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Safety and Efficacy of Eculizumab in High-risk TA-TMA
Sponsor: First Affiliated Hospital of Zhejiang University
Summary
High-risk, complement-mediated, untreated transplant-associated thrombotic microangiopathy (hrTA-TMA) carries a very poor prognosis due to multiple organ dysfunction syndrome (MODS). The complement C5 inhibitor eculizumab has shown promising efficacy in children with hrTA-TMA, but has not been prospectively studied in adult allogeneic hematopoietic stem cell transplantation (HSCT) recipients. The investigators plan to conduct the first multicenter prospective study in adults to evaluate eculizumab as an early targeted intervention for hrTA-TMA. The investigators hypothesize that eculizumab will more than double the survival rate of hrTA-TMA in adult HSCT recipients compared with untreated hrTA-TMA patients from our previous study, who will serve as historical controls. Inclusion criteria are a confirmed diagnosis of TA-TMA with at least one of the following hrTA-TMA features: random urine protein-to-creatinine ratio (rUPCR) ≥2 mg/mg, multiple organ dysfunction syndrome (MODS), or elevated plasma IL-10 (≥2× upper limit of normal). The primary endpoint is survival at 6 months after diagnosis of hrTA-TMA. Secondary endpoints are the cumulative incidence of MODS at 6 months after diagnosis of hrTA-TMA, and 1-year post-transplant survival. The eculizumab regimen consists of an intensive loading dose, an induction dose, and a maintenance dose, with a total treatment duration of up to 24 weeks. This study aims to investigate the safety and efficacy of eculizumab in the treatment of high-risk TA-TMA.
Official title: The Safety and Efficacy of Eculizumab for High-risk Transplant-associated Thrombotic Microangiopathy.
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
INTERVENTIONAL
Enrollment
24
Start Date
2026-07-10
Completion Date
2028-07-10
Last Updated
2026-07-16
Healthy Volunteers
No
Interventions
Eculizumab
Dosing Regimen Weight-based induction therapy: Eculizumab 10-\<40 kg: 600 mg * 40 kg: 900 mg Dosing frequency: Loading phase (first 5 doses) First 5 doses: 1 dose every 48 hours × 2 doses, then 1 dose every 72 hours × 3 doses Induction phase (subsequent 4 doses) Subsequent 4 doses: once weekly for 4 weeks Maintenance phase Once every 2 weeks, continued up to 24 weeks Dose adjustment principles: Based on eculizumab trough concentration (target ≥100 μg/mL), CH50 level (\<10% of the lower limit of normal), and sC5b-9 target: \<244 ng/mL Monitoring frequency: Loading phase: daily monitoring Induction and maintenance phases: monitoring prior to each dose
Locations (8)
Xiangya Hospital of Central South University
Changsha, Hunan, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
The First Affiliated Hospital, Zhejiang University School of Medicine.
Hangzhou, Zhejiang, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
Jinhua Central Hospital
Jinhua, Zhejiang, China
The Affiliated People's Hospital of Ningbo University
Ningbo, Zhejiang, China
The First Affiliated Hospital of Ningbo University
Ningbo, Zhejiang, China
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, China