Efficacy of Ocrelizumab in Autoimmune Encephalitis

NCT03835728 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: STU-2018-0185
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Had Clinical Worsening

  The number of participants who had clinical worsening within 12 months.

  12 months

Secondary Outcomes (3)

• Time to Treatment Failure

  12 months

• Change in TFLS T-score (Texas Functional Living Scale) Score at 6 Months

  Baseline, 6 month

• Change in TFLS T Score (Texas Functional Living Scale) Score at 12 Months

  Baseline, 12 months

Study Arms (2)

Treatment Arm

ACTIVE COMPARATOR

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.

Drug: Ocrelizumab

Treatment Placebo Arm

PLACEBO COMPARATOR

Saline will be used as the matching placebo

Drug: Saline

Interventions

Ocrelizumab 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 Arm

Saline DRUG

This will be the matching placebo used in the study.

Treatment Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 or greater
• Able to obtain informed consent from patient or appropriate designee
• Possible autoimmune encephalitis as defined by Table 1:
• Subacute onset (\< 3 months) of memory deficits, altered consciousness, and/or psychiatric symptoms
• 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)
• Completed initial treatment with iv steroids (at least 3000mg solumedrol) and plasma exchange (at least 3 exchanges) within the past 8 weeks
• Presence of one (or more) of the following autoantibodies in serum or CSF
• NMDA receptor
• LGI1
• CASPR2
• DPPX

You may not qualify if:

• Prior immunosuppression treatment in past year (other than steroids, intravenous immunoglobulin and plasma exchange)
• Active malignancy requiring chemotherapy
• Pregnancy
• Evidence of active hepatitis or tuberculosis infection
• Medical condition that (in investigators opinion) precludes the use of ocrelizumab

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (4)

• 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.

  PMID: 26906964 BACKGROUND

• 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.

  PMID: 23290630 BACKGROUND

• 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.

  PMID: 26439968 BACKGROUND

• 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.

  PMID: 35129803 DERIVED

MeSH Terms

Conditions

Autoimmune Diseases of the Nervous System

Interventions

ocrelizumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Nervous System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Early termination of trial due to inadequate recruitment. Small numbers of subjects prevents definitive analysis of results

Results Point of Contact

• Title: Dr. Steven Vernino
• Organization: UT Southwestern, Dept of Neurology

steven.vernino@utsouthwestern.edu

214-645-8800

Study Officials

• Steven Vernino, MD, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PROFESSOR

Study Record Dates

• First Submitted: February 5, 2019
• First Posted: February 11, 2019
• Study Start: January 22, 2019
• Primary Completion: October 2, 2020
• Study Completion: October 2, 2020
• Last Updated: October 19, 2021
• Results First Posted: October 19, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)