Clinical trial NCT02473952: A Study to Evaluate the Efficacy and Safety of IGIV-C in Symptomatic Subjects With Generalized Myasthenia Gravis
Official title: A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) in Symptomatic Subjects With Generalized Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myasthenia Gravis, Generalized
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2015-06-17
Enrollment: 62
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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Improvement in Myasthenia Gravis (MG) Symptoms as Measured by the Mean Change in Quantitative Myasthenia Gravis (QMG) Total Score.
timeFrame: Baseline (Week 0) to Week 24
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Neurological Associates, Ltd.
state: Arizona
city: Orange
country: United States
facility: University of California-Irvine
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Jacksonville
country: United States
facility: University of Florida Health Science Center
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
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: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Nice cedex 3
country: France
facility: CHU Nice - Hôpital de l'Archet 1, Ctre de Réf Maladies Neuromusculaires et SLA
state: Alpes Maritimes
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: Bron cedex
country: France
facility: Hopital Neurologique Pierre Wertheimer, Neuro-musculaire - Electromyographie
state: Rhone
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg, Parent
state: Bayern
city: Göttingen
country: Germany
facility: Universitaetsmedizin Göttingen, Parent
state: Niedersachsen
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln, Neurologie und Psychiatrie
state: Nordrhein Westfalen
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie
state: Sachsen Anhalt
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
state: Sachsen
city: Jena
country: Germany
facility: Universitaetsklinikum Jena, Klinik fuer Neurologie
state: Thueringen
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fuer Neurologie
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, Dept of Neurology
Study officials:
References:
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.