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

NCT02473965 | Completed Phase 2 Results

• 1 other identifier: GTI1306
• Study Type: interventional
• Target: 60
• Locations: 10 countries
• Sites: 39

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).

Conditions

Myasthenia Gravis

Outcome Measures

Primary Outcomes (1)

• Percent of Subjects Achieving a 50% or Greater Reduction in CS Dose (Prednisone or Equivalent) From Baseline to Week 39

  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.

  Baseline/Week 0 (Visit 1) and Week 39 (Visit 14).

Secondary Outcomes (2)

• 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).

• Median Time to First Episode of MG Worsening

  From Baseline/Week 0 (Visit 1) to Week 39 (Visit 14).

Study Arms (2)

IGIV-C

EXPERIMENTAL

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.

Drug: IGIV-C

Placebo

PLACEBO COMPARATOR

0.9% sodium chloride injection, USP or equivalent

Drug: Placebo

Interventions

IGIV-C 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

IGIV-C

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead

Study Sites (39)

University of California-Irvine

Orange, California, 92868, United States

Location

Yale University School of Medicine, Department of Neurology

New Haven, Connecticut, 06510, United States

Location

University of Florida at Shands Jacksonville

Jacksonville, Florida, 32209, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, 66160, United States

Location

Rutgers New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Ohio State University Wexner Medical Center, Neurology Department

Columbus, Ohio, 43220, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Houston Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05405, United States

Location

University of Washington Medical Center

Seattle, Washington, 98105, United States

Location

UZ Leuven

Leuven, 3000, Belgium

Location

London Health Sciences Centre- University Hospital

London, Ontario, N6A 5A5, Canada

Location

University Health Network (UHN) - Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Fakultni nemocnice Brno, Dept of Neurologicka klinika

Brno, 625 00, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava - Poruba, 708 52, Czechia

Location

Vseobecna fakultni nemocnice v Praze, Dept of Neurologicka klinika

Prague, 128 21, Czechia

Location

East Tallinn Central Hospital

Tallinn, 10138, Estonia

Location

CHU Strasbourg - Nouvel Hôpital Civil, Clinique Neurologique

Strasbourg, Bas Rhin, 67091, France

Location

CHU de Toulouse - Hôpital Purpan, Service de Neurologie Générale

Toulouse, Haute Garonne, 31059, France

Location

Universitaetsklinikum Regensburg, Parent

Regensburg, Bavaria, 93053, Germany

Location

Universitaetsklinikum Giessen und Marburg GmbH Standort Marburg

Marburg, Hesse, 35043, Germany

Location

Universitaetsmedizin Goettingen, Parent

Göttingen, Lower Saxony, 37075, Germany

Location

Fachkrankenhaus Hubertusburg gGmbH, Klinik f. Neurologie

Wermsdorf, Saxony, 4779, Germany

Location

Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie

Halle, Saxony-Anhalt, 6120, Germany

Location

Universitaetsklinikum Jena, Klinik fuer Neurologie

Jena, Thuringia, 7747, Germany

Location

Charité Universitaetsmedizin Berlin, Klinik für Neurologie

Berlin, 10117, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik

Hamburg, 20246, Germany

Location

Jahn Ferenc Del-pesti Korhaz es Rendelointezet, Neurologiai Osztaly

Budapest, 1204, Hungary

Location

Pest Megyei Flor Ferenc Korhaz, Neurologia es Stroke Osztaly

Kistarcsa, 2143, Hungary

Location

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, 6725, Hungary

Location

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, 50161, Lithuania

Location

Uniwersyteckie Centrum Kliniczne, Dept of Neurology

Gdansk, 80-952, Poland

Location

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

Krakow, 31-505, Poland

Location

III Szpital Miejski w Lodzi im. Dr K. Jonschera

Lodz, 93-113, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny

Warsaw, 02-097, Poland

Location

Related Publications (2)

• 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.

  PMID: 36270895 DERIVED

• 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.

  PMID: 35350948 DERIVED

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Rhonda Griffin
• Organization: Grifols Therapeutics LLC

rhonda.griffin@grifols.com

919-316-6693

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2015
• First Posted: June 17, 2015
• Study Start: June 1, 2015
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: March 30, 2020
• Results First Posted: February 26, 2020

Record last verified: 2020-03

Locations

ES (1); BE (1); PL (4); LI (1); FR (2); CZ (3); DE (8); CA (2); HU (3); US (14)