interleukin (IL)-6 promotes the survival of plasma cells and their production of AQP4-ab in vitro. And blockade of IL-6 receptor signaling by an anti-IL-6 receptor antibody reduces the survival of plasma cells in vitro. Tocilizumab (ACTEMRA®), a humanized monoclonal antibody against the IL-6 receptor, has shown beneficial clinical effects in some patients with NMOSD when concomitant immunosuppressive medications were administered. However, the long-lasting biological effects of preceding immunotherapies such as rituximab might overlap with the subsequent tocilizumab therapy. To reduce the side effects of concomitant treatments to large extent and verify the beneficial effects of tocilizumab, we evaluate the safety and efficacy of tocilizumab as monotherapy in patients with NMOSD.
Detailed description
The purpose of this study is to determine if the drug tocilizumab as monotherapy contributes to reduce the average relapsing rate (ARR) and improve neurological disability in NMOSD patients, who still have experienced relapses when common immunosuppressive medications including rituximab had been used.
The primary (most important) objectives of this study are to determine: Whether bortezomib reduces relapse frequency in patients with relapsing NMO. The number of attacks during the one year treatment period will be compared to the number of attacks that occurred prior to initiation of tocilizumab treatment.
The secondary objectives are to determine:
The safety profile of tocilizumab in patients with NMO and whether tocilizumab improves walking, visual function and quality of life as measured by a variety of established disability scales.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ACTEMRA® (Tocilizumab) | Experimental | Drug: TocilizumabTocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, 6 weeks if possible. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of NMOSD, as defined by 2015 criteria.
- NMOSD patients with at least one attack requiring rescue therapy in the last year or two attacks requiring rescue therapy in the last 2 years.
- Provision of written informed consent to participate in the study.
- Peripheral blood B cell count must be normal (5-20% of total lymphocytes) in subjects before administration of tocilizumab.
- EDSS <= 7.5 (8 in special circumstances).
Key exclusion criteria (10 listed)
- 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
- 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 |
|---|---|---|
| TocilizumabAlso: ACTEMRA®Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, 6 weeks if possible, without concurrent other immunosuppressive treatments. | Drug | ACTEMRA® (Tocilizumab) |
Primary outcome
Median Number of Neuromyelitis Optica Spectrum Disorder (NMOSD) Attacks Per Year
Time frame: Baseline, 12 months
Compare annual relapses rate before and one year after initial tocilizumab administration
10 secondary outcomes
Number of Participants with Adverse Events
Time frame: Baseline, 12 months
Neurological Disability - Expanded Disability Scale Score (EDSS)
Time frame: Baseline, 12 months
Timed 25-foot Walk
Time frame: Baseline, 12 months
Change in Visual Acuity in eyes involved in NMOSD
Time frame: Baseline, 12 months
Retinal Nerve Fiber Layer (RNFL) Thickness Determination
Time frame: Baseline, 12 months
Ganglion Cell Complex (GCC) Thickness Determination
Time frame: Baseline, 12 months
Full Field Visual Evoked Response (VEP) P100 waves
Time frame: Baseline, 12 months
Number of new lesions by T2 hyperintensity in the spinal cord and brain MRI
Time frame: Baseline, 12 months
Counts of peripheral blood plasma cells
Time frame: Baseline, 12 months
Determination of serum immunoglobulins
Time frame: Baseline, 12 months
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 11 Apr 2024.
- 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 1/2 study testing Tocilizumab in people with Neuromyelitis Optica Spectrum Disorders and Neuromyelitis Optica, run by Fu-Dong Shi 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 5 inclusion and 10 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 11 Apr 2024. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Median Number of Neuromyelitis Optica Spectrum Disorder (NMOSD) Attacks Per Year (time frame: Baseline, 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Apr 2024.