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

Myasthenia Gravis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02473965
• Other study ID #: GTI1306
• Status: Completed
• Phase: Phase 2
• Start date: June 2015
• Est. completion date: February 2019

Study information

• Verified date: March 2020
• Source: Grifols Therapeutics LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis

Intervention

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

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven
Canada	London Health Sciences Centre- University Hospital	London	Ontario
Canada	University Health Network (UHN) - Toronto General Hospital	Toronto	Ontario
Czechia	Fakultni nemocnice Brno, Dept of Neurologicka klinika	Brno
Czechia	Fakultni nemocnice Ostrava	Ostrava - Poruba
Czechia	Vseobecna fakultni nemocnice v Praze, Dept of Neurologicka klinika	Praha 2
Estonia	East Tallinn Central Hospital	Tallinn
France	CHU Strasbourg - Nouvel Hôpital Civil, Clinique Neurologique	Strasbourg cedex	Bas Rhin
France	CHU de Toulouse - Hôpital Purpan, Service de Neurologie Générale	Toulouse cedex 9	Haute Garonne
Germany	Charité Universitaetsmedizin Berlin, Klinik für Neurologie	Berlin
Germany	Universitaetsmedizin Goettingen, Parent	Göttingen	Niedersachsen
Germany	Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Neurologie	Halle	Sachsen Anhalt
Germany	Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik	Hamburg
Germany	Universitaetsklinikum Jena, Klinik fuer Neurologie	Jena	Thueringen
Germany	Universitaetsklinikum Giessen und Marburg GmbH Standort Marburg	Marburg	Hessen
Germany	Universitaetsklinikum Regensburg, Parent	Regensburg	Bayern
Germany	Fachkrankenhaus Hubertusburg gGmbH, Klinik f. Neurologie	Wermsdorf	Sachsen
Hungary	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
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics	Kaunas
Poland	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	Warszawa
United States	Georgia Regents University	Augusta	Georgia
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Ohio State University Wexner Medical Center, Neurology Department	Columbus	Ohio
United States	Houston Methodist Neurological Institute	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Florida at Shands Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center Research Institute, Inc.	Kansas City	Kansas
United States	Yale University School of Medicine, Department of Neurology	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	University of California-Irvine	Orange	California
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Washington Medical Center	Seattle	Washington
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Grifols Therapeutics LLC

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Subjects Achieving a 50% or Greater Reduction in CS Dose (Prednisone or Equivalent) From Baseline to Week 39	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	Mean Percent Change in Daily CS Dose (Prednisone or Equivalent) From Baseline to Week 39	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).
Secondary	Median Time to First Episode of MG Worsening	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).