Efficacy and Safety of IGIV-C in Corticosteroid Dependent Patients With Generalized Myasthenia Gravis

March 13, 2020 updated by: Grifols Therapeutics LLC

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

60

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
      • Praha 2, Czechia, 128 21
        • Vseobecna fakultni nemocnice v Praze, Dept of Neurologicka klinika
  • Estonia
      • Tallinn, Estonia, 10138
        • East Tallinn Central Hospital
  • France
    • 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
  • Germany
      • Berlin, Germany, 10117
        • Charité Universitaetsmedizin Berlin, Klinik für Neurologie
      • Hamburg, Germany, 20246
        • Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik
    • Bayern
      • Regensburg, Bayern, Germany, 93053
        • Universitaetsklinikum Regensburg, Parent
    • Hessen
      • Marburg, Hessen, Germany, 35043
        • Universitaetsklinikum Giessen und Marburg GmbH Standort Marburg
    • Niedersachsen
      • Göttingen, Niedersachsen, Germany, 37075
        • Universitaetsmedizin Goettingen, Parent
    • Sachsen
      • Wermsdorf, Sachsen, Germany, 4779
        • Fachkrankenhaus Hubertusburg gGmbH, Klinik f. Neurologie
    • 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, 50161
        • 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
  • United States
    • California
      • Orange, California, United States, 92868
        • University of California-Irvine
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University School of Medicine, Department of Neurology
    • Florida
      • Jacksonville, Florida, United States, 32209
        • University of Florida at Shands Jacksonville
      • 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, Neurology Department
    • 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, 98105
        • 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 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

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
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: IGIV-C
An IGIV-C loading dose of 2 g/kg and maintenance dose of 1 g/kg will be administered in CS dependent subjects with MG.
Drug: IGIV-C

Run-Phase: 1 loading dose of 2 g/kg IGIV-C and 2 maintenance doses of 1 g/kg IGIV-C

Corticosteroid Tapering/IGIV-C Maintenance Phase: 1 g/kg IGIV-C every 3 weeks for up to 36 weeks
PLACEBO_COMPARATOR: Placebo
0.9% sodium chloride injection, USP or equivalent
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent of Subjects Achieving a 50% or Greater Reduction in CS Dose (Prednisone or Equivalent) From Baseline to Week 39
Time Frame: Baseline/Week 0 (Visit 1) and Week 39 (Visit 14).
The average daily CS dose was derived for each subject at each scheduled visit based on the prescribed dose and the time interval taking into account any prescribed dose changes between routinely scheduled visits. Subjects who discontinued the study early with adverse outcomes related to MG were considered as not achieving a 50% or greater reduction. The missing dose reduction at Week 39 was imputed using the worst observation carried forward (WOCF) method. For subjects who did not have CS dose prescribed at Week 39 due to other reasons, the last observation carried forward (LOCF) method was used to impute the prescribed CS dose at Week 39. Baseline was defined as the last non-missing measurement taken prior to first dose of study medication. The percent of subjects achieving ≥50% reduction in CS dose from baseline to Week 39 is presented for each treatment group overall and for the baseline daily prednisone equivalent dose level stratification categories.
Baseline/Week 0 (Visit 1) and Week 39 (Visit 14).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Percent Change in Daily CS Dose (Prednisone or Equivalent) From Baseline to Week 39
Time Frame: Baseline/Week 0 (Visit 1) and Week 39 (Visit 14).
The average daily CS dose was derived for each subject at each scheduled visit based on the prescribed dose and the time interval taking into account any prescribed dose changes between routinely scheduled visits. For subjects who discontinued the study early with adverse outcomes related to MG, the missing dose reduction at Week 39 was imputed using the WOCF method. For subjects who had missing CS dose reduction at Week 39 due to other reasons, the missing CS dose was imputed using the LOCF method. Baseline was defined as the last non-missing measurement taken prior to first dose of study medication. The least squares (LS) mean percent change from baseline in daily CS dose to Week 39 is presented for each treatment group.
Baseline/Week 0 (Visit 1) and Week 39 (Visit 14).
Median Time to First Episode of MG Worsening
Time Frame: From Baseline/Week 0 (Visit 1) to Week 39 (Visit 14).
The time to the first episode of MG worsening was defined as the time between baseline and the first instance of QMG total score increase by ≥4 points relative to Baseline/Week 0. The QMG total score is the sum of all 13 items and ranges from 0 to 39. Higher values represent greater severity of illness. If one or more items were missing at a given assessment, the total score was set to missing. The median time to MG worsening was calculated based on Kaplan-Meier methodology. Baseline was defined as the last non-missing measurement taken prior to the first dose of study medication.
From Baseline/Week 0 (Visit 1) to Week 39 (Visit 14).

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

June 1, 2015

Primary Completion (ACTUAL)

February 1, 2019

Study Completion (ACTUAL)

February 1, 2019

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 30, 2020

Last Update Submitted That Met QC Criteria

March 13, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GTI1306

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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