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

NCT03062579 | Completed Phase 1

• 1 other identifier: IRB2017-YX-006
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuromyelitis Optica Spectrum Disorders; Neuromyelitis Optica; Devic's Disease

Outcome Measures

Primary Outcomes (1)

• Median Number of Neuromyelitis Optica Spectrum Disorder (NMOSD) Attacks Per Year

  Compare annual relapses rate before and one year after initial tocilizumab administration

  Baseline, 12 months

Secondary Outcomes (10)

• Number of Participants with Adverse Events

  Baseline, 12 months

• Neurological Disability - Expanded Disability Scale Score (EDSS)

  Baseline, 12 months

• Timed 25-foot Walk

  Baseline, 12 months

• Change in Visual Acuity in eyes involved in NMOSD

  Baseline, 12 months

• Retinal Nerve Fiber Layer (RNFL) Thickness Determination

  Baseline, 12 months

Study Arms (1)

ACTEMRA® (Tocilizumab)

EXPERIMENTAL

Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, 6 weeks if possible.

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

Tocilizumab will be intravenously administered as the dosage of 8 mg/kg every 4 weeks, 6 weeks if possible, without concurrent other immunosuppressive treatments.

Also known as: ACTEMRA®

ACTEMRA® (Tocilizumab)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fu-Dong Shi: lead

Study Sites (1)

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300052, China

Location

MeSH Terms

Conditions

Neuromyelitis Optica

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Fu-Dong Shi, MD,PhD

  Tianjin Medical University General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Adjunct Professor of Neurology Department

Study Record Dates

• First Submitted: February 13, 2017
• First Posted: February 23, 2017
• Study Start: February 1, 2017
• Primary Completion: February 15, 2018
• Study Completion: May 15, 2018
• Last Updated: April 11, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)