Safety and Efficacy of Eculizumab in High-risk TA-TMA

ClinicalTrials.gov ID

NCT07707687

Lead Sponsor

First Affiliated Hospital of Zhejiang UniversityOTHER

Overall Status

Recruiting

Study Type

Interventional

Phase

Phase 2

Enrollment

24Estimated

Last Update Posted

Jul 17, 2026Actual

Start Date

Jul 10, 2026Estimated

Primary Completion Date

Jul 10, 2028Estimated

Completion Date

Jul 10, 2028Estimated

Official Title

The Safety and Efficacy of Eculizumab for High-risk Transplant-associated Thrombotic Microangiopathy.

Brief 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.

Detailed Description

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.

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

• Transplant-Associated Thrombotic Microangiopathy (TA-TMA)

• Eculizumab

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria:

• Age ≥18 years.
• Patients who have undergone hematopoietic stem cell transplantation for any indication within 12 months prior to enrollment.
• Meet the diagnostic criteria for TA-TMA within ≤14 days prior to enrollment (at least 4 of the following 7 criteria present simultaneously):① Lactate dehydrogenase (LDH) above the age-adjusted upper limit of normal;② Presence of schistocytes on peripheral blood smear;③ New-onset thrombocytopenia or requirement for platelet transfusions;④ New-onset anemia or requirement for red blood cell transfusions;⑤ Hypertension;⑥ Random urine protein-to-creatinine ratio (rUPCR) ≥1 mg/mg;⑦ Elevated plasma soluble C5b-9 (sC5b-9) level (≥244 ng/mL).
• Meet the criteria for high-risk TA-TMA (presence of any of the following):① Proteinuria (rUPCR ≥2 mg/mg);②Multiple organ dysfunction syndrome (MODS);③ Elevated IL-10 (≥2× upper limit of normal [ULN]).
• Meet the following condition: TA-TMA has not resolved after ≥72 hours of management of triggering factors/conditions, including: ① Discontinuation or dose reduction of inciting medications (e.g., calcineurin inhibitors, CNI); ② Treatment of any underlying infection; ③ Treatment of underlying acute graft-versus-host disease (aGVHD).
• Provide written informed consent.

Exclusion Criteria:

• Known hypersensitivity to eculizumab.
• Uncontrolled severe infection (including meningococcal infection).
• Prior treatment with complement inhibitors.
• Known hereditary or acquired ADAMTS13 deficiency (activity <10%).
• Disseminated intravascular coagulation (DIC).
• Respiratory failure (any cause) requiring mechanical ventilation, occurring within 72 hours prior to enrollment.
• Acute and/or chronic heart failure with ejection fraction ≤40%.
• Expected survival <48 hours.
• Any subject who, in the investigator's opinion, is not suitable for participation in this study.

Primary Purpose

Treatment

Allocation

N/A

Interventional Model

Single Group Assignment

Masking

None (Open Label)

Lead Sponsor

First Affiliated Hospital of Zhejiang UniversityOTHER

Collaborators

Second Affiliated Hospital, Zhejiang University, School of MedicineOTHER

Sir Run Run Shaw HospitalOTHER

Xiangya Hospital of Central South UniversityOTHER

First Affiliated Hospital of Wenzhou Medical UniversityOTHER

First Affiliated Hospital of Ningbo UniversityNETWORK

The Affiliated People's Hospital of Ningbo UniversityOTHER_GOV

Jinhua Central HospitalOTHER

nilihongwy@163.com+8657187233801

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