CD7 CAR T Cells (RD13-02) in the Treatment of Relapsed/Refractory Severe Aplastic Anemia

Inclusion Criteria:

• Willing and able to provide written informed consent.

• Age ≥18 years and ≤75 years.

• Diagnosed with severe aplastic anemia: Diagnostic criteria refer to the UKHematology Guidelines (Br J Haematol, 2024, 204(3): 784-804): 1) Bone marrowcellularity <25% (or 25-50% but <30% residual hematopoietic cell area); 2) At leasttwo of the following conditions must be met: ANC <0.5×10^9/L, PLT <20×10^9/L,absolute reticulocyte count <60×10^9/L; 3) Exclusion of other congenital or acquiredhematopoietic failure disorders.

• Had at least one course of standard-dose therapy with anti-thymocyte globulin (ATG)or anti-lymphocyte globulin (ALG) combined with TPO-RA that was ineffective orrelapsed after remission within the past 6 months.

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance statusof 0-2.

• Willing and able to comply with the study procedures.

Exclusion Criteria:

• Blood cell reduction and hypoplastic bone marrow diseases due to other causes (e.g.,hemolytic PNH, hypoplastic MDS/AML, antibody-mediated pancytopenia).

• Received ATG/ALG treatment less than 6 months ago; received TPO-RA treatment lessthan 4 months ago. Note: Patients on stable doses of cyclosporine or hematopoieticagents at screening can be enrolled if laboratory values are stable.

• Significant neurological disease history, including dementia, stroke withoutparalysis, aphasia, seizures, or any neurological history that may pose safety risksregarding cell therapy as judged by the investigator.

• History of allogeneic bone marrow or stem cell transplantation, or solid organtransplantation (e.g., kidney, lung, heart), or plans for such transplantation inthe future.

• History of autologous or allogeneic CAR T therapy.

• Any primary immunodeficiency disease.

• Significant cardiovascular dysfunction history or current significant cardiovasculardysfunction, particularly:

• Signs or symptoms of congestive heart failure classified as NYHA class ≥III within 12 months prior to enrollment.

1. Echocardiogram showing left ventricular ejection fraction (LVEF) <45% (assessedduring screening).

2. History of any serious arrhythmia, currently on treatment for arrhythmias,significant history of myocardial infarction, clinically significant valvularheart disease (including mild or greater aortic regurgitation or moderate orgreater mitral regurgitation), recurrent syncope, or significanthypercoagulable vascular events (e.g., transient ischemic attack or stroke);history of pulmonary embolism.

• Liver or lung dysfunction, defined as:

1. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≥2.5× theupper limit of normal (ULN);

2. Total bilirubin ≥1.5×ULN, except in subjects with Gilbert's syndrome.

3. Pulmonary hypertension, including secondary pulmonary hypertension, classifiedas WHO functional class >2.

• Males with QTcF >450 msec; females with QTcF >470 msec, based on a single ECG or theaverage of three repeat ECGs taken more than 3 minutes apart.

• History of malignancy, excluding adequately treated or surgically removednon-melanoma skin cancer or in situ cancers (e.g., cervical cancer, bladder cancer,breast cancer) without residual disease.

• Pregnant or breastfeeding females, or females planning to become pregnant during thestudy or within 12 months after RD13-02 infusion.

• History or signs of significant chronic active or recurrent infections, orsignificant chronic active or recurrent infections requiring antibiotics,antivirals, or antifungal treatments based on screening laboratory results.

• Uncontrolled infections at screening. Patients with uncomplicated urinary tractinfections (UTIs) and uncomplicated bacterial pharyngitis responding to activetreatment may be included with investigator and medical monitor approval.

• Positive screening for HBsAg, HCV RNA, or HIV. If a subject is HBsAg negative butHBcAb positive, hepatitis B virus DNA testing should be performed; subjects withpositive hepatitis B virus DNA should be excluded from the study.

• Vaccination with live attenuated vaccines within 4 weeks prior to enrollment, orplans to receive live attenuated vaccines during the study.

• PT, APTT, or INR >1.2×ULN, except for subjects on stable doses of anticoagulants whocan discontinue treatment prior to using intravenous access procedures.

• eGFR <30 mL/min/1.73 m² calculated using the CKD-EPI formula; if eGFR ≥30mL/min/1.73 m² but <45 mL/min/1.73 m², adjust fludarabine dosing in thelymphodepleting regimen based on renal function.

• History of drug or alcohol abuse within the past year.

• Currently enrolled in other experimental device or drug studies, or less than 30days since ending other experimental device or drug interventions, or less than 5half-lives (whichever is longer).

• History of hypersensitivity or life-threatening reactions to any component orformulation of the study drug or treatment (including lymphodepleting regimen). Fordetailed information about study drug components, refer to the investigator brochure (IB).

• Any condition the investigator believes may affect participation, pose safety risksto the subjects, or potentially confound the interpretation of study results.