Efficacy and Safety of Low-Dose Blinatumomab in the Treatment of Refractory Autoimmune Encephalitis and Autoimmune Cerebellitis

NCT07686042 | Not Yet Recruiting Phase 4

• 1 other identifier: BTHospital
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, single-arm, continuous, prospective, interventional registry study designed to systematically evaluate the efficacy and safety of low-dose blinatumomab in patients with antibody-mediated refractory autoimmune encephalitis (AE) and autoimmune cerebellitis. Eligible participants will be patients with a confirmed diagnosis of refractory AE or autoimmune cerebellitis who have provided written informed consent. All enrolled patients will receive blinatumomab treatment according to a unified protocol, consisting of two cycles: Cycle 1 (Week 1): Continuous intravenous infusion at 9 µg/day for 5 consecutive days (total dose: 45 µg). Cycle 2 (Week 3): Continuous intravenous infusion at 9 µg/day for 5 consecutive days (total dose: 45 µg). If there is no improvement in the modified Rankin Scale (mRS) score at Week 3 and the proportion of peripheral blood B cells (CD3-/CD19+) remains \>1%, the dose may be optimized to 15 µg/m²/day (maximum 28 µg/day). During the study, all patients will undergo regular follow-up visits to collect data on clinical symptoms, functional scores, immunological biomarkers, and adverse events, to comprehensively assess the efficacy and safety of the treatment. This study uses a non-randomized, open-label design with no blinding or control group.

Conditions

Autoimmune Encephalitis (AE); Autoimmune Cerebellitis

Outcome Measures

Primary Outcomes (5)

• Proportion of participants with mRS score 0-2

  Proportion of participants with modified Rankin Scale (mRS) score of 0 to 2 points at scheduled follow-up time points.

  Week 3 (±1 day), Week 4 (±1 day), Week 5 (±1 day), Week 6 (±1 day), Week 8 (±1 day), Week 12 (±1 day), Week 24 (±3 days), Week 36 (±5 days), Week 48 (±10 days)

• Distribution of mRS scores

  Distribution of modified Rankin Scale (mRS) scores at scheduled follow-up time points.

  Week 3 (±1 day), Week 4 (±1 day), Week 5 (±1 day), Week 6 (±1 day), Week 8 (±1 day), Week 12 (±1 day), Week 24 (±3 days), Week 36 (±5 days), Week 48 (±10 days)

• Proportion of participants with mRS improvement ≥1 point

  Proportion of participants with a decrease of ≥1 point in modified Rankin Scale (mRS) score from baseline at scheduled follow-up time points.

  Week 3 (±1 day), Week 4 (±1 day), Week 5 (±1 day), Week 6 (±1 day), Week 8 (±1 day), Week 12 (±1 day), Week 24 (±3 days), Week 36 (±5 days), Week 48 (±10 days)

• Change in CASE score from baseline

  Change in Clinical Assessment Scale for Autoimmune Encephalitis (CASE) score from baseline at scheduled follow-up time points.

  Week 3 (±1 day), Week 4 (±1 day), Week 5 (±1 day), Week 6 (±1 day), Week 8 (±1 day), Week 12 (±1 day), Week 24 (±3 days), Week 36 (±5 days), Week 48 (±10 days)

• Relapse rate within 48 weeks

  Relapse rate of autoimmune encephalitis and autoimmune cerebellitis within 48 weeks after treatment initiation.

  Up to Week 48 (±10 days)

Secondary Outcomes (7)

• Changes in MMSE scores from baseline

  Week 3 (±1 day), Week 8 (±1 day), Week 12 (±1 day), Week 24 (±3 days), Week 36 (±5 days), Week 48 (±10 days)

• Changes in MoCA scores from baseline

  Week 8 (±1 day), Week 12 (±1 day), Week 24 (±3 days), Week 36 (±5 days), Week 48 (±10 days)

• Changes in PSQI scores from baseline

  Week 3 (±1 day), Week 4 (±1 day), Week 5 (±1 day), Week 6 (±1 day), Week 8 (±1 day), Week 12 (±1 day), Week 24 (±3 days), Week 36 (±5 days), Week 48 (±10 days)

• Changes in NPI scores from baseline

  Week 3 (±1 day), Week 4 (±1 day), Week 5 (±1 day), Week 6 (±1 day), Week 8 (±1 day), Week 12 (±1 day), Week 24 (±3 days), Week 36 (±5 days), Week 48 (±10 days)

• Changes in SDMT scores from baseline

  Week 3 (±1 day), Week 4 (±1 day), Week 5 (±1 day), Week 6 (±1 day), Week 8 (±1 day), Week 12 (±1 day), Week 24 (±3 days), Week 36 (±5 days), Week 48 (±10 days)

Study Arms (1)

Low-Dose Blinatumomab

EXPERIMENTAL

All enrolled patients in this arm will receive low-dose blinatumomab according to the study protocol. The treatment consists of two cycles: Cycle 1 (Week 1) at 9 μg/day for 5 consecutive days, and Cycle 2 (Week 3) at 9 μg/day for 5 consecutive days (45 μg per cycle). If no clinical improvement is observed at Week 3 and peripheral blood B-cell proportion remains \>1%, the dose may be optimized to 15 µg/m²/day (maximum 28 µg/day).

Drug: Blinatumomab

Interventions

Blinatumomab DRUG

Low-dose blinatumomab administered intravenously in two cycles: Cycle 1 (Week 1) at 9 μg/day for 5 consecutive days, and Cycle 2 (Week 3) at 9 μg/day for 5 consecutive days (45 μg per cycle). If no clinical improvement is observed at Week 3 and peripheral blood B-cell proportion (CD3-/CD19+) remains \>1%, the dose may be optimized to 15 µg/m²/day (maximum 28 µg/day).

Low-Dose Blinatumomab

Eligibility Criteria

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

You may qualify if:

• Aged ≥18 years, male or female.
• Confirmed diagnosis of antibody-positive autoimmune encephalitis (AE) or autoimmune cerebellitis (ACA).
• Refractory AE/ACA defined as antibody-positive disease meeting all of the following:
• Modified Rankin Scale (mRS) score \>3 (stable for at least 24 hours) at baseline.
• Received first-line acute therapy more than 6 weeks prior to baseline visit, defined as at least 3 days of intravenous methylprednisolone (≥500 mg/day) or equivalent oral corticosteroids, and/or at least 3 days of IVIG and/or plasma exchange (PE), or any combination thereof.
• Received additional immunotherapy beyond the first acute course, meeting the following:
• For rituximab: treatment initiated at least 2 months prior to screening, last dose at least 4 weeks prior to baseline, and no improvement in mRS score for 2 months before baseline.
• For other immunosuppressive therapies (IST; e.g., mycophenolate mofetil, cyclophosphamide, azathioprine): treatment for at least 2 months prior to screening, stable dose for at least 4 weeks prior to baseline, and no improvement in mRS score for 4 weeks before baseline.
• For oral corticosteroids: stable dose \>20 mg/day prednisone equivalent, no dose increase for 4 weeks prior to baseline, and no improvement in mRS score for 4 weeks before baseline.
• For repeated first-line therapy courses: completed at least 2 weeks prior to baseline visit.
• For patients on oral corticosteroids: stable dose ≥20 mg/day prednisone equivalent, no dose increase for 4 weeks prior to enrollment, and no improvement in mRS score for 4 weeks before enrollment.
• For patients on rituximab: treatment initiated at least 2 months prior to enrollment, last dose at least 4 weeks prior to enrollment, and no improvement in mRS score for 4 weeks before enrollment.
• For patients on other IST (e.g., azathioprine, mycophenolate mofetil): treatment for at least 2 months prior to enrollment, stable dose for at least 4 weeks prior to enrollment, and no improvement in mRS score for 4 weeks before enrollment.
• For patients on repeated first-line therapy courses: completed at least 2 weeks prior to enrollment.
• Patient or legally authorized representative provides written informed consent.

You may not qualify if:

• Systemic or central nervous system tumors (e.g., gliomatosis cerebri), history of cancer (excluding ovarian/extra-ovarian teratoma, skin squamous cell carcinoma, or basal cell carcinoma with documented cure ≥3 months prior to enrollment); hereditary diseases (e.g., mitochondrial encephalopathy); neurodegenerative diseases (e.g., Lewy body dementia); prior epilepsy with ongoing seizures; severe traumatic brain injury; metabolic/toxic encephalopathy (e.g., Wernicke encephalopathy).
• Infectious diseases (e.g., viral encephalitis); active or uncontrolled infection requiring systemic treatment within 1 week prior to screening; history of severe recurrent or chronic infections, especially respiratory infections.
• Positive hepatitis B surface antigen/核心 antigen and/or positive hepatitis C PCR at screening.
• Active tuberculosis at screening.
• Diseases requiring long-term corticosteroid or immunosuppressive therapy.
• Known history of primary immunodeficiency (congenital or acquired) or conditions predisposing to infection (e.g., HIV infection, splenectomy).
• History of solid organ or hematopoietic stem cell transplantation within 3 months prior to screening.
• Live or attenuated vaccine within 3 weeks prior to enrollment (inactivated vaccines are allowed); BCG vaccine within 1 year prior to enrollment.
• Congenital heart disease, acute myocardial infarction within 6 months prior to screening, severe arrhythmias (e.g., polymorphic ventricular tachycardia), moderate to large pericardial effusion, severe myocarditis, hemodynamic instability requiring vasopressors, left ventricular ejection fraction (LVEF) ≤55%, or significant ECG abnormalities.
• Any of the following laboratory abnormalities:
• Absolute lymphocyte count (ALC) ≤0.5×10⁹/L
• Absolute neutrophil count (ANC) ≤0.5×10⁹/L
• Immunoglobulin G (IgG) ≤5.0 g/L
• CD4 T-cell count \<300 cells/µL
• Hemoglobin ≤80 g/L

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

Location

MeSH Terms

Conditions

Autoimmune Diseases of the Nervous System

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Nervous System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Wangshu Xu

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wangshu Xu

CONTACT

+8613621017376; xuwangshu@mail.ccmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2026
• First Posted: July 6, 2026
• Study Start: June 24, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)