Clinical trial NCT02473965: Efficacy and Safety of IGIV-C in Corticosteroid Dependent Patients With Generalized Myasthenia Gravis
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of lGIV-C as a Corticosteroid Sparing Agent in Corticosteroid Dependent Patients With Generalized Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myasthenia Gravis
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2015-06-17
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percent of Subjects Achieving a 50% or Greater Reduction in CS Dose (Prednisone or Equivalent) From Baseline to Week 39
timeFrame: Baseline/Week 0 (Visit 1) and Week 39 (Visit 14).
Secondary outcomes:
measure: Mean Percent Change in Daily CS Dose (Prednisone or Equivalent) From Baseline to Week 39
timeFrame: Baseline/Week 0 (Visit 1) and Week 39 (Visit 14).
measure: Median Time to First Episode of MG Worsening
timeFrame: From Baseline/Week 0 (Visit 1) to Week 39 (Visit 14).
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California-Irvine
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine, Department of Neurology
state: Connecticut
city: Jacksonville
country: United States
facility: University of Florida at Shands Jacksonville
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute, Inc.
state: Kansas
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center, Neurology Department
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist Neurological Institute
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Leuven
country: Belgium
facility: UZ Leuven
city: London
country: Canada
facility: London Health Sciences Centre- University Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network (UHN) - Toronto General Hospital
state: Ontario
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno, Dept of Neurologicka klinika
city: Ostrava - Poruba
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze, Dept of Neurologicka klinika
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Strasbourg cedex
country: France
facility: CHU Strasbourg - Nouvel Hôpital Civil, Clinique Neurologique
state: Bas Rhin
city: Toulouse cedex 9
country: France
facility: CHU de Toulouse - Hôpital Purpan, Service de Neurologie Générale
state: Haute Garonne
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg, Parent
state: Bayern
city: Marburg
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH Standort Marburg
state: Hessen
city: Göttingen
country: Germany
facility: Universitaetsmedizin Goettingen, Parent
state: Niedersachsen
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie
state: Sachsen Anhalt
city: Wermsdorf
country: Germany
facility: Fachkrankenhaus Hubertusburg gGmbH, Klinik f. Neurologie
state: Sachsen
city: Jena
country: Germany
facility: Universitaetsklinikum Jena, Klinik fuer Neurologie
state: Thueringen
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin, Klinik für Neurologie
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik
city: Budapest
country: Hungary
facility: Jahn Ferenc Del-pesti Korhaz es Rendelointezet, Neurologiai Osztaly
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flor Ferenc Korhaz, Neurologia es Stroke Osztaly
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas Clinics
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Dept of Neurology
city: Krakow
country: Poland
facility: Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii Klinicznej
city: Lodz
country: Poland
facility: III Szpital Miejski w Lodzi im. Dr K. Jonschera
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny
Study officials:
References:
citation: 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.
citation: 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.