The goal of this clinical trial is to evaluate the efficacy and safety of Iptacopan as a second-line treatment for high-risk hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA). Iptacopan is a selective oral small-molecule complement factor B inhibitor. It acts by inhibiting factor B, blocking the formation of C3 convertase, reducing C3b deposition, thereby suppressing C5 convertase (C3bBbC3b) and ultimately decreasing the formation of the membrane attack complex (MAC), which is expected to mitigate endothelial damage in TA-TMA pathology. The main questions this study aims to answer are:
* Does Iptacopan improve 6-month overall survival in high-risk TA-TMA patients? * What adverse events do participants experience while taking Iptacopan? * Does Iptacopan provide hematological response and organ function recovery in TA-TMA patients? In this prospective, multicenter, open-label, single-arm Phase II study, all participants will receive Iptacopan treatment. The primary endpoint of this study is the 6-month overall survival rate from TA-TMA diagnosis. Secondary endpoints include safety evaluation, hematological response, and organ function recovery.
During the study, participants will:
* Receive Iptacopan treatment according to protocol * Undergo regular assessments for safety and efficacy monitoring * Be followed for up to 24 months post-treatment initiation
Age ≥12 years at the time of ICF signature.
Previous recipient of autologous or allogeneic HSCT.
Persistent TA-TMA despite initial management of potential triggers (e.g., CNI/mTOR inhibitor reduction, infection or GVHD treatment), with TMA activity sustained for ≥72 hours post-intervention.
LDH ≥2× ULN
Known familial or acquired ADAMTS13 deficiency (activity <5%).
Known Shiga toxin-associated HUS (positive Shiga toxin assay or culture).
Positive direct Coombs test with clinically significant immune-mediated hemolysis per investigator.
Clinically overt disseminated intravascular coagulation (DIC) according to ISTH criteria.
First Affiliated Hospital of Zhejiang University
Lead sponsor
Ruijin Hospital
Collaborator
The First Affiliated Hospital of Zhengzhou University
Collaborator
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Collaborator
Tongji Hospital
Collaborator
The Children's Hospital of Zhejiang University School of Medicine
Collaborator
First Affiliated Hospital of Ningbo University
Collaborator
Nanfang Hospital, Southern Medical University
Collaborator
Peking University People's Hospital
Collaborator
Fujian Medical University Union Hospital
Collaborator
Hebei Yanda Ludaopei Hospital
Collaborator