Transplant-Associated Thrombotic Microangiopathy (TA-TMA)Phase 2NCT07707687
Safety and Efficacy of Eculizumab in High-risk TA-TMA
A Phase 2 study testing Eculizumab in people with Transplant-Associated Thrombotic Microangiopathy (TA-TMA), run by First Affiliated Hospital of Zhejiang University at 8 sites in China.
Trial summary
High-risk, complement-mediated, untreated transplant-associated thrombotic microangiopathy (hrTA-TMA) carries a very poor prognosis due to multiple organ dysfunction syndrome (MODS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transplant-Associated Thrombotic Microangiopathy (TA-TMA)
- What is being tested?
- Eculizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 8 sitesChina
- Study dates
- 10 Jul 2026to 10 Jul 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
China8 sites, 8 recruiting
- Recruiting
Xiangya Hospital of Central South University
Changsha, Hunan
Yajing Xu, +8657187233801, xyyajingxu@csu.edu.cn
- Recruiting
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang
Haowen Xiao, +8657187233801, haowenxiaoxiao@zju.edu.cn
- Recruiting
The First Affiliated Hospital, Zhejiang University School of Medicine.
Hangzhou, Zhejiang
YIBO WU, +8657187233801, wuyibo7@126.com
wuyibo7@126.com
- Recruiting
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang
Yang Xu, +8657187233801, yxu@zju.edu.cn
- Recruiting
Jinhua Central Hospital
Jinhua, Zhejiang
Lihong Ni, +8657187233801, nilihongwy@163.com
- Recruiting
The Affiliated People's Hospital of Ningbo University
Ningbo, Zhejiang
Ying Lu, +8657187233801, rmluying@nbu.edu.cn
- Recruiting
The First Affiliated Hospital of Ningbo University
Ningbo, Zhejiang
Lieguang Chen, +8657187233801, fyychenlieguang@nbu.edu.cn
- Recruiting
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang
Yi Chen, +8657187233801, chenyi19527@163.com
About this study
Official title: 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.
Read the 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
- Being tested
- Eculizumab
- Keywords
- transplant-associated thrombotic microangiopathy (TA-TMA), allogeneic hematopoietic stem cell transplantation, Eculizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabDrug
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 group | Role | What they receive |
|---|---|---|
| Eculizumab group | Experimental | Eculizumab treatment for High-Risk TA-TMA Receives: Drug: Eculizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months after diagnosis of TA-TMA
Secondary outcomes (9)
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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 6 months after diagnosis of TA-TMA
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2026
- Study start10 Jul 2026 (estimated)
- Primary completion10 Jul 2028 (estimated)
- Study completion10 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transplant-Associated Thrombotic Microangiopathy (TA-TMA)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Zhejiang University
- Sponsor type
- University, hospital or other
- Collaborators
- Second Affiliated Hospital, Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Xiangya Hospital of Central South University, First Affiliated Hospital of Wenzhou Medical University, First Affiliated Hospital of Ningbo University, The Affiliated People's Hospital of Ningbo University, Jinhua Central Hospital
- Responsible party
- Principal investigator, Yi Luo, First Affiliated Hospital of Zhejiang University
- Investigators
- YI LUO, Principal investigator, First Affiliated Hospital of Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07707687
- Sponsor's protocol ID
- ZJU-TA-TMA
- Status last verified
- Jul 2026
- First submitted
- 5 Jul 2026
- Last updated
- 17 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.