Clinical trial NCT00727194: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myasthenia Gravis
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2008-08-01
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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

Primary outcomes:
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.
timeFrame: 16 weeks
Secondary outcomes:
measure: Mean Change From Baseline in QMG Total Score
timeFrame: 16 weeks
measure: Change From Baseline in the MGFA Post-Intervention Status (PIS)
timeFrame: 16 weeks
measure: Change From Baseline in the MG-Activity of Daily Living Profile (MG-ADL)
timeFrame: 16 weeks
measure: Change From Baseline in the QoL Instrument, SF-36.
timeFrame: 16 weeks
measure: Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles.
timeFrame: 16 weeks
measure: Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles.
timeFrame: 16 weeks
measure: 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)
timeFrame: 16 weeks
measure: Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Ptosis)
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Sacramento
country: United States
facility: University of California - Davis
state: California
city: Jacksonville
country: United States
facility: University of Florida & Shands Neuroscience Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Wishard Hospital
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Caritas St. Elizabeths' Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals - Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Providence
country: United States
facility: The Warren Alpert Medical School of Brown University
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical School
state: Texas
city: Burlington
country: United States
facility: The University of Vermont College of Medicine
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Edmonton
country: Canada
facility: The Northern Alberta Clinical trials and Research Centre
state: Alberta
city: Glasgow
country: United Kingdom
facility: Institute of Neurological Sciences, Department of Neurology, Southern General Hospital,
city: London
country: United Kingdom
facility: Institute of Neurology
city: Oxford
country: United Kingdom
facility: Department of Clinical Neurology, West Wing, John Radcliffe Hospital
Study officials:
References:
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.