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

This study has been completed.
Sponsor:
Collaborator:
Alexion Pharmaceuticals
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00904826
First received: May 18, 2009
Last updated: June 19, 2012
Last verified: June 2012
  Purpose

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


Condition Intervention Phase
Neuromyelitis Optica
Devic's Disease
Drug: Eculizumab
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Reduction in number of neuromyelitis optica (NMO)relapses, compared to before entering study. [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • Safety of eculizumab in patients with NMO [ Time Frame: 15 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Improvement of quality of life [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • Improvement in visual function [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • Improvement in walking [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics of the drug in blood [ Time Frame: 15 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics of drug in CSF [ Time Frame: 15 months ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: April 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eculizumab 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 your home by a company which will send a nurse to the patient's home to administer the infusion (Coram Home infusion services). This will be coordinated by either a Study physician or coordinator.

Other Name: Soliris

Detailed Description:

It has been shown in some scientific studies that the the antibody marker specific for neuromyelitis optica (NMO), known as NMO-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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of NMO, as defined by 2006 criteria OR NMO seropositive spectrum disorder (Recurrent ON or longitudinally extensive TM[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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00904826

Locations
United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Alexion Pharmaceuticals
Investigators
Principal Investigator: Sean J. Pittock, M.D. Mayo Clinic
  More Information

Additional Information:
Publications:
Responsible Party: Sean J. Pittock, M.D., Mayo Clinic
ClinicalTrials.gov Identifier: NCT00904826     History of Changes
Other Study ID Numbers: 09-001240
Study First Received: May 18, 2009
Last Updated: June 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
NMO
Devic's disease
Neuromyelitis optica
NMO-IgG
Aquaporin-4 antibody
Eculizumab
Complement

Additional relevant MeSH terms:
Myelitis, Transverse
Neuromyelitis Optica
Multiple Sclerosis
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

ClinicalTrials.gov processed this record on May 19, 2013