Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

An Open Label Study of the Effects of Eculizumab in Neuromyelitis Optica

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00904826
Recruitment Status : Completed
First Posted : May 20, 2009
Results First Posted : November 4, 2013
Last Update Posted : November 4, 2013
Sponsor:
Collaborator:
Alexion Pharmaceuticals
Information provided by:
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE May 18, 2009
First Posted Date  ICMJE May 20, 2009
Results First Submitted Date  ICMJE August 30, 2013
Results First Posted Date  ICMJE November 4, 2013
Last Update Posted Date November 4, 2013
Study Start Date  ICMJE April 2009
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 30, 2013)
Median Number of Neuromyelitis Optica (NMO) Attacks Per Year [ Time Frame: baseline, after 12 months of treatment ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 18, 2009)
  • 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 ]
Change History Complete list of historical versions of study NCT00904826 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2013)
  • 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 Measures  ICMJE
 (submitted: May 18, 2009)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Open Label Study of the Effects of Eculizumab in Neuromyelitis Optica
Official Title  ICMJE 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 Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuromyelitis Optica
  • Devic's Disease
Intervention  ICMJE Drug: Eculizumab

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
Study Arms  ICMJE Experimental: Eculizumab
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.
Intervention: Drug: Eculizumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 18, 2009)
14
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2011
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Diagnosis of NMO, as defined by 2006 criteria OR NMO seropositive spectrum disorder (Recurrent ON or longitudinally extensive transverse myelitis (LETM)). All patients must be NMO-IgG seropositive.
  2. Clinical evidence of at least 2 relapses in last 6 months or 3 relapses in the last 12 months (with at least 1 relapse occurring in the preceding 6 months).
  3. Age ≥18 years
  4. Corrected visual acuity 20/100 or better in at least one eye. If fails item # 4 then entry allowed but only if last attack was myelitis and only attacks of myelitis are considered as outcome measurement.
  5. Ambulatory (with or without walker). If fails item # 5 then entry allowed but only if last attack was ON and only attacks of ON are considered as outcome measurement.
  6. Provision of written informed consent (see attached) to participate in the study.
  7. N. meningitidis vaccination at least 14 days prior to receiving the first eculizumab infusion. If patient in midst of an acute relapse, then relapse will be treated with standard therapy and vaccination given only after a minimum of 4 weeks post attack onset.

Exclusion Criteria:

Candidates will be excluded from study entry if any of the following criteria are met at the time of randomization:

  1. Progressive neurological deterioration unrelated to relapses of ON or myelitis.
  2. Pregnant, breastfeeding, or intending to conceive 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. Patients with a history of splenectomy, because of a potential increased risk of developing meningococcal infection.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00904826
Other Study ID Numbers  ICMJE 09-001240
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sean J. Pittock, M.D., Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE Alexion Pharmaceuticals
Investigators  ICMJE
Principal Investigator: Sean J. Pittock, M.D. Mayo Clinic
PRS Account Mayo Clinic
Verification Date August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP