Clinical trial NCT02413580: A Study to Assess the Efficacy and Safety of IGIV-C in Patients With Myasthenia Gravis Exacerbations
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myasthenia Gravis Exacerbations
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2015-04-10
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Quantitative Myasthenia Gravis (QMG) Scale Score
timeFrame: From Baseline (Day 0) to Day 14
Secondary outcomes:
measure: Percentage of Subjects With Clinical Improvement Assessed by QMG
timeFrame: Baseline (Day 0) to Day 14
measure: Percentage of Subjects With Clinical Improvement Assessed by MG-Activities of Daily Living (MG-ADL) Scale
timeFrame: Baseline (Day 0) to Day 14
measure: Percentage of Subjects With Clinical Improvement Assessed by the MG Composite
timeFrame: Baseline (Day 0) to Day 14
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Hospital Italiano
city: Buenos Aires
country: Argentina
facility: Hospital General de Agudos Dr. J. M.
city: Cordoba
country: Argentina
facility: Hospital Cordoba
city: Ghent
country: Belgium
facility: AZ St Lucas Gent
state: East Flanders
city: Leuven
country: Belgium
facility: UZ Leuven
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network (UHN) - Toronto General Hospital
state: Ontario
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno, Neurologicka klinika
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava, Neurologická klinika
city: Prague
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Bron
country: France
facility: Hopital Neurologique Pierre Wertheimer
state: Lyon
city: Grenoble
country: France
facility: Hôpital Albert Michallon
city: Lille
country: France
facility: Hopital Roger Salengro
city: Marseille
country: France
facility: Hôpital de la Timone
city: Strasbourg
country: France
facility: Hôpital Hautepierre Strasbourg
city: Toulouse
country: France
facility: CHU de Toulouse - Hôpital Purpan
city: Budapest
country: Hungary
facility: Jahn Ferenc Del-Pesti Korhaz
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flor Ferenc Korhaz
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház
city: Szeged
country: Hungary
facility: University of Szeged, Faculty of Medicine
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Korhaz
city: Riga
country: Latvia
facility: Riga East Clinical University Hospital
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Bucuresti
country: Romania
facility: Institutul Clinic Fundeni
city: Targu Mures
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Targu-Mures
city: Nizhniy Novgorod
country: Russian Federation
facility: State Budgetary Institution of Healthcare of Nizhniy Novgorod region. Nizhniy Novgorod Regional Clinical Hospital named after N.A.Semashko
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg State Budgetary Institution of Healthcare. City Multi-field Hospital # 2
city: Samara
country: Russian Federation
facility: State Budgetary Institution of Healthcare "Samara Regional Clinical Hospital. V.D.Seredavin
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital,
Study officials:
References: