What side effects are associated with this type of intervention?

Treatments for Thrombotic Microangiopathy (TMA) that are similar to Nomacopan, which inhibits Complement C5 and Leukotriene B4, commonly have side effects including an increased risk of infections (notably meningococcal infections), headaches, hypertension, and gastrointestinal disturbances. Additionally, leukotriene inhibitors may cause neuropsychiatric events, though these are rare.

What prior FDA approvals exist?

The FDA has approved several treatments for Thrombotic Microangiopathy (TMA), particularly those targeting the complement system. Eculizumab (Soliris) is a well-known C5 inhibitor approved for conditions like atypical hemolytic uremic syndrome (aHUS), a type of TMA. Ravulizumab (Ultomiris), another C5 inhibitor, has also been approved for similar indications. These drugs work by inhibiting the complement protein C5, thereby preventing the formation of the membrane attack complex and reducing inflammation and hemolysis. Nomacopan, which inhibits both Complement C5 and Leukotriene B4, is being studied for its potential to provide a broader anti-inflammatory effect in TMA treatment.

What other types of research exist?

Promising alternatives to Nomacopan for TMA patients include pegcetacoplan, a C3 inhibitor, and eculizumab, a C5 inhibitor. Both have shown efficacy in complement-mediated diseases and may offer therapeutic benefits for TMA.

← Back to Search

Complement Inhibitor

Nomacopan for Transplant-Associated Thrombotic Microangiopathy

Q: What is the mechanism of action of this treatment?

Thrombotic Microangiopathy (TMA) involves the formation of clots in small blood vessels, leading to organ damage. Common treatments target the complement system, a part of the immune system that, when overactivated, contributes to TMA. Nomacopan, for example, inhibits Complement C5, preventing the formation of the membrane attack complex that damages endothelial cells, and Leukotriene B4, reducing inflammation. These mechanisms are crucial as they help to prevent further vascular injury and inflammation, thereby mitigating the progression of TMA and improving patient outcomes.

Phase 3

Waitlist Available

Research Sponsored by AKARI Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Clinical or histological diagnosis of TMA

Aged ≥ 0.5 and < 18 years at the time of diagnosis of TMA

Must not have

Received eculizumab or any other complement blocker therapy at any time

Patients weighing less than 5 kg

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 28 weeks

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing nomacopan, a medication that helps reduce inflammation and prevent blood clots. It targets children who have developed a serious blood vessel condition after a stem cell transplant. The study aims to see if nomacopan is safe and effective for these patients.

Who is the study for?

This trial is for children and teenagers under 18 who've had a stem cell transplant within the last 100 days and are diagnosed with Thrombotic Microangiopathy (TMA). They must not be allergic to the drug being tested, weigh at least 5 kg, have no severe infections or acute GVHD grade 4, haven't used complement blocker therapy before, and don't have a positive ADAMTS13 test.

What is being tested?

The study tests nomacopan (rVA576) in young patients with TMA following a stem cell transplant. It's conducted across multiple centers to see how well this treatment works for these patients. The participants will receive nomacopan after their diagnosis of TMA.

What are the potential side effects?

While specific side effects of nomacopan in this context aren't listed here, common side effects may include reactions at the injection site, potential allergic responses due to hypersensitivity to ingredients, or complications related to immune system interactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been diagnosed with TMA.

Select...

I was diagnosed with TMA before turning 18 but after 6 months old.

Select...

I have had a stem cell transplant.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have taken eculizumab or similar medications before.

Select...

I weigh less than 5 kg.

Select...

I have the most severe form of acute graft-versus-host disease.

Select...

I do not have any severe or worsening infections.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 28 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~28 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 28 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

RBC transfusion independence for ≥ 28 days immediately prior to any scheduled clinical visit up to Week 24 or Urine protein creatinine ratio ≤ 2 mg/mg maintained over ≥ 28 days immediately prior to any scheduled clinical visit up to week 24

Secondary study objectives

Normalisation of lab parameters

Platelet transfusion independence

Renal Function Improvement

+1 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: nomacopan (rVA576)Experimental Treatment1 Intervention

The study population will consist of paediatric patients who have undergone allogeneic or autologous HSCT and develop HSCT-TMA within a year of HSCT

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Thrombotic Microangiopathy (TMA) involves the formation of clots in small blood vessels, leading to organ damage. Common treatments target the complement system, a part of the immune system that, when overactivated, contributes to TMA. Nomacopan, for example, inhibits Complement C5, preventing the formation of the membrane attack complex that damages endothelial cells, and Leukotriene B4, reducing inflammation. These mechanisms are crucial as they help to prevent further vascular injury and inflammation, thereby mitigating the progression of TMA and improving patient outcomes.

MASP-1 of the complement system enhances clot formation in a microvascular whole blood flow model.