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Autoimmune EncephalitisPhase 2NCT03835728

Efficacy of Ocrelizumab in Autoimmune Encephalitis

A Phase 2 study testing Ocrelizumab and Saline in people with Autoimmune Encephalitis, run by University of Texas Southwestern Medical Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Autoimmune Encephalitis
What is being tested?
Ocrelizumab and Saline
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
3 participants
Where
1 siteUnited States
Study dates
22 Jan 2019to 2 Oct 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 or greater
  • Able to obtain informed consent from patient or appropriate designee
  • Possible autoimmune encephalitis as defined by Table 1:
  • Reasonable exclusion of alternative causes
  • Subacute onset (< 3 months) of memory deficits, altered consciousness, and/or psychiatric symptoms
  • One or more of the following:
Show all 16Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

Other trials in United States

About this study

Official title: Exploratory Study of Efficacy of Ocrelizumab in Autoimmune Encephalitis

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.

Being tested
Ocrelizumab, Saline
Medical subject headings
Autoimmune Diseases of the Nervous System

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OcrelizumabDrug

    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.

  • SalineDrug

    This will be the matching placebo used in the study.

Study groups in NCT03835728
Study groupRoleWhat they receive
Treatment ArmActive comparatorOcrelizumab 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.
Receives: Drug: Ocrelizumab
Treatment Placebo ArmPlacebo comparatorSaline will be used as the matching placebo
Receives: Drug: Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Had Clinical Worsening

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

    Measured: 12 months

Secondary outcomes (3)

  1. Time to Treatment Failure

    Definition of clinical worsening (treatment failure):

    1. Clinician or patient/caregiver perception of clinical decline
    2. Worsening of patient/family reported IADL (by one point or more)
    3. 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

    Measured: 12 months

  2. 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

    Measured: Baseline, 6 month

  3. 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

    Measured: Baseline, 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Feb 2019
  2. Study start22 Jan 2019
  3. Primary completion2 Oct 2020
  4. Study completion2 Oct 2020

Why it stopped: Failed to meet target enrollment and study was discontinued

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03835728
Sponsor's protocol ID
STU-2018-0185
Status last verified
Sep 2021
First submitted
5 Feb 2019
Last updated
19 Oct 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • 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.

    PubMed 26906964

  • 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.

    PubMed 23290630

  • 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.

    PubMed 26439968

  • 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.

    PubMed 35129803

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ocrelizumab and Saline in people with Autoimmune Encephalitis, run by University of Texas Southwestern Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Had Clinical Worsening (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03835728, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2021.

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