This is an Open-Label Study to Assess the Safety and Efficacy of GC012F in Patients With Multiple Sclerosis

Treatment tested

• GC012F CAR-T Cell Injection

Other measures (19)

Inclusion Criteria: * 1.Subjects or their legal representatives voluntarily sign a written informed consent form and are willing and able to comply with the procedures of this study; * 2.Age 18 to 75 years (inclusive) at the time of signing the ICF, regardless of gender; * 3.Women of childbearing potential must (women who have had a hysterectomy or have been postmenopausal for at least 2 years are not considered to be of potential childbearing potential): * a) At screening, the result of serum β human chorionic gonadotropin pregnancy test is negative; * b) Agree to refrain from breastfeeding for the duration of study participation until at least 2 years after GC012F injection infusion or until 2 consecutive flow cytometry tests show no more CAR-T cells (whichever occurs later); * 4. Male subjects with sexual partners and female subjects of potential childbearing potential agree to use highly effective contraceptive methods (e.g.: birth control pills, intrauterine devices, or condoms) from screening until then GC012F injection is no longer present for at least 2 years after infusion or until 2 consecutive flow cytometry tests show no more In CAR-T cells (whichever occurs later). Male subjects must agree to use a condom during sexual contact with a pregnant woman or a woman of childbearing potential for at least 2 years after GC012F injection infusion, even after a successful vasectomy; * 5. The venous access required for collection can be established, and there are no contraindications to leukocyte collection; * 6.The laboratory test results at screening must meet the following criteria: * Organ and bone marrow function: * a)Absolute neutrophil count ≥ 1.0 × 10\^9/L (no growth factor is given for supportive care within 7 days prior to testing); * b)Absolute lymphocyte count ≥ 1.0×10\^9/L; * c)Hemoglobin ≥ 80 g/L (no red blood cell transfusion is given within 7 days prior to testing); * d)Platelet count ≥ 50×10\^9/L (no blood transfusion is given within 7 days prior to testing); * e)Serum IgG ≥ 500 mg/dL; * f)Activated partial thromboplastin time ≤ 1.5 × upper limit of normal (ULN), prothrombin time (PT) ≤ 1.5 × ULN; * g)Adequate renal, hepatic, cardiopulmonary function (as defined below): * i.Serum alanine aminotransferase and aspartate aminotransferase ≤ 3 × ULN; * ii.Total bilirubin \< 2 × ULN (direct bilirubin ≤ 1.5 × ULN for subjects with Gilbert's syndrome); * iii.Creatinine ≤ 2 mg/dL or creatinine clearance ≥ 60 mL/min (estimated according to the Cockcroft Gault formula); * iv.Subjects with left ventricular ejection fraction ≥ 45% (performed within 8 weeks prior to apheresis) as diagnosed by echocardiography (ECHO) or multi-gated acquisition scan and no evidence of pericardial effusion as determined by ECHO and no clinically significant electrocardiographic findings; * v.Baseline oxygen saturation > 92% under indoor air conditions; * vi.Estimated glomerular filtration rate ≥ 60 mL/min/1.73 m\^2. * 7.Confirmed diagnosis of MS based on the 2017 McDonald diagnostic criteria and diagnosis of relapsing or progressive MS based on the 2013 Lublin phenotype criteria for multiple sclerosis; * Relapsing-remitting multiple sclerosis (RRMS): * a) patients with RRMS who have failed ≥ 1 highly effective disease modifying therapy (DMT) (fingolimod, siponimod, ozanimod, and anti-leukocyte cluster of differentiation [CD] 20 monoclonal antibody therapy, etc.) (defined as at least 12 months of continuous use). * b) At least 2 clinical relapses in the past 2 years, or 1 clinical relapse in the past 2 years with ≥ 1 new Gd-enhancing lesion on MRI, or ≥ 1 new Gd-enhancing lesion on MRI within the past 6 months; c) ≥ 2 Gd-enhancing lesions on T1-weighted brain MRI at screening. * Primary progressive multiple sclerosis (PPMS): * a) patients with primary progressive MS who have failed highly effective DMT and whose disease activity has worsened recently (i.e., within 1 year) (EDSS disease progression score ≥ 0.5); * b) no Gd-enhancing lesions on brain MRI at screening. * Secondary progressive multiple sclerosis (SPMS): * a) patients with secondary progressive MS who have failed highly effective DMT and whose disease activity has worsened recently (i.e., within 1 year) (EDSS disease progression score ≥ 0.5); * b) no Gd-enhancing lesions on brain MRI at screening. * 8.EDSS score ≥ 2.0 and ≤ 6.5; * 9.Documented history or confirmation at screening of the presence of oligoclonal bands or an elevated IgG index in CSF. Exclusion Criteria: * 1.Have received any investigational drug treatment within 3 months prior to screening or within 5 half-lives (whichever is longer); * 2.Fungal, bacterial, viral, or other infection not controlled and/or requiring hospitalization or intravenous antimicrobial therapy within 4 weeks prior to screening. Uncomplicated urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to current therapy; * 3.Active tuberculosis or latent tuberculosis that has not been treated appropriately prior to screening; * 4.History of severe hypersensitivity or allergy; * 5.Primary immunodeficiency; * 6.Impaired cardiac function or clinically significant cardiac disease; * 7.History of serious respiratory diseases or current serious respiratory diseases, including moderate or severe or above asthma or chronic obstructive pulmonary disease, interstitial lung disease, or pulmonary fibrosis; * 8.History of severe respiratory disease or current severe respiratory disease; * 9.Current or history of cirrhosis; * 10.History of Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus within the past 2 years, and the need for continuous use of systemic immunosuppressants/systemic disease-modifying drugs; * 11.Any active malignancy or history of malignancy within 5 years prior to screening. The following are exceptions: early-stage tumors that have undergone radical treatment (carcinoma in situ or stage I tumors, non-ulcerative primary melanoma with a depth \< 1 mm and no lymph node involvement), basal cell carcinoma of the skin, squamous cell carcinoma of the skin, thyroid carcinoma in situ or early-stage thyroid cancer that has undergone radical treatment, cervical carcinoma in situ, or breast cancer in situ that has undergone potentially radical treatment; * 12.Those who have clinically significant bleeding symptoms or definite haemorrhagic diathesis within 6 months prior to screening; * 13.Arterial or venous thrombotic events such as cerebrovascular disorders (including cerebral hemorrhage, cerebral infarction, etc), deep venous thrombosis, and/or pulmonary embolism within 6 months prior to screening; * 14.Hematologic disorders: History of cytopenia consistent with myelodysplastic syndrome; history of sickle-cell anemia or other hemoglobinopathies; * 15.Severe underlying medical conditions, such as: 1. Significant clinical evidence of dementia or mental status changes; 2. History of any other central nervous system (CNS) disorders or neurodegenerative diseases, such as epilepsy, seizure, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, and psychosis; 3. Mental disorders or psychosocial conditions that place patients at unacceptable risk. * 16.Positive results in any of the following tests: 1. Positive for human immunodeficiency virus (HIV) antibody; 2. Positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core antibody (HBcAb) with hepatitis B virus deoxyribonucleic acid (DNA) above the lower limit of detection of the assay; 3. Positive for hepatitis C virus (HCV) antibody with HCV ribonucleic acid (RNA) above the lower limit of detection of the assay; 4. Positive for antibodies against human T-cell lymphotropic virus types I and II; 5. Positive for syphilis antibody. As the immunosuppression included in this study may pose an unacceptable risk, those with active HIV infection, he

This is an open-label,early-stage exploratory clinical study to evaluate the safety and preliminary efficacy of GC012F CAR T cell injection in Multiple Sclerosis subjects.