Efficacy of Ocrelizumab in Autoimmune Encephalitis

NCT ID: NCT03835728

Last Updated: 2021-10-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-22
• Study Completion Date: 2020-10-02

Brief 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.

Conditions

Autoimmune Encephalitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment Arm

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.

Group Type: ACTIVE_COMPARATOR

Ocrelizumab

Intervention Type: DRUG

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.

Treatment Placebo Arm

Saline will be used as the matching placebo

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

This will be the matching placebo used in the study.

Interventions

Ocrelizumab

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.

Intervention Type: DRUG

Saline

This will be the matching placebo used in the study.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Steven Vernino

PROFESSOR

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven Vernino, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

UT Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

References

Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Hoftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Pruss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostasy K, Saiz A, Venkatesan A, Vincent A, Wandinger KP, Waters P, Dalmau J. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016 Apr;15(4):391-404. doi: 10.1016/S1474-4422(15)00401-9. Epub 2016 Feb 20.

Reference Type: BACKGROUND

PMID: 26906964 (View on PubMed)

Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013 Feb;12(2):157-65. doi: 10.1016/S1474-4422(12)70310-1. Epub 2013 Jan 3.

Reference Type: BACKGROUND

PMID: 23290630 (View on PubMed)

Dubey D, Sawhney A, Greenberg B, Lowden A, Warnack W, Khemani P, Stuve O, Vernino S. The spectrum of autoimmune encephalopathies. J Neuroimmunol. 2015 Oct 15;287:93-7. doi: 10.1016/j.jneuroim.2015.08.014. Epub 2015 Aug 28.

Reference Type: BACKGROUND

PMID: 26439968 (View on PubMed)

Blackburn KM, Denney DA, Hopkins SC, Vernino SA. Low Recruitment in a Double-Blind, Placebo-Controlled Trial of Ocrelizumab for Autoimmune Encephalitis: A Case Series and Review of Lessons Learned. Neurol Ther. 2022 Jun;11(2):893-903. doi: 10.1007/s40120-022-00327-x. Epub 2022 Feb 7.

Reference Type: DERIVED

PMID: 35129803 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

STU-2018-0185

Identifier Type: -

Identifier Source: org_study_id