AzTrials
AzTrials

Thrombotic MicroangiopathyNCT07347990

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

A study testing iptacopan in people with Thrombotic Microangiopathy and Hematopoietic Stem Cell Transplantation (HSCT), run by First Affiliated Hospital of Zhejiang University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
iptacopan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteChina
Study dates
25 Aug 2026to 31 Dec 2029
Phase
Interventional
Are there results?
Not yet: the study is under way

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 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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:
  • 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:
  • LDH ≥2× ULN
Show all 15Show fewer
  • Elevated sC5b-9
  • Proteinuria (rUPCR ≥1 mg/mg)
  • Multi-organ dysfunction syndrome (MODS)
  • Concurrent Grade II-IV acute GVHD
  • 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.

Who cannot join

  • 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).
Show all 15Show fewer
  • 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).

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Fei Gao, Attending, MD contact

+86 19857035073

gf0906@zju.edu.cn

China1 site, 1 recruiting

  • The First Affiliated Hospital of Zhejiang University School of Medicine

    Hangzhou, China, 310003

    The First Affiliated Hospital of Zhejiang University, gf0906@zju.edu.cn

    yanminzhao@zju.edu.cn

    Recruiting

Other trials in China

About this study

Official title: 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.
Read more

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
Being tested
iptacopan
Keywords
hematopoietic stem cell transplantation, transplantation-associated thrombotic microangiopathy, Iptacopan
Medical subject headings
Thrombotic Microangiopathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • iptacopanDrug

    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.

Study groups in NCT07347990
Study groupRoleWhat they receive
Iptacopan groupExperimentalThis 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.
Receives: Drug: iptacopan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From the date of TA-TMA diagnosis until 6 months post-diagnosis.

Secondary outcomes (11)

  1. 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.

    Measured: 12 weeks from start of treatment.

  2. 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.

    Measured: 12 weeks from start of treatment.

  3. Overall Survival (OS)

    Time from TA-TMA diagnosis to death from any cause.

    Measured: Up to 24 months from diagnosis.

  4. Non-Relapse Mortality (NRM)

    Time from TA-TMA diagnosis to death not attributable to hematologic disease relapse or progression.

    Measured: Up to 24 months from diagnosis.

  5. Cumulative Incidence of Relapse (CIR)

    Time from TA-TMA diagnosis to hematologic disease relapse or progression.

    Measured: Up to 24 months from diagnosis.

  6. Mean Hemoglobin Change from Baseline

    Change in mean hemoglobin level (g/dL) from baseline to specified time points

    Measured: Baseline to 12 weeks.

  7. Exploratory Biomarker Analysis

    Exploratory analysis of complement pathway biomarkers including C5b-9 (ng/mL) and Factor B (ng/mL) levels .

    Measured: Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks after treatment .

  8. Failure-Free Survival (FFS)

    Time (in days) from treatment initiation to first occurrence of TA-TMA response among responders.

    Measured: Up to 12 weeks from treatment initiation.

  9. Incidence of Acute and Chronic GVHD

    Incidence of acute and chronic graft-versus-host disease.

    Measured: Up to 24 months from treatment initiation.

  10. Multiple Organ Dysfunction Syndrome (MODS) Involvement and Resolution

    Assessment of MODS organ involvement and resolution status during treatment.

    Measured: Baseline, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after treatment; thereafter, every three months until study completion

  11. 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.

    Measured: From treatment initiation to 30 days after last dose.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jan 2026
  2. Study start25 Aug 2026
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2029 (estimated)

Resources

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 N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07347990
Sponsor's protocol ID
IPTA-TMA-001
Status last verified
Jan 2026
First submitted
27 Dec 2025
Last updated
26 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Risitano AM, Kulasekararaj AG, Scheinberg P, Roth A, Han B, Maciejewski JP, Ueda Y, de Castro CM, Di Bona E, Fu R, Zhang L, Griffin M, Langemeijer SMC, Panse J, Schrezenmeier H, Barcellini W, Mauad VAQ, Schafhausen P, Tavitian S, Beggiato E, Chew LP, Gaya A, Huang WH, Jang JH, Kitawaki T, Kutlar A, Notaro R, Pullarkat V, Schubert J, Terriou L, Uchiyama M, Lee LWL, Yap ES, Frieri C, Marano L, de Fontbrune FS, Gandhi S, Trikha R, Alashkar F, Yang C, Liu H, Kelly RJ, Hochsmann B, Lawniczek T, Mahajan N, Solar-Yohay S, Kerloeguen C, Ferber P, Kumar R, Wang Z, Thorburn C, Maitra S, Li S, Verles A, Dahlke M, de Latour RP. Oral iptacopan monotherapy in paroxysmal nocturnal haemoglobinuria: final 48-week results from the open-label, randomised, phase 3 APPLY-PNH trial in anti-C5-treated patients and the open-label, single-arm, phase 3 APPOINT-PNH trial in patients previously untreated with complement inhibitors. Lancet Haematol. 2025 Jun;12(6):e414-e430. doi: 10.1016/S2352-3026(25)00081-X.

    PubMed 40447351

  • Peffault de Latour R, Roth A, Kulasekararaj AG, Han B, Scheinberg P, Maciejewski JP, Ueda Y, de Castro CM, Di Bona E, Fu R, Zhang L, Griffin M, Langemeijer SMC, Panse J, Schrezenmeier H, Barcellini W, Mauad VAQ, Schafhausen P, Tavitian S, Beggiato E, Chew LP, Gaya A, Huang WH, Jang JH, Kitawaki T, Kutlar A, Notaro R, Pullarkat V, Schubert J, Terriou L, Uchiyama M, Wong Lee Lee L, Yap ES, Sicre de Fontbrune F, Marano L, Alashkar F, Gandhi S, Trikha R, Yang C, Liu H, Kelly RJ, Hochsmann B, Kerloeguen C, Banerjee P, Levitch R, Kumar R, Wang Z, Thorburn C, Maitra S, Li S, Verles A, Dahlke M, Risitano AM. Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2024 Mar 14;390(11):994-1008. doi: 10.1056/NEJMoa2308695.

    PubMed 38477987

  • Ardissino G, Capone V, Tedeschi S, Porcaro L, Cugno M. Complement System as a New Target for Hematopoietic Stem Cell Transplantation-Related Thrombotic Microangiopathy. Pharmaceuticals (Basel). 2022 Jul 9;15(7):845. doi: 10.3390/ph15070845.

    PubMed 35890144

  • Sartain S, Shubert S, Wu MF, Wang T, Martinez C. The alternative complement pathway activation product Ba as a marker for transplant-associated thrombotic microangiopathy. Pediatr Blood Cancer. 2020 Mar;67(3):e28070. doi: 10.1002/pbc.28070. Epub 2019 Nov 27.

    PubMed 31774252

  • Okamura H, Nakamae H, Shindo T, Ohtani K, Hidaka Y, Ohtsuka Y, Makuuchi Y, Kuno M, Takakuwa T, Harada N, Nishimoto M, Nakashima Y, Koh H, Hirose A, Nakamae M, Wakamiya N, Hino M, Inoue N. Early Elevation of Complement Factor Ba Is a Predictive Biomarker for Transplant-Associated Thrombotic Microangiopathy. Front Immunol. 2021 Jul 13;12:695037. doi: 10.3389/fimmu.2021.695037. eCollection 2021.

    PubMed 34326846

  • Jodele S, Licht C, Goebel J, Dixon BP, Zhang K, Sivakumaran TA, Davies SM, Pluthero FG, Lu L, Laskin BL. Abnormalities in the alternative pathway of complement in children with hematopoietic stem cell transplant-associated thrombotic microangiopathy. Blood. 2013 Sep 19;122(12):2003-7. doi: 10.1182/blood-2013-05-501445. Epub 2013 Jun 27.

    PubMed 23814021

  • Rotz SJ, Luebbering N, Dixon BP, Gavriilaki E, Brodsky RA, Dandoy CE, Jodele S, Davies SM. In vitro evidence of complement activation in transplantation-associated thrombotic microangiopathy. Blood Adv. 2017 Aug 23;1(20):1632-1634. doi: 10.1182/bloodadvances.2017008250. eCollection 2017 Sep 12.

    PubMed 29296809

  • Han W, Han Y, Chen J, Ma X, Chen F, Wu XJ, Qi JQ, Qiu HY, Sun AN, Wu DP. [Allogeneic hematopoietic stem cell transplantation associated thrombotic microangiopathy: 16 cases report and literature review]. Zhonghua Xue Ye Xue Za Zhi. 2016 Aug 14;37(8):666-70. doi: 10.3760/cma.j.issn.0253-2727.2016.08.007. Chinese.

    PubMed 27587247

  • Jodele S, Davies SM, Lane A, Khoury J, Dandoy C, Goebel J, Myers K, Grimley M, Bleesing J, El-Bietar J, Wallace G, Chima RS, Paff Z, Laskin BL. Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a study in children and young adults. Blood. 2014 Jul 24;124(4):645-53. doi: 10.1182/blood-2014-03-564997. Epub 2014 May 29.

    PubMed 24876561

  • Jodele S, Dandoy CE, Lane A, Laskin BL, Teusink-Cross A, Myers KC, Wallace G, Nelson A, Bleesing J, Chima RS, Hirsch R, Ryan TD, Benoit S, Mizuno K, Warren M, Davies SM. Complement blockade for TA-TMA: lessons learned from a large pediatric cohort treated with eculizumab. Blood. 2020 Mar 26;135(13):1049-1057. doi: 10.1182/blood.2019004218.

    PubMed 31932840

Questions about this trial

What is this clinical trial studying?

A study testing iptacopan in people with Thrombotic Microangiopathy and Hematopoietic Stem Cell Transplantation (HSCT), run by First Affiliated Hospital of Zhejiang University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Fei Gao, Attending, MD (+86 19857035073, gf0906@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Six-month Overall Survival Rate Following TA-TMA Diagnosis (time frame: From the date of TA-TMA diagnosis until 6 months post-diagnosis.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07347990, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in