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

NCT07707687 | Recruiting Phase 2 DMC

• 1 other identifier: ZJU-TA-TMA
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 8

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.

Conditions

Transplant-Associated Thrombotic Microangiopathy (TA-TMA)

Keywords

transplant-associated thrombotic microangiopathy (TA-TMA); allogeneic hematopoietic stem cell transplantation; Eculizumab

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Complete TMA response (cTMA-R)

  26-week treatment period

• Cumulative incidence and recovery rate of MODS at 6 months after diagnosis of TA-TMA

  6 months after diagnosis of TA-TMA

• 1-year overall survival rate after HSCT

  1 year (365 days) from the date of hematopoietic stem cell infusion

• 1-year non-relapse mortality (NRM) after HSCT

  1-year (365-day) after transplantation.

• Organ-specific functional recovery (kidney, lung, cardiovascular, etc.)

  6 months after diagnosis of TA-TMA

Study Arms (1)

Eculizumab group

EXPERIMENTAL

Eculizumab treatment for High-Risk TA-TMA

Drug: Eculizumab

Interventions

Eculizumab DRUG

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

Eculizumab group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead
• Second Affiliated Hospital, School of Medicine, Zhejiang University: collaborator
• Sir Run Run Shaw Hospital: collaborator
• Xiangya Hospital of Central South University: collaborator
• First Affiliated Hospital of Wenzhou Medical University: collaborator
• First Affiliated Hospital of Ningbo University: collaborator
• The Affiliated People's Hospital of Ningbo University: collaborator
• Jinhua Central Hospital: collaborator

Study Sites (8)

Xiangya Hospital of Central South University

Changsha, Hunan, China

RECRUITING

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

The First Affiliated Hospital, Zhejiang University School of Medicine.

Hangzhou, Zhejiang, China

RECRUITING

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

Jinhua Central Hospital

Jinhua, Zhejiang, China

RECRUITING

The Affiliated People's Hospital of Ningbo University

Ningbo, Zhejiang, China

RECRUITING

The First Affiliated Hospital of Ningbo University

Ningbo, Zhejiang, China

RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

RECRUITING

MeSH Terms

Interventions

eculizumab

Study Officials

• YI LUO

  Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

YIBO WU

CONTACT

+8657187233801; wuyibo7@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 5, 2026
• First Posted: July 16, 2026
• Study Start: July 10, 2026
• Primary Completion (Estimated): July 10, 2028
• Study Completion (Estimated): July 10, 2028
• Last Updated: July 17, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After the publication of the primary results
• 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.

Locations

CN (8)