Efficacy and Safety of Calculus Bovis Sativus (CBS) for Idiopathic Inflammatory Demyelinating Disease (CBSinIIDD)

Inclusion Criteria:

• IIDD cohort:

• Subjects are capable of understanding the purpose and risks of the study,providing informed consent and authorizing the use of confidential healthinformation in accordance with national and local privacy regulations.

• Both men and women are welcome, and the age at the time of providing informedconsent is 18-65 years (inclusive).

• All women of childbearing age and all men must use contraceptive measuresduring the study and for at least 30 days after the last dose of studytreatment. In addition, subjects should not donate sperm or eggs during thestudy and for at least 30 days after the last dose of study treatment.

• Must be diagnosed with ① Multiple sclerosis, meet the 2017 revised McDonald criteria, and enter the MScohort; ② Aquaporin Protein-4-positive (AQP4) neuromyelitis optica spectrum disease,meet the 2015 international consensus diagnostic criteria for neuromyelitisoptica spectrum disease (NMOSD), and AQP4 antibody positive, enter theAQP4-NMOSD cohort; ③ Myelin oligodendrocyte glycoprotein antibody-related disease, clinicallydiagnosed as MOGAD according to the 2023 international MOGAD diagnosticcriteria, and positive MOG autoantibody test by cell-based-assay method; ④ Acute disseminated encephalomyelitis, clinically diagnosed as ADEM accordingto the 2013 International Pediatric Multiple Sclerosis Study Group (IPMSSG)diagnostic criteria, characterized by multifocal neurological deficits, musthave encephalopathy manifestations (behavioral changes and/or changes inconsciousness that cannot be explained by fever, including irritability), andexclude other specific antibody-positive IIDD.

• EDSS score ≤ 4 points at baseline (visit 1).

• Stable neurological examination within 30 days prior to Baseline (Visit 1).

• Healthy cohort:

• Age ≥ 18 years old when signing the informed consent form

• Healthy adult subjects without underlying diseases

Exclusion Criteria:

• Any clinically significant cardiac, endocrine, hematologic, hepatic, immune,infectious, metabolic, urologic, pulmonary, neurological, dermatologic, psychiatric,and renal disease or other major medical history that the investigator determineswould preclude participation in the clinical trial.

• Any untreated teratoma or thymoma at the baseline visit (randomization)

• Other causes of symptoms, including central nervous system infection, septicencephalopathy, metabolic encephalopathy, epileptic disorders, mitochondrialdisease, Klein-Levin syndrome, Creutzfeldt-Jakob disease, rheumatic disease, Reyessyndrome, or inborn errors of metabolism.

• History of herpes simplex encephalitis within the previous 24 weeks. 1.5. Anysurgical procedure within 4 weeks prior to baseline, except laparoscopic surgery orminor surgery (defined as surgery requiring only local anesthesia or conscioussedation, i.e., surgery that does not require general, neuraxial, or regionalanesthesia and can be performed on an outpatient basis; e.g., toenail surgery, molesurgery, wisdom tooth extraction), excluding thymoma or teratoma removal.

• Planned surgery during the study (except minor surgery).

• History of severe allergic or anaphylactic reactions, or any allergic reaction thatthe investigator believes may be exacerbated by any component of study treatment.

• Current or history of malignant disease, including solid tumors and hematologicmalignancies (except for basal cell carcinoma and squamous cell carcinoma that havebeen completely resected and considered cured for at least 12 months prior to Day -1). Subjects with cancer remission for more than 5 years prior to baseline (Visit

1. may be included after discussion with the sponsor/sponsor approval.

• A history of gastrointestinal surgery (except appendectomy or cholecystectomyperformed more than 6 months before screening), irritable bowel syndrome,inflammatory bowel disease (Crohn's disease, ulcerative colitis), or otherclinically significant active gastrointestinal diseases in the opinion of theinvestigator.

• A history of clinically significant recurrent or active gastrointestinal symptoms (e.g., nausea, diarrhea, dyspepsia, constipation) within 90 days before screening,including the need to start symptomatic treatment (e.g., start medication forgastroesophageal reflux disease) or a change in symptomatic treatment within 90 daysbefore screening (e.g., dose increase).

• A history of diverticulitis or concurrent severe gastrointestinal (GI) abnormalities (e.g., symptomatic diverticular disease) because the investigator believes that thismay lead to an increased risk of complications such as GI perforation.

• A history of blood donation (1 unit or more), plasma donation, or platelet donationwithin 90 days before screening.

• Active suicidal ideation within 6 months before screening, or a history of suicideattempt within 3 years before screening.

• Based on the investigator's judgment, there are serious diseases or abnormalities inthe clinical laboratory test results that prevent the patient from completing thestudy or participating in the study safely.

• Pregnant or lactating, or planning to become pregnant during the study or within 3months after the last dose of the study drug; women of childbearing potential musthave a negative serum pregnancy test result at screening and a negative urinepregnancy test result before the start of the study.

• The subject's mental or physical condition will hinder the evaluation of efficacyand safety.

• Systolic blood pressure >150 mmHg or <90 mmHg after sitting still for 5 minutes orbefore dosing at screening. If out of range, it can be measured again at screeningand before dosing. If the repeated measurement value is still out of range, thesubject shall not receive the drug.

• Subjects with second or third degree atrioventricular block or sick sinus syndrome,poorly controlled atrial fibrillation, severe or unstable angina, congestive heartfailure, myocardial infarction, or significant ECG abnormalities, includingcorrected QT interval >450 msec (male) or 470 msec (female), where corrected QTinterval is determined based on the Fridericia correction method, within 3 monthsprior to the screening visit.

• Planned elective procedures or surgeries at any time after signing the InformedConsent Form by follow-up visit.

• Any condition that affects the absorption of study treatment (e.g., gastrectomy).

• History of hypersensitivity to heparin or history of heparin-inducedthrombocytopenia.

• Subjects with abnormalities in medical history, physical examination, ECG, ordiagnostic laboratory tests that the investigator considers to be clinicallyrelevant.

• History of human immunodeficiency virus (HIV) or positive test results at screening.

• Current infection with hepatitis C (defined as positive hepatitis C virus (HCV)antibodies and detectable HCV RNA). Subjects with positive HCV antibodies and HCVRNA below the limit of detection are eligible to participate in the study.

• Current infection with hepatitis B (defined as positive HBsAg and/or positive totalanti-HBc).

• Chronic, recurrent, or severe infection (e.g., pneumonia, sepsis) within 90 daysprior to baseline (visit 1).

• History of tuberculosis (TB) diagnosis or positive latent TB test result.

• Symptoms of bacterial, fungal, or viral infection (including upper respiratory tractinfection) within 28 days prior to baseline (visit 1). Subjects with localizedfungal infection (e.g., candidiasis, tinea) are eligible for rescreening aftersuccessful treatment of the infection.

• Infection requiring hospitalization or IV anti-infective medication within 4 weeksprior to baseline visit.

• Any live or live attenuated vaccine within 28 days prior to baseline (visit 1) orplanned during the study.

• Contraindications to all of the following salvage therapies: rituximab, intravenousimmunoglobulin, high-dose corticosteroids, or IV cyclophosphamide.

• History of or receipt of the following treatments: Total lymphoid irradiation,cladribine, T-cell or T Cell recipient vaccination, total body irradiation, or totallymphoid irradiation at any time. Stem cell transplantation at any time.

• Abnormal laboratory values determined by the investigator to be clinicallysignificant at Screening or Baseline (Visit 1).

• Any of the following blood test abnormalities at Screening: a. White blood cellcount < 3.0 × 10^3/µL. b. Absolute neutrophil count < 2.0 × 10^3/µL. c. Absolutelymphocyte count < 0.5 × 10^3/µL. d. Platelet count < × 10 × 10^4/µL. e.glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase, or γ-glutamyltranspeptidase ≥ 3 x upper limit of normal (ULN) or bilirubin > 2 x ULN. f.glomerular filtration rate ≤ 60 mL/min/1.73 m2. g. Lymphocyte count < lower limit ofnormal

• Any of the following urine test abnormalities at Screening: a. β-2-microglobulin>0.3 μg/mL. b. Albumin/creatinine ratio>22.6 mg/mmol.

• Previous participation in this study.

• Blood donation (1 unit or more) within 90 days before screening, plasma donationwithin 1 week before screening, and platelet donation within 6 weeks beforescreening.

• History of alcohol or drug abuse in the past year (determined by the investigator).

• Pregnant or lactating subjects, as well as subjects planning to become pregnant orstart breastfeeding at any time during the study and within 30 days after completionof study treatment.

• Participating in a clinical trial or having participated in a clinical trial within 90 days before screening.

• History of clinically significant suicidal thoughts or behaviors in the past 12months as assessed by Columbia-Suicide Severity Rating Scale at screening.

• Unwilling or unable to comply with protocol requirements.

• The patient has obvious hearing or vision impairment, language barriers,claustrophobia, etc., which makes the patient unable to cooperate with theneuropsychological scale assessment and MRI examination.

• The researcher or sponsor believes that there are other unknown reasons that makethe subject unsuitable for inclusion.