Myasthenia GravisPhase 2NCT00727194
Safety and Efficacy Study of Eculizumab in Patients With Refractory Generalized Myasthenia Gravis
A Phase 2 study testing eculizumab in people with Myasthenia Gravis, run by Alexion Pharmaceuticals, Inc. at 25 sites in 3 countries.
Trial summary
The purpose of this study is to determine whether eculizumab is safe and effective in the treatment of patients with generalized myasthenia gravis despite treatment with various immunosuppressants, such as prednisone, methotrexate, Cellcept, cyclosporine, and cyclophosphamide, that are currently available. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Myasthenia Gravis
- What is being tested?
- eculizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 25 sitesin 3 countries
- Study dates
- Oct 2008to Jul 2011
- Phase
- Phase 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Generalized MG
- MGFA Clinical Classification Class II, III or IVa.
- QMG total score ≥12
- Minimum score of two (2) in four (4) or more test items in the QMG
- Able to give informed consent.
- Have failed at least two immunosuppressants after one year of treatment
- A positive serologic test for binding anti-acetylcholine receptor Abs at Screening and one of the following a) history of abnormal neuromuscular transmission test demonstrated by single-fiber electromyography or repetitive nerve stimulation, or b) history of positive anticholinesterase test, eg, edrophonium chloride test, or c) patient has demonstrated improvement in MG signs on acetylcholinesterase inhibitors as assessed by treating physician.
Who cannot join
- History of thymoma or other neoplasms of the thymus.
- History of thymectomy within 12 months prior to screening.
- Pregnancy or lactation
- Current or chronic use of plasmapheresis/plasma exchange
- IVIG treatment within 8 weeks prior to screening.
- Use of etanercept within 2 months prior to screening.
Show all 9Show fewer
- Use of rituximab (RITUXAN®) within 6 months prior to screening.
- MGFA Class I, IVb, and V
- Crisis or impending crisis
Trial locations and contacts
25 sites in 3 countries.
25 sites in 3 countries
United States21 sites
Emory University
Atlanta, Georgia, 30322
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Massachusetts General Hospital
Boston, Massachusetts, 02114
Caritas St. Elizabeths' Medical Center
Boston, Massachusetts, 02135
The University of Vermont College of Medicine
Burlington, Vermont, 05405
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599-1651
University of Virginia
Charlottesville, Virginia, 22908-0394
University Hospitals - Case Medical Center
Cleveland, Ohio, 44106-5098
The Ohio State University
Columbus, Ohio, 43210
University of Texas Southwestern Medical School
Dallas, Texas, 75390
Wayne State University
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27710
Wishard Hospital
Indianapolis, Indiana, 46202
University of Florida & Shands Neuroscience Institute
Jacksonville, Florida, 32209
University of Kansas Medical Center
Kansas City, Kansas, 66160
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Mount Sinai School of Medicine
New York, New York, 10029-6574
University of California, Irvine
Orange, California, 92868
The Warren Alpert Medical School of Brown University
Providence, Rhode Island, 02905
University of California - Davis
Sacramento, California, 95817
United Kingdom3 sites
Institute of Neurological Sciences, Department of Neurology, Southern General Hospital,
Glasgow
Institute of Neurology
London
Department of Clinical Neurology, West Wing, John Radcliffe Hospital
Oxford
Canada1 site
The Northern Alberta Clinical trials and Research Centre
Edmonton, Alberta
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over, Multi-Center Study of Eculizumab in Patients With Generalized Myasthenia Gravis (gMG) Who Have Moderate to Severe Muscle Weakness Despite Treatment With Immunosuppressants
The purpose of this study is to determine whether eculizumab is safe and effective in the treatment of patients with generalized myasthenia gravis despite treatment with various immunosuppressants, such as prednisone, methotrexate, Cellcept, cyclosporine, and cyclophosphamide, that are currently available.
- Conditions
- Myasthenia Gravis
- Being tested
- eculizumab, Placebo
- Medical subject headings
- Myasthenia Gravis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
eculizumabDrug
Also called Soliris
eculizumab 600 mg IV weekly for 4 doses followed by eculizumab 900 mg IV every two weeks for 7 doses
PlaceboDrug
Placebo IV weekly for 4 doses then every two weeks for 7 doses
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | eculizumab Receives: Drug: eculizumab |
| 2 | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantitative Myasthenia Gravis (QMG): The Primary Efficacy Endpoint in This Study Was the Percentage of Patients With a 3-point Reduction From Baseline in the QMG Total Score for Disease Severity.
The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that the QMG score be used in prospective studies of therapy for MG.
Measured: 16 weeks
Secondary outcomes (8)
Mean Change From Baseline in QMG Total Score
The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The Myasthenia Gravis Foundation of America task force has recommended that the QMG score be used in prospective studies of therapy for MG. The QMG scoring system consists of 13 items. Each item is graded 0 to 3, with 3 being the most severe. The range of total QMG score is 0-39.
Measured: 16 weeks
Change From Baseline in the MGFA Post-Intervention Status (PIS)
The MGFA PIS is designed to assess the clinical state of MG patients at any time after treatment of MG is initiated. Change in status categories of Improved, Unchanged, Worse, Exacerbation, and Died of MG was to be assessed and recorded at every visit from Visits 3 to 24 (Weeks 1 to 16). Minimal manifestations were to be assessed at these visits.
Measured: 16 weeks
Change From Baseline in the MG-Activity of Daily Living Profile (MG-ADL)
The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living (ADL) in MG patients. The 8 items of the MG-ADL were derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 - 24. MG-ADL was to be performed at every study visit. The recall period for MG-ADL was since the preceding study visit (1 or 2 weeks).
Measured: 16 weeks
Change From Baseline in the QoL Instrument, SF-36.
The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (physical functioning, role-physical, bodily pain, general health, mental health, role-emotional, social functioning and vitality) as well as psychometrically-based physical and mental health summary measures. It is a generic measure, as opposed to one that targets a specific age, disease or treatment group. The lower the score the more disability; the higher the score the less disability. Norm-based scoring involving a linear T-score transformation method was used so that scores for each of the health domain scales and component summary measures have a mean of 50 and a standard deviation of 10 based on the 1998 US general population. Thus, scores above and below 50 are above and below the average, respectively, in the 1998 US general.
Measured: 16 weeks
Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles.
Change from Baseline in Forced Vital Capacity
Measured: 16 weeks
Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles.
Change from Baseline in Negative Inspiratory Force. NIF is a measurement of respiratory muscle strength and ventilator reserve. NIF is represented by centimeters of water pressure (cmH2O). A normal NIF measurement is negative 60 cmH2O, or as 100% predicted value.
Measured: 16 weeks
Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Double Vision)
The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that the QMG score be used in prospective studies of therapy for MG. All individual QMG items are scored 0 to 3, with 3 being the most severe. Negative values imply an improvement in QMG Item Score.
Measured: 16 weeks
Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Ptosis)
The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that the QMG score be used in prospective studies of therapy for MG. All individual QMG items are scored 0 to 3, with 3 being the most severe. Negative values imply an improvement in QMG Item Score.
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2008 (estimated)
- Study startOct 2008
- Primary completionMar 2011
- Study completionJul 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 (1)Papers the sponsor has linked to this study.
- Other trials for Myasthenia GravisStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00727194
- Sponsor's protocol ID
- C08-001
- Status last verified
- Sep 2019
- First submitted
- 30 Jul 2008
- Last updated
- 24 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Howard JF Jr, Barohn RJ, Cutter GR, Freimer M, Juel VC, Mozaffar T, Mellion ML, Benatar MG, Farrugia ME, Wang JJ, Malhotra SS, Kissel JT; MG Study Group. A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis. Muscle Nerve. 2013 Jul;48(1):76-84. doi: 10.1002/mus.23839. Epub 2013 Apr 30.
PubMed 23512355
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Cross-Over, Multi-Center Study of Eculizumab in Patients With Generalized Myasthenia Gravis (gMG) Who Have Moderate to Severe Muscle Weakness Despite Treatment With Immunosuppressants
- ClinicalTrials.gov ID
- NCT00727194
- Acronym / sponsor ID
- C08-001
- Conditions
- Myasthenia Gravis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2008
- Primary completion
- Mar 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 1 Aug 2008 (estimated)
- Results
- Posted 12 Dec 2016
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 whether eculizumab is safe and effective in the treatment of patients with generalized myasthenia gravis despite treatment with various immunosuppressants, such as prednisone, methotrexate, Cellcept, cyclosporine, and cyclophosphamide, that are currently available.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: eculizumabeculizumab |
| 2 | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Generalized MG
- MGFA Clinical Classification Class II, III or IVa.
- QMG total score ≥12
- Minimum score of two (2) in four (4) or more test items in the QMG
- Able to give informed consent.
Key exclusion criteria (9 listed)
- History of thymoma or other neoplasms of the thymus.
- History of thymectomy within 12 months prior to screening.
- Pregnancy or lactation
- Current or chronic use of plasmapheresis/plasma exchange
- IVIG treatment within 8 weeks prior to screening.
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: Soliriseculizumab 600 mg IV weekly for 4 doses followed by eculizumab 900 mg IV every two weeks for 7 doses | Drug | 1 |
| PlaceboPlacebo IV weekly for 4 doses then every two weeks for 7 doses | Drug | 2 |
Primary outcome
Quantitative Myasthenia Gravis (QMG): The Primary Efficacy Endpoint in This Study Was the Percentage of Patients With a 3-point Reduction From Baseline in the QMG Total Score for Disease Severity.
Time frame: 16 weeks
The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that the QMG score be used in prospective studies of therapy for MG.
8 secondary outcomes
Mean Change From Baseline in QMG Total Score
Time frame: 16 weeks
Change From Baseline in the MGFA Post-Intervention Status (PIS)
Time frame: 16 weeks
Change From Baseline in the MG-Activity of Daily Living Profile (MG-ADL)
Time frame: 16 weeks
Change From Baseline in the QoL Instrument, SF-36.
Time frame: 16 weeks
Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles.
Time frame: 16 weeks
Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles.
Time frame: 16 weeks
Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Double Vision)
Time frame: 16 weeks
Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Ptosis)
Time frame: 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23512355Howard JF Jr, Barohn RJ, Cutter GR, Freimer M, Juel VC, Mozaffar T, Mellion ML, Benatar MG, Farrugia ME, Wang JJ, Malhotra SS, Kissel JT; MG Study Group. A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis. Muscle Nerve. 2013 Jul;48(1):76-84. doi: 10.1002/mus.23839. Epub 2013 Apr 30.
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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.
The record lists no contact. Use the official record to reach the sponsor.
25 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing eculizumab in people with Myasthenia Gravis, run by Alexion Pharmaceuticals, Inc. at 25 sites in 3 countries.
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 9 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: stopped early, as of the sponsor's last update on 24 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, United Kingdom, Canada. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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 12 Dec 2016). 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?
Quantitative Myasthenia Gravis (QMG): The Primary Efficacy Endpoint in This Study Was the Percentage of Patients With a 3-point Reduction From Baseline in the QMG Total Score for Disease Severity. (time frame: 16 weeks). 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 NCT00727194, which also lists 1 linked publication.
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 24 Sep 2019; AzTrials last refreshed its copy on 7 Nov 2026.