A Study to Evaluate the Efficacy and Safety of IGIV-C in Symptomatic Subjects With Generalized Myasthenia Gravis

Myasthenia Gravis, Generalized Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02473952
• Other study ID #: GTI1408
• Status: Completed
• Phase: Phase 2
• Start date: August 2015
• Est. completion date: January 2018

Study information

• Verified date: March 2019
• Source: Grifols Therapeutics LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to evaluate whether IGIV-C improves MG symptoms as compared to placebo in subjects with MG.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: January 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis
• Myasthenia Gravis, Generalized

Intervention

Drug:
• IGIV-C
IGIV-C: Immune Globulin Injection (Human), 10%, Caprylate/Chromatography Purified
• Placebo

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven
Canada	London Health Sciences Centre - University Hospital	London	Ontario
Canada	University Health Network (UHN) - Toronto General Hospital	Toronto	Ontario
Czechia	Fakultni nemocnice Brno, Dept of Neurologicka klinika	Brno
Czechia	Fakultni nemocnice Ostrava	Ostrava - Poruba
Estonia	East Tallinn Central Hospital	Tallinn
France	Hopital Neurologique Pierre Wertheimer, Neuro-musculaire - Electromyographie	Bron cedex	Rhone
France	CHU Nice - Hôpital de l'Archet 1, Ctre de Réf Maladies Neuromusculaires et SLA	Nice cedex 3	Alpes Maritimes
France	CHU Strasbourg - Nouvel Hôpital Civil, Clinique Neurologique	Strasbourg cedex	Bas Rhin
France	CHU de Toulouse - Hôpital Purpan, Service de Neurologie Générale	Toulouse cedex 9	Haute Garonne
Germany	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden	Sachsen
Germany	Universitaetsmedizin Göttingen, Parent	Göttingen	Niedersachsen
Germany	Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie	Halle	Sachsen Anhalt
Germany	Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fuer Neurologie	Hamburg
Germany	Universitaetsklinikum Jena, Klinik fuer Neurologie	Jena	Thueringen
Germany	Universitaetsklinikum Koeln, Neurologie und Psychiatrie	Koeln	Nordrhein Westfalen
Germany	Universitaetsklinikum Regensburg, Parent	Regensburg	Bayern
Hungary	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
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics	Kaunas
Poland	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, Dept of Neurology	Warszawa
United States	Georgia Regents University	Augusta	Georgia
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Houston Methodist Neurological Institute	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Florida Health Science Center	Jacksonville	Florida
United States	University of Kansas Medical Center Research Institute, Inc.	Kansas City	Kansas
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	University of California-Irvine	Orange	California
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Phoenix Neurological Associates, Ltd.	Phoenix	Arizona
United States	University of Washington Medical Center	Seattle	Washington
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Grifols Therapeutics LLC

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in Myasthenia Gravis (MG) Symptoms as Measured by the Mean Change in Quantitative Myasthenia Gravis (QMG) Total Score.	To measure improvement in MG symptoms by the mean change in QMG total score from Baseline (Week 0) to Week 24 as compared to placebo. Evaluators score 13 individual items (range from 0=best to 3=worst) and the individual scores are added together for the total score (range 0-39). An average 3-point improvement in QMG score indicates clinically meaningful improvement.	Baseline (Week 0) to Week 24