IASO206 in Patients With Relapsed/Refractory Autoimmune Hemolytic Anemia

Phase I Clinical Study on the Safety and Tolerability of IASO206 Injection in Patients With Relapsed/Refractory Autoimmune Hemolytic Anemia

This study is an open-label, single-arm early exploratory clinical study, aiming to evaluate the safety, tolerability and preliminary efficacy of IASO206 Injection (In Vivo CAR-T) in Patients with Relapsed/Refractory Autoimmune Hemolytic Anemia

Inclusion Criteria:

• Age 18 to 75 years, gender unrestricted.
• Diagnosis of AIHA (including warm antibody type, warm-cold antibody type, cold agglutinin disease) or Evans syndrome, consistent with Chinese Expert Consensus on Diagnosis and Treatment of Autoimmune Hemolytic Anemia (2023), 2019 International Consensus for Diagnosis and Management of Autoimmune Hemolytic Anemia (Blood Rev, 2020), or Chinese Expert Consensus on Diagnosis and Treatment of Evans Syndrome (2024 Edition).
• Patients with relapsed/refractory disease after multiple lines of therapy must meet all of the following criteria: hemoglobin < 10 g/dL with clinical manifestations of hemolytic anemia; prior treatment with at least 2 immunosuppressive drugs (must include CD20 monoclonal antibody); glucocorticoid therapy for at least 3 months (excluded are patients with contraindications to glucocorticoids, severe infection, severe osteoporosis, previous fracture, or inability to tolerate glucocorticoids); cumulative dose of CD20 monoclonal antibody at least 375 mg/m² × 4, or total dose 2.0 g, or at least 6 administrations (at least 1 week apart each time).
• ECOG score ≤ 2.
• Expected survival time ≥ 12 weeks.
• Adequate organ function confirmed by laboratory tests: serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × upper limit of normal (ULN); minimum pulmonary reserve defined as grade ≤ 1 dyspnea and oxygen saturation ≥ 93% without oxygen supplementation; creatinine clearance (estimated by Cockcroft-Gault) ≥ 45 mL/min; cardiac ejection fraction ≥ 50%, no pericardial effusion on echocardiogram (ECHO), and no clinically significant abnormal electrocardiogram (ECG).
• Subjects and their partners agree to use effective barrier or medical contraceptive measures (excluding rhythm method) from signing informed consent until 1 year after administration.
• Subjects must provide written informed consent approved by the Ethics Committee prior to initiation of screening procedures

Exclusion Criteria:

• Subject with confirmed lymphoproliferative neoplasms.

• Subject with secondary AIHA induced by drugs or infection.

• Subject with congenital immunodeficiency diseases, other hereditary or acquired hemolytic diseases.

• Subject with a history of organ or stem cell transplantation.

• Subject with a history of organ infarction within the past 6 months.

• Subject who have received prior BCMA-targeted therapy.

• Subject who received plasma cell-targeted cell therapy within 3 months before screening, or in whom prior cell therapy products are still detectable in peripheral blood.

• Subject who received any of the following treatments within the specified periods prior to study enrollment:

  1. Anti-CD20 monoclonal antibody < 12 weeks;
  2. Sutimlimab or other marketed biological products < 5 half-lives;
  3. Plasma exchange < 4 weeks;
  4. Splenectomy < 12 weeks.

• Subject with any of the following cardiovascular diseases:

  1. Left ventricular ejection fraction (LVEF) ≤ 45%;
  2. Active heart disease or congestive heart failure (New York Heart Association [NYHA] Class III or IV);
  3. Severe arrhythmia requiring treatment (excluding atrial fibrillation, paroxysmal supraventricular tachycardia);
  4. QTcB interval ≥ 450 ms for males, ≥ 470 ms for females;
  5. Myocardial infarction, bypass surgery, or stent implantation within 6 months before study;
  6. Other cardiac diseases judged by the investigator to be unsuitable for enrollment.

• Unstable systemic diseases judged by the investigator, including but not limited to severe hepatic or renal diseases requiring medical treatment.

• Subject with a history of other primary malignancies within 5 years before screening, except:

  1. Resected and cured non-melanoma skin cancer (e.g., basal cell carcinoma);
  2. Cured carcinoma in situ (e.g., cervical, bladder, or breast cancer);
  3. Other primary cancers with no evidence of recurrence for more than 5 years after treatment.

• Subject who underwent major surgery within 4 weeks before screening and are judged unsuitable for enrollment by the investigator.

• Subject with uncontrolled active fungal, viral, bacterial, mycobacterial, or other infections (persistent infection-related signs/symptoms without improvement after appropriate anti-infective therapy) or infections requiring intravenous anti-infective therapy.

• Positive hepatitis B surface antigen (HBs-Ag) or hepatitis B e antigen (HBe-Ag); positive hepatitis B e antibody (HBe-Ab) or hepatitis B core antibody (HBc-Ab) with HBV-DNA copy number above the lower limit of quantification; positive hepatitis C (HCV) antibody; positive human immunodeficiency virus (HIV) antibody; active syphilis infection (excluding those with only positive syphilis-specific antibody).

• Subject who received live viral vaccines within 4 weeks before enrollment.

• Subject who are participating in other interventional clinical studies during IASO206 Injection treatment with a drug half-life < 5; subject receiving active investigational drugs during the entire study period, or who intend to participate in another clinical trial, or receive treatments outside the protocol.

• Pregnant or lactating females.

• Subject with psychiatric disorders, disturbance of consciousness, or central nervous system diseases, including but not limited to epilepsy and Parkinson's disease.

• Subject with hypersensitivity to components of IASO206 Injection or supportive medications required for the management of CAR-T therapy-related toxicities (e.g., tocilizumab).

• Other conditions judged by the investigator to be unsuitable for enrollment.10. Other Information