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Failed to meet target enrollment and study was discontinued
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| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Treatment Placebo Arm | Placebo Comparator | Saline will be used as the matching placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Had Clinical Worsening | The number of participants who had clinical worsening within 12 months. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Treatment Failure | Definition of clinical worsening (treatment failure):
|
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Inclusion Criteria:
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:
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
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Steven Vernino, MD, PhD | University of Texas Southwestern Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UT Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26906964 | Background | 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. | |
| 23290630 |
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Failed to meet target enrollment and study was discontinued
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. 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. |
| FG001 | Treatment Placebo Arm | Saline will be used as the matching placebo Saline: This will be the matching placebo used in the study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Had Clinical Worsening | The number of participants who had clinical worsening within 12 months. | Posted | Count of Participants | Participants | 12 months |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
Early termination of trial due to inadequate recruitment. Small numbers of subjects prevents definitive analysis of results
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Steven Vernino | UT Southwestern, Dept of Neurology | 214-645-8800 | steven.vernino@utsouthwestern.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 21, 2019 | Aug 25, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D020274 | Autoimmune Diseases of the Nervous System |
| ID | Term |
|---|---|
| D009422 | Nervous System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C533411 | ocrelizumab |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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|
| Saline | Drug | This will be the matching placebo used in the study. |
|
| 12 months |
| 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 |
| 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 |
| 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. |
| 26439968 | 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. |
| 35129803 | Derived | 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. |
| BG001 | Treatment Placebo Arm | Saline will be used as the matching placebo Saline: This will be the matching placebo used in the study. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Encephalitis antibody | Count of Participants | Participants |
|
| OG001 |
| Treatment Placebo Arm |
Saline will be used as the matching placebo Saline: This will be the matching placebo used in the study. |
|
|
| Secondary | Time to Treatment Failure | Definition of clinical worsening (treatment failure):
| There were no treatment failures in the treatment arm. Thus, there was no data for this secondary outcome measure in the treatment arm | Posted | Number | weeks | 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 | Participant in placebo arm met study endpoint prior to 6 month outcome measure so change in TFLS score at 6 months was not analyzable for efficacy purposes. | Posted | Median | Full Range | score on a scale | 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 | Participant in placebo arm met study endpoint prior to 6 month outcome measure so change in TFLS score at 12 months was not analyzable for efficacy purposes. | Posted | Median | Full Range | score on a scale | Baseline, 12 months |
|
|
|
| 0 |
| 2 |
| 0 |
| 2 |
| 2 |
| 2 |
| EG001 | Treatment Placebo Arm | Saline will be used as the matching placebo Saline: This will be the matching placebo used in the study. | 0 | 1 | 0 | 1 | 1 | 1 |
| Elevated transaminases | Hepatobiliary disorders | Systematic Assessment |
|
| Seizures | Nervous system disorders | Systematic Assessment | related to encephalitis - unrelated to treatment |
|
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| D017670 |
| Sodium Compounds |