What is the mechanism of action of this treatment?

Thrombotic Microangiopathy (TMA) treatments often target the underlying mechanisms of endothelial damage and abnormal blood clotting. Complement inhibitors like Ravulizumab work by blocking the complement system, a part of the immune system that, when overactivated, can lead to endothelial injury and the formation of microthrombi. This inhibition helps prevent further vascular damage and reduces the risk of organ failure, which is crucial for improving outcomes in TMA patients. By controlling the complement pathway, these treatments address the root cause of the disease, offering a targeted approach to managing and potentially mitigating the severe complications associated with TMA.

What side effects are associated with this type of intervention?

Common side effects of complement inhibition therapies for Thrombotic Microangiopathy, such as Ravulizumab, include infusion-related reactions, increased risk of infections due to immunosuppression, and hypersensitivity reactions. These treatments aim to inhibit components of the complement system, which can lead to these adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Thrombotic Microangiopathy (TMA), particularly focusing on complement inhibition. Eculizumab, a monoclonal antibody that inhibits the complement protein C5, was one of the first complement inhibitors approved for atypical Hemolytic Uremic Syndrome (aHUS), a type of TMA. Ravulizumab, a newer complement inhibitor with a similar mechanism of action but a longer half-life, has also been approved for the treatment of aHUS. These drugs work by preventing the activation of the complement system, which plays a key role in the pathogenesis of TMA.

What other types of research exist?

Promising novel alternatives to Ravulizumab for Thrombotic Microangiopathy (TMA) patients include other complement inhibitors such as Eculizumab, which has been widely used and studied. Additionally, emerging therapies like Narsoplimab (OMS721), a MASP-2 inhibitor, and Avacopan, a C5a receptor inhibitor, are showing potential in clinical trials. These alternatives offer different mechanisms of action within the complement pathway and have demonstrated efficacy in managing TMA.

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Monoclonal Antibodies

Ravulizumab for Thrombotic Microangiopathy

Phase 3

Waitlist Available

Research Sponsored by Alexion

Eligibility Criteria Checklist

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

Must have

Be younger than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 26 weeks (treatment period) and 52 weeks

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial will test the safety and effectiveness of ravulizumab, an IV medication, in children with HSCT-TMA. The treatment aims to stop the immune system from damaging blood vessels. Ravulizumab is a longer-acting medication developed to reduce blood cell destruction and improve quality of life in patients with a specific blood condition.

Who is the study for?

This trial is for children and teens from 1 month to under 18 years who've had a stem cell transplant in the last year and are suffering from HSCT-TMA. They must be able to consent, use effective birth control if applicable, be vaccinated against meningococcal infections or on antibiotics, weigh at least 5 kg, and not have certain other health conditions.

What is being tested?

The study tests Ravulizumab given by IV to kids with HSCT-TMA. It looks at how safe it is, how well it works, what the body does with it (pharmacokinetics), and what it does to the body (pharmacodynamics) over a treatment period of 26 weeks plus another 26 weeks of follow-up without treatment.

What are the potential side effects?

Possible side effects include reactions where the drug enters the body, headache, nausea, vomiting; also potential risks like infections due to weakened immune defenses or interference with normal blood clotting.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 26 weeks (treatment period) and 52 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~26 weeks (treatment period) and 52 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 26 weeks (treatment period) and 52 weeks for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Proportion of Participants with Change from Baseline in TMA-associated Organ Dysfunction

Proportion of Participants with Changes from Baseline in Selected Laboratory Tests

Proportion of Participants with Hematologic Response

+5 more

Side effects data

From 2022 Phase 4 trial • 18 Patients • NCT04320602

33%

Fatigue

17%

COVID-19

17%

Abdominal pain

17%

SARS-CoV-2 test positive

17%

Cough

11%

Back pain

11%

Nasopharyngitis

11%

Non-cardiac chest pain

11%

Dyspnoea

Pain

Chest discomfort

Body temperature abnormal

Upper respiratory tract congestion

Rash

Herpes zoster

Nail ridging

Arthralgia

Peripheral swelling

Influenza like illness

Pneumonia

Asthenia

Retinal haemorrhage

Headache

Pain in extremity

Haemoglobinuria

Neurodermatitis

Pyrexia

Skin lesion

Chromaturia

Nephrolithiasis

Upper respiratory tract infection

Urinary tract infection

Constipation

Extravascular haemolysis

Haemoglobin decreased

Oropharyngeal pain

100%

80%

60%

40%

20%

Study treatment Arm

Ravulizumab

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: Ravulizumab plus Best Supportive CareExperimental Treatment2 Interventions

Participants will receive ravulizumab plus Best Supportive Care as background therapy.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ravulizumab

2016

Completed Phase 4

~1090

Do I qualify?Apply below to find out

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) treatments often target the underlying mechanisms of endothelial damage and abnormal blood clotting. Complement inhibitors like Ravulizumab work by blocking the complement system, a part of the immune system that, when overactivated, can lead to endothelial injury and the formation of microthrombi. This inhibition helps prevent further vascular damage and reduces the risk of organ failure, which is crucial for improving outcomes in TMA patients. By controlling the complement pathway, these treatments address the root cause of the disease, offering a targeted approach to managing and potentially mitigating the severe complications associated with TMA.