Neuromyelitis OpticaPhase 1/2NCT00904826
An Open Label Study of the Effects of Eculizumab in Neuromyelitis Optica
A Phase 1/2 study testing Eculizumab in people with Neuromyelitis Optica and Devic's Disease, run by Mayo Clinic at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuromyelitis Optica, Devic's Disease
- What is being tested?
- Eculizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2009to Dec 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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).
- Age ≥18 years
- 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.
- 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.
- Provision of written informed consent (see attached) to participate in the study.
- 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.
Who cannot join
- Candidates will be excluded from study entry if any of the following criteria are met at the time of randomization:
- Progressive neurological deterioration unrelated to relapses of ON or myelitis.
- Pregnant, breastfeeding, or intending to conceive during the course of the study
- 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
- Patients with a history of splenectomy, because of a potential increased risk of developing meningococcal infection.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mayo Clinic
Rochester, Minnesota, 55905
Mayo Clinic
Scottsdale, Arizona, 85259
About this study
The purpose of this study is to determine if the drug eculizumab reduces the attack rate and improves outcome in patients with neuromyelitis optica.
Read the 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.
- Conditions
- Neuromyelitis Optica, Devic's Disease
- Being tested
- Eculizumab
- Keywords
- NMO, Devic's disease, Neuromyelitis optica, NMO-IgG, Aquaporin-4 antibody, Eculizumab, Complement
- Medical subject headings
- Neuromyelitis Optica
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabDrug
Also called Soliris
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.
| Study group | Role | What they receive |
|---|---|---|
| Eculizumab | Experimental | 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. Receives: Drug: Eculizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Number of Neuromyelitis Optica (NMO) Attacks Per Year
Measured: baseline, after 12 months of treatment
Secondary outcomes (8)
Number Subjects Experiencing an NMO Attack in 12 Months of Eculizumab Treatment
Measured: 12 months
Change in Expanded Disability Status Scale (EDDS) Score
The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death) in half-point increments.
Measured: baseline, 12 months
Number of Subjects With Change in Visual Acuity in at Least One Eye by at Least One Point
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).
Measured: 12 months
Number of Subjects With Change in Ambulation by at Least 1 Point
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.)
Measured: 12 months
Mean Serum Concentration of Eculizumab
Measured: 6 weeks, 3 months, 6 months, 9 months, 12 months
Percentage Hemolysis
Percentage of hemolysis is a measure of complement activity. Less than 20% lysis is deemed to be complete complement inhibition.
Measured: baseline, 6 weeks, 3 months, 6 months, 9 months, 12 months
Mean Eculizumab Concentration in Cerebrospinal Fluid (CSF)
Measured: 3 months
Mean Complement Protein 5 (C5) Concentration in CSF
Measured: baseline, 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2009 (estimated)
- Study startApr 2009
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Neuromyelitis OpticaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Investigators
- Sean J. Pittock, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00904826
- Sponsor's protocol ID
- 09-001240
- Status last verified
- Aug 2013
- First submitted
- 18 May 2009
- Last updated
- 4 Nov 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol. 2007 Sep;6(9):805-15. doi: 10.1016/S1474-4422(07)70216-8.
PubMed 17706564Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004 Dec 11-17;364(9451):2106-12. doi: 10.1016/S0140-6736(04)17551-X.
PubMed 15589308Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005 Aug 15;202(4):473-7. doi: 10.1084/jem.20050304. Epub 2005 Aug 8.
PubMed 16087714Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology. 2006 May 23;66(10):1485-9. doi: 10.1212/01.wnl.0000216139.44259.74.
PubMed 16717206Hinson SR, Pittock SJ, Lucchinetti CF, Roemer SF, Fryer JP, Kryzer TJ, Lennon VA. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology. 2007 Dec 11;69(24):2221-31. doi: 10.1212/01.WNL.0000289761.64862.ce. Epub 2007 Oct 10.
PubMed 17928579Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007 Nov;25(11):1256-64. doi: 10.1038/nbt1344.
PubMed 17989688Hinson SR, McKeon A, Fryer JP, Apiwattanakul M, Lennon VA, Pittock SJ. Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4-expressing cells. Arch Neurol. 2009 Sep;66(9):1164-7. doi: 10.1001/archneurol.2009.188.
PubMed 19752309Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, O'Toole O, Wingerchuk DM. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol. 2013 Jun;12(6):554-62. doi: 10.1016/S1474-4422(13)70076-0. Epub 2013 Apr 26.
PubMed 23623397
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Study of the Effects of Eculizumab in Neuromyelitis Optica
- ClinicalTrials.gov ID
- NCT00904826
- Acronym / sponsor ID
- 09-001240
- Conditions
- Neuromyelitis Optica, Devic's Disease
- Keywords
- NMO, Devic's disease, Neuromyelitis optica, NMO-IgG, Aquaporin-4 antibody, Eculizumab, Complement
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Study start
- Apr 2009
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 20 May 2009 (estimated)
- Results
- Posted 4 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eculizumab | Experimental | Drug: EculizumabThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
- 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).
- Age ≥18 years
- 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.
- 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.
Key exclusion criteria (5 listed)
- Candidates will be excluded from study entry if any of the following criteria are met at the time of randomization:
- Progressive neurological deterioration unrelated to relapses of ON or myelitis.
- Pregnant, breastfeeding, or intending to conceive during the course of the study
- 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
- Patients with a history of splenectomy, because of a potential increased risk of developing meningococcal infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EculizumabAlso: SolirisThe 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. | Drug | Eculizumab |
Primary outcome
Median Number of Neuromyelitis Optica (NMO) Attacks Per Year
Time frame: baseline, after 12 months of treatment
8 secondary outcomes
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
Number of Subjects With Change in Visual Acuity in at Least One Eye by at Least One Point
Time frame: 12 months
Number of Subjects With Change in Ambulation by at Least 1 Point
Time frame: 12 months
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
Mean Eculizumab Concentration in Cerebrospinal Fluid (CSF)
Time frame: 3 months
Mean Complement Protein 5 (C5) Concentration in CSF
Time frame: baseline, 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17706564Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol. 2007 Sep;6(9):805-15. doi: 10.1016/S1474-4422(07)70216-8.
- Background: PubMed 15589308Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004 Dec 11-17;364(9451):2106-12. doi: 10.1016/S0140-6736(04)17551-X.
- Background: PubMed 16087714Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. 2005 Aug 15;202(4):473-7. doi: 10.1084/jem.20050304. Epub 2005 Aug 8.
- Background: PubMed 16717206Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology. 2006 May 23;66(10):1485-9. doi: 10.1212/01.wnl.0000216139.44259.74.
- Background: PubMed 17928579Hinson SR, Pittock SJ, Lucchinetti CF, Roemer SF, Fryer JP, Kryzer TJ, Lennon VA. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology. 2007 Dec 11;69(24):2221-31. doi: 10.1212/01.WNL.0000289761.64862.ce. Epub 2007 Oct 10.
- Background: PubMed 17989688Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007 Nov;25(11):1256-64. doi: 10.1038/nbt1344.
- Background: PubMed 19752309Hinson SR, McKeon A, Fryer JP, Apiwattanakul M, Lennon VA, Pittock SJ. Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4-expressing cells. Arch Neurol. 2009 Sep;66(9):1164-7. doi: 10.1001/archneurol.2009.188.
- Results publication: PubMed 23623397Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, O'Toole O, Wingerchuk DM. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol. 2013 Jun;12(6):554-62. doi: 10.1016/S1474-4422(13)70076-0. Epub 2013 Apr 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sean J. Pittock, M.D. principal investigator
Mayo Clinic
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Eculizumab in people with Neuromyelitis Optica and Devic's Disease, run by Mayo Clinic at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Number of Neuromyelitis Optica (NMO) Attacks Per Year (time frame: baseline, after 12 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00904826, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2013.