A Study to Evaluate the Efficacy and Safety of IGIV-C in Symptomatic Subjects With Generalized Myasthenia Gravis
Condition: Myasthenia Gravis, Generalized
MeSH terms: Myasthenia Gravis; Muscle Weakness
Intervention: IGIV-C; Placebo
Intervention description: IGIV-C: Immune Globulin Injection (Human), 10%, Caprylate/Chromatography Purified
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 62.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

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

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):

               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