A Study to Evaluate the Efficacy and Safety of IGIV-C in Symptomatic Subjects With Generalized Myasthenia Gravis
Myasthenia Gravis, Generalized
About this trial
This is an interventional treatment trial for Myasthenia Gravis, Generalized
Eligibility Criteria
Inclusion Criteria:
- Anti-acetylcholine receptor (AChR) antibody positive
- Confirmed diagnosis of generalized myasthenia gravis (MG).
- Myasthenia Gravis Foundation of America (MGFA) classification of Class II, III, or IVa inclusive at Screening.
- QMG >= 10 at Screening. Note: Subjects who only have a history of ocular MG may not enroll.
Receiving standard of care MG treatment at a stable dose consisting of any one of the following for the time intervals delineated below (time intervals apply to medications and maintenance of stable dose level):
- Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to Screening and no immunosuppressants
Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to Screening AND/OR only one of the following:
- Prednisone (up to 60 mg/day or equivalent) for at least 2 months prior to Screening, OR
- Azathioprine for at least 6 months prior to Screening, OR
- Mycophenolate mofetil for at least 6 months prior to Screening, OR
- Methotrexate for at least 6 months prior to Screening, OR
- Cyclosporine or tacrolimus for at least 3 months prior to Screening
Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to Screening AND/OR prednisone (up to 60 mg/day or equivalent) for at least one month prior to Screening and only one of the following:
- Azathioprine for at least 6 months prior to Screening, OR
- Mycophenolate mofetil for at least 6 months prior to Screening, OR
- Methotrexate for at least 6 months prior to Screening, OR
- Cyclosporine or tacrolimus for at least 3 months prior to Screening
Exclusion Criteria:
- Have received cyclophosphamide or any other immunosuppressive agent apart from the ones allowed per inclusion criteria within the past 6 months
- Any change in MG treatment regimen between Screening (Week -3, Visit 0) and Baseline (Week 0, Visit 1)
- Greater than two point change in QMG score, increased or decreased, between Screening (Week -3, Visit 0) and Baseline (Week 0, Visit 1)
- Any episode of myasthenic crisis in the one month prior to Screening
- Evidence of malignancy within the past 5 years (non-melanoma skin cancer, carcinoma in situ of cervix is allowed) or thymoma potentially requiring surgical intervention during the course of the trial (intent to perform thymectomy)
- Thymectomy within the preceding 6 months
- Rituximab, belimumab, eculizumab or any monoclonal antibody used for immunomodulation within the past 12 months
- Have received immune globulin (Ig) treatment given by intravenous (IV), subcutaneous, or intramuscular route within the last 3 months
- Current known hyperviscosity or hypercoagulable state
- Currently receiving anti-coagulation therapy (vitamin K antagonists, nonvitamin K antagonist oral anticoagulants [e.g., dabigatran etexilate, rivaroxaban, edoxaban, and apixaban], parenteral anticoagulants [e.g., fondaparinux]). Note that oral anti-platelet agents are allowed (e.g., aspirin, clopidogrel, ticlodipine)
- Documented diagnosis of thrombotic complications to polyclonal intravenous immunoglobulin (IVIg) therapy in the past
- History of recent (within the last year) myocardial infarction or stroke
- Uncontrolled congestive heart failure; embolism; or historically documented (within the last year) electrocardiogram (ECG) changes indicative of myocardial ischemia or atrial fibrillation
- History of chronic alcoholism or illicit drug abuse (addiction) in the 12 months preceding the Screening/Week -3 (Visit 0)
- Plasma exchange (PLEX) performed within the last 3 months
- Renal impairment (i.e., serum creatinine exceeds more than 1.5 times the upper limit of normal [ULN] for the expected normal range for the testing laboratory).
- Hemoglobin levels less than 9 g per dL
Sites / Locations
- Phoenix Neurological Associates, Ltd.
- University of California-Irvine
- Yale University School of Medicine
- University of Florida Health Science Center
- University of South Florida
- Georgia Regents University
- Indiana University
- University of Kansas Medical Center Research Institute, Inc.
- Rutgers New Jersey Medical School
- Columbia University Medical Center
- Ohio State University Wexner Medical Center
- Thomas Jefferson University Hospital
- Houston Methodist Neurological Institute
- University of Vermont Medical Center
- University of Washington Medical Center
- UZ Leuven
- London Health Sciences Centre - University Hospital
- University Health Network (UHN) - Toronto General Hospital
- Fakultni nemocnice Brno, Dept of Neurologicka klinika
- Fakultni nemocnice Ostrava
- East Tallinn Central Hospital
- CHU Nice - Hôpital de l'Archet 1, Ctre de Réf Maladies Neuromusculaires et SLA
- CHU Strasbourg - Nouvel Hôpital Civil, Clinique Neurologique
- CHU de Toulouse - Hôpital Purpan, Service de Neurologie Générale
- Hopital Neurologique Pierre Wertheimer, Neuro-musculaire - Electromyographie
- Universitaetsklinikum Regensburg, Parent
- Universitaetsmedizin Göttingen, Parent
- Universitaetsklinikum Koeln, Neurologie und Psychiatrie
- Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie
- Universitaetsklinikum Carl Gustav Carus TU Dresden
- Universitaetsklinikum Jena, Klinik fuer Neurologie
- Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fuer Neurologie
- Jahn Ferenc Del-pesti Korhaz es Rendelointezet, Neurologiai Osztaly
- Pest Megyei Flor Ferenc Korhaz, Neurologia es Stroke Osztaly
- Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
- Hospital of Lithuanian University of Health Sciences Kaunas Clinics
- Uniwersyteckie Centrum Kliniczne, Dept of Neurology
- Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii Klinicznej
- III Szpital Miejski w Lodzi im. Dr K. Jonschera
- Samodzielny Publiczny Centralny Szpital Kliniczny, Dept of Neurology
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
IGIV-C
Placebo
IGIV-C: Immune Globulin Injection (Human), 10%, Caprylate/Chromatography Purified. An initial loading dose of 2 g/kg of body weight will be administered at Baseline (Week 0, Visit 1) followed by maintenance doses of 1 g/kg of body weight administered every third week through Week 21 (Visit 8).
Placebo: Sterile 0.9% sodium chloride injection or equivalent. Placebo will be infused at the Baseline/Week 0 Visit (Visit 1) using the same volume as would be required for the IGIV-C loading dose. Subsequent placebo maintenance doses will be matched in volume to the IGIV-C maintenance doses and administered every third week until Week 21 (Visit 8).