Safety and Efficacy Study of Eculizumab in Patients With Refractory Generalized Myasthenia Gravis
- Registration Number
- NCT00727194
- Lead Sponsor
- Alexion Pharmaceuticals, Inc.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 14
- 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.
- 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.
- Use of rituximab (RITUXAN®) within 6 months prior to screening.
- MGFA Class I, IVb, and V
- Crisis or impending crisis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description 1 eculizumab eculizumab 2 Placebo Placebo
- Primary Outcome Measures
Name Time Method 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. 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.
- Secondary Outcome Measures
Name Time Method Mean Change From Baseline in QMG Total Score 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 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.
Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Ptosis) 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. All individual QMG items are scored 0 to 3, with 3 being the most severe. Negative values imply an improvement in QMG Item Score.
Change From Baseline in the MGFA Post-Intervention Status (PIS) 16 weeks 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.
Change From Baseline in the QoL Instrument, SF-36. 16 weeks 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.
Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles. 16 weeks 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.
Change From Baseline in the MG-Activity of Daily Living Profile (MG-ADL) 16 weeks 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).
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) 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. All individual QMG items are scored 0 to 3, with 3 being the most severe. Negative values imply an improvement in QMG Item Score.
Trial Locations
- Locations (25)
University of California, Irvine
🇺🇸Orange, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Johns Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Department of Clinical Neurology, West Wing, John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Institute of Neurology
🇬🇧London, United Kingdom
The Ohio State University
🇺🇸Columbus, Ohio, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of California - Davis
🇺🇸Sacramento, California, United States
Wishard Hospital
🇺🇸Indianapolis, Indiana, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Caritas St. Elizabeths' Medical Center
🇺🇸Boston, Massachusetts, United States
The Warren Alpert Medical School of Brown University
🇺🇸Providence, Rhode Island, United States
University of Texas Southwestern Medical School
🇺🇸Dallas, Texas, United States
The Northern Alberta Clinical trials and Research Centre
🇨🇦Edmonton, Alberta, Canada
The University of Vermont College of Medicine
🇺🇸Burlington, Vermont, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Institute of Neurological Sciences, Department of Neurology, Southern General Hospital,
🇬🇧Glasgow, United Kingdom
University of Florida & Shands Neuroscience Institute
🇺🇸Jacksonville, Florida, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University Hospitals - Case Medical Center
🇺🇸Cleveland, Ohio, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States