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

August 30, 2013 updated by: Mayo Clinic
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 Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

14

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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 Names:
  • Soliris

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number Subjects Experiencing an NMO Attack in 12 Months of Eculizumab Treatment
Time Frame: 12 months
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.
baseline, 12 months
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).
12 months
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.)
12 months
Mean Serum Concentration of Eculizumab
Time Frame: 6 weeks, 3 months, 6 months, 9 months, 12 months
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.
baseline, 6 weeks, 3 months, 6 months, 9 months, 12 months
Mean Eculizumab Concentration in Cerebrospinal Fluid (CSF)
Time Frame: 3 months
3 months
Mean Complement Protein 5 (C5) Concentration in CSF
Time Frame: baseline, 3 months
baseline, 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

Alexion Pharmaceuticals

Investigators

  • Principal Investigator: Sean J. Pittock, M.D., Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

May 18, 2009

First Submitted That Met QC Criteria

May 18, 2009

First Posted (Estimate)

May 20, 2009

Study Record Updates

Last Update Posted (Estimate)

November 3, 2013

Last Update Submitted That Met QC Criteria

August 30, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09-001240

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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