Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia

Launched by BEIJING HOSPITAL · Aug 11, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called Telitacicept for patients with connective tissue disease-associated thrombocytopenia, which is a condition that causes low platelet counts and can lead to bleeding problems. The trial aims to find out if Telitacicept is safe and effective for people who have not responded well to standard treatments like steroids and other immune-suppressing medications. It is currently looking for participants aged 18 and older who have been diagnosed with certain types of connective tissue diseases, such as lupus or Sjögren syndrome, and are experiencing ongoing low platelet counts despite receiving treatment.

Participants in the trial will receive either the experimental drug Telitacicept or a placebo (a treatment without active medication) and will be monitored closely to assess how well the treatment works and if there are any side effects. It's important to note that individuals with certain serious health issues, like severe bleeding disorders or active infections, may not be eligible for the study. If you or someone you know is interested in participating, they should discuss it with their healthcare provider to see if they meet the criteria and to understand what being part of the trial would involve.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Subjects who have been diagnosed with connective tissue disease (CTD)-associated thrombocytopenia. And CTD includes primary Sjögren syndrome (according to the 2002 American College of Rheumatology (ACR)/ European League against Rheumatism (EULAR) classification criteria), systemic lupus erythematosus (SLE, according to the 1997 or the 2009 ACR classification criteria), and undifferentiated connective tissue disease (according to the 1999 international classification criteria)
• * Refractory thrombocytopenia defined as:
• • Either: Failure to maintain sustained remission after treatment by glucocorticoid and at least one immunosuppressant (i.e. cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, methotrexate, leflunomide and hydroxychloroquine, et al.) Or: Relapse during oral glucocorticoid tapering or after withdrawal
• • 50×10\^9/L\>PLT
• • anti-nuclear antibody (ANA) positive (≥1:80, any karyotype) detected in the laboratory of each research center
• • Standard therapy should be maintained stable for at least 14 days prior to the first dose of the experimental drug or placebo. Standard therapy refers to the following treatment (monotherapy or in combination): glucocorticoid, hydroxychloroquine, and other immunosuppressants (i.e. cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, methotrexate and leflunomide, et al.)
• • Signed informed consent form, willing or able to participate in all required study evaluations and procedures
• Exclusion Criteria:
• • 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