Efficacy of Ocrelizumab in Autoimmune Encephalitis

Autoimmune Encephalitis Clinical Trial

Official title:

Exploratory Study of Efficacy of Ocrelizumab in Autoimmune Encephalitis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03835728
• Other study ID #: STU-2018-0185
• Status: Terminated
• Phase: Phase 2
• Start date: January 22, 2019
• Est. completion date: October 2, 2020

Study information

• Verified date: September 2021
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: October 2, 2020
• Est. primary completion date: October 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Encephalitis
• Encephalitis
• Hashimoto Disease

Intervention

Drug:
• 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.
• Saline
This will be the matching placebo used in the study.

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, Cortese I, Dale RC, Gelfand JM, Geschwind M, Glaser CA, Honnorat J, Höftberger R, Iizuka T, Irani SR, Lancaster E, Leypoldt F, Prüss H, Rae-Grant A, Reindl M, Rosenfeld MR, Rostásy 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. Review. — View Citation

Titulaer MJ, McCracken L, Gabilondo I, Armangué 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Had Clinical Worsening	The number of participants who had clinical worsening within 12 months.	12 months
Secondary	Time to Treatment Failure	Definition of clinical worsening (treatment failure): Clinician or patient/caregiver perception of clinical decline; Worsening of patient/family reported IADL (by one point or more); One of the following additional features: Significant worsening of Texas Functional Living Scale (by = 5 T points, 0.5 st deviation); Other clinical worsening leading to hospitalization	12 months
Secondary	Change in TFLS T-score (Texas Functional Living Scale) Score at 6 Months	Change in TFLS T-score (Texas Functional Living Scale) scores at 6 months compared to baseline. - A performance-based measure of functional competence designed to assess instrumental activities of daily living (e.g., managing money) that are thought to be more susceptible to cognitive change than basic activities of daily living (e.g., dressing).; Content and Structure: The TFLS is comprised of 24 items divided into four subscales assessing abilities related to Time, Money and Calculation, Communication, and Memory. Many items provide a range of possible points allowing the instrument to account for the varying levels of functioning that may be observed in clinical populations.; Total raw score ranges between 0 and 50 with standardized T-score values between 20 and 66. The higher the score, the better the performance.; Change in TFLS T-score was used in this study	Baseline, 6 month
Secondary	Change in TFLS T Score (Texas Functional Living Scale) Score at 12 Months	Change in TFLS T-score (Texas Functional Living Scale) scores at 12 months compared to baseline. - A performance-based measure of functional competence designed to assess instrumental activities of daily living (e.g., managing money) that are thought to be more susceptible to cognitive change than basic activities of daily living (e.g., dressing).; Content and Structure: The TFLS is comprised of 24 items divided into four subscales assessing abilities related to Time, Money and Calculation, Communication, and Memory. Many items provide a range of possible points allowing the instrument to account for the varying levels of functioning that may be observed in clinical populations.; Total raw score ranges between 0 and 50 with standardized T-score values between 20 and 66. The higher the score, the better the performance.; Change in TFLS T-score was used in this study	Baseline, 12 months