NCT03835728

Efficacy of Ocrelizumab in Autoimmune Encephalitis

Terminated Phase 2 Results posted Last updated 19 October 2021

What this trial tests

Phase 2 trial testing Ocrelizumab in Autoimmune Encephalitis in 3 participants. Terminated before completion.

Timeline

22 January 2019

Primary endpoint
2 October 2020

2 October 2020

Quick facts

Lead sponsor	University of Texas Southwestern Medical Center
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	3
Start date	22 January 2019
Primary completion	2 October 2020
Estimated completion	2 October 2020
Sites	1 location across United States

Drugs / interventions tested

• Ocrelizumab (OCRELIZUMAB) — full drug profile →
• Saline

Conditions studied

• Autoimmune Encephalitis — all drugs for Autoimmune Encephalitis →

Sponsor

University of Texas Southwestern Medical Center

Who can join

18 and older, any sex, with Autoimmune Encephalitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Had Clinical Worsening Primary · 12 months

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

Group	Value	95% CI
Treatment Arm	0
Treatment Placebo Arm	1

Time to Treatment Failure Secondary · 12 months

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

Group	Value	95% CI
Treatment Placebo Arm	12

Change in TFLS T-score (Texas Functional Living Scale) Score at 6 Months Secondary · Baseline, 6 month

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 accou

Group	Value	95% CI
Treatment Arm	12.75	3 – 22.5

Change in TFLS T Score (Texas Functional Living Scale) Score at 12 Months Secondary · Baseline, 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 acco

Group	Value	95% CI
Treatment Arm	24.5	3 – 46

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 year. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment Arm

Serious: 0/2 (0%)

Deaths: 0/2

Treatment Placebo Arm

Serious: 0/1 (0%)

Deaths: 0/1

Other adverse events (3 terms — click to expand)

Reaction	System	Treatment Arm	Treatment Placebo Arm
rash	Skin and subcutaneous tissue disorders	—	—
Seizures	Nervous system disorders	—	—
Elevated transaminases	Hepatobiliary disorders	—	—

Data from ClinicalTrials.gov NCT03835728 adverse events section.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Generate-Boost: study protocol for a prospective, multicenter, randomized controlled, double-blinded phase II trial to evaluate efficacy and safety of bortezomib in patients with severe autoimmune encephalitis.
   Wickel J, Chung HY, Platzer S, Lehmann T, et al · · 2020 · cited 38× · PMID 32641101 · DOI 10.1186/s13063-020-04516-7
2. Antibody Therapies in Autoimmune Encephalitis.
   Smets I, Titulaer MJ. · · 2022 · cited 33× · PMID 35060089 · DOI 10.1007/s13311-021-01178-4
3. Immune Mechanisms in Epileptogenesis: Update on Diagnosis and Treatment of Autoimmune Epilepsy Syndromes.
   Flammer J, Neziraj T, Rüegg S, Pröbstel AK. · · 2023 · cited 30× · PMID 36696027 · DOI 10.1007/s40265-022-01826-9
4. Low Recruitment in a Double-Blind, Placebo-Controlled Trial of Ocrelizumab for Autoimmune Encephalitis: A Case Series and Review of Lessons Learned.
   Blackburn KM, Denney DA, Hopkins SC, Vernino SA. · · 2022 · cited 16× · PMID 35129803 · DOI 10.1007/s40120-022-00327-x
5. Innovation and optimization in autoimmune encephalitis trials: the design and rationale for the Phase 3, randomized study of satralizumab in patients with NMDAR-IgG-antibody-positive or LGI1-IgG-antibody-positive autoimmune encephalitis (CIELO).
   Lee ST, Abboud H, Irani SR, Nakajima H, et al · · 2024 · cited 10× · PMID 39193150 · DOI 10.3389/fneur.2024.1437913
6. B-cell targeted therapies in autoimmune encephalitis: mechanisms, clinical applications, and therapeutic potential.
   Shang H, Shen X, Yu X, Zhang J, et al · · 2024 · cited 10× · PMID 38562943 · DOI 10.3389/fimmu.2024.1368275
7. Medical Applications of Molecular Biotechnologies in the Context of Hashimoto's Thyroiditis.
   Trovato M, Valenti A. · · 2023 · cited 1× · PMID 37371008 · DOI 10.3390/diagnostics13122114