An interventional study of iptacopan in Thrombotic Microangiopathy and Hematopoietic Stem Cell Transplantation (HSCT), sponsored by First Affiliated Hospital of Zhejiang University. Recruiting at 1 site in China. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2026-08-26.
Sponsored by First Affiliated Hospital of Zhejiang University · Not applicable, Interventional, and Treatment
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:
During the study, participants will:
(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) 5. High-risk TMA features (per 2023 consensus), meeting ≥1 criterion:
8. Life expectancy >8 weeks. 9. 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.
Exclusion Criteria:
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.
Drug: iptacopan
Iptacopan will be administered under the supervision of hospital staff during inpatient stays or self-managed by patients in an outpatient setting. The induction phase lasts 4 weeks at a dosage of 200 mg twice daily (BID). Starting from Day 29, patients will enter the maintenance phase at a dosage of 200 mg once daily (QD), continuing until treatment completion at Week 12.
Six-month Overall Survival Rate Following TA-TMA 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.
Time frame: From the date of TA-TMA diagnosis until 6 months post-diagnosis.
TA-TMA Complete Response Rate by Week 12 (Jodele Criteria)
Proportion of patients achieving complete response of TA-TMA according to Jodele criteria within 12 weeks of treatment initiation.
Time frame: 12 weeks from start of treatment.
TA-TMA Partial Response Rate by Week 12 (Jodele Criteria)
Proportion of patients achieving partial response of TA-TMA (defined as response between complete response and no response) within 12 weeks of treatment initiation.
Time frame: 12 weeks from start of treatment.
Overall Survival (OS)
Time from TA-TMA diagnosis to death from any cause.
Time frame: Up to 24 months from diagnosis.
Non-Relapse Mortality (NRM)
Time from TA-TMA diagnosis to death not attributable to hematologic disease relapse or progression.
Time frame: Up to 24 months from diagnosis.
Cumulative Incidence of Relapse (CIR)
Time from TA-TMA diagnosis to hematologic disease relapse or progression.
Time frame: Up to 24 months from diagnosis.
Mean Hemoglobin Change from Baseline
Change in mean hemoglobin level (g/dL) from baseline to specified time points
Time frame: Baseline to 12 weeks.
Exploratory Biomarker Analysis
Exploratory analysis of complement pathway biomarkers including C5b-9 (ng/mL) and Factor B (ng/mL) levels .
Time frame: Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks after treatment .
Failure-Free Survival (FFS)
Time (in days) from treatment initiation to first occurrence of TA-TMA response among responders.
Time frame: Up to 12 weeks from treatment initiation.
Incidence of Acute and Chronic GVHD
Incidence of acute and chronic graft-versus-host disease.
Time frame: Up to 24 months from treatment initiation.
Multiple Organ Dysfunction Syndrome (MODS) Involvement and Resolution
Assessment of MODS organ involvement and resolution status during treatment.
Time frame: Baseline, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after treatment; thereafter, every three months until study completion
Safety and Tolerability Assessment
Frequency, duration, and severity of adverse events monitored through physical examinations and laboratory assessments, including infections and secondary primary malignancies. Adverse events will be graded according to CTCAE v4.03.
Time frame: From treatment initiation to 30 days after last dose.
Plan to share: Undecided
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First Affiliated Hospital of Zhejiang University