Narsoplimab for Post-Transplant TMA

Recruiting at 17 trial locations

Overseen By Omeros Clinical Trial Information

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Omeros Corporation

Must not be taking: Eculizumab, Ravulizumab, Defibrotide

Disqualifiers: STEC-HUS, ADAMTS13 < 10%, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug narsoplimab is safe and effective for children with thrombotic microangiopathy (TMA) following a stem cell transplant. TMA can lead to issues such as low platelets and hemolysis, the breakdown of red blood cells. The trial targets children who have undergone a stem cell transplant and are experiencing TMA symptoms, including persistent problems after medication adjustments or high-risk signs like kidney issues or breathing difficulties. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on eculizumab, ravulizumab, or defibrotide at the start of the study. Other treatments for HSCT-TMA are allowed.

Is there any evidence suggesting that narsoplimab is likely to be safe for humans?

In earlier studies, narsoplimab proved safe for people with thrombotic microangiopathies (TMA) following a stem cell transplant. Research shows no increase in infections or other major safety issues. One study found that 94% of patients who responded well to narsoplimab treatment survived, suggesting the treatment is well-tolerated. Additionally, the FDA has given narsoplimab special designations, indicating it shows promise in being safe and effective. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Narsoplimab is unique because it targets a specific protein called MASP-2, which plays a crucial role in the immune system's complement pathway. Unlike other treatments for post-transplant thrombotic microangiopathy (TMA), which often involve plasma exchange or immunosuppressive therapies, Narsoplimab directly inhibits this protein to prevent the harmful overactivation of the immune system. Researchers are excited about Narsoplimab because it offers a targeted approach that might reduce complications and improve outcomes for patients without the need for more invasive procedures.

What evidence suggests that narsoplimab might be an effective treatment for post-transplant TMA?

Research has shown that narsoplimab can help treat blood vessel problems called thrombotic microangiopathies (TMA) following a stem cell transplant. In earlier studies, 61% of adults with TMA responded well to narsoplimab, with more than half experiencing positive effects from the treatment. For children with high-risk TMA, about 62% survived for at least one year. Importantly, narsoplimab did not increase infections or other major safety concerns. These findings suggest that narsoplimab could be a promising treatment option for TMA in patients after a stem cell transplant. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for pediatric patients under 18 who've had a bone marrow transplant and are now facing a complication called TMA. They should have certain lab markers like elevated C5b-9, signs of hemolysis, or risk of severe GVHD. Girls able to have children must use effective birth control. Consent from parents/guardians and patient assent where applicable is required.

Inclusion Criteria

Have at least one of the following HSCT-TMA high-risk criteria

I have been diagnosed with HSCT-TMA.

Have informed consent from at least one parent or legal guardian as required by local law and regulation

Exclusion Criteria

Patient or family member affiliation with specific entities

If pregnant or lactating

Have ADAMTS13 activity < 10%

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive narsoplimab 4 mg/kg for 8 weeks

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Narsoplimab

Trial Overview

The study tests the safety and effectiveness of narsoplimab in treating TMA after stem cell transplants in kids. It aims to see if this biological treatment can help manage symptoms associated with high-risk TMA conditions following transplantation.

How Is the Trial Designed?

Group I: Narsoplimab single arm-treatment Experimental Treatment 1 Intervention

Narsoplimab 4 mg/kg

Who Is Running the Clinical Trial?

Omeros Corporation

Lead Sponsor

Trials

29

Recruited

3,800+

Published Research Related to This Trial

In a study of 20 adult patients with transplant-associated thrombotic microangiopathy (TA-TMA), those treated with eculizumab showed significantly better outcomes, with 7 patients achieving a hematologic response compared to none in the conventional therapy group.

Overall survival was also higher in the eculizumab group at 60%, compared to 30% in the conventional group, suggesting that combining eculizumab with alternative immunosuppressants like sirolimus may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approaching treatment of transplant-associated thrombotic Microangiopathy from two directions with Eculizumab and transitioning from Tacrolimus to Sirolimus. Jan, AS., Hosing, C., Aung, F., et al.[2020]

A case study of a young kidney transplant recipient with de novo thrombotic microangiopathy (TMA) showed that switching to belatacept, a novel immunosuppressant, allowed for effective management of TMA without the adverse effects associated with traditional drugs like ciclosporin and tacrolimus.

The patient experienced excellent early graft outcomes and no adverse events, suggesting that belatacept could be a promising alternative treatment for patients with posttransplant TMA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept as maintenance immunosuppression for postrenal transplant de novo drug-induced thrombotic microangiopathy. Ashman, N., Chapagain, A., Dobbie, H., et al.[2023]

In a study of 262 kidney transplant recipients, basiliximab was found to have a lower incidence of lung infections and blood-related complications compared to anti-thymocyte globulin (ATG), indicating a safer profile for basiliximab.

Basiliximab treatment resulted in higher one-year patient and graft survival rates (98% and 97%) compared to ATG (95% and 73%), suggesting it may be a more effective option for immuno-induction therapy in kidney transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparison of the efficacy and safety in kidney transplant recipients with basiliximab and anti-thymocyte globulin. Wang, W., Yin, H., Li, XB., et al.[2018]

In a study of 278 renal transplant recipients, rabbit antithymocyte globulin (TMG) induction was associated with significantly lower rates of acute rejection at one year compared to basiliximab (BAS), particularly in patients receiving standard criteria donor (SCD) kidneys.

TMG showed the most benefit in patients with normotensive, deceased SCD kidneys, resulting in lower rejection rates (odds ratio 0.47) and reduced mortality (odds ratio 0.17) compared to those treated with BAS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rabbit antithymocyte globulin is more beneficial in standard kidney than in extended donor recipients. Hardinger, KL., Brennan, DC., Schnitzler, MA.[2009]

A six-year-old girl with transplant-associated thrombotic microangiopathy (TA-TMA) following a hematopoietic stem cell transplant showed significant improvement after treatment with Narsoplimab, a monoclonal antibody that inhibits the lectin complement pathway.

Narsoplimab treatment led to a decrease in lactate dehydrogenase levels and resolution of gastrointestinal symptoms, proteinuria, and cytopenia, suggesting its potential efficacy in managing TA-TMA complications in pediatric transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Narsoplimab for severe transplant-associated thrombotic microangiopathy. Pandrowala, A., Ganatra, P., Krishnan, VP., et al.[2023]

In a study of 124 deceased donor kidney transplant recipients, those treated with antithymocyte globulin (ATG) experienced significantly lower rates of delayed graft function (DGF) compared to those treated with basiliximab (17.7% vs. 33.9%).

ATG not only reduced the incidence of DGF but also shortened its duration, making it a potentially safer option for patients at higher risk for DGF, while showing comparable rates of acute rejection and one-year graft survival to basiliximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of clinical outcomes between antithymocyte globulin and basiliximab in renal transplantation from donation after citizen death: a matched pair study]. Lin, KL., Zhu, L., Fu, C., et al.[2018]

In a study of 33 pediatric patients undergoing renal transplantation, TMG induction therapy demonstrated safety and effectiveness, with 100% graft survival at one week and 73% at three years, and no patient deaths reported.

While TMG was effective, late graft loss remains a concern, especially in adolescents, with a total of 10 graft losses observed during the follow-up period, indicating the need for ongoing monitoring and management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five years' experience with thymoglobulin induction in a pediatric renal transplant population. Colleen Hastings, M., Wyatt, RJ., Lau, KK., et al.[2016]

In a study comparing 60 renal transplant patients receiving antithymocyte globulin (ATG) induction to 60 patients receiving Basiliximab, ATG showed a trend towards improved patient (91.7% vs. 85%) and graft survival (89.7% vs. 83.6%) at 6 years, although these differences were not statistically significant.

However, patients receiving ATG experienced a higher incidence of cytomegalovirus (CMV) infections (22% vs. 5%) and more hematological complications, indicating a trade-off between potential benefits and increased risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of ATG vs. Basiliximab induction. Ulrich, F., Niedzwiecki, S., Pascher, A., et al.[2018]

Transplant-associated thrombotic microangiopathy (TA-TMA) affects 15-30% of allogeneic transplant patients and can lead to severe complications, including a 100% mortality rate in cases with multi-organ dysfunction.

The condition is caused by damage to blood vessel linings from factors like chemotherapy, total-body irradiation, and infections, highlighting the need for careful monitoring and management in transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of transplant-associated thrombotic microangiopathy]. Ikezoe, T.[2019]

Thrombotic microangiopathy (TMA) is a rare but serious complication in post-transplant patients, with a cumulative incidence of 0.93% observed in a study of 89 patients, where early onset TMA occurred in 51% of cases.

The study found that acute antibody-mediated rejection (ABMR) significantly impacts allograft survival, with a 41% survival rate in patients with ABMR compared to 70% in those without, highlighting the importance of monitoring for this condition post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and pathological features of thrombotic microangiopathy influencing long-term kidney transplant outcomes. Teixeira, CM., Tedesco Silva Junior, H., Moura, LAR., et al.[2023]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12516664/

Narsoplimab Results in Excellent Survival in Adults and ...

Thirty‐seven (84.1%) allogeneic HCT recipients had high‐risk TA‐TMA, and 1‐year OS of all high‐risk TA‐TMA children was 61.7% (95% CI: 44.3, ...

2.

nature.com

nature.com/articles/s41409-024-02305-3

Safety and efficacy of narsoplimab in pediatric and adult ...

Narsoplimab proved to be effective and safe in the treatment of high-risk TA-TMA, with no increased infectious complications or other safety signals of concern ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666636725000806

Narsoplimab Treatment for Hematopoietic Cell Transplant ...

In a pivotal trial, the MASP-2 inhibitor narsoplimab resulted in a 61% response rate in adults with TA-TMA. This study's objective is to report overall survival ...

4.

astctjournal.org

astctjournal.org/article/S2666-6367(25)00081-8/pdf

TOXICITY AND SUPPORTIVE CARE Narsoplimab ...

These prom- ising real-world results provide additional supportive evi- dence that narsoplimab is an effective treatment for TA-TMA. Abstracts / Transplantation ...

5.

investor.omeros.com

investor.omeros.com/news-releases/news-release-details/omeros-announces-publication-highlighting-survival-outcomes-ta

Press Release

Narsoplimab has received breakthrough therapy and orphan drug designations from the FDA for TA-TMA and for the prevention (inhibition) of ...

6.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/full/10.1002/ajh.70044

Narsoplimab Results in Excellent Survival in Adults and ...

Narsoplimab Results in Excellent Survival in Adults and Children With Hematopoietic Cell Transplant Associated Thrombotic Microangiopathy (TA- ...

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ashpublications.org

ashpublications.org/blood/article/142/Supplement%201/3543/500867/Clinical-Safety-and-Efficacy-of-Narsoplimab-in

Clinical Safety and Efficacy of Narsoplimab in Pediatric and ...

We report the results of a real-world experience with narsoplimab in a series of pediatric and adult patients with TA-TMA.

8.

thrombosisjournal.biomedcentral.com

thrombosisjournal.biomedcentral.com/articles/10.1186/s12959-023-00464-9

Narsoplimab for severe transplant-associated thrombotic ...

One-hundred-day survival after HSCT-TMA diagnosis was 68% in the entire cohort and 94% in the responders. It was well tolerated without any ...