Back to resultsA Longitudinal Study of ACTEMRA® (Tocilizumab) as Monotherapy in Highly Active NMOSD
Primary Purpose
Neuromyelitis Optica Spectrum Disorders, Neuromyelitis Optica, Devic's Disease
Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Tocilizumab
Sponsored by
About this trial
This is an interventional treatment trial for Neuromyelitis Optica Spectrum Disorders
Eligibility Criteria
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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
- 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.
Sites / Locations
- Tianjin Medical University General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ACTEMRA® (Tocilizumab)
Arm Description
Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, 6 weeks if possible.
Outcomes
Primary Outcome Measures
Median Number of Neuromyelitis Optica Spectrum Disorder (NMOSD) Attacks Per Year
Compare annual relapses rate before and one year after initial tocilizumab administration
Secondary Outcome Measures
Number of Participants with Adverse Events
All adverse events and side effects related to this drug will be recorded.
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.
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.
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.
Retinal Nerve Fiber Layer (RNFL) Thickness Determination
Compared RNFL by use of Optical Coherence Tomography (OCT) before and one year after initial tocilizumab administration
Ganglion Cell Complex (GCC) Thickness Determination
Compared GCC by use of Optical Coherence Tomography (OCT) before and one year after initial tocilizumab administration
Full Field Visual Evoked Response (VEP) P100 waves
To determine the latency and amplitude of full field visual evoked response.
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.
Counts of peripheral blood plasma cells
Compare peripheral blood plasma cells before and one year after initial tocilizumab administration
Determination of serum immunoglobulins
Compare immunoglobulins before and one year after initial tocilizumab administration
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03062579
Brief Title
A Longitudinal Study of ACTEMRA® (Tocilizumab) as Monotherapy in Highly Active NMOSD
Official Title
Single-center, Open Label Trial of ACTEMRA® (Tocilizumab) as Monotherapy in Highly Active Neuromyelitis Optica Spectrum Disorders (NMOSD)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
February 1, 2017 (Actual)
Primary Completion Date
February 15, 2018 (Actual)
Study Completion Date
May 15, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Fu-Dong Shi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuromyelitis Optica Spectrum Disorders, Neuromyelitis Optica, Devic's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ACTEMRA® (Tocilizumab)
Arm Type
Experimental
Arm Description
Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, 6 weeks if possible.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
ACTEMRA®
Intervention Description
Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, 6 weeks if possible, without concurrent other immunosuppressive treatments.
Primary Outcome Measure Information:
Title
Median Number of Neuromyelitis Optica Spectrum Disorder (NMOSD) Attacks Per Year
Description
Compare annual relapses rate before and one year after initial tocilizumab administration
Time Frame
Baseline, 12 months
Secondary Outcome Measure Information:
Title
Number of Participants with Adverse Events
Description
All adverse events and side effects related to this drug will be recorded.
Time Frame
Baseline, 12 months
Title
Neurological Disability - Expanded Disability Scale Score (EDSS)
Description
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.
Time Frame
Baseline, 12 months
Title
Timed 25-foot Walk
Description
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.
Time Frame
Baseline, 12 months
Title
Change in Visual Acuity in eyes involved in NMOSD
Description
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.
Time Frame
Baseline, 12 months
Title
Retinal Nerve Fiber Layer (RNFL) Thickness Determination
Description
Compared RNFL by use of Optical Coherence Tomography (OCT) before and one year after initial tocilizumab administration
Time Frame
Baseline, 12 months
Title
Ganglion Cell Complex (GCC) Thickness Determination
Description
Compared GCC by use of Optical Coherence Tomography (OCT) before and one year after initial tocilizumab administration
Time Frame
Baseline, 12 months
Title
Full Field Visual Evoked Response (VEP) P100 waves
Description
To determine the latency and amplitude of full field visual evoked response.
Time Frame
Baseline, 12 months
Title
Number of new lesions by T2 hyperintensity in the spinal cord and brain MRI
Description
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.
Time Frame
Baseline, 12 months
Title
Counts of peripheral blood plasma cells
Description
Compare peripheral blood plasma cells before and one year after initial tocilizumab administration
Time Frame
Baseline, 12 months
Title
Determination of serum immunoglobulins
Description
Compare immunoglobulins before and one year after initial tocilizumab administration
Time Frame
Baseline, 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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).
Exclusion Criteria:
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
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fu-Dong Shi, MD,PhD
Organizational Affiliation
Tianjin Medical University General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tianjin Medical University General Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300052
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Longitudinal Study of ACTEMRA® (Tocilizumab) as Monotherapy in Highly Active NMOSD
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