Clinical Trial: An Open Label Study of the Effects of Eculizumab in Neuromyelitis Optica

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open Label Study of the Effects of Eculizumab in Neuromyelitis Optica

Brief Summary: The purpose of this study is to determine if the drug eculizumab reduces the attack rate and improves outcome in patients with neuromyelitis optica.

Detailed Summary:

It has been shown in some scientific studies that the the antibody marker specific for neuromyelitis optica (NMO), known as NMO-Immunoglobulin G (IgG), causes inflammation in brain tissues by activating a substance called complement. Complement can greatly increase the immune attack in the optic nerves (causing optic neuritis (ON)), spinal cords (causing transverse myelitis (TM)) and brains of patients with NMO. Eculizumab has already been shown to be effective in a rare blood disorder known as paroxysmal nocturnal hemoglobinuria (PNH). Attacks of PNH are also mediated through complement. Therefore, the investigators of this study are investigating whether by 'turning off' complement in NMO, further attacks of NMO can be prevented.

The primary (most important) objectives of this study are to determine:

Whether Eculizumab 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 eculizumab treatment. For patients with more than 2 year disease duration, the average number of attacks in the preceding 2 years will be calculated. For patients with less than 2 years disease duration the number of attacks in the preceding year will be used.

The safety profile of eculizumab in patients with NMO.

The secondary objectives are to determine:

Whether eculizumab maintains or improves walking, visual function and quality of life as measured by a variety of established disability scales. We will also assess the severity of an individual attack and the degree of recovery.

How the drug behaves in the patient'
Sponsor: Mayo Clinic

Current Primary Outcome: Median Number of Neuromyelitis Optica (NMO) Attacks Per Year [ Time Frame: baseline, after 12 months of treatment ]

Original Primary Outcome:

  • Reduction in number of neuromyelitis optica (NMO)relapses, compared to before entering study. [ Time Frame: 15 months ]
  • Safety of eculizumab in patients with NMO [ Time Frame: 15 months ]


Current Secondary Outcome:

  • Number Subjects Experiencing an NMO Attack in 12 Months of Eculizumab Treatment [ Time Frame: 12 months ]
  • Change in Expanded Disability Status Scale (EDDS) Score [ Time Frame: baseline, 12 months ]
    The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death) in half-point increments.
  • Number of Subjects With Change in Visual Acuity in at Least One Eye by at Least One Point [ Time Frame: 12 months ]
    Visual acuity was measured using the the Visual Acuity subscale of the Opticospinal Impairment Score (OSIS) for Exacerbations. This subscale ranges from 0 (normal) to 8 (no light perception).
  • Number of Subjects With Change in Ambulation by at Least 1 Point [ Time Frame: 12 months ]
    Ambulation was measured by the Hauser Ambulation Index, which ranges from 0 (asymptomatic; fully active) to 9 (restricted to wheelchair; unable to transfer self independently.)
  • Mean Serum Concentration of Eculizumab [ Time Frame: 6 weeks, 3 months, 6 months, 9 months, 12 months ]
  • Percentage Hemolysis [ Time Frame: baseline, 6 weeks, 3 months, 6 months, 9 months, 12 months ]
    Percentage of hemolysis is a measure of complement activity. Less than 20% lysis is deemed to be complete complement inhibition.
  • Mean Eculizumab Concentration in Cerebrospinal Fluid (CSF) [ Time Frame: 3 months ]
  • Mean Complement Protein 5 (C5) Concentration in CSF [ Time Frame: baseline, 3 months ]


Original Secondary Outcome:

  • Improvement of quality of life [ Time Frame: 15 months ]
  • Improvement in visual function [ Time Frame: 15 months ]
  • Improvement in walking [ Time Frame: 15 months ]
  • Pharmacokinetics of the drug in blood [ Time Frame: 15 months ]
  • Pharmacokinetics of drug in CSF [ Time Frame: 15 months ]


Information By: Mayo Clinic

Dates:
Date Received: May 18, 2009
Date Started: April 2009
Date Completion:
Last Updated: August 30, 2013
Last Verified: August 2013