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

Primary Purpose

Myasthenia Gravis, Generalized

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IGIV-C
Placebo
Sponsored by
Grifols Therapeutics LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myasthenia Gravis, Generalized

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Phoenix Neurological Associates, Ltd.
  • University of California-Irvine
  • Yale University School of Medicine
  • University of Florida Health Science Center
  • University of South Florida
  • Georgia Regents University
  • Indiana University
  • University of Kansas Medical Center Research Institute, Inc.
  • Rutgers New Jersey Medical School
  • Columbia University Medical Center
  • Ohio State University Wexner Medical Center
  • Thomas Jefferson University Hospital
  • Houston Methodist Neurological Institute
  • University of Vermont Medical Center
  • University of Washington Medical Center
  • UZ Leuven
  • London Health Sciences Centre - University Hospital
  • University Health Network (UHN) - Toronto General Hospital
  • Fakultni nemocnice Brno, Dept of Neurologicka klinika
  • Fakultni nemocnice Ostrava
  • East Tallinn Central Hospital
  • CHU Nice - Hôpital de l'Archet 1, Ctre de Réf Maladies Neuromusculaires et SLA
  • CHU Strasbourg - Nouvel Hôpital Civil, Clinique Neurologique
  • CHU de Toulouse - Hôpital Purpan, Service de Neurologie Générale
  • Hopital Neurologique Pierre Wertheimer, Neuro-musculaire - Electromyographie
  • Universitaetsklinikum Regensburg, Parent
  • Universitaetsmedizin Göttingen, Parent
  • Universitaetsklinikum Koeln, Neurologie und Psychiatrie
  • Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie
  • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Universitaetsklinikum Jena, Klinik fuer Neurologie
  • Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fuer Neurologie
  • Jahn Ferenc Del-pesti Korhaz es Rendelointezet, Neurologiai Osztaly
  • Pest Megyei Flor Ferenc Korhaz, Neurologia es Stroke Osztaly
  • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
  • Hospital of Lithuanian University of Health Sciences Kaunas Clinics
  • Uniwersyteckie Centrum Kliniczne, Dept of Neurology
  • Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii Klinicznej
  • III Szpital Miejski w Lodzi im. Dr K. Jonschera
  • Samodzielny Publiczny Centralny Szpital Kliniczny, Dept of Neurology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

IGIV-C

Placebo

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
June 14, 2015
Last Updated
March 1, 2019
Sponsor
Grifols Therapeutics LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02473952
Brief Title
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

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
August 2015 (Actual)
Primary Completion Date
January 2018 (Actual)
Study Completion Date
January 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grifols Therapeutics LLC

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myasthenia Gravis, Generalized

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
62 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IGIV-C
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
IGIV-C
Intervention Description
IGIV-C: Immune Globulin Injection (Human), 10%, Caprylate/Chromatography Purified
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Improvement in Myasthenia Gravis (MG) Symptoms as Measured by the Mean Change in Quantitative Myasthenia Gravis (QMG) Total Score.
Description
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.
Time Frame
Baseline (Week 0) to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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): Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to Screening and no immunosuppressants Cholinesterase inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to Screening AND/OR only one of the following: Prednisone (up to 60 mg/day or equivalent) for at least 2 months prior to Screening, OR Azathioprine for at least 6 months prior to Screening, OR Mycophenolate mofetil for at least 6 months prior to Screening, OR Methotrexate for at least 6 months prior to Screening, OR Cyclosporine or tacrolimus for at least 3 months prior to Screening 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: Azathioprine for at least 6 months prior to Screening, OR Mycophenolate mofetil for at least 6 months prior to Screening, OR Methotrexate for at least 6 months prior to Screening, OR 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
Facility Information:
Facility Name
Phoenix Neurological Associates, Ltd.
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85018
Country
United States
Facility Name
University of California-Irvine
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
University of Florida Health Science Center
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Georgia Regents University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Kansas Medical Center Research Institute, Inc.
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Rutgers New Jersey Medical School
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43220
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Houston Methodist Neurological Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Vermont Medical Center
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05405
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
London Health Sciences Centre - University Hospital
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
University Health Network (UHN) - Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Fakultni nemocnice Brno, Dept of Neurologicka klinika
City
Brno
ZIP/Postal Code
625 00
Country
Czechia
Facility Name
Fakultni nemocnice Ostrava
City
Ostrava - Poruba
ZIP/Postal Code
708 52
Country
Czechia
Facility Name
East Tallinn Central Hospital
City
Tallinn
ZIP/Postal Code
10138
Country
Estonia
Facility Name
CHU Nice - Hôpital de l'Archet 1, Ctre de Réf Maladies Neuromusculaires et SLA
City
Nice cedex 3
State/Province
Alpes Maritimes
ZIP/Postal Code
6202
Country
France
Facility Name
CHU Strasbourg - Nouvel Hôpital Civil, Clinique Neurologique
City
Strasbourg cedex
State/Province
Bas Rhin
ZIP/Postal Code
67091
Country
France
Facility Name
CHU de Toulouse - Hôpital Purpan, Service de Neurologie Générale
City
Toulouse cedex 9
State/Province
Haute Garonne
ZIP/Postal Code
31059
Country
France
Facility Name
Hopital Neurologique Pierre Wertheimer, Neuro-musculaire - Electromyographie
City
Bron cedex
State/Province
Rhone
ZIP/Postal Code
69677
Country
France
Facility Name
Universitaetsklinikum Regensburg, Parent
City
Regensburg
State/Province
Bayern
ZIP/Postal Code
93053
Country
Germany
Facility Name
Universitaetsmedizin Göttingen, Parent
City
Göttingen
State/Province
Niedersachsen
ZIP/Postal Code
37075
Country
Germany
Facility Name
Universitaetsklinikum Koeln, Neurologie und Psychiatrie
City
Koeln
State/Province
Nordrhein Westfalen
ZIP/Postal Code
50937
Country
Germany
Facility Name
Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie
City
Halle
State/Province
Sachsen Anhalt
ZIP/Postal Code
6120
Country
Germany
Facility Name
Universitaetsklinikum Carl Gustav Carus TU Dresden
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
1307
Country
Germany
Facility Name
Universitaetsklinikum Jena, Klinik fuer Neurologie
City
Jena
State/Province
Thueringen
ZIP/Postal Code
7747
Country
Germany
Facility Name
Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fuer Neurologie
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Jahn Ferenc Del-pesti Korhaz es Rendelointezet, Neurologiai Osztaly
City
Budapest
ZIP/Postal Code
1204
Country
Hungary
Facility Name
Pest Megyei Flor Ferenc Korhaz, Neurologia es Stroke Osztaly
City
Kistarcsa
ZIP/Postal Code
2143
Country
Hungary
Facility Name
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
City
Szeged
ZIP/Postal Code
6725
Country
Hungary
Facility Name
Hospital of Lithuanian University of Health Sciences Kaunas Clinics
City
Kaunas
ZIP/Postal Code
50009
Country
Lithuania
Facility Name
Uniwersyteckie Centrum Kliniczne, Dept of Neurology
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii Klinicznej
City
Krakow
ZIP/Postal Code
31-505
Country
Poland
Facility Name
III Szpital Miejski w Lodzi im. Dr K. Jonschera
City
Lodz
ZIP/Postal Code
93-113
Country
Poland
Facility Name
Samodzielny Publiczny Centralny Szpital Kliniczny, Dept of Neurology
City
Warszawa
ZIP/Postal Code
02-097
Country
Poland

12. IPD Sharing Statement

Citations:
PubMed Identifier
35350948
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.
Results Reference
derived

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

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