Efficacy and Safety of IGIV-C in Corticosteroid Dependent Patients With Generalized Myasthenia Gravis

Phase 2

Completed

Conditions: Myasthenia Gravis

Interventions: Drug: Placebo
Drug: IGIV-C

Registration Number: NCT02473965

Lead Sponsor: Grifols Therapeutics LLC

Brief Summary: This is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) as a corticosteroid (CS)-sparing agent in subjects with CS-dependent Myasthenia Gravis (MG).

Detailed Description: This study consists of 2 phases: IGIV-C Run-in Phase and Corticosteroid Tapering/IGIV-C Maintenance Phase.

In the Run-in Phase, subjects will receive a total of 3 doses of IGIV-C (1 loading dose of 2 g/kg and 2 maintenance doses of 1 g/kg) while maintaining a stable dose of corticosteroids.

In the CS Tapering/IGIV-C Maintenance Phase, subjects will continue 1 g/kg IGIV-C and begin a prescribed CS tapering regimen where the CS dose is decreased every 3 weeks.

Approximately 60 subjects are planned to be enrolled in the study across multiple centers in North America and Europe. The total duration of study participation for each subject is up to 45 weeks.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

Inclusion Criteria

Anti-acetylcholine receptor antibody positive
Confirmed diagnosis of generalized MG historically meeting the clinical criteria for diagnosis of MG defined by the Myasthenia Gravis Foundation of America (MGFA) classification of Class II, III, IV, or V historically
At Screening, subjects may have symptoms controlled by CS or were MGFA Class II-IVa inclusive (Class IVb and Class V excluded). Subjects who only have a history of ocular MG may not enroll.
On systemic CS for a minimum period of at least 3 months and on a stable CS dose of >=15 mg/day and <=60 mg/day (prednisone equivalent) for the month prior to Screening.
Had a tapering CS dose that the study investigator considered to be appropriate.
At least 1 previous completed attempt to taper CS in order to minimize CS dose (lowest feasible dose based on observed MG signs and symptoms)

Exclusion Criteria

Any dose change in concomitant immunosuppressant therapy, other than CS, in the prior 6 months
Any change in CS dose or acetylcholinesterase inhibitor (e.g., pyridostigmine) dose in the 1 month prior to Screening
A 3-point change in Quantitative Myasthenia Gravis score, increased or decreased, between the Screening/Week -3 (Visit 0) and Baseline (Week 0 [Visit 1])
Any episode of myasthenic crisis (MC) in the 1 month prior to Screening, or (at any time in the past) MC or hospitalization for MG exacerbation associated with a previous CS taper attempt
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 prior to Screening
Rituximab, belimumab, eculizumab or any monoclonal antibody used for immunomodulation within the past 12 months prior to Screening
Have received immune globulin treatment given by IV, subcutaneous, or intramuscular route within the last 3 months prior to Screening
Received plasma exchange performed within the last 3 months prior to Screening
History of anaphylactic reactions or severe reactions to any blood-derived product
History of recent (within the last year) myocardial infarction or stroke
Uncontrolled congestive heart failure; embolism; or historically documented (within the last year) electrocardiogram changes indicative of myocardial ischemia or atrial fibrillation
Current known hyperviscosity or hypercoagulable state
Currently receiving anti-coagulation therapy. Oral anti-platelet agents are allowed (e.g., aspirin, clopidogrel, ticlopidine)
Females of child-bearing potential who are pregnant, have a positive serum pregnancy test, breastfeeding, or are unwilling to practice a highly effective method of contraception throughout the study.
Renal impairment
Aspartate aminotransferase or alanine aminotransferase levels exceeding more than 2.5 times the upper limit of normal for the expected normal range for the testing laboratory.
Hemoglobin (Hb) levels <9 g/dL

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	0.9% sodium chloride injection, USP or equivalent
IGIV-C	IGIV-C	An IGIV-C loading dose of 2 g/kg and maintenance dose of 1 g/kg will be administered in CS dependent subjects with MG.

Primary Outcome Measures

Name	Time	Method
Percent of Subjects Achieving a 50% or Greater Reduction in CS Dose (Prednisone or Equivalent) From Baseline to Week 39	Baseline/Week 0 (Visit 1) and Week 39 (Visit 14).	The average daily CS dose was derived for each subject at each scheduled visit based on the prescribed dose and the time interval taking into account any prescribed dose changes between routinely scheduled visits. Subjects who discontinued the study early with adverse outcomes related to MG were considered as not achieving a 50% or greater reduction. The missing dose reduction at Week 39 was imputed using the worst observation carried forward (WOCF) method. For subjects who did not have CS dose prescribed at Week 39 due to other reasons, the last observation carried forward (LOCF) method was used to impute the prescribed CS dose at Week 39. Baseline was defined as the last non-missing measurement taken prior to first dose of study medication. The percent of subjects achieving ≥50% reduction in CS dose from baseline to Week 39 is presented for each treatment group overall and for the baseline daily prednisone equivalent dose level stratification categories.

Secondary Outcome Measures

Name	Time	Method
Mean Percent Change in Daily CS Dose (Prednisone or Equivalent) From Baseline to Week 39	Baseline/Week 0 (Visit 1) and Week 39 (Visit 14).	The average daily CS dose was derived for each subject at each scheduled visit based on the prescribed dose and the time interval taking into account any prescribed dose changes between routinely scheduled visits. For subjects who discontinued the study early with adverse outcomes related to MG, the missing dose reduction at Week 39 was imputed using the WOCF method. For subjects who had missing CS dose reduction at Week 39 due to other reasons, the missing CS dose was imputed using the LOCF method. Baseline was defined as the last non-missing measurement taken prior to first dose of study medication. The least squares (LS) mean percent change from baseline in daily CS dose to Week 39 is presented for each treatment group.
Median Time to First Episode of MG Worsening	From Baseline/Week 0 (Visit 1) to Week 39 (Visit 14).	The time to the first episode of MG worsening was defined as the time between baseline and the first instance of QMG total score increase by ≥4 points relative to Baseline/Week 0. The QMG total score is the sum of all 13 items and ranges from 0 to 39. Higher values represent greater severity of illness. If one or more items were missing at a given assessment, the total score was set to missing. The median time to MG worsening was calculated based on Kaplan-Meier methodology. Baseline was defined as the last non-missing measurement taken prior to the first dose of study medication.

Trial Locations

Locations (39): University of California-Irvine
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Orange, California, United States
University of Florida at Shands Jacksonville
🇺🇸
Jacksonville, Florida, United States
Columbia University Medical Center
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New York, New York, United States
London Health Sciences Centre- University Hospital
🇨🇦
London, Ontario, Canada
Fakultni nemocnice Brno, Dept of Neurologicka klinika
🇨🇿
Brno, Czechia
Vseobecna fakultni nemocnice v Praze, Dept of Neurologicka klinika
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Praha 2, Czechia
Fakultni nemocnice Ostrava
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Ostrava - Poruba, Czechia
East Tallinn Central Hospital
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Tallinn, Estonia
CHU de Toulouse - Hôpital Purpan, Service de Neurologie Générale
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Toulouse cedex 9, Haute Garonne, France
CHU Strasbourg - Nouvel Hôpital Civil, Clinique Neurologique
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Strasbourg cedex, Bas Rhin, France
Universitaetsklinikum Regensburg, Parent
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Regensburg, Bayern, Germany
Universitaetsklinikum Giessen und Marburg GmbH Standort Marburg
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Marburg, Hessen, Germany
Universitaetsmedizin Goettingen, Parent
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Göttingen, Niedersachsen, Germany
Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie
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Halle, Sachsen Anhalt, Germany
Fachkrankenhaus Hubertusburg gGmbH, Klinik f. Neurologie
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Wermsdorf, Sachsen, Germany
Universitaetsklinikum Jena, Klinik fuer Neurologie
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Jena, Thueringen, Germany
Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik
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Hamburg, Germany
Charité Universitaetsmedizin Berlin, Klinik für Neurologie
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Berlin, Germany
Hospital of Lithuanian University of Health Sciences Kaunas Clinics
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Kaunas, Lithuania
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
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Szeged, Hungary
Uniwersyteckie Centrum Kliniczne, Dept of Neurology
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Gdansk, Poland
Samodzielny Publiczny Centralny Szpital Kliniczny
🇵🇱
Warszawa, Poland
Georgia Regents University
🇺🇸
Augusta, Georgia, United States
Ohio State University Wexner Medical Center, Neurology Department
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Columbus, Ohio, United States
Thomas Jefferson University Hospital
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Philadelphia, Pennsylvania, United States
University Health Network (UHN) - Toronto General Hospital
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Toronto, Ontario, Canada
Indiana University
🇺🇸
Indianapolis, Indiana, United States
Houston Methodist Neurological Institute
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Houston, Texas, United States
University of Washington Medical Center
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Seattle, Washington, United States
University of South Florida
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Tampa, Florida, United States
Yale University School of Medicine, Department of Neurology
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New Haven, Connecticut, United States
University of Vermont Medical Center
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Burlington, Vermont, United States
Rutgers New Jersey Medical School
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Newark, New Jersey, United States
UZ Leuven
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Leuven, Belgium
Jahn Ferenc Del-pesti Korhaz es Rendelointezet, Neurologiai Osztaly
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Budapest, Hungary
Pest Megyei Flor Ferenc Korhaz, Neurologia es Stroke Osztaly
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Kistarcsa, Hungary
Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii Klinicznej
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Krakow, Poland
III Szpital Miejski w Lodzi im. Dr K. Jonschera
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Lodz, Poland
University of Kansas Medical Center Research Institute, Inc.
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Kansas City, Kansas, United States