An Open Label Study of the Effects of Eculizumab in Neuromyelitis Optica
The purpose of this study is to determine if the drug eculizumab reduces the attack rate and improves outcome in patients with neuromyelitis optica.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label Study of the Effects of Eculizumab in Neuromyelitis Optica|
- Median Number of Neuromyelitis Optica (NMO) Attacks Per Year [ Time Frame: baseline, after 12 months of treatment ] [ Designated as safety issue: No ]
- Number Subjects Experiencing an NMO Attack in 12 Months of Eculizumab Treatment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Change in Expanded Disability Status Scale (EDDS) Score [ Time Frame: baseline, 12 months ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
- Percentage Hemolysis [ Time Frame: baseline, 6 weeks, 3 months, 6 months, 9 months, 12 months ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
- Mean Complement Protein 5 (C5) Concentration in CSF [ Time Frame: baseline, 3 months ] [ Designated as safety issue: No ]
|Study Start Date:||April 2009|
|Study Completion Date:||December 2011|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks. Subjects will receive therapy for a total of 12 months.
The patient will receive eculizumab at a dose of 600mg intravenously (an infusion given into the vein) each week for 4 weeks, then 900mg intravenously at the fifth week, then 900mg every 2 weeks for 48 weeks.
The first infusion will be given at Mayo Clinic site; subsequent infusions will be administered in the subject's home by a company which will send a nurse to administer the infusion. Subjects will receive therapy for a total of 12 months.
Other Name: Soliris
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's blood (called pharmacodynamics and pharmacokinetics).
Depending on our preliminary investigations we may evaluate patient cerebrospinal fluid in the laboratory to see how effective eculizumab is at getting into the cerebrospinal fluid from the blood stream, and to see if the drug reverses the biological effects of the NMO-IgG antibody.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00904826
|United States, Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Sean J. Pittock, M.D.||Mayo Clinic|