UCAR-T Targeting CD19/BCMA in Subjects With Autoantibody-Mediated Autoimmune Benign Hematological Diseases

Clinical Study on Safety, Efficacy, and Pharmacokinetics of Universal CAR-T Cell Injection Targeting CD19/BCMA in Subjects With Autoantibody-Mediated Autoimmune Benign Hematological Diseases

This is a single-arm, open-label, investigator-initiated trial (IIT) designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of RD06-05 in subjects with autoantibody-mediated autoimmune hematological diseases. The enrolled population consists of patients with active autoimmune hematological diseases, including primary immune thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), and Evans syndrome.

This study sets two dose groups: 6 × 10⁶ CAR⁺T cells/kg and 10 × 10⁶ CAR⁺T cells/kg, with the initial dose being 6 × 10⁶ CAR⁺T cells/kg. To reduce efficacy risks, the dose may be escalated to 10 × 10⁶ CAR⁺T cells/kg following evaluation and recommendation by the Safety Review Committee (SRC). The SRC's recommendation on dose escalation will be based on a comprehensive assessment of all available safety, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy data.

Inclusion Criteria:

• Subjects voluntarily participate in this trial and sign the informed consent form.

• Aged ≥ 18 years and ≤ 75 years, regardless of gender.

• Organ function and laboratory tests:

  1. Liver function: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 × Upper Limit of Normal (ULN); Total Bilirubin (TBIL) ≤ 2 × ULN (except for Gilbert's Syndrome).
  2. Renal function: Creatinine ≤ 1.5 × ULN or Creatinine Clearance Rate ≥ 40 ml/min.
  3. Oxygen saturation (SpO2) ≥ 92% in room air at rest.
  4. Echocardiography shows Left Ventricular Ejection Fraction (LVEF) ≥ 50%.

• Female subjects of childbearing potential must have a negative result in serum or urine pregnancy test at screening.

• Female subjects of childbearing potential must agree to use highly effective contraceptive methods from at least 28 days before the start of lymphodepletion to 12 months after reinfusion on RD06-05. Male subjects of childbearing potential must agree to use effective barrier contraceptive methods from the start of lymphodepletion to 12 months after reinfusion on RD06-05, and must not donate semen or sperm during the entire trial period.

• Subjects with primary Immune Thrombocytopenia (ITP), with a disease duration of at least > 6 months.

• Refractory or relapsed ITP: Subjects show no response, unsustained response, or intolerance to at least 2 different categories of standard treatments (e.g., glucocorticoids, splenectomy, intravenous immunoglobulin (IVIg), thrombopoietin receptor agonists (TPO-RA), Bruton's tyrosine kinase (BTK) inhibitors, etc.); among which, subjects must have received at least one or more treatments from IVIg, TPO-RA, or BTK inhibitors. In addition, platelet counts must be < 30,000/μL in two tests conducted within 15 days before the start of study treatment, with an interval of at least 7 days between the two tests.

• Complete blood count: Neutrophil count ≥ 1,000/µL, hemoglobin ≥ 60g/L.

• Subjects with Autoimmune Hemolytic Anemia (AIHA), including warm autoimmune hemolytic anemia (wAIHA), mixed autoimmune hemolytic anemia (mix-AIHA), and cold agglutinin disease (CAD), with a disease duration of at least > 6 months.

• Refractory or relapsed AIHA: Subjects show no response, unsustained response, or intolerance to at least 3 lines of systemic treatments (e.g., glucocorticoids, rituximab, immunosuppressants, splenectomy, complement inhibitors, etc.).

• Laboratory evidence of hemolysis: At least one of the following conditions exists in either the screening period or any test within the past 3 months: haptoglobin below the lower limit of normal, or total bilirubin (especially indirect bilirubin) above the upper limit of normal, or lactate dehydrogenase (LDH) above the upper limit of normal, and/or elevated reticulocyte count.

• Complete blood count: Neutrophil count ≥ 1,000/µL, hemoglobin (Hb) < 100g/L.

• Diagnosed with Evans Syndrome (ES), with a disease duration of at least > 6 months.

• Refractory or relapsed ES: After at least 3 lines of systemic treatments (e.g., glucocorticoids, intravenous immunoglobulin (IVIg), rituximab, immunosuppressants, splenectomy, thrombopoietin receptor agonists (TPO-RA), complement inhibitors, etc.), at least one type of cytopenia (thrombocytopenia or hemolytic anemia) still shows no response, unsustained response, or intolerance.

• Laboratory evidence of active blood cell destruction: Platelet count < 30,000/μL or manifestations of hemolysis exist during the screening period or within the past 3 months, such as haptoglobin < lower limit of normal, or total bilirubin (especially indirect bilirubin) > upper limit of normal, or LDH > upper limit of normal, and/or elevated reticulocyte count.

• Definite response to at least one previous treatment:

Platelet (PLT) treatment response: Platelet count reaches ≥ 50,000/μL in at least 2 tests, with an increase of ≥ 20,000/μL compared to the baseline.

Hemoglobin (Hb) treatment response: Hb increases by ≥ 10-15 g/L or hemolysis indicators improve.

Exclusion Criteria:

• Has a coexisting autoimmune disease that may seriously interfere with the attribution of study disease activity or pose additional safety risks. However, if the subject's condition has been clinically stable for ≥ 3 months, and it is expected not to interfere with study assessments, the subject may be enrolled after confirmation by the investigator and approval by the sponsor's medical monitor (or their designee).

• Has rapidly progressive glomerulonephritis (RPGN), defined as any of the following:

  • Renal biopsy shows crescent formation in ≥ 50% of glomeruli.
  • Sustained doubling of serum creatinine level within 2 months before screening.
  • The investigator assesses that the subject has RPGN.

• Subjects with the following cardiac diseases will be excluded:

  • History of heart failure classified as New York Heart Association (NYHA) Class III or IV.
  • History of myocardial infarction, cardiovascular angioplasty or stenting, unstable angina, or other serious cardiac diseases within 12 months before enrollment.

• Has a history of severe central nervous system (CNS) diseases that may affect the subject's ability to comply with the study protocol or interfere with the accuracy of study assessments, such as: traumatic brain injury, disturbance of consciousness, epilepsy, cerebral vascular ischemia, or cerebral vascular hemorrhage.

• Has a history of malignant tumors other than cured non-melanoma skin cancer or carcinoma in situ (e.g., carcinoma in situ of the cervix, bladder, or breast), unless the subject has been disease-free for at least 3 years.

• Primary immunodeficiency.

• Has uncontrolled infection; simple urinary tract infections and upper respiratory tract infections are permitted as judged by the investigator and the sponsor's medical monitor (or their designee).

• Has a known history of infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or syphilis.

• Active or latent hepatitis B virus (HBV) infection.

• Positive results for Epstein-Barr virus (EBV) or cytomegalovirus (CMV) DNA or IgM antibodies during the screening period.

• Has a history of recurrent tuberculosis or known recurrent tuberculosis.

• Has a history of previous chimeric antigen receptor T-cell (CAR-T) therapy or any other genetically modified immune cell therapy.

• Has received a live-attenuated vaccine within 4 weeks before enrollment.

• Has a history of allergy to any component of the cell therapy product.

• Has a history of hypersensitivity to tacrolimus, or has experienced ≥ Grade 3 tacrolimus-related toxicity in the past (including but not limited to neurological, gastrointestinal, hepatic, renal, or hematological toxicity), especially subjects who required hospitalization will be excluded. Other cases may be considered eligible after confirmation by the investigator and the sponsor's medical monitor (or their designee).

• Has participated in another clinical trial within 30 days before screening.

• Pregnant or lactating subjects, as well as subjects of childbearing potential who cannot take effective contraceptive measures.