Subcutaneous Ig Maintenance Therapy for Myasthenia Gravis

The study is a pilot study to ascertain the feasibility and tolerability of subcutaneous
immunoglobulin (SCIG or IGSC) as a maintenance therapy for patients with non-thymomatous MG
patients (MGFA class II-IV) at entry, aged 18-80 years, positive acetylcholine receptor
antibody, receiving greater than 30mg of prednisone daily. Patients may or may not be
receiving anticholinesterase agents.

The neurologist principal investigator at each site will have the overall responsibility for
study performance is designated the medical coordinator (MC). The MC will assess patients
from the sites clinic populations and identify potential subjects for inclusion and exclusion
criteria. Once a subject is identified and provided informed consent to participate the Visit
Schedule will be initiated.

At the initial visit the MC will perform the acetylcholine receptor antibody level, and
record the prednisone and anticholinesterase doses. The MC will be responsible for assessment
of adverse events. The research coordinator will arrange for the initial laboratory testing
at the patient's local Quest, where the blood will be drawn. Baseline lab tests to be done
will include IgA level to evaluate for deficiency, IgG level, CBC, AchR antibody, pregnancy
tests in women, LFT's, PT/PTT and BUN/Creatinine. The patient will complete the SF-36 quality
of life, MG, and MGFA ADL The research coordinator will be responsible for training subjects
in performance of IGSC infusion. Subjects will have outpatient clinic assessments in one week
and then monthly for the remainder of the study. Patients will receive 2gms/kg divided over 4
weeks initially and then will be given 250mgs/kg/wk for total of 6 months. This is similar to
the standard IV treatment for patients which is 2 gm/kg given over 2-5 days for the initial
dose. After the initial dose, a patient is started on monthly IV maintenance dose of 1 gm/kg
each month given over 1-3 days.

The subject will be evaluated monthly for assessment of whether minimal manifestation (MM)
status has been reached, which then allows reduction of corticosteroids by 5mg or more if
clinically indicated. The MC will record adverse events and symptoms. The dose of
anticholinesterase drugs will be decreased at the discretion of the MC. The prednisone dose
will be decreased unless the MM status is lost; in that situation the prednisone dose will be
increased 10mg every 2 weeks until the MM is again achieved. Titration of the prednisone and
cholinesterase inhibitor medications will be at the discretion of the physician and will be
based on the patient's symptoms as measured by symptoms and examination, leading to a
determination of the MM. The patient will complete the SF-36 quality of life assessment.

Inclusion Criteria:

1. AChR Ab positive myasthenia gravis (acetylcholine receptor antibody).

2. Age 18-80 years.

3. MGFA Classification II-IV (The scale used to determine the severity of symptoms of
MG).

4. Receiving > or equal 30mg of Prednisone per day.

5. No new MG-specific treatments in prior 3 months.

6. Willingness to participate in study protocol.

7. QMG > 10 (quantitative myasthenia gravis score: the sum of grades given for symptoms
of MG).

8. Treatment with any immunomodulator > than or equal to 3 months prior to trial
initiation.

Exclusion Criteria:

1. IgA deficiency (a major class of immunoglobulins found in serum and external body
secretions such as saliva, tears, and sweat as well as in the gastrointestinal,
respiratory, and genitourinary tracts).

2. Previous thromboembolic events, including deep vein thrombosis, stroke and myocardial
infarction

3. MGFA Class I, IV (if patient requires hospitalization) or V

4. History of thymoma

5. Thymectomy in previous year or planning to undergo thymectomy in next six months

6. Pregnancy or lactation; unwillingness to avoid pregnancy

7. Serious concurrent medical, neurological or psychiatric condition that would interfere
with IGSC administration or subsequent clinical assessments

8. Unwillingness or incapacity to participate, agree to necessary follow-up visits, or
give written and informed consent

9. Patients who have had an anaphylactic or severe systemic reaction to the
administration of human immune globulin or to components of Hizentra, such as
polysorbate 80, or patients with hyperprolinemia because it contains the stabilizer
L-proline

10. Cholinesterase inhibitor no more than 240 mg/day

11. Body weight greater than 120 kg.