Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia

Exclusion Criteria25

• Vital organ lethal bleeding (including but not limited to central nervous system bleeding, digestive tract bleeding) at screening, or intracranial bleeding 6 months prior to screening
• Antiphospholipid syndrome, thrombotic thrombocytopenia purpura, hemolytic uremic syndrome, or thrombocytopenia secondary to other causes (such as sepsis, Epstein-Barr virus infection, cytomegalovirus infection, Corona Virus Disease-19 (COVID-19) infection, drugs, etc.)
• Hematopoietic system disorders, such as myelodysplastic syndrome, paroxysmal sleep hemoglobinuria, aplastic anemia, leukemia, lymphoma, myelofibrosis and so on
• Severe cardiovascular system disease, including: unstable or uncontrollable disease or condition affecting the function of the heart (such as angina pectoris, congestive heart failure, uncontrolled hypertension or arrhythmia)
• Arteriovenous thromboembolism events
• Receiving antiplatelet or anticoagulant therapy at screening
• Clinically significant electrocardiogram changes
• corrected Q-T interval (QTc)\>450ms for male, QTc\>470ms for female
• Severe pulmonary disease, including: unstable or uncontrollable disease or condition affecting respiratory function \[e.g., diffuse alveolar hemorrhage, severe pulmonary hypertension, severe pulmonary interstitial disease (peripheral blood oxygen saturation \<92% at rest without oxygen, or forced vital capacity (FVC)\<50%, or carbon monoxide diffusing capacity (DLCO)\<50%)\]
• Severe kidney disease, including: severe lupus nephritis (urinary protein \> 6 g/24 hours or endogenous creatinine clearance \< 30 ml /min) 8 weeks prior to randomization, active nephritis requiring current protocol disallowed drugs, severe renal insufficiency requiring hemodialysis or prednisone ≥100mg/ day (or equivalent) for ≥14 days
• SLE or non-SLE related central nervous system disease (including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis) 8 weeks prior to randomization
• Active hepatitis, a history of severe liver disease. Subjects positive for hepatitis B surface antigen (HBsAg) or antibodies to hepatitis C virus are excluded. As for subjects with antibodies to hepatitis B core antigen (HBcAb), further hepatitis B virus (HBV)-DNA should be tested. If HBV-DNA is negative, subjects could be enrolled; otherwise, subjects should be excluded
• Abnormal laboratory results (including but not limited to: alanine aminotransferase (ALT) or aspertate aminotransferase (AST)≥3×ULN (upper limit of normal), white blood cell count \<1.5×10\^9/L)
• Subjects with known active infections (e.g., shingles, COVID-19, HIV, active tuberculosis, etc.), and active or recurrent gastrointestinal ulcers
• Pregnant or lactating women, and subjects with a during plan during the trial
• Allergic reaction: history of allergic reactions to human biological products
• Treatment with B cell-targeting agents such as Rituximab or Epratuzumab or Belimumab six months prior to randomization
• Treatment with tumor necrosis factor (TNF) inhibitors or TNF-receptor blockers six months prior to randomization
• Participating in clinical trial 28 days or 5 drug half-lives of the investigational agents prior to randomization
• Received live vaccine 28 days prior to randomization
• Treatment with unstable dosage of thrombopoietin receptor agonists such as Eltrombopag or Romiplostim 14 days prior to randomization
• Subjects with depression or suicidal thoughts
• Previous treatment with telitacicept
• B cell targeting drug therapy is not tolerated or responsive
• Investigator considers candidates not appropriating for the study