Phase 1 Study of F182112 in Relapsed/Refractory Autoimmune Hemolytic Anemia

A Phase 1 Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of F182112 in Patients With Relapsed/Refractory Autoimmune Hemolytic Anemia

This is an open-label, phase I clinical study of F182112 in patients with relapsed or refractory autoimmune hemolytic anemia (AIHA). Participants will receive F182112 at different dose levels. The main purpose of the study is to evaluate the safety and tolerability of F182112 and to identify an appropriate dose for further clinical development.

Inclusion Criteria:

• Age 18-75 years.
• Diagnosis of AIHA according to established Chinese or international criteria, including warm AIHA, mixed AIHA, cold agglutinin disease, or Evans syndrome.
• Refractory to multiple lines of therapy, meeting all of the following: HGB <100 g/L with evidence of hemolytic anemia; Prior treatment with ≥2 immunosuppressive therapies, including a CD20 monoclonal antibody; Glucocorticoid treatment for ≥3 months, unless contraindicated or intolerable; Adequate prior CD20 monoclonal antibody treatment (≥4 doses of 100 mg or 375 mg/m², or 2 doses of 1,000 mg).
• ECOG performance status ≤2.
• Participants and their partners agree to use effective contraception from informed consent through 1 year after study treatment.
• Written informed consent must be obtained before any study-specific screening procedures.

Exclusion Criteria:

• Diagnosed lymphoproliferative malignancy.
• Secondary AIHA caused by drugs or infection.
• Congenital immunodeficiency or other inherited or acquired hemolytic disorders.
• Prior organ or hematopoietic stem cell transplantation.
• New thrombotic events or organ infarction within 6 months before enrollment.
• Prior BCMA-targeted therapy within 6 months before enrollment.
• Any of the following prior treatments within the specified washout periods: Anti-CD20 monoclonal antibody within 12 weeks; Sutimlimab or other approved biologic therapy within 5 half-lives; Plasma exchange within 4 weeks; Splenectomy within 12 weeks.
• Any of the following cardiovascular conditions: LVEF ≤45%; Active cardiac disease or NYHA class III/IV heart failure; Clinically significant arrhythmia requiring treatment, except atrial fibrillation or paroxysmal supraventricular tachycardia; QTc ≥450 ms in males or ≥470 ms in females; Myocardial infarction, coronary artery bypass grafting, or coronary stent placement within 6 months; Other clinically significant cardiac disease considered unsuitable by the investigator.
• Unstable systemic disease, including severe hepatic or renal disease requiring treatment.
• History of another primary malignancy within 5 years before screening, except adequately treated non-melanoma skin cancer, carcinoma in situ, or other malignancies without recurrence for ≥5 years.
• Major surgery within 4 weeks before screening if considered unsuitable for enrollment by the investigator.
• Uncontrolled active fungal, viral, bacterial, tuberculosis, or other infection, or infection requiring intravenous antimicrobial therapy.
• Active or clinically significant HBV, HCV, HIV, or syphilis infection
• Live-virus vaccination within 4 weeks before enrollment.
• Participation in another interventional clinical study within 5 half-lives of the investigational treatment before screening, or planned use of another investigational treatment during this study.
• Pregnant or breastfeeding women.
• Psychiatric disorders, impaired consciousness, or central nervous system disorders, including a history of epilepsy or Parkinson's disease.
• Known hypersensitivity to any component of F182112.
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.