Back to resultsSafety and Efficacy Study of Eculizumab in Patients With Refractory Generalized Myasthenia Gravis
Primary Purpose
Myasthenia Gravis
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
eculizumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Myasthenia Gravis
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Sites / Locations
- University of Alabama at Birmingham
- University of California, Irvine
- University of California - Davis
- University of Florida & Shands Neuroscience Institute
- Emory University
- Wishard Hospital
- University of Kansas Medical Center
- Johns Hopkins University School of Medicine
- Massachusetts General Hospital
- Caritas St. Elizabeths' Medical Center
- Wayne State University
- Mount Sinai School of Medicine
- University of North Carolina at Chapel Hill
- Duke University Medical Center
- University Hospitals - Case Medical Center
- The Ohio State University
- The Warren Alpert Medical School of Brown University
- Vanderbilt University Medical Center
- University of Texas Southwestern Medical School
- The University of Vermont College of Medicine
- University of Virginia
- The Northern Alberta Clinical trials and Research Centre
- Institute of Neurological Sciences, Department of Neurology, Southern General Hospital,
- Institute of Neurology
- Department of Clinical Neurology, West Wing, John Radcliffe Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
eculizumab
Placebo
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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).
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.
Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles.
Change from Baseline in Forced Vital Capacity
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00727194
Brief Title
Safety and Efficacy Study of Eculizumab in Patients With Refractory Generalized Myasthenia Gravis
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Terminated
Study Start Date
October 2008 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
July 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alexion
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myasthenia Gravis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
eculizumab
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
eculizumab
Other Intervention Name(s)
Soliris
Intervention Description
eculizumab 600 mg IV weekly for 4 doses followed by eculizumab 900 mg IV every two weeks for 7 doses
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo IV weekly for 4 doses then every two weeks for 7 doses
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in QMG Total Score
Description
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.
Time Frame
16 weeks
Title
Change From Baseline in the MGFA Post-Intervention Status (PIS)
Description
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.
Time Frame
16 weeks
Title
Change From Baseline in the MG-Activity of Daily Living Profile (MG-ADL)
Description
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).
Time Frame
16 weeks
Title
Change From Baseline in the QoL Instrument, SF-36.
Description
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.
Time Frame
16 weeks
Title
Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles.
Description
Change from Baseline in Forced Vital Capacity
Time Frame
16 weeks
Title
Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles.
Description
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.
Time Frame
16 weeks
Title
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)
Description
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.
Time Frame
16 weeks
Title
Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Ptosis)
Description
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.
Time Frame
16 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of California, Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of California - Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of Florida & Shands Neuroscience Institute
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Wishard Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Johns Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Caritas St. Elizabeths' Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02135
Country
United States
Facility Name
Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029-6574
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-1651
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
University Hospitals - Case Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5098
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
The Warren Alpert Medical School of Brown University
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas Southwestern Medical School
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
The University of Vermont College of Medicine
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05405
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908-0394
Country
United States
Facility Name
The Northern Alberta Clinical trials and Research Centre
City
Edmonton
State/Province
Alberta
Country
Canada
Facility Name
Institute of Neurological Sciences, Department of Neurology, Southern General Hospital,
City
Glasgow
Country
United Kingdom
Facility Name
Institute of Neurology
City
London
Country
United Kingdom
Facility Name
Department of Clinical Neurology, West Wing, John Radcliffe Hospital
City
Oxford
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
23512355
Citation
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.
Results Reference
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Safety and Efficacy Study of Eculizumab in Patients With Refractory Generalized Myasthenia Gravis
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