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

NCT ID: NCT02473952

Last Updated: 2019-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2018-01-31

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.

Conditions

Myasthenia Gravis, Generalized

Study Design

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

Study Groups

IGIV-C

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

An initial loading dose of 2 g/kg of body weight will be administered at Baseline (Week 0, Visit 1) followed by maintenance doses of 1 g/kg of body weight administered every third week through Week 21 (Visit 8).

Group Type: EXPERIMENTAL

IGIV-C

Intervention Type: DRUG

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

Placebo

Placebo: Sterile 0.9% sodium chloride injection or equivalent. Placebo will be infused at the Baseline/Week 0 Visit (Visit 1) using the same volume as would be required for the IGIV-C loading dose. Subsequent placebo maintenance doses will be matched in volume to the IGIV-C maintenance doses and administered every third week until Week 21 (Visit 8).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

IGIV-C

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

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

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

• 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

• 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

Phoenix Neurological Associates, Ltd.

Phoenix, Arizona, United States

University of California-Irvine

Orange, California, United States

Yale University School of Medicine

New Haven, Connecticut, United States

University of Florida Health Science Center

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

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

East Tallinn Central Hospital

Tallinn, , Estonia

CHU Nice - Hôpital de l'Archet 1, Ctre de Réf Maladies Neuromusculaires et SLA

Nice, Alpes Maritimes, France

CHU Strasbourg - Nouvel Hôpital Civil, Clinique Neurologique

Strasbourg, Bas Rhin, France

CHU de Toulouse - Hôpital Purpan, Service de Neurologie Générale

Toulouse, Haute Garonne, France

Hopital Neurologique Pierre Wertheimer, Neuro-musculaire - Electromyographie

Bron, Rhone, France

Universitaetsklinikum Regensburg, Parent

Regensburg, Bavaria, Germany

Universitaetsmedizin Göttingen, Parent

Göttingen, Lower Saxony, Germany

Universitaetsklinikum Koeln, Neurologie und Psychiatrie

Cologne, North Rhine-Westphalia, Germany

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony, Germany

Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie

Halle, Saxony-Anhalt, Germany

Universitaetsklinikum Jena, Klinik fuer Neurologie

Jena, Thuringia, Germany

Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fuer Neurologie

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, Dept of Neurology

Warsaw, , Poland

Countries

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

References

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: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GTI1408

Identifier Type: -

Identifier Source: org_study_id