Efficacy of Ocrelizumab in Autoimmune Encephalitis

The University of Texas System (UT)

Status and phase: Terminated; Phase 2

Conditions: Autoimmune Encephalitis

Treatments: Drug: Saline; Drug: Ocrelizumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03835728

STU-2018-0185

Details and patient eligibility

About

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.

Enrollment: 3 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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3 participants in 2 patient groups, including a placebo group

Treatment Arm

Active Comparator group

Description:

Ocrelizumab will be administered 3 times over a 1 year study period. Subjects will receive a dose of 300 mg at week 0 (baseline) and again at week 2. The final dose of 600 mg will be administered at week 24.

Treatment:

Drug: Ocrelizumab

Treatment Placebo Arm

Placebo Comparator group

Description:

Saline will be used as the matching placebo

Treatment:

Drug: Saline