A Phase II Trial of Rituximab In Myasthenia Gravis (NN103)
- CTRC Outpatient
- Clements University Hospital
- UT Southwestern Ambulatory Services
Sharon Nations, M.D.
We plan on conducting a multicenter randomized, double-blind, placebo controlled Phase ii
clinical trial utilizing a futility design. The study would include acetylcholine receptor (aChR)
antibody positive generalized MG subjects. This study also presents a unique opportunity to
study both drug and disease mechanisms because unlike many other autoimmune diseases in
which rituximab has been used, MG affords the investigation of antigen-specific components
that participate in the immunopathology of the disease, namely autoantibodies, autoantibodyproducing
B cells, and antigen-specific T cells. This work will further our understanding of MG
immunopathology and it represents the first step toward gaining a more complete understanding
of the immune mechanisms underlying treatment of MG with rituximab leading to new ways to
treat the disease.
The specific aim of this study is to determine whether rituximab is a safe and effective treatment
for subjects with MG. although not part of the current protocol, we believe that adding
exploratory mechanistic studies to the protocol would be important in order to identify
biomarkers that can potentially be used in future MG clinical trials as well as exploring whether
B cell therapy is effective in MG. With this in mind, the investigators have applied for funding of
an ancillary exploratory mechanistic study grant through the national institute of allergy and
infectious Diseases (niaiD). if funded, further details of the mechanistic work will be made
available with the notice of award.
Subject selection will be based on a diagnosis of MG and the following specific criteria:
1. Subjects 21 to 90 years old
2. Subjects must have a history of generalized MG, defined as MGFA clinical classification grades 2, 3, 4 or 5. These grades correspond to mild (2), moderate (3), severe (4) and intubation (5).
3. Elevated AChR antibody titer
4. Subject[Single Quote]s signs and symptoms should not be better explained by another disease
5. Subjects must be on a stable standard immunosuppresive regimen:
a. Prednisone only. Prednisone dose must be at least 15 mg/day (or the equivalent in alternate days) and the dose of prednisone must have been stable for at least 4 weeks (28 days) prior to the baseline visit.
b. Prednisone plus another immunosuppressive therapy (IST). Immunosuppressive therapies other than prednisone such as azathioprine, mycophenolate mofetile, cyclosporine, tacrolimus or methotrexate, are permitted, but the dose must have been stable for at least 6 months prior to the baseline visit. Note: The predinisone dose must be stable as defined in the prednisone only group.
6. Subjects must be willing to complete the study and return for follow-up visits.
7. No history of thymoma, tumor, infection, or interstitial lung disease on chest CT, MRI,
or chest x-ray. Note: Chest x-ray will be completed at screening to look of interstitial
lung disease. A chest CT or MRI to evaluate for thymoma must have been
completed as part of prescreening.
8. Able and willing to give written informed consent and comply with the requirements
of the study protocol.
9. Subjects must to able to give written informed consent before participating in this
study. A copy of the signed consent must be kept in the subject[Single Quote]s medical record.
10. Men and women of reproductive potential must agree to use an acceptable method
of birth control during treatment and for twelve months (1 year) after completion of