Efficacy of Ocrelizumab in Autoimmune Encephalitis
Condition: Autoimmune Encephalitis
MeSH terms: Encephalitis; Autoimmune Diseases of the Nervous System; Hashimoto Disease
Intervention: Ocrelizumab; Saline
Intervention description: Subjects will be randomized in a 1:1 fashion to receive infusion of Ocrelizumab (2 doses at 300 mg and 1 dose at 600 mg) or matched placebo. The 2 300 mg doses will be administered at day 2 and day 14. The 600 mg dose will be administered during the 6 month visit. The drug will be administered via infusion three times throughout the trial period: after the initial screening, at two weeks from initial infusion, and at 6 months.; This will be the matching placebo used in the study.
Intervention MeSH terms: Ocrelizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This pilot study is a randomized, double-blind, placebo controlled study of the efficacy of
      ocrelizumab in autoimmune encephalitis. Subjects with new diagnosis of autoimmune
      encephalitis will be invited to enroll in this study. Subjects will be randomized to receive
      ocrelizumab (an anti-CD20 therapy) or matched placebo, and will undergo three infusions over
      a six month period. Subjects will complete clinical visits over the study period, during
      which safety monitoring and neuropsychological assessments will be performed to assess for
      signs of clinical worsening from encephalitis. The primary outcome of this study is the
      proportion of patients who fail to complete the twelve month period without clinical
      worsening, as defined by the protocol. Subjects who experience early clinical worsening
      during the study may be offered open-label treatment with ocrelizumab at the discretion of
      the investigators.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18 or greater

          2. Able to obtain informed consent from patient or appropriate designee

          3. Possible autoimmune encephalitis as defined by Table 1:

               1. Reasonable exclusion of alternative causes

               2. Subacute onset (< 3 months) of memory deficits, altered consciousness, and/or
                  psychiatric symptoms

               3. One or more of the following:

                    -  CSF (cerebrospinal fluid) pleocytosis (>5 cells/µl corrected, if necessary,
                       for traumatic lumbar puncture)

                    -  EEG (electroencephalogram) with epileptiform or focal slow wave
                       abnormalities involving temporal lobes

                    -  Brain abnormalities on T2/FLAIR MRI restricted to the mesial temporal
                       (limbic) lobes

                    -  Associated dyskinesias (faciobrachial dystonic movements or orofacial
                       dyskinesias)

          4. Completed initial treatment with iv steroids (at least 3000mg solumedrol) and plasma
             exchange (at least 3 exchanges) within the past 8 weeks

          5. Presence of one (or more) of the following autoantibodies in serum or CSF

               -  NMDA receptor

               -  LGI1

               -  CASPR2

               -  DPPX

        Exclusion Criteria:

          1. Prior immunosuppression treatment in past year (other than steroids, intravenous
             immunoglobulin and plasma exchange)

          2. Active malignancy requiring chemotherapy

          3. Pregnancy

          4. Evidence of active hepatitis or tuberculosis infection

          5. Medical condition that (in investigators opinion) precludes the use of ocrelizumab