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

NCT02473952 | Completed Phase 2 Results

• 1 other identifier: GTI1408
• Study Type: interventional
• Target: 62
• Locations: 10 countries
• Sites: 40

Brief Summary

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

Conditions

Myasthenia Gravis, Generalized

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

IGIV-C

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

IGIV-C DRUG

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

IGIV-C

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead

Study Sites (40)

Phoenix Neurological Associates, Ltd.

Phoenix, Arizona, 85018, United States

Location

University of California-Irvine

Orange, California, 92868, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

University of Florida Health Science Center

Jacksonville, Florida, 32209, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, 66160, United States

Location

Rutgers New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43220, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Houston Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05405, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

UZ Leuven

Leuven, 3000, Belgium

Location

London Health Sciences Centre - University Hospital

London, Ontario, N6A 5A5, Canada

Location

University Health Network (UHN) - Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Fakultni nemocnice Brno, Dept of Neurologicka klinika

Brno, 625 00, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava - Poruba, 708 52, Czechia

Location

East Tallinn Central Hospital

Tallinn, 10138, Estonia

Location

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

Nice, Alpes Maritimes, 6202, France

Location

CHU Strasbourg - Nouvel Hôpital Civil, Clinique Neurologique

Strasbourg, Bas Rhin, 67091, France

Location

CHU de Toulouse - Hôpital Purpan, Service de Neurologie Générale

Toulouse, Haute Garonne, 31059, France

Location

Hopital Neurologique Pierre Wertheimer, Neuro-musculaire - Electromyographie

Bron, Rhone, 69677, France

Location

Universitaetsklinikum Regensburg, Parent

Regensburg, Bavaria, 93053, Germany

Location

Universitaetsmedizin Göttingen, Parent

Göttingen, Lower Saxony, 37075, Germany

Location

Universitaetsklinikum Koeln, Neurologie und Psychiatrie

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony, 1307, Germany

Location

Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie

Halle, Saxony-Anhalt, 6120, Germany

Location

Universitaetsklinikum Jena, Klinik fuer Neurologie

Jena, Thuringia, 7747, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fuer Neurologie

Hamburg, 20246, Germany

Location

Jahn Ferenc Del-pesti Korhaz es Rendelointezet, Neurologiai Osztaly

Budapest, 1204, Hungary

Location

Pest Megyei Flor Ferenc Korhaz, Neurologia es Stroke Osztaly

Kistarcsa, 2143, Hungary

Location

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, 6725, Hungary

Location

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, 50009, Lithuania

Location

Uniwersyteckie Centrum Kliniczne, Dept of Neurology

Gdansk, 80-952, Poland

Location

Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii Klinicznej

Krakow, 31-505, Poland

Location

III Szpital Miejski w Lodzi im. Dr K. Jonschera

Lodz, 93-113, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny, Dept of Neurology

Warsaw, 02-097, Poland

Location

Related Publications (1)

• 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.

  PMID: 35350948 DERIVED

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Rhonda Griffin, BSN
• Organization: Grifols Therapeutics, LLC

Rhonda.Griffin@Grifols.com

919-316-6693

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2015
• First Posted: June 17, 2015
• Study Start: August 1, 2015
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: March 5, 2019
• Results First Posted: March 5, 2019

Record last verified: 2019-03

Locations

DE (7); US (15); FR (4); CA (2); BE (1); HU (3); CZ (2); ES (1); PL (4); LI (1)