A Study of CNCT19 in the Treatment of Relapsed or Refractory Neurological Autoimmune Diseases

Inclusion Criteria:

1. Patients who are willing to sign the informed consent form;

2. Aged 18-75 years, male or female;

3. At screening, subjects with relapsed/refractory antibody-mediated inflammatoryneurological diseases without effective treatment, the expression of CD19+ B cellsin peripheral blood and meeting the special criteria for different indicationsinclude:

• Neuromyelitis optica spectrum disorder (NMOSD): Comply with the diagnosticcriteria for NMOSD of the International panel for NMO diagnosis (IPND) in 2015and meet the following requirements:

1. aquaporin 4 (AQP4) -IgG positive
2. At least one immunosuppressant has been used for more than one year andthe symptoms have not been well controlled;
3. EDSS score ≤8 points;
4. There must be at least two relapses within 24 months prior to screening orat least one relapse within the past 12 months, and the relapses should bestable for at least 4 weeks.

• Myasthenia gravis (MG): MG subjects who meet the MGFA classification II-IV asdefined by the 2020 American Myasthenia Gravis Foundation (MGFA) diagnosticcriteria and satisfy the following requirements:

1. AChR-Ab serum positive or MuSK antibody positive;
2. The MG-ADL score is ≥6 points, and the eye muscle score is less than 50%of the total score;
3. There is one of the following poor control conditions in the previoustreatment: i. After at least two conventional immunotherapy drugs (including hormone and non-hormone immunosuppressants) have been used for ≥1 year without treatment failure, that is, despite receiving ISTtreatment, ADL remains persistently impaired (persistent weakness, crisisor inability to tolerate IST); ii. At least one IST treatment has failed,and long-term PE or IVIg treatment is required to control symptoms, thatis, PE or IVIg treatment for muscle weakness needs to be carried outregularly for at least two cycles in the past 12 months.

• Chronic inflammatory demyelinating polyradiculopathy (CIDP): Meet the 2021EAN/PNS diagnostic criteria (progressive or recurrent type), and have acorrected INCAT disability scale total score of 2-9 (with 2 points coming fromleg disability), and meet the following requirements:

1. Standardized use of at least one first-line therapy (cortisol hormonetherapy, γ -globulin or plasma exchange therapy) for more than 3 monthswith poor symptom control;
2. Inability to tolerate cortisol hormone, gamma globulin and plasma exchangedue to side effects or other circumstances;
3. Determined as an active disease (CIDP disease activity status [CDAS] score ≥2), (the disease must show activity and present clinically significantdeterioration on at least one CIDP clinical assessment tool (includingINCAT, I-RODS or mean grip strength)

• Multiple Sclerosis (MS): According to the revised McDonald diagnostic criteriain 2017, a clinical diagnosis of MS is made, and the following three points aresimultaneously met:a) Before ICF and in any of the following circumstances: i. Two relapses havebeen recorded in the past two years. ii. One recurrence was recorded within thepast year. iii. The result of Gd enhanced MRI scan was positive within one yearbefore screening. Note: If there is no positive result of Gd enhanced scanrecorded in the previous year, the screening MRI scan results can be used.b) Neurological stability within one month before screening and baseline (including no recurrence of MS at this stage)

• Autoimmune encephalitis (AE): According to the 2016 International DiagnosticCriteria for Autoimmune Encephalitis, the subject was diagnosed with autoimmuneencephalitis and met all of the following requirements:

1. At least one pathogenic antibody, NMDAR or LGI1, is positive;
2. Previously standardized use of corticosteroids, at least oneimmunosuppressant/modulator, including CD20 monoclonal antibodies withpoor symptom control or intolerance;
3. Autoimmune encephalitis occurred within 3 months before screening;
4. Modified Rankin Scale (mRS) score ≥2 or Clinical Assessment Scale forAutoimmune Encephalitis (CASE) score ≥4.

• Anti-myelin oligodendrocyte glycoprotein immunoglobulin G antibody-relateddisease (MOGAD): Comply with the diagnostic criteria released by theInternational MOGAD Expert Group in 2023 and meet all of the followingrequirements:

1. Serum positive for anti-MOG antibodies

2. There was a history of ≥1 recurrence of MOGAD within 12 months prior toscreening, or ≥2 episodes within 24 months prior to screening.

3. Proper organ function, complying with the following criteria :

• Blood routine: Absolute lymphocyte count (ALC) ≥0.4×109/L, platelet count (PLT) ≥50×109/L, hemoglobin ≥80 g/L;

• Coagulation function: International Normalized ratio (INR) ≤1.5 times the upperlimit of normal (ULN), and activated partial prothrombin time (APTT) ≤1.5 timesULN;

• Liver function: Serum aspartate aminotransferase (AST) and alanineaminotransferase (ALT) ≤3 times ULN, total bilirubin ≤1.5 times ULN;

• Renal function: Serum creatinine ≤1.5×ULN or creatinine clearance rate (Cockcroft Gault formula) ≥60 mL/min;

• Pulmonary function: Under indoor ventilation conditions, the blood oxygensaturation in the non-oxygen inhalation state is ≥92%; There is no clinicallysignificant pleural effusion.

5. The clinical physician evaluated the patient's condition and allowed the use ofglucocorticoids at a dose not exceeding 10mg of prednisone or its equivalent duringthe study period, and permitted the discontinuation of all immunosuppressants.

6. The subjects whose partners are fertile agree to use effective contraceptivemeasures throughout the treatment period and for 24 months after the treatment, andduring this period, they are not allowed to donate eggs/sperm for assistedreproduction. Female subjects of childbearing age (women who have undergonesterilization surgery or have been menopausal for ≥12 months are not consideredfertile) have negative urine pregnancy or blood pregnancy tests during the screeningperiod.

Exclusion Criteria:

1. Current medical conditions or neurological disorders that may affect theeffectiveness assessment, such as dementia, schizophrenia, bipolar disorder, majordepressive disorder, history of multiple traumatic brain injury, currentalcohol/drug abuse or dependence, or alcohol/drug dependence within the past twoyears.

2. Pregnancy or breastfeeding;

3. Have received organ or hematopoietic stem cell transplantation in the past;

4. There has been a history of new thrombosis or organ infarction within the past sixmonths;

5. Patients diagnosed with active connective tissue diseases and requiring non-hormonalimmunosuppressants/modulators for treatment;

6. Combined with active infections (such as sepsis, bacteremia, mycosis, uncontrolledpulmonary infection and active tuberculosis, etc.);

7. Positive for hepatitis B surface antigen (HBsAg) and/or hepatitis Be antigen (HBeAg); Positive hepatitis Be antibody (HBe-Ab) and/or hepatitis B core antibody (HBc-Ab), and HBV-DNA copy number greater than the measurable lower limit; Positivefor hepatitis C (HCV) antibody Positive for human immunodeficiency virus (HIV)antibody; Those who test positive for syphilis (TP); The copy numbers of EBV-DNA andCMV-DNA are greater than the measurable lower limit.

8. Having undergone major surgery that was evaluated by the researcher as unsuitablefor inclusion within 4 weeks prior to screening;

9. Other malignant tumors that have occurred or are currently present within the fiveyears prior to screening are excluded, except for those with negligible risk ofmetastasis or death and curable tumors, such as well-treated cervical carcinoma insitu and basal cell carcinoma of the skin.

10. The patient's heart meets any of the following conditions:

• Left ventricular ejection fraction (LVEF) ≤45%;

• Persistent hypertension (≥160/100 MMHG) that remains uncontrolled despitestandardized treatment

• New York Heart Association (NYHA) Grade III or IV congestive heart failure oractive heart disease;

• Severe arrhythmias requiring treatment (excluding atrial fibrillation andparoxysmal supraventricular tachycardia);

• The QTcB interval is ≥450ms for males and ≥470ms for females (QTcB=QT/RR1/2);

• Had myocardial infarction, bypass surgery or stent surgery within 6 monthsprior to the study;

• Other heart diseases that the researcher judged as unsuitable for enrollment;

11. Have received a live vaccine within 6 weeks before screening.

12. Participate in other interventional clinical studies before cell reinfusion,orreceiving treatment of an active investigational drug within 5 half-lives . Thosewho have received active trial drug treatment, or who intend to participate inanother clinical trial or receive treatment other than that stipulated in theprotocol throughout the study period.

13. Those who are known to have hypersensitivity reactions to the components of thepreparations used in the test;

14. Previously received CAR-T cell therapy;

15. Other conditions that the investigator considers unsuitable for participation in thestudy.