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

Recruiting

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 follow up period (183-365 days after start of study medication)

Awards & highlights

Study Summary

This trial will study the safety and effectiveness of a new drug, ravulizumab, in children who have undergone a stem cell transplant for a rare blood disorder. The treatment period is 26 weeks, followed by a 26-week follow-up period.

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.Check my eligibility

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.See study design

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 ~ follow up period (183-365 days after start of study medication)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~follow up period (183-365 days after start of study medication)

This trial's timeline: 3 weeks for screening, Varies for treatment, and follow up period (183-365 days after start of study medication) for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

TMA Response

Secondary outcome measures

Hematologic Response

Number of Participants with a Change from Baseline in TMA-associated Organ Dysfunction in Renal System, Cardiovascular System, Pulmonary System, CNS, and GI System.

Overall Survival

+4 more

Side effects data

From 2022 Phase 3 trial • 195 Patients • NCT03056040

31%

Headache

30%

Nasopharyngitis

28%

Upper respiratory tract infection

21%

Fatigue

19%

Diarrhoea

19%

Pyrexia

18%

Nausea

17%

Cough

15%

Abdominal pain

14%

Back pain

14%

Dizziness

13%

Pain in extremity

11%

Arthralgia

11%

Influenza like illness

10%

Oropharyngeal pain

10%

Rhinitis

Vomiting

Abdominal pain upper

Dyspnoea

Urinary tract infection

Anaemia

Constipation

Chest pain

Dysphagia

Gastroenteritis

Pruritus

Myalgia

Palpitations

Influenza

Haemolysis

Lower respiratory tract infection

Haemolytic anaemia

Basal cell carcinoma

Hyperthermia

Cholelithiasis

Foot deformity

Colitis

Bone marrow failure

Infection

Pneumonia

Post procedural infection

Liver disorder

Depression

Epilepsy

Respiratory failure

Enteritis

Pneumoperitoneum

Toothache

Bile duct stone

Biliary colic

Cholecystitis

COVID-19

Bacteraemia

Escherichia sepsis

Escherichia urinary tract infection

Pneumonia bacterial

Postoperative wound infection

Rhinovirus infection

Septic shock

Ankle fracture

Ligament injury

Transfusion reaction

Cerebrospinal fluid retention

Loss of consciousness

Dupuytren's contracture

Intervertebral disc degeneration

Osteonecrosis

Ureterolithiasis

Urinary retention

Major depression

Suicide attempt

Dermal cyst

Invasive papillary breast carcinoma

Aplastic anaemia

Breakthrough haemolysis

Tibia fracture

Lower limb fracture

Deep vein thrombosis

Endometrial cancer

Lung cancer metastatic

Renal cancer metastatic

Seborrhoeic keratosis

Pharyngitis

Pneumococcal infection

Liver function test increased

Road traffic accident

Suspected COVID-19

100%

80%

60%

40%

20%

Study treatment Arm

Ravulizumab

Eculizumab

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

2021

Completed Phase 4

~1080

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.