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.
Single group
iptacopan
DrugIptacopan will be administered under the supervision of hospital staff during inpatient stays or self-managed by patients in an outpatient setting. The induction phase lasts 4 weeks at a dosage of 200 mg twice daily (BID). Starting from Day 29, patients will enter the maintenance phase at a dosage of 200 mg once daily (QD), continuing until treatment completion at Week 12.
Six-month Overall Survival Rate Following TA-TMA Diagnosis
The primary endpoint is defined as the proportion of patients who remain alive at 6 months after the initial diagnosis of transplantation-associated thrombotic microangiopathy (TA-TMA). Survival status will be systematically assessed through follow-up visits, medical record review, or direct patient contact at the 6-month timepoint.
TA-TMA Complete Response Rate by Week 12 (Jodele Criteria)
Proportion of patients achieving complete response of TA-TMA according to Jodele criteria within 12 weeks of treatment initiation.
TA-TMA Partial Response Rate by Week 12 (Jodele Criteria)
Proportion of patients achieving partial response of TA-TMA (defined as response between complete response and no response) within 12 weeks of treatment initiation.
Overall Survival (OS)
Time from TA-TMA diagnosis to death from any cause.
Non-Relapse Mortality (NRM)
Time from TA-TMA diagnosis to death not attributable to hematologic disease relapse or progression.
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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
