A Randomized, Double-blind, Placebo-controlled, and Multi-center Clinical Study of CM313 in the Treatment of Immune Thrombocytopenia

Inclusion Criteria:

• Age ≥18 years, male or female.

• Before enrollment, the subjects have been clinically diagnosed with primary immunethrombocytopenia for no less than three months according to the American Society ofHematology guidelines 2011 Evidence-Based Practice Guideline (Neunert et al. 2011)or the International Consensus Report for the Investigation and Management ofPrimary Immune Thrombocytopenia (Provan et al. 2010), as applicable locally.

• Patients have failed glucocorticoid therapy (either due to inefficacy, efficacycould not be maintained, or relapse). Patients were required to have a responsehistory (PLT≥50×10^9/L) to standard first-line treatment of ITP (glucocorticoidand/or intravenous immunoglobulin).

• Subjects with a platelet count of <30×10^9/L within the 24 hours prior to the firstdose of the study drug; The mean platelet count of at least two separate assessments (at least 1 week apart) <30×10^9/L during the screening visit, and no platelet count > 35×10^9/L.

• ECOG performance status score of ≤2.

• Enrollment of subjects receiving maintenance therapy with a stable dosage ispermitted, including glucocorticoids (≤0.5 mg/kg of prednisone or equivalent) or TPOreceptor agonists. However, at the time of enrollment, subjects are restricted tousing only one concomitant medication with a stable dose, and the concomitantmedication must have been stable for a minimum of 4 weeks prior to the initialinfusion of the study drug.

• For fertile female patients, a negative pregnancy test result is required. Fertilefemale and male patients must use effective contraception separately during thestudy and for 4 or 6 months after the cessation of study drug treatment.

• Subjects comprehensively understand and can adhere to the study protocolrequirements and willingly signed the informed consent form.

Exclusion Criteria:

• Subjects with a known allergy to anti-CD38 monoclonal antibodies or excipients, orthose who have previously received anti-CD38 monoclonal antibodies with ineffectivetherapeutic outcomes.

• Subjects who are diagnosed with autoimmune hemolytic anemia or various secondarythrombocytopenic disorders.

• Subjects with history of any thrombotic or embolic events or extensive and severebleeding, such as hemoptysis, major upper gastrointestinal bleeding, intracranialhemorrhage, or the presence of sepsis or other irregular bleeding within the 12months preceding the initiation of the first dose of study drug.

• Subjects who have participated in any other investigational drug studies (includingvaccine studies) or been exposed to other investigational drugs within the first 4weeks or 5 half-lives (whichever was longer) prior to the first dose of study drug.

• Subjects who have used anticoagulants or any agents with antiplatelet effects, suchas aspirin, within 3 weeks prior to the first dose of study drug.

• Subjects who have received emergency treatment for ITP (e.g., methylprednisolone,platelet transfusion, intravenous immunoglobulin infusion, or thrombopoietinreceptor agonist therapy) within 2 weeks prior to the first dose of study drug.

• Subjects who have been treated with medications including azathioprine, danazol,dapsone, cyclosporine A, tacrolimus, and sirolimus within 4 weeks prior to the firstdose of study drug. Subjects who have receive anti-CD20 monoclonal antibodies suchas rituximab, or medications including cyclophosphamide and vindesine within 6months prior to the first dose of study drug.

• Subjects who have undergone splenectomy within 6 months prior to the first dose ofstudy drug.

• Subjects who have received live vaccines within 4 weeks prior to the first dose ofstudy drug, or plan to receive any live vaccines during the course of the study.

• Subjects who are diagnosed with Myelodysplastic syndromes (MDS); Subjects with awith a history of malignancy within the 5 years prior to screening (excludingcompletely cured in situ cervical cancer and non-metastatic skin squamous cellcarcinoma or basal cell carcinoma).

• Subjects who have undergone allogeneic stem cell transplantation or organtransplantation.

• Subjects with a clinically significant medical history, as perceived byinvestigators, that will pose risks to subjects' safety during the study orpotentially affect the safety or efficacy analyses, includes major clinicalhistories such as circulatory system abnormalities, endocrine system abnormalities,nervous system diseases, blood system diseases, immune system diseases, mentaldiseases and metabolic abnormalities and so on. e.g., subjects with acute myocardialinfarction, unstable angina pectoris, or severe arrhythmias (multifocal ventricularpremature contractions, ventricular tachycardia, or ventricular fibrillation) withinthe 6 months before screening ; New York Heart Association (NYHA) class III-IV heartfailure; subjects who were known to have had moderate or severe persistent asthma orchronic obstructive pulmonary disease within the 5 years prior to screening, orwhose condition was currently poorly controlled;

• Subjects with a history of severe recurrent or chronic infections, or acuteinfections requiring systemic treatment with antibiotics, antiviral drugs,antiparasitic drugs, anti-amoebic drugs, or antifungal drugs within 4 weeks prior tothe first dose and during the screening period, or superficial skin infectionsrequiring systemic treatment within one week prior to the first dose of study drug.Notably, after the resolution of the infection, the subject may be re-screened.

• Subjects with a history of known or suspected immunosuppression, including invasiveopportunistic infections such as histoplasmosis, listeriosis, coccidioidomycosis,pneumocystis pneumonia, and aspergillosis, even if the infection has resolved; orunusually frequent, recurrent, or prolonged infections (as judged by theinvestigator).

• Significant laboratory abnormalities during screening included:

1. Alanine aminotransferase or aspartate aminotransferase greater than three timesthe upper limit of normal (ULN).

2. Total bilirubin greater than 1.5 times the ULN (note: subjects diagnosed withGilbert syndrome based on medical records should not be excluded based on thiscriterion).

3. absolute neutrophil count < 1500/mm3.

4. hemoglobin < 9g/dL; IgG < 500 mg/dL. f) lymphocyte count < 500/mm3. g) Creatinine clearance (CrCl) < 30 mL/min (i.e.,CrCl ≥30 mL/min is allowed)

• Positive for HIV antibodies or syphilis antibodies.

• Subjects test positive for Hepatitis B surface antigen (HBsAg) or subjects testpositive for hepatitis B core antibody and HBV-DNA (through polymerase chainreaction testing), or subjects test positive for hepatitis C virus antibody andHCV-RNA during the screening period. Subjects with positive hepatitis B coreantibody but negative HBV-DNA can be enrolled, with HBV-DNA monitoring every 4weeks.

• Pregnant or lactating women, or those intending to conceive or breastfeed during thestudy; and male partners intending to induce pregnancy during the study.

• Any other conditions unsuitable for participation in this study, as assessed by theinvestigator.