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

March 1, 2019 updated by: Grifols Therapeutics LLC

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

62

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, 3000
        • UZ Leuven
  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 5A5
        • London Health Sciences Centre - University Hospital
      • Toronto, Ontario, Canada, M5G 2C4
        • University Health Network (UHN) - Toronto General Hospital
  • Czechia
      • Brno, Czechia, 625 00
        • Fakultni nemocnice Brno, Dept of Neurologicka klinika
      • Ostrava - Poruba, Czechia, 708 52
        • Fakultni Nemocnice Ostrava
  • Estonia
      • Tallinn, Estonia, 10138
        • East Tallinn Central Hospital
  • France
    • Alpes Maritimes
      • Nice cedex 3, Alpes Maritimes, France, 6202
        • CHU Nice - Hôpital de l'Archet 1, Ctre de Réf Maladies Neuromusculaires et SLA
    • Bas Rhin
      • Strasbourg cedex, Bas Rhin, France, 67091
        • CHU Strasbourg - Nouvel Hôpital Civil, Clinique Neurologique
    • Haute Garonne
      • Toulouse cedex 9, Haute Garonne, France, 31059
        • CHU de Toulouse - Hôpital Purpan, Service de Neurologie Générale
    • Rhone
      • Bron cedex, Rhone, France, 69677
        • Hopital Neurologique Pierre Wertheimer, Neuro-musculaire - Electromyographie
  • Germany
      • Hamburg, Germany, 20246
        • Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fuer Neurologie
    • Bayern
      • Regensburg, Bayern, Germany, 93053
        • Universitaetsklinikum Regensburg, Parent
    • Niedersachsen
      • Göttingen, Niedersachsen, Germany, 37075
        • Universitaetsmedizin Göttingen, Parent
    • Nordrhein Westfalen
      • Koeln, Nordrhein Westfalen, Germany, 50937
        • Universitaetsklinikum Koeln, Neurologie und Psychiatrie
    • Sachsen
      • Dresden, Sachsen, Germany, 1307
        • Universitaetsklinikum Carl Gustav Carus TU Dresden
    • Sachsen Anhalt
      • Halle, Sachsen Anhalt, Germany, 6120
        • Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie
    • Thueringen
      • Jena, Thueringen, Germany, 7747
        • Universitaetsklinikum Jena, Klinik fuer Neurologie
  • Hungary
      • Budapest, Hungary, 1204
        • Jahn Ferenc Del-pesti Korhaz es Rendelointezet, Neurologiai Osztaly
      • Kistarcsa, Hungary, 2143
        • Pest Megyei Flor Ferenc Korhaz, Neurologia es Stroke Osztaly
      • Szeged, Hungary, 6725
        • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
  • Lithuania
      • Kaunas, Lithuania, 50009
        • Hospital of Lithuanian University of Health Sciences Kaunas Clinics
  • Poland
      • Gdansk, Poland, 80-952
        • Uniwersyteckie Centrum Kliniczne, Dept of Neurology
      • Krakow, Poland, 31-505
        • Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii Klinicznej
      • Lodz, Poland, 93-113
        • III Szpital Miejski w Lodzi im. Dr K. Jonschera
      • Warszawa, Poland, 02-097
        • Samodzielny Publiczny Centralny Szpital Kliniczny, Dept of Neurology
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85018
        • Phoenix Neurological Associates, Ltd.
    • California
      • Orange, California, United States, 92868
        • University of California-Irvine
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University School Of Medicine
    • Florida
      • Jacksonville, Florida, United States, 32209
        • University of Florida Health Science Center
      • Tampa, Florida, United States, 33612
        • University of South Florida
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Georgia Regents University
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center Research Institute, Inc.
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Rutgers New Jersey Medical School
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • Ohio
      • Columbus, Ohio, United States, 43220
        • Ohio State University Wexner Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • Houston Methodist Neurological Institute
    • Vermont
      • Burlington, Vermont, United States, 05405
        • University of Vermont Medical Center
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
Drug: IGIV-C
IGIV-C: Immune Globulin Injection (Human), 10%, Caprylate/Chromatography Purified
Placebo Comparator: 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).
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement in Myasthenia Gravis (MG) Symptoms as Measured by the Mean Change in Quantitative Myasthenia Gravis (QMG) Total Score.
Time Frame: Baseline (Week 0) to Week 24
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Grifols Therapeutics LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2015

Primary Completion (Actual)

January 1, 2018

Study Completion (Actual)

January 1, 2018

Study Registration Dates

First Submitted

June 14, 2015

First Submitted That Met QC Criteria

June 16, 2015

First Posted (Estimate)

June 17, 2015

Study Record Updates

Last Update Posted (Actual)

March 5, 2019

Last Update Submitted That Met QC Criteria

March 1, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GTI1408

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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