Safety and Tolerability of Rituximab in Neuromyelitis Optica

Inclusion criteria

1. Criteria for neuromyelitis optica:

   1. acute transverse myelitis and optic neuritis occurring within 30 days of each other followed by a second attack of either optic neuritis and/or acute transverse myelitis at least 3 months following the heralding attack OR
   2. acute transverse myelitis followed by optic neuritis at least 3 months later OR
   3. optic neuritis followed by acute transverse myelitis at least 3 months later
2. Criteria for high risk for neuromyelitis optica:

   1. recurrent idiopathic recurrent acute transverse myelitis with at least 3 months time between each attack OR
   2. recurrent bilateral simultaneous optic neuritis with at least 3 months time between each attack.

      * Subjects should also have no clinical evidence of disease outside the optic nerve or spinal cord.
      * In addition patients should have one major supportive criteria OR two minor supportive criteria:

        1. Negative brain MRI at onset (Does not meet criteria for multiple sclerosis (Paty, 1998)
        2. Spinal cord MRI with signal abnormality extending over ≥3 vertebral segments
        3. CSF pleocytosis of \> 50 WBC/mm3 OR \> 5 PMNs/mm3
      * Minor supportive criteria:

        1. Bilateral optic neuritis
        2. Severe optic neuritis with fixed visual acuity worse than 20/200 in at least one eye
        3. Severe, fixed, attack-related weakness (MRC ≤2) in one or more limbs
      * Subjects must have exhibited evidence of treatment failure, defined as at least one attack of either acute transverse myelitis or optic neuritis within six months of screening despite treatment within steroids or other immunomodulatory drug for the preceding attack.
      * Able and willing to give written informed consent and comply with the requirements of the study protocol.
      * Adequate renal function as indicated by normal serum sodium, potassium, chloride, bicarbonate, creatinine, and blood urea nitrogen studies.
      * Adequate liver function, as indicated by normal bilirubin and alkaline phosphatase, and transaminases (AST and ALT) within 2X upper limit of normal.
      * Negative serum pregnancy test (for women of child bearing age).
      * 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 treatment.

Exclusion Criteria:

1. Treatment with broad-spectrum immunosuppressant medications such as cyclophosphamide, mitoxantrone, methotrexate, azathioprine, and cladribine, within 60 days of screening.
2. Treatment with any investigational agent within 4 weeks of screening
3. Receipt of a live vaccine within 4 weeks prior to randomization
4. Previous Treatment with Rituximab (MabThera® / Rituxan®)
5. Prior antibody therapy
6. History of exposure to clioquinol
7. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
8. History of HIV (positive HIV, HIV conducted during screening if applicable)
9. History of Hepatitis B and/or Hepatitis C (Hep B/C at screening)
10. History of recurrent significant infection or history of recurrent bacterial infections
11. Known active bacterial, viral fungal mycobacterial, or other infection or any major episode of infection requiring hospitalization
12. Ongoing daily steroid use
13. History of drug, alcohol, or chemical abuse within 6 months prior to screening
14. Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment) or lactation
15. Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
16. History of psychiatric disorder