A Study to Assess the Efficacy and Safety of IGIV-C in Patients With Myasthenia Gravis Exacerbations

A Multicenter, Prospective, Open-label, Non-controlled Clinical Trial to Assess the Efficacy and Safety of Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) in Patients With Myasthenia Gravis Exacerbations

This was a multicenter, prospective, open-label, non-controlled study to assess the efficacy and safety of an IV dose of 2 g/kg of IGIV-C in subjects with MG exacerbations.

Study Overview

• Status: Completed
• Conditions: Myasthenia Gravis Exacerbations
• Intervention / Treatment: Biological: IGIV-C

Detailed Description

The study consisted of a single dose course of IGIV-C treatment followed by 28-days of post-infusion assessments. The total duration of study participation for each subject was up to 28 ± 2 days. Approximately 50 subjects, ages 18 or greater, were planned to be enrolled in the study and receive a single, total dose of 2 g/kg of IGIV-C over 2 consecutive days (dose of 1 g/kg per day) across multiple centers in Argentina, Canada, Europe, and South Africa.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1181ACH
    • Hospital Italiano
  • Buenos Aires, Argentina, C1221ADC
    • Hospital General de Agudos Dr. J. M.
  • Cordoba, Argentina, X5004CDT
    • Hospital Cordoba
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
  • East Flanders
    • Ghent, East Flanders, Belgium, 9000
      • AZ St Lucas Gent
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network (UHN) - Toronto General Hospital
• Czechia
  • Brno, Czechia
    • Fakultni nemocnice Brno, Neurologicka klinika
  • Ostrava, Czechia, 70800
    • Fakultní nemocnice Ostrava, Neurologická klinika
  • Prague, Czechia, 12808
    • Vseobecna fakultni nemocnice v Praze
• Estonia
  • Tallinn, Estonia, 10138
    • East Tallinn Central Hospital
• France
  • Grenoble, France, 38700
    • Hôpital Albert Michallon
  • Lille, France, 59037
    • Hopital Roger Salengro
  • Marseille, France, 13385
    • Hôpital de la Timone
  • Strasbourg, France, 67200
    • Hôpital Hautepierre Strasbourg
  • Toulouse, France, 31059
    • CHU de Toulouse - Hôpital Purpan
  • Lyon
    • Bron, Lyon, France, 69677
      • Hôpital Neurologique Pierre Wertheimer
• Hungary
  • Budapest, Hungary, 1204
    • Jahn Ferenc Dél-Pesti Kórház
  • Kistarcsa, Hungary, 2143
    • Pest Megyei Flor Ferenc Korhaz
  • Nyíregyháza, Hungary
    • Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház
  • Szeged, Hungary, 4400
    • University of Szeged, Faculty of Medicine
  • Zalaegerszeg, Hungary, 8900
    • Zala Megyei Kórház
• Latvia
  • Riga, Latvia, LV-1038
    • Riga East Clinical University Hospital
• Poland
  • Gdansk, Poland
    • Uniwersyteckie Centrum Kliniczne
• Romania
  • Bucuresti, Romania, 22328
    • Institutul Clinic Fundeni
  • Targu Mures, Romania, RO540136
    • Spitalul Clinic Judetean de Urgenta Targu-Mures
• Russian Federation
  • Nizhniy Novgorod, Russian Federation, 603126
    • State Budgetary Institution of Healthcare of Nizhniy Novgorod region. Nizhniy Novgorod Regional Clinical Hospital named after N.A.Semashko
  • Saint Petersburg, Russian Federation, 357538
    • Saint-Petersburg State Budgetary Institution of Healthcare. City Multi-field Hospital # 2
  • Samara, Russian Federation, 443095
    • State Budgetary Institution of Healthcare "Samara Regional Clinical Hospital. V.D.Seredavin
• South Africa
  • Cape Town, South Africa
    • Groote Schuur Hospital,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Was male or female aged ≥18 years.
• Subjects must be willing and able to provide written informed consent (if applicable, a legally authorized representative may provide informed consent on behalf of the subject).
• Subjects who met the clinical criteria for diagnosis of MG with an exacerbation defined as worsening of MG symptoms as defined by an Myasthenia Gravis Foundation of America (MGFA) classification IVb or V.
• Subjects on long-term (8 weeks) corticosteroid treatment for MG.
• Female subjects of child-bearing potential must have a negative test for pregnancy (human chorionic gonadotropin [HCG]-based assay).
• Subjects must be willing to comply with all aspects of the clinical trial protocol, including blood sampling and long-term storage of extra samples, for the entire duration of the study.

Exclusion Criteria:

• Subjects who had received immune globulin treatment given by IV, subcutaneous or intramuscular route within the last 30 days.
• Subjects with documentation of a lack of clinical response to intravenous immunoglobulin (IVIg) therapy for MG.
• Subjects documented positive for antibodies directed against Muscle specific kinase (MuSK).
• Subjects with corticosteroid (CS) treatment initiated within the last 8 weeks or modified within the last 2 weeks.
• Subjects with plasma exchange (PLEX) within the last 30 days.
• Subjects with MG exacerbation attributable to change in medication or infection or evident infection as defined by, but not limited to, the presence of at least one of the following diagnostic features: 1) axillary temperature ≥38°C, 2) positive blood culture of infective microorganism, 3) white blood cell count >12×10^9/L and differential white blood cell count of >10% band neutrophils (>1.2×10^9/L), and 4) pulmonary infiltrate with consolidation on chest X-ray. Alternatively, other signs and symptoms may be considered for the diagnosis of evident infection according to the Investigator's judgement.
• Subjects with inadequate venous access.
• Subjects with a history of anaphylactic reactions or severe reactions to any blood-derived product.
• Subjects with a history of intolerance to any component of the investigational products.
• Subjects with a documented diagnosis of thrombotic complications to polyclonal IVIG therapy in the past.
• Subjects with a history of recent (within the last year) myocardial infarction, stroke or uncontrolled hypertension.
• Subjects who suffered from uncontrolled congestive heart failure, embolism or documented electrocardiogram (ECG) changes indicative of myocardial ischemia or atrial fibrillation.
• Subjects with current known hyperviscosity or hypercoagulable state.
• Subjects currently receiving anti-coagulation therapy.
• Subjects with a history of chronic alcoholism or illicit drug abuse (addiction) in the 12 months preceding the Baseline Visit.
• Subjects currently receiving, or having received within 3 months prior to the Baseline Visit, any investigational medicinal product or device.
• Subjects with a known Immunoglobulin A (IgA) deficiency and anti-IgA serum antibodies.
• Subjects with 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).
• Subjects with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceeding more than 2.5 times the ULN for the expected normal range for the testing laboratory.
• Subjects with haemoglobin levels <9 g/dL.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IGIV-C Treatment; In this arm, subjects with myasthenia gravis exacerbations were treated with an IV dose of 2 g/kg of IGIV-C, which was administered over 2 consecutive days at a dose of 1 g/kg per day.	Biological: IGIV-C; An IV dose of 2 g/kg of IGIV-C was administered over 2 consecutive days at a dose of 1 g/kg per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quantitative Myasthenia Gravis (QMG) Scale Score	Mean Change in Quantitative Myasthenia Gravis (QMG) Scale Score from Baseline (Day 0) to Day 14. The minimum and maximum scores of the QMG Scale are 0 and 39, respectively, and a higher score means a worse outcome.	From Baseline (Day 0) to Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Clinical Improvement Assessed by QMG	The percentage of subjects with clinical improvement at Day 14 as assessed by the Quantitative Myasthenia Gravis (QMG) scale in the Evaluable population is presented, in which clinical improvement is defined as at least 3-point decrease in QMG score from Baseline (Day 0) to Day 14. The minimum and maximum scores of the QMG scale are 0 and 39, respectively, and a higher score means a worse outcome.	Baseline (Day 0) to Day 14
Percentage of Subjects With Clinical Improvement Assessed by MG-Activities of Daily Living (MG-ADL) Scale	The percentage of subjects with clinical improvement at Day 14 as assessed by the MG-ADL Scale in the Evaluable population is presented, in which clinical improvement is defined as at least 2-point decrease in the MG-ADL score. The minimum and maximum scores of the MG-DAL scale are 0 and 24, respectively, and a higher score means a worse outcome.	Baseline (Day 0) to Day 14
Percentage of Subjects With Clinical Improvement Assessed by the MG Composite	The percentage of subjects with clinical improvement at Day 14 as assessed by the MG Composite scale in the Evaluable population is presented in which clinical improvement is defined as at least 3-point decrease in the MG Composite score. The minimum and maximum scores of the MG Composite scale are 0 and 50, respectively, with a higher score meaning a worse outcome.	Baseline (Day 0) to Day 14

Collaborators and Investigators

• Sponsor: Grifols Therapeutics LLC

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: April 7, 2015
• First Submitted That Met QC Criteria: April 9, 2015
• First Posted (Estimate): April 10, 2015

Study Record Updates

• Last Update Posted (Actual): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 9, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis
• Other Study ID Numbers: GTI1305