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

NCT ID: NCT02473965

Last Updated: 2020-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2019-02-28

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.

Conditions

Myasthenia Gravis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

IGIV-C

Intervention Type: DRUG

Run-Phase: 1 loading dose of 2 g/kg IGIV-C and 2 maintenance doses of 1 g/kg IGIV-C

Corticosteroid Tapering/IGIV-C Maintenance Phase: 1 g/kg IGIV-C every 3 weeks for up to 36 weeks

Placebo

0.9% sodium chloride injection, USP or equivalent

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

IGIV-C

Run-Phase: 1 loading dose of 2 g/kg IGIV-C and 2 maintenance doses of 1 g/kg IGIV-C

Corticosteroid Tapering/IGIV-C Maintenance Phase: 1 g/kg IGIV-C every 3 weeks for up to 36 weeks

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grifols Therapeutics LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of California-Irvine

Orange, California, United States

Yale University School of Medicine, Department of Neurology

New Haven, Connecticut, United States

University of Florida at Shands Jacksonville

Jacksonville, Florida, United States

University of South Florida

Tampa, Florida, United States

Georgia Regents University

Augusta, Georgia, United States

Indiana University

Indianapolis, Indiana, United States

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, United States

Rutgers New Jersey Medical School

Newark, New Jersey, United States

Columbia University Medical Center

New York, New York, United States

Ohio State University Wexner Medical Center, Neurology Department

Columbus, Ohio, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Houston Methodist Neurological Institute

Houston, Texas, United States

University of Vermont Medical Center

Burlington, Vermont, United States

University of Washington Medical Center

Seattle, Washington, United States

UZ Leuven

Leuven, , Belgium

London Health Sciences Centre- University Hospital

London, Ontario, Canada

University Health Network (UHN) - Toronto General Hospital

Toronto, Ontario, Canada

Fakultni nemocnice Brno, Dept of Neurologicka klinika

Brno, , Czechia

Fakultni nemocnice Ostrava

Ostrava - Poruba, , Czechia

Vseobecna fakultni nemocnice v Praze, Dept of Neurologicka klinika

Prague, , Czechia

East Tallinn Central Hospital

Tallinn, , Estonia

CHU Strasbourg - Nouvel Hôpital Civil, Clinique Neurologique

Strasbourg, Bas Rhin, France

CHU de Toulouse - Hôpital Purpan, Service de Neurologie Générale

Toulouse, Haute Garonne, France

Universitaetsklinikum Regensburg, Parent

Regensburg, Bavaria, Germany

Universitaetsklinikum Giessen und Marburg GmbH Standort Marburg

Marburg, Hesse, Germany

Universitaetsmedizin Goettingen, Parent

Göttingen, Lower Saxony, Germany

Fachkrankenhaus Hubertusburg gGmbH, Klinik f. Neurologie

Wermsdorf, Saxony, Germany

Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie

Halle, Saxony-Anhalt, Germany

Universitaetsklinikum Jena, Klinik fuer Neurologie

Jena, Thuringia, Germany

Charité Universitaetsmedizin Berlin, Klinik für Neurologie

Berlin, , Germany

Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik

Hamburg, , Germany

Jahn Ferenc Del-pesti Korhaz es Rendelointezet, Neurologiai Osztaly

Budapest, , Hungary

Pest Megyei Flor Ferenc Korhaz, Neurologia es Stroke Osztaly

Kistarcsa, , Hungary

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, , Hungary

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, , Lithuania

Uniwersyteckie Centrum Kliniczne, Dept of Neurology

Gdansk, , Poland

Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii Klinicznej

Krakow, , Poland

III Szpital Miejski w Lodzi im. Dr K. Jonschera

Lodz, , Poland

Samodzielny Publiczny Centralny Szpital Kliniczny

Warsaw, , Poland

Countries

United States; Belgium; Canada; Czechia; Estonia; France; Germany; Hungary; Lithuania; Poland

References

Bril V, Szczudlik A, Vaitkus A, Rozsa C, Kostera-Pruszczyk A, Hon P, Bednarik J, Tyblova M, Kohler W, Toomsoo T, Nowak RJ, Mozaffar T, Freimer ML, Nicolle MW, Magnus T, Pulley MT, Rivner M, Dimachkie MM, Distad BJ, Pascuzzi RM, Babiar D, Lin J, Querolt Coll M, Griffin R, Mondou E. Randomized Double-Blind Placebo-Controlled Trial of the Corticosteroid-Sparing Effects of Immunoglobulin in Myasthenia Gravis. Neurology. 2023 Feb 14;100(7):e671-e682. doi: 10.1212/WNL.0000000000201501. Epub 2022 Oct 21.

Reference Type: DERIVED

PMID: 36270895 (View on PubMed)

Dalakas MC, Meisel A. Immunomodulatory effects and clinical benefits of intravenous immunoglobulin in myasthenia gravis. Expert Rev Neurother. 2022 Apr;22(4):313-318. doi: 10.1080/14737175.2022.2057223. Epub 2022 Apr 5.

Reference Type: DERIVED

PMID: 35350948 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

GTI1306

Identifier Type: -

Identifier Source: org_study_id