Refractory Autoimmune Encephalitis, Refractory Autoimmune Cerebellitis
Conditions
Interventions
Experimental group:Low-dose blinatumomab treatment:
Cycle 1 (Week 1): Starting dose of 9 µg/day, administered as a continuous intravenous infusion for 5 days (total dose: 45 µg).
Cycle 2 (Week 3): The
Sponsors
Beijing Tiantan Hospital, Capital Medical University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Aged at onset >= 18 years, male and female eligible. 2.Definite diagnosis of antibody-positive autoimmune encephalitis and autoimmune cerebellitis; 3.Subjects with definite antibody-positive autoimmune encephalitis (AE) and autoimmune cerebellitis (ACA) who meet the following criteria are defined as having refractory AE: A stable modified Rankin Scale (mRS) score > 3 measured at baseline for at least 24 hours. Received the first-line acute treatment more than 6 weeks prior to the baseline visit. First-line acute treatment is defined as: Methylprednisolone intravenous infusion (IV) at a dose of >=500 mg/day for at least 3 consecutive days (or equivalent oral glucocorticoid), and/or intravenous immunoglobulin (IVIG) therapy for at least 3 consecutive days, and/or plasma exchange (PE), or any combination of the above regimens. Subjects have received additional immunotherapy beyond the initial course of first-line acute treatment, and must meet one of the following criteria: (1) For subjects receiving rituximab: the treatment course was initiated at least 2 months prior to screening, the last administration was given at least 4 weeks before randomization, and no improvement in mRS score was observed within 2 months prior to the baseline visit. (2) For subjects receiving other immunosuppressive therapy (IST), including mycophenolate mofetil, cyclophosphamide, azathioprine, etc., for a 4-week treatment period: treatment duration of at least 2 months before screening with a stable dose maintained for at least 4 weeks prior to screening, and no improvement in mRS score within 4 weeks before the baseline visit. (3) For subjects on oral glucocorticoids: receiving a stable daily dose of prednisolone >20 mg (or equivalent), with no dose increase within 4 weeks prior to screening, and no improvement in mRS score within 4 weeks before the baseline visit. (4) For subjects receiving a repeated course of first-line acute treatment: the repeated course must be completed = 2 weeks prior to the baseline visit. 4.Before enrollment: For subjects receiving oral glucocorticoid therapy: receiving a stable daily dose of >= 20 mg prednisone (or other equivalents), with no increase in steroid dose within 4 weeks before enrollment, and no improvement in mRS score within 4 weeks before enrollment. For subjects receiving rituximab therapy: the treatment course was initiated at least 2 months before enrollment, the last administration was given at least 4 weeks before enrollment, and no improvement in mRS score was observed within 4 weeks before enrollment. For subjects receiving other immunosuppressants (such as azathioprine, mycophenolate mofetil, etc.): treatment duration of at least 2 months before enrollment, with a stable dose maintained for at least 4 weeks prior to enrollment, and no improvement in mRS score within 4 weeks before enrollment. For subjects receiving a repeated course of first-line acute treatment: the repeated course must be completed >= 2 weeks before enrollment. 5.The patient himself/herself and/or his/her authorized relatives/family members have been fully informed, consented and signed the informed consent form. 6.For females of childbearing potential: Agree to practice abstinence (avoid heterosexual intercourse) or use appropriate contraceptive measures during treatment and for at least 3 months after the last administration. Females who have had menarche, have not yet reached a postmenopausal state (>= 12 consecutive months of ame
Exclusion criteria
Exclusion criteria: 1.There are systemic tumors and central nervous system tumors, such as cerebral gliomatosis, or a past history of cancer (excluding ovarian or extraovarian teratomas, also known as dermoid cysts, germ cell tumors, cutaneous squamous cell carcinoma, or cutaneous basal cell carcinoma); for squamous cell carcinoma and basal cell carcinoma, there should be records showing that they have been successfully cured for more than 3 months before randomization; hereditary diseases, such as mitochondrial encephalopathy; neurodegenerative diseases of the nervous system, such as Lewy body dementia; a past history of epilepsy with ongoing epileptic seizures; severe craniocerebral trauma, such as traffic accidents; metabolic and toxic encephalopathy, such as Wernicke encephalopathy. 2.Infectious diseases, such as viral encephalitis, etc.; having active infections requiring systemic treatment within one week before screening, or a history of severe recurrent or chronic infections, especially a history of recurrent or chronic infections related to respiratory diseases. 3.Serologically confirmed positive hepatitis B (hepatitis B surface antigen and hepatitis B core antibody) and/or positive hepatitis C PCR at screening. 4.Confirmed active tuberculosis at screening. 5.Having other diseases requiring long-term use of glucocorticoids or immunosuppressive agents. 6.Known history or underlying conditions of primary immunodeficiency (congenital or acquired), such as human immunodeficiency virus (HIV) infection or splenectomy, which render the participant susceptible to infection. 7.Having received solid organ transplantation or hematopoietic stem cell transplantation within 3 months prior to screening. 8.Receipt of any live or attenuated vaccine within 3 weeks prior to enrollment (inactivated vaccines are permitted). Receipt of Bacillus Calmette-Guérin (BCG) vaccine within 1 year prior to enrollment. 9.Patients with congenital heart disease, or a history of acute myocardial infarction within 6 months prior to screening, or severe arrhythmia (including polymorphic ventricular tachycardia, ventricular tachycardia, etc.); those complicated with moderate to large pericardial effusion, severe myocarditis, etc.; those with unstable vital signs requiring vasopressor agents to maintain blood pressure; or those with left ventricular ejection fraction (LVEF) = 3 × upper limit of normal (ULN); total bilirubin >= 2 × upper limit of normal (ULN). 11.Females who are pregnant or breastfeeding, as well as those planning to become pregnant during the trial period. 12.Patients with incomplete medical records or those who refuse to participate in registration and investigation. 13.Known history of allergy or adverse reaction to any ingredient of the investigational medicinal product, or history of hypersensitivity to any biological therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Modified Rankin Scale, mRS;Clinical Assessment Scale for Autoimmune Encephalitis, CASE;International Cooperative Ataxia Rating Scale,ICARS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Montreal Cognitive Assessment, MoCA;Minimum Mental State Examination, MMSE;Adverse Events; | — |
Countries
China
Contacts
Public ContactWangshu Xu
Beijing Tiantan Hospital, Capital Medical University
Outcome results
None listed