Safety and Efficacy Study of Eculizumab in Patients With Refractory Generalized Myasthenia Gravis

Myasthenia Gravis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00727194
• Other study ID #: C08-001
• Status: Terminated
• Phase: Phase 2
• Start date: October 2008
• Est. completion date: July 2011

Study information

• Verified date: September 2019
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: July 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis

Intervention

Drug:
• eculizumab
eculizumab 600 mg IV weekly for 4 doses followed by eculizumab 900 mg IV every two weeks for 7 doses
• Placebo
Placebo IV weekly for 4 doses then every two weeks for 7 doses

Locations

Country	Name	City	State
Canada	The Northern Alberta Clinical trials and Research Centre	Edmonton	Alberta
United Kingdom	Institute of Neurological Sciences, Department of Neurology, Southern General Hospital,	Glasgow
United Kingdom	Institute of Neurology	London
United Kingdom	Department of Clinical Neurology, West Wing, John Radcliffe Hospital	Oxford
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Caritas St. Elizabeths' Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The University of Vermont College of Medicine	Burlington	Vermont
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	University Hospitals - Case Medical Center	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	University of Texas Southwestern Medical School	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Wishard Hospital	Indianapolis	Indiana
United States	University of Florida & Shands Neuroscience Institute	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Mount Sinai School of Medicine	New York	New York
United States	University of California, Irvine	Orange	California
United States	The Warren Alpert Medical School of Brown University	Providence	Rhode Island
United States	University of California - Davis	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

References & Publications (1)

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 refracto — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	16 weeks
Secondary	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.	16 weeks
Secondary	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.	16 weeks
Secondary	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).	16 weeks
Secondary	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.	16 weeks
Secondary	Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles.	Change from Baseline in Forced Vital Capacity	16 weeks
Secondary	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.	16 weeks
Secondary	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.	16 weeks
Secondary	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.	16 weeks