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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Transplant-Associated Thrombotic Microangiopathy (TA-TMA)
• Intervention / Treatment: Drug: Eculizumab

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

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: YIBO WU; Phone Number: +8657187233801; Email: wuyibo7@126.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China
      • Xiangya Hospital of Central South University
      • Contact: Yajing Xu; Phone Number: +8657187233801; Email: xyyajingxu@csu.edu.cn
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The Second Affiliated hospital of Zhejiang University school of medicine
      • Contact: Yang XU; Phone Number: +8657187233801; Email: yxu@zju.edu.cn
    • Hangzhou, Zhejiang, China
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
      • Contact: Haowen Xiao; Phone Number: +8657187233801; Email: haowenxiaoxiao@zju.edu.cn
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital, Zhejiang University School of Medicine.
      • Contact: YIBO WU; Phone Number: +8657187233801; Email: wuyibo7@126.com
      • Contact: Email: wuyibo7@126.com
    • Jinhua, Zhejiang, China
      • Jinhua Central Hospital
      • Contact: Lihong Ni; Phone Number: +8657187233801; Email: nilihongwy@163.com
    • Ningbo, Zhejiang, China
      • The Affiliated People's Hospital of Ningbo University
      • Contact: Ying Lu; Phone Number: +8657187233801; Email: rmluying@nbu.edu.cn
    • Ningbo, Zhejiang, China
      • The First Affiliated Hospital of Ningbo University
      • Contact: Lieguang Chen; Phone Number: +8657187233801; Email: fyychenlieguang@nbu.edu.cn
    • Wenzhou, Zhejiang, China
      • The First Affiliated Hospital of Wenzhou Medical University
      • Contact: Yi Chen; Phone Number: +8657187233801; Email: chenyi19527@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Eculizumab group; Eculizumab treatment for High-Risk TA-TMA

Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-month overall survival rate after diagnosis of TA-TMA	This endpoint is defined as the proportion of patients who survive for 6 months (180 days) from the date of TA-TMA diagnosis among all enrolled patients with confirmed TA-TMA in the study population.	6 months after diagnosis of TA-TMA

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete TMA response (cTMA-R)	Within the 26-week treatment period, the subject must meet all of the following criteria: 1) platelet count improvement of ≥50% from baseline; 2) urine protein-to-creatinine ratio (UPCR) reduction of ≥50% from baseline; 3) lactate dehydrogenase (LDH) returning to the normal range and no schistocytes on peripheral blood smear. All three criteria must be met in at least two consecutive assessments separated by ≥4 weeks, and must be maintained in all subsequent assessments from the first consecutive achievement through the end of Week 26. This is defined as a sustained cTMA-R.	26-week treatment period
Cumulative incidence and recovery rate of MODS at 6 months after diagnosis of TA-TMA	Over the 6-month (180-day) observation period following the diagnosis of TA-TMA, the proportion of patients with newly developed or worsened multiple organ dysfunction syndrome (MODS). This is calculated as a cumulative incidence under a competing risks model, considering death as a competing event (since patients who die cannot experience a new MODS event).	6 months after diagnosis of TA-TMA
1-year overall survival rate after HSCT	The proportion of patients who are alive at 1 year (365 days) from the date of hematopoietic stem cell infusion, among all transplanted patients in the intention-to-treat population.	1 year (365 days) from the date of hematopoietic stem cell infusion
1-year non-relapse mortality (NRM) after HSCT	The cumulative incidence of any death not attributable to disease relapse or progression within the 1-year (365-day) observation period after transplantation.	1-year (365-day) after transplantation.
Organ-specific functional recovery (kidney, lung, cardiovascular, etc.)	Following hematopoietic stem cell transplantation or a specific disease (e.g., TA-TMA), the recovery of one or more specific organ functions from a dysfunctional state during treatment or at the nadir of illness to a predefined, clinically meaningful normal or near-normal functional level, with the improvement sustained for a specified period to confirm stability.	6 months after diagnosis of TA-TMA
Safety assessments (infection, infusion-related reactions, etc.	Infection: Clinically significant disease caused by pathogenic microorganisms (e.g., bacteria, viruses, fungi, parasites) requiring medical intervention. Infusion-related reaction: Any adverse event occurring during the study drug infusion or within a specified time window (e.g., within 1 hour or 24 hours) after the infusion ends.	6 months after diagnosis of TA-TMA
Maximum Plasma Concentration [Cmax] of eculizumab	Quantitative characterization of the maximum plasma concentration [Cmax] of eculizumab. This describes the processes of absorption, distribution, metabolism, and excretion of eculizumab in the human body-i.e., the action of the body on the drug.	6 months after diagnosis of TA-TMA
Safety assessments (CD3+ T cells, CD19+ B cells, CD56+ NK cells)	Quantitative description of the effects of eculizumab treatment on the absolute counts and relative percentages of peripheral blood CD3+ T cells, CD19+ B cells, and CD56+ NK cells in patients.	6 months after diagnosis of TA-TMA
Minimum Plasma Concentration [Cmin] of eculizumab	Quantitative characterization of the minimum plasma concentration [Cmin] of eculizumab. This describes the processes of absorption, distribution, metabolism, and excretion of eculizumab in the human body-i.e., the action of the body on the drug.	6 months after diagnosis of TA-TMA

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Collaborators: Xiangya Hospital of Central South University; Second Affiliated Hospital, School of Medicine, Zhejiang University; Sir Run Run Shaw Hospital; First Affiliated Hospital of Wenzhou Medical University; Jinhua Central Hospital; The Affiliated People's Hospital of Ningbo University; First Affiliated Hospital of Ningbo University
• Investigators: Principal Investigator: YI LUO, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): July 10, 2026
• Primary Completion (Estimated): July 10, 2028
• Study Completion (Estimated): July 10, 2028

Study Registration Dates

• First Submitted: July 5, 2026
• First Submitted That Met QC Criteria: July 12, 2026
• First Posted (Actual): July 16, 2026

Study Record Updates

• Last Update Posted (Actual): July 16, 2026
• Last Update Submitted That Met QC Criteria: July 12, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Eculizumab; allogeneic hematopoietic stem cell transplantation; transplant-associated thrombotic microangiopathy (TA-TMA)
• Additional Relevant MeSH Terms: eculizumab
• Other Study ID Numbers: ZJU-TA-TMA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The IPD will be made available after the publication of the primary results, upon reasonable request, and subject to approval by the study steering committee and the relevant ethics committees. Data will be de-identified (anonymized) and will be shared under a formal data-use agreement that ensures confidentiality and restricts use to approved secondary analyses. The detailed sharing plan, including the timeline and criteria for access, will be described in the study protocol and will comply with applicable data protection regulations.
• IPD Sharing Time Frame: After the publication of the primary results
• IPD Sharing Access Criteria: The IPD will be made available after the publication of the primary results, upon reasonable request, and subject to approval by the study steering committee and the relevant ethics committees. Data will be de-identified (anonymized) and will be shared under a formal data-use agreement that ensures confidentiality and restricts use to approved secondary analyses. The detailed sharing plan, including the timeline and criteria for access, will be described in the study protocol and will comply with applicable data protection regulations.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No