A Study to Evaluate the Efficacy and Safety of IGIV-C in Symptomatic Subjects With Generalized Myasthenia Gravis

Phase 2

Completed

• Conditions: Myasthenia Gravis, Generalized
• Interventions: Drug: IGIV-C; Drug: Placebo

• Registration Number: NCT02473952
• Lead Sponsor: Grifols Therapeutics LLC

Brief Summary

The primary objective is to evaluate whether IGIV-C improves MG symptoms as compared to placebo in subjects with MG.

Detailed Description

The primary objective is to evaluate the efficacy of IGIV-C in subjects with generalized myasthenia gravis (MG) on standard of care treatment at study entry in terms of improvement in MG symptoms as measured by the mean change in Quantitative Myasthenia Gravis (QMG) score from Baseline (Week 0) to Week 24 as compared to placebo.

The safety objective of this study is to evaluate the safety and tolerability of IGIV-C loading dose of 2 g/kg followed by 7 maintenance dosages of 1 g/kg every 3 weeks through Week 21 in subjects with MG.

Study Timeline

• Study First Submitted: 2015-06-14
• Study First Submitted QC: 2015-06-16
• Study First Posted: 2015-06-17
• Study Start: 2015-08
• Primary Completion: 2018-01
• Study Completion: 2018-01
• Results First Submitted: 2019-01-29
• Status Verified: 2019-03
• Results First Submitted QC: 2019-03-01
• Last Update Submitted: 2019-03-01
• Results First Posted: 2019-03-05
• Last Update Posted: 2019-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 62

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):

  1. Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to Screening and no immunosuppressants

  2. Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to Screening AND/OR only one of the following:

     1. Prednisone (up to 60 mg/day or equivalent) for at least 2 months prior to Screening, OR
     2. Azathioprine for at least 6 months prior to Screening, OR
     3. Mycophenolate mofetil for at least 6 months prior to Screening, OR
     4. Methotrexate for at least 6 months prior to Screening, OR
     5. Cyclosporine or tacrolimus for at least 3 months prior to Screening

  3. 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:

     1. Azathioprine for at least 6 months prior to Screening, OR
     2. Mycophenolate mofetil for at least 6 months prior to Screening, OR
     3. Methotrexate for at least 6 months prior to Screening, OR
     4. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IGIV-C	IGIV-C	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	Placebo	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).

Primary Outcome Measures

Name	Time	Method
Improvement in Myasthenia Gravis (MG) Symptoms as Measured by the Mean Change in Quantitative Myasthenia Gravis (QMG) Total Score.	Baseline (Week 0) to Week 24	To measure improvement in MG symptoms by the mean change in QMG total score from Baseline (Week 0) to Week 24 as compared to placebo. Evaluators score 13 individual items (range from 0=best to 3=worst) and the individual scores are added together for the total score (range 0-39). An average 3-point improvement in QMG score indicates clinically meaningful improvement.

Trial Locations

Locations (40)

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Florida Health Science Center; 🇺🇸 Jacksonville, Florida, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

UZ Leuven; 🇧🇪 Leuven, Belgium

University of Kansas Medical Center Research Institute, Inc.; 🇺🇸 Kansas City, Kansas, United States

Ohio State University Wexner Medical Center; 🇺🇸 Columbus, Ohio, United States

East Tallinn Central Hospital; 🇪🇪 Tallinn, Estonia

Uniwersyteckie Centrum Kliniczne, Dept of Neurology; 🇵🇱 Gdansk, Poland

Georgia Regents University; 🇺🇸 Augusta, Georgia, United States

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States

Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie; 🇩🇪 Halle, Sachsen Anhalt, Germany

III Szpital Miejski w Lodzi im. Dr K. Jonschera; 🇵🇱 Lodz, Poland

University of California-Irvine; 🇺🇸 Orange, California, United States

Jahn Ferenc Del-pesti Korhaz es Rendelointezet, Neurologiai Osztaly; 🇭🇺 Budapest, Hungary

Samodzielny Publiczny Centralny Szpital Kliniczny, Dept of Neurology; 🇵🇱 Warszawa, Poland

Rutgers New Jersey Medical School; 🇺🇸 Newark, New Jersey, United States

London Health Sciences Centre - University Hospital; 🇨🇦 London, Ontario, Canada

Universitaetsmedizin Göttingen, Parent; 🇩🇪 Göttingen, Niedersachsen, Germany

University of Vermont Medical Center; 🇺🇸 Burlington, Vermont, United States

Pest Megyei Flor Ferenc Korhaz, Neurologia es Stroke Osztaly; 🇭🇺 Kistarcsa, Hungary

Fakultni nemocnice Brno, Dept of Neurologicka klinika; 🇨🇿 Brno, Czechia

Fakultni nemocnice Ostrava; 🇨🇿 Ostrava - Poruba, Czechia

Hopital Neurologique Pierre Wertheimer, Neuro-musculaire - Electromyographie; 🇫🇷 Bron cedex, Rhone, France

Universitaetsklinikum Carl Gustav Carus TU Dresden; 🇩🇪 Dresden, Sachsen, Germany

Universitaetsklinikum Regensburg, Parent; 🇩🇪 Regensburg, Bayern, Germany

Universitaetsklinikum Jena, Klinik fuer Neurologie; 🇩🇪 Jena, Thueringen, Germany

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Houston Methodist Neurological Institute; 🇺🇸 Houston, Texas, United States

University of Washington Medical Center; 🇺🇸 Seattle, Washington, United States

Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fuer Neurologie; 🇩🇪 Hamburg, Germany

CHU de Toulouse - Hôpital Purpan, Service de Neurologie Générale; 🇫🇷 Toulouse cedex 9, Haute Garonne, France

CHU Nice - Hôpital de l'Archet 1, Ctre de Réf Maladies Neuromusculaires et SLA; 🇫🇷 Nice cedex 3, Alpes Maritimes, France

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont; 🇭🇺 Szeged, Hungary

University of South Florida; 🇺🇸 Tampa, Florida, United States

Phoenix Neurological Associates, Ltd.; 🇺🇸 Phoenix, Arizona, United States

University Health Network (UHN) - Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada

CHU Strasbourg - Nouvel Hôpital Civil, Clinique Neurologique; 🇫🇷 Strasbourg cedex, Bas Rhin, France

Universitaetsklinikum Koeln, Neurologie und Psychiatrie; 🇩🇪 Koeln, Nordrhein Westfalen, Germany

Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii Klinicznej; 🇵🇱 Krakow, Poland

Hospital of Lithuanian University of Health Sciences Kaunas Clinics; 🇱🇹 Kaunas, Lithuania