Safety and Efficacy of Iptacopan in Patients With High-Risk Transplantation-Associated Thrombotic Microangiopathy

January 9, 2026 updated by: Yanmin Zhao, First Affiliated Hospital of Zhejiang University

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)

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Fei Gao, Attending, MD
  • Phone Number: +86 19857035073
  • Email: gf0906@zju.edu.cn

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥12 years at the time of ICF signature.
  2. Previous recipient of autologous or allogeneic HSCT.
  3. 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.
  4. 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) 5. High-risk TMA features (per 2023 consensus), meeting ≥1 criterion:

  1. LDH ≥2× ULN
  2. Elevated sC5b-9
  3. Proteinuria (rUPCR ≥1 mg/mg)
  4. Multi-organ dysfunction syndrome (MODS)
  5. Concurrent Grade II-IV acute GVHD
  6. Active systemic infection 6. Able to receive oral medication. 7. Failure of first-line therapy (e.g., CNI/mTOR inhibitor adjustment, plasma exchange, rituximab, defibrotide), excluding prior complement inhibitors.

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:

  1. Known familial or acquired ADAMTS13 deficiency (activity <5%).
  2. Known Shiga toxin-associated HUS (positive Shiga toxin assay or culture).
  3. Positive direct Coombs test with clinically significant immune-mediated hemolysis per investigator.
  4. Clinically overt disseminated intravascular coagulation (DIC) according to ISTH criteria.
  5. Bone marrow/graft failure.
  6. Known HIV infection (confirmed by testing within 6 months prior to screening).
  7. Active meningococcal disease.
  8. Septic shock requiring vasopressor support within 7 days prior to enrollment.
  9. Pregnant or breastfeeding.
  10. 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).
  11. All-cause respiratory failure requiring mechanical ventilation within 72 hours prior to enrollment.
  12. Acute/chronic heart failure with left ventricular ejection fraction ≤40%.
  13. Prior treatment with iptacopan, eculizumab, or other complement inhibitors within 60 days before first study dose.
  14. Use of any investigational agent within 30 days or 5 half-lives (whichever is longer) prior to screening.
  15. Recurrent primary malignancy or post-transplant lymphoproliferative disorder (PTLD).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Iptacopan group
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Six-month Overall Survival Rate Following TA-TMA Diagnosis
Time Frame: 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.
From the date of TA-TMA diagnosis until 6 months post-diagnosis.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
TA-TMA Complete Response Rate by Week 12 (Jodele Criteria)
Time Frame: 12 weeks from start of treatment.
Proportion of patients achieving complete response of TA-TMA according to Jodele criteria within 12 weeks of treatment initiation.
12 weeks from start of treatment.
TA-TMA Partial Response Rate by Week 12 (Jodele Criteria)
Time Frame: 12 weeks from start of treatment.
Proportion of patients achieving partial response of TA-TMA (defined as response between complete response and no response) within 12 weeks of treatment initiation.
12 weeks from start of treatment.
Overall Survival (OS)
Time Frame: Up to 24 months from diagnosis.
Time from TA-TMA diagnosis to death from any cause.
Up to 24 months from diagnosis.
Non-Relapse Mortality (NRM)
Time Frame: Up to 24 months from diagnosis.
Time from TA-TMA diagnosis to death not attributable to hematologic disease relapse or progression.
Up to 24 months from diagnosis.
Cumulative Incidence of Relapse (CIR)
Time Frame: Up to 24 months from diagnosis.
Time from TA-TMA diagnosis to hematologic disease relapse or progression.
Up to 24 months from diagnosis.
Mean Hemoglobin Change from Baseline
Time Frame: Baseline to 12 weeks.
Change in mean hemoglobin level (g/dL) from baseline to specified time points
Baseline to 12 weeks.
Exploratory Biomarker Analysis
Time Frame: Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks after treatment .
Exploratory analysis of complement pathway biomarkers including C5b-9 (ng/mL) and Factor B (ng/mL) levels .
Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks after treatment .
Failure-Free Survival (FFS)
Time Frame: Up to 12 weeks from treatment initiation.
Time (in days) from treatment initiation to first occurrence of TA-TMA response among responders.
Up to 12 weeks from treatment initiation.
Incidence of Acute and Chronic GVHD
Time Frame: Up to 24 months from treatment initiation.
Incidence of acute and chronic graft-versus-host disease.
Up to 24 months from treatment initiation.
Multiple Organ Dysfunction Syndrome (MODS) Involvement and Resolution
Time Frame: Baseline, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after treatment; thereafter, every three months until study completion
Assessment of MODS organ involvement and resolution status during treatment.
Baseline, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after treatment; thereafter, every three months until study completion
Safety and Tolerability Assessment
Time Frame: From treatment initiation to 30 days after last dose.
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.
From treatment initiation to 30 days after last dose.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital of Zhejiang University

Collaborators

Peking University People's Hospital
Tongji Hospital
Ruijin Hospital
The First Affiliated Hospital of Zhengzhou University
Fujian Medical University Union Hospital
Hebei Yanda Ludaopei Hospital
The Children's Hospital of Zhejiang University School of Medicine
Nanfang Hospital, Southern Medical University
First Affiliated Hospital of Ningbo University
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2026

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2029

Study Registration Dates

First Submitted

December 27, 2025

First Submitted That Met QC Criteria

January 9, 2026

First Posted (Estimated)

January 16, 2026

Study Record Updates

Last Update Posted (Estimated)

January 16, 2026

Last Update Submitted That Met QC Criteria

January 9, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IPTA-TMA-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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