NCT07347990招募中不适用
A Prospective, Multicenter, Single-Arm Study: Safety and Efficacy of Iptacopan in the Treatment of High-Risk Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy (TA-TMA)
First Affiliated Hospital of Zhejiang University1 个研究点 分布在 1 个国家目标入组 30 人开始时间: 2026年8月25日最近更新:
适应症
干预措施
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Six-month Overall Survival Rate Following TA-TMA Diagnosis
研究概览
简要总结
The goal of this clinical trial is to evaluate the efficacy and safety of Iptacopan as a second-line treatment for high-risk hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA). Iptacopan is a selective oral small-molecule complement factor B inhibitor. It acts by inhibiting factor B, blocking the formation of C3 convertase, reducing C3b deposition, thereby suppressing C5 convertase (C3bBbC3b) and ultimately decreasing the formation of the membrane attack complex (MAC), which is expected to mitigate endothelial damage in TA-TMA pathology. The main questions this study aims to answer are:
- Does Iptacopan improve 6-month overall survival in high-risk TA-TMA patients?
- What adverse events do participants experience while taking Iptacopan?
- Does Iptacopan provide hematological response and organ function recovery in TA-TMA patients? In this prospective, multicenter, open-label, single-arm Phase II study, all participants will receive Iptacopan treatment. The primary endpoint of this study is the 6-month overall survival rate from TA-TMA diagnosis. Secondary endpoints include safety evaluation, hematological response, and organ function recovery.
During the study, participants will:
- Receive Iptacopan treatment according to protocol
- Undergo regular assessments for safety and efficacy monitoring
- Be followed for up to 24 months post-treatment initiation
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥12 years at the time of ICF signature.
- •Previous recipient of autologous or allogeneic HSCT.
- •Persistent TA-TMA despite initial management of potential triggers (e.g., CNI/mTOR inhibitor reduction, infection or GVHD treatment), with TMA activity sustained for ≥72 hours post-intervention.
- •TA-TMA diagnosis, confirmed ≤14 days prior to or during screening by either biopsy-proven microthrombi or ≥4 of the following:
- •(1) LDH > ULN (2) Proteinuria (rUPCR ≥1 mg/mg) (3) Hypertension (age-adjusted) (4) New-onset thrombocytopenia (platelet decrease ≥50%, count ≤50,000/mm³, or transfusion-refractory) (5) New-onset anemia or increased transfusion need (6) Microangiopathy on blood smear (schistocytes ≥1%) or biopsy (7) Elevated terminal complement complex (C5b-9)
- •High-risk TMA features (per 2023 consensus), meeting ≥1 criterion:
- •LDH ≥2× ULN
- •Elevated sC5b-9
- •Proteinuria (rUPCR ≥1 mg/mg)
- •Multi-organ dysfunction syndrome (MODS)
- •Concurrent Grade II-IV acute GVHD
- •Active systemic infection
- •Able to receive oral medication.
- •Failure of first-line therapy (e.g., CNI/mTOR inhibitor adjustment, plasma exchange, rituximab, defibrotide), excluding prior complement inhibitors.
- •8. Life expectancy >8 weeks.
- •Required vaccination against encapsulated bacteria (meningococcal, pneumococcal) per local guidelines, administered ≥2 weeks prior to first dose. If vaccination is delayed, antimicrobial prophylaxis is required.
- •10. For subjects unable to receive meningococcal vaccines, antibiotic prophylaxis must be continued throughout treatment and for 8 months post-last dose.
- •11. For subjects of reproductive potential: agreement to use effective contraception and, for females, a negative pregnancy test at screening.
- •12. Provision of signed informed consent and compliance with study procedures.
排除标准
- •Known familial or acquired ADAMTS13 deficiency (activity <5%).
- •Known Shiga toxin-associated HUS (positive Shiga toxin assay or culture).
- •Positive direct Coombs test with clinically significant immune-mediated hemolysis per investigator.
- •Clinically overt disseminated intravascular coagulation (DIC) according to ISTH criteria.
- •Bone marrow/graft failure.
- •Known HIV infection (confirmed by testing within 6 months prior to screening).
- •Active meningococcal disease.
- •Septic shock requiring vasopressor support within 7 days prior to enrollment.
- •Pregnant or breastfeeding.
- •Any concurrent or prior medical condition unrelated to TA-TMA that, in the opinion of the investigator or sponsor, could increase risk or confound study outcomes (e.g., significant cardiac, pulmonary, renal, endocrine, or hepatic disease).
- •All-cause respiratory failure requiring mechanical ventilation within 72 hours prior to enrollment.
- •Acute/chronic heart failure with left ventricular ejection fraction ≤40%.
- •Prior treatment with iptacopan, eculizumab, or other complement inhibitors within 60 days before first study dose.
- •Use of any investigational agent within 30 days or 5 half-lives (whichever is longer) prior to screening.
- •Recurrent primary malignancy or post-transplant lymphoproliferative disorder (PTLD).
研究组 & 干预措施
Iptacopan group
Experimental
This experimental arm includes patients diagnosed with transplantation-associated thrombotic microangiopathy (TA-TMA) who have failed first-line therapy; all participants will receive Iptacopan as second-line treatment.
干预措施: iptacopan (Drug)
结局指标
主要结局
Six-month Overall Survival Rate Following TA-TMA Diagnosis
时间窗: From the date of TA-TMA diagnosis until 6 months post-diagnosis.
The primary endpoint is defined as the proportion of patients who remain alive at 6 months after the initial diagnosis of transplantation-associated thrombotic microangiopathy (TA-TMA). Survival status will be systematically assessed through follow-up visits, medical record review, or direct patient contact at the 6-month timepoint.
次要结局
- TA-TMA Complete Response Rate by Week 12 (Jodele Criteria)(12 weeks from start of treatment.)
- TA-TMA Partial Response Rate by Week 12 (Jodele Criteria)(12 weeks from start of treatment.)
- Overall Survival (OS)(Up to 24 months from diagnosis.)
- Non-Relapse Mortality (NRM)(Up to 24 months from diagnosis.)
- Cumulative Incidence of Relapse (CIR)(Up to 24 months from diagnosis.)
- Mean Hemoglobin Change from Baseline(Baseline to 12 weeks.)
- Exploratory Biomarker Analysis(Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks after treatment .)
- Failure-Free Survival (FFS)(Up to 12 weeks from treatment initiation.)
- Incidence of Acute and Chronic GVHD(Up to 24 months from treatment initiation.)
- Multiple Organ Dysfunction Syndrome (MODS) Involvement and Resolution(Baseline, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after treatment; thereafter, every three months until study completion)
- Safety and Tolerability Assessment(From treatment initiation to 30 days after last dose.)
研究者
Yanmin Zhao
Vice Director, Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University
First Affiliated Hospital of Zhejiang University
研究点 (1)
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