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A Longitudinal Study of ACTEMRA® (Tocilizumab) as Monotherapy in Highly Active NMOSD

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ClinicalTrials.gov Identifier: NCT03062579
Recruitment Status : Completed
First Posted : February 23, 2017
Last Update Posted : October 17, 2018
Sponsor:
Information provided by (Responsible Party):
Fu-Dong Shi, Tianjin Medical University General Hospital

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.

Condition or disease Intervention/treatment Phase
Neuromyelitis Optica Spectrum Disorders Neuromyelitis Optica Devic's Disease Drug: Tocilizumab Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single-center, Open Label Trial of ACTEMRA® (Tocilizumab) as Monotherapy in Highly Active Neuromyelitis Optica Spectrum Disorders (NMOSD)
Actual Study Start Date : February 1, 2017
Actual Primary Completion Date : February 15, 2018
Actual Study Completion Date : May 15, 2018


Arm Intervention/treatment
Experimental: ACTEMRA® (Tocilizumab)
Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, 6 weeks if possible.
Drug: Tocilizumab
Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, 6 weeks if possible, without concurrent other immunosuppressive treatments.
Other Name: ACTEMRA®




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Number of Participants with Adverse Events [ Time Frame: Baseline, 12 months ]
    All adverse events and side effects related to this drug will be recorded.

  2. Neurological Disability - Expanded Disability Scale Score (EDSS) [ Time Frame: Baseline, 12 months ]
    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.

  3. Timed 25-foot Walk [ Time Frame: Baseline, 12 months ]
    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.

  4. Change in Visual Acuity in eyes involved in NMOSD [ Time Frame: Baseline, 12 months ]
    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.

  5. Retinal Nerve Fiber Layer (RNFL) Thickness Determination [ Time Frame: Baseline, 12 months ]
    Compared RNFL by use of Optical Coherence Tomography (OCT) before and one year after initial tocilizumab administration

  6. Ganglion Cell Complex (GCC) Thickness Determination [ Time Frame: Baseline, 12 months ]
    Compared GCC by use of Optical Coherence Tomography (OCT) before and one year after initial tocilizumab administration

  7. Full Field Visual Evoked Response (VEP) P100 waves [ Time Frame: Baseline, 12 months ]
    To determine the latency and amplitude of full field visual evoked response.

  8. Number of new lesions by T2 hyperintensity in the spinal cord and brain MRI [ Time Frame: Baseline, 12 months ]
    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.

  9. Counts of peripheral blood plasma cells [ Time Frame: Baseline, 12 months ]
    Compare peripheral blood plasma cells before and one year after initial tocilizumab administration

  10. Determination of serum immunoglobulins [ Time Frame: Baseline, 12 months ]
    Compare immunoglobulins before and one year after initial tocilizumab administration



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of NMOSD, as defined by 2015 criteria.
  2. 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.
  3. Provision of written informed consent to participate in the study.
  4. Peripheral blood B cell count must be normal (5-20% of total lymphocytes) in subjects before administration of tocilizumab.
  5. EDSS <= 7.5 (8 in special circumstances).

Exclusion Criteria:

  1. Current evidence or known history of clinically significant infection (HSV, VZV, CMV, EBV, HIV, 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. Receipt of rituximab or any experimental B-cell depleting agent within 6 months prior screening and B-cells below the lower limit of normal.
  9. Receipt of IVIG within 1 month prior to randomization.
  10. Receipt of any other concomitant immunosuppressive therapies including corticosteroids, azathioprine, mycophenolate mofetil.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03062579


Locations
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China, Tianjin
Tianjin Medical University General Hospital
Tianjin, Tianjin, China, 300052
Sponsors and Collaborators
Fu-Dong Shi
Investigators
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Principal Investigator: Fu-Dong Shi, MD,PhD Tianjin Medical University General Hospital

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Responsible Party: Fu-Dong Shi, Adjunct Professor of Neurology Department, Tianjin Medical University General Hospital
ClinicalTrials.gov Identifier: NCT03062579     History of Changes
Other Study ID Numbers: IRB2017-YX-006
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: October 17, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Neuromyelitis Optica
Myelitis, Transverse
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Optic Neuritis
Optic Nerve Diseases
Cranial Nerve Diseases
Demyelinating Diseases
Eye Diseases
Autoimmune Diseases
Immune System Diseases