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Efficacy of Ocrelizumab in Autoimmune Encephalitis

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ClinicalTrials.gov Identifier: NCT03835728
Recruitment Status : Recruiting
First Posted : February 11, 2019
Last Update Posted : February 11, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Steven Vernino, University of Texas Southwestern Medical Center

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.

Condition or disease Intervention/treatment Phase
Autoimmune Encephalitis Drug: Ocrelizumab Drug: Saline Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Exploratory Study of Efficacy of Ocrelizumab in Autoimmune Encephalitis
Actual Study Start Date : January 22, 2019
Estimated Primary Completion Date : January 22, 2022
Estimated Study Completion Date : January 22, 2022


Arm Intervention/treatment
Active Comparator: 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.
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.

Placebo Comparator: Treatment Placebo Arm
Saline will be used as the matching placebo
Drug: Saline
This will be the matching placebo used in the study.




Primary Outcome Measures :
  1. failure rate [ Time Frame: 12 months ]
    The primary outcome of the treatment trial will be the proportion of patients who fail to complete the 12 month study without clinical worsening.


Secondary Outcome Measures :
  1. Treatment failure [ Time Frame: 12 months ]
    Secondary outcome will be time to treatment failure.

  2. change in TFLS (Texas Functional Living Scale) scores [ Time Frame: 6-12 months ]

    Secondary outcome: TFLS (Texas Functional Living Scale) scores at 6 and 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.

    Subscale ranges:

    Time: 0-9 Money and Calculation: 0-8 Communication: 0-28 Memory: 0-5




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 and plasma exchange)
  2. Treatment with intravenous immunoglobulin in past year
  3. Active malignancy requiring chemotherapy
  4. Pregnancy
  5. Evidence of active hepatitis or tuberculosis infection
  6. Medical condition that (in investigators opinion) precludes the use of ocrelizumab

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03835728


Contacts
Contact: Steven Hopkins 2146489275 steve.hopkins@utsouthwestern.edu
Contact: Kyle Blackburn, MD 2146489275 kyle.blackburn@utsouthwestern.edu

Locations
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Steven Hopkins    214-648-9275    steve.hopkins@utsouthwestern.edu   
Contact: Kyle Blackburn, MD    2146489275    kyle.blackburn@utsouthwestern.edu   
Principal Investigator: Steven Vernino, MD, PhD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Genentech, Inc.
Investigators
Principal Investigator: Steven Vernino, MD, PhD UT Southwestern Medical Center

Publications:
Responsible Party: Steven Vernino, PROFESSOR, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT03835728     History of Changes
Other Study ID Numbers: STU-2018-0185
First Posted: February 11, 2019    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Encephalitis
Hashimoto Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Thyroiditis, Autoimmune
Thyroiditis
Thyroid Diseases
Endocrine System Diseases