Ongoing Clinical Trials for Thrombotic Microangiopathy
There are currently 4 clinical trials ongoing for thrombotic microangiopathy, a serious condition where small blood vessels become damaged and form clots, often occurring after stem cell transplantation. These trials are testing different medications to help prevent blood vessel damage and improve outcomes for both children and adults. The studies are taking place across multiple European countries including Germany, Spain, France, Italy, Greece, Netherlands, Belgium, Poland, and Sweden.
Clinical trial locations
- Belgium
- France
- Study of Pegcetacoplan (APL-2) in Patients with Transplant-associated Thrombotic Microangiopathy After Stem Cell Transplantation
- Study of Ravulizumab for Children with Thrombotic Microangiopathy After Stem Cell Transplant
- Study on Ravulizumab for Patients with Thrombotic Microangiopathy After Stem Cell Transplant
- Germany
- Greece
- Italy
- Study of Pegcetacoplan (APL-2) in Patients with Transplant-associated Thrombotic Microangiopathy After Stem Cell Transplantation
- Study of Ravulizumab for Children with Thrombotic Microangiopathy After Stem Cell Transplant
- Study on Ravulizumab for Patients with Thrombotic Microangiopathy After Stem Cell Transplant
- Netherlands
- Poland
- Spain
- Study of Narsoplimab for Children with High-Risk Blood Vessel Damage After Stem Cell Transplant
- Study of Pegcetacoplan (APL-2) in Patients with Transplant-associated Thrombotic Microangiopathy After Stem Cell Transplantation
- Study of Ravulizumab for Children with Thrombotic Microangiopathy After Stem Cell Transplant
- Study on Ravulizumab for Patients with Thrombotic Microangiopathy After Stem Cell Transplant
- Sweden
Study of Narsoplimab for Children with High-Risk Blood Vessel Damage After Stem Cell Transplant
This trial is testing a medication called narsoplimab in children who develop a serious complication after receiving a stem cell transplant. The condition, known as thrombotic microangiopathy, causes damage to small blood vessels and can lead to problems with blood clotting and organ function.
Who can participate: Children aged from 28 days to under 18 years can join if they have received a stem cell transplant from a donor and developed high-risk thrombotic microangiopathy. This includes having a low platelet count (below 50,000 per microliter) and signs of blood cell damage. Participants must also meet at least one high-risk criterion, such as the condition lasting 2 weeks or more despite treatment changes, kidney problems shown by protein in the urine, digestive system involvement confirmed by biopsy, nervous system complications, fluid around the heart or lungs, or elevated levels of certain blood proteins. Both parents or legal guardians must provide consent, and age-appropriate agreement from the child is required. Those who are sexually active must use effective birth control during the study and for 12 weeks afterward.
Who cannot participate: Children who have had a stem cell transplant but do not have thrombotic microangiopathy, those not meeting the high-risk criteria, or those outside the specified age range cannot join. Participants must also belong to the specific patient groups the study is focusing on.
What the trial involves: The medication narsoplimab is given directly into a vein through an infusion. The study monitors how children respond to treatment over time, tracking survival rates 100 days after diagnosis and longer-term health outcomes. Researchers will also examine how the body processes the medication and watch for any side effects. Regular blood tests and health assessments help measure whether the treatment improves the condition.
How narsoplimab works: This medication is a type of monoclonal antibody that blocks a protein called MASP-2, which plays a role in the immune system’s complement pathway. By blocking this protein, narsoplimab aims to reduce inflammation and prevent further blood vessel damage.
Study of Pegcetacoplan (APL-2) in Patients with Transplant-associated Thrombotic Microangiopathy After Stem Cell Transplantation
This study focuses on adults who develop thrombotic microangiopathy after receiving a stem cell transplant. The trial is testing pegcetacoplan, a medication that targets part of the immune system called the complement system, which contributes to blood vessel damage in this condition.
Who can participate: Adults aged 18 and older who have received a stem cell transplant from a related or unrelated donor can join. Eligible participants must have been diagnosed with transplant-associated thrombotic microangiopathy that continues despite initial treatment. This diagnosis requires a low platelet count (below 50 x 10⁹/L or more than 50% decrease), high LDH levels, and at least 2 additional signs such as damaged red blood cells in blood tests, low hemoglobin or need for blood transfusions, protein in urine, elevated blood proteins called sC5b-9, or high blood pressure. Participants must also have elevated protein levels in urine and be able to understand and sign the consent form. Women who can become pregnant must have a negative pregnancy test and use approved birth control during the study and for 8 weeks after. Men must also use birth control and cannot donate sperm during this time.
Who cannot participate: The trial excludes anyone under 18 years old, those who have had organ transplants other than stem cell transplants, and patients with active uncontrolled infections. People who received another experimental treatment within 30 days, pregnant or breastfeeding women, and those with severe liver or kidney problems cannot participate. Patients with active cancer requiring treatment, severe heart conditions, recent major surgery, allergies to the study medication, or those unable to follow study procedures are also excluded.
What the trial involves: Pegcetacoplan is given through an injection under the skin. Treatment continues for 24 weeks with regular monitoring visits. Blood and urine tests track how well the treatment works, measuring changes in blood markers and organ function. Doctors assess kidney, lung, digestive system, and nervous system function, along with blood pressure and other health measures. Success is determined by improvements in blood test results, organ function, and reduced need for blood transfusions at week 24. Long-term survival is monitored up to 100 days from diagnosis.
How pegcetacoplan works: This medication is a complement inhibitor that targets and blocks the complement protein C3, which plays a crucial role in the immune system’s complement cascade. By blocking this protein, pegcetacoplan helps prevent the excessive immune activation that leads to blood vessel damage and blood clot formation.
Study of Ravulizumab for Children with Thrombotic Microangiopathy After Stem Cell Transplant
This trial investigates whether ravulizumab, given alongside standard supportive care, can effectively treat children who develop thrombotic microangiopathy following a stem cell transplant. The study aims to evaluate how quickly the condition responds to treatment and monitor improvements in organ function.
Who can participate: Children between 28 days and under 18 years old who received a stem cell transplant within the past 12 months can join. Participants must have a confirmed diagnosis of thrombotic microangiopathy, which includes new onset of low platelet counts or resistance to platelet transfusions, plus signs of red blood cell breakdown (either high LDH enzyme levels or fragmented red blood cells visible in blood tests), protein in the urine, and new onset of anemia or high blood pressure. The condition must persist for at least 72 hours after initial treatment. Children must weigh at least 5 kilograms and should be vaccinated against meningococcal infections when possible, following national guidelines for immune recovery after transplant. Preventive antibiotics are required according to institutional guidelines. Participants or their legally authorized representative must provide informed consent.
Who cannot participate: Children who had a stem cell transplant but do not have thrombotic microangiopathy, those outside the specified age range, or those not meeting the health requirements cannot join. Patients unable to follow study procedures, currently participating in another clinical trial, or having certain interfering medical conditions are excluded. Pregnant or breastfeeding individuals and those with a history of allergic reactions to the study medication also cannot participate.
What the trial involves: Ravulizumab is given through an intravenous infusion directly into a vein. The dosage and frequency follow the study protocol. Participants receive the medication in addition to standard supportive care, which includes measures to manage symptoms and improve quality of life. Regular monitoring tracks how the condition responds to treatment, focusing on symptom resolution, changes in organ function, and overall health over a period of up to one year. The study measures time to response, any relapses, overall survival, and other health indicators.
How ravulizumab works: This monoclonal antibody medication inhibits part of the immune system called the complement system. By blocking certain proteins in the blood that cause inflammation and blood vessel damage, ravulizumab aims to reduce the harmful effects common in thrombotic microangiopathy.
Study on Ravulizumab for Patients with Thrombotic Microangiopathy After Stem Cell Transplant
This study compares ravulizumab to a placebo to determine how effective the medication is in treating thrombotic microangiopathy in adults and adolescents following a stem cell transplant. The trial will assess whether ravulizumab can improve symptoms and prevent complications over several months.
Who can participate: People aged 12 years or older who received a stem cell transplant within the past 12 months can participate. Eligible individuals must have a confirmed diagnosis of thrombotic microangiopathy, including new onset of low platelet count or lack of response to platelet transfusions, signs of red blood cell breakdown (high LDH levels or presence of fragmented red blood cells), protein in urine, and new onset of anemia or high blood pressure. The condition must continue for at least 72 hours despite initial treatment. Participants must weigh 30 kilograms or more and should be vaccinated against meningococcal infections if possible, following guidelines for immune recovery after transplant. Those under 18 should also be revaccinated against other infections when possible. All participants must receive preventive antibiotics, including protection against certain bacteria for at least 2 weeks after vaccination, or throughout treatment if vaccination is not possible. Participants must agree to use contraception if applicable and provide signed informed consent.
Who cannot participate: Patients who had a stem cell transplant but do not have thrombotic microangiopathy, those outside the specified age range, or those not part of the study’s target patient groups cannot join.
What the trial involves: Participants receive either ravulizumab or a placebo through an intravenous infusion. Regular monitoring occurs throughout the study to assess how the condition responds to treatment, with specific evaluations at 26 weeks and 52 weeks to track changes from the starting point. The study measures improvements in thrombotic microangiopathy symptoms, changes in organ function, any relapses, and overall survival. Follow-up continues at specific time points including Day 100, Week 26, and Week 52. The trial is expected to conclude by June 2025.
How ravulizumab works: This medication is a monoclonal antibody designed to target specific proteins in the immune system’s complement pathway. By inhibiting this system, ravulizumab helps reduce damage to blood vessels and improves blood flow, potentially helping patients recover from thrombotic microangiopathy more effectively.
Summary
All four clinical trials focus on treating thrombotic microangiopathy that develops after stem cell transplantation, though they target different age groups and test different medications. Two trials specifically focus on pediatric patients, while the other two include adults or adolescents aged 12 and older.
Geographically, the trials show significant concentration in Western European countries. Spain, France, Germany, and Italy each host three or all four trials, making them the primary research centers for this condition. Greece, Netherlands, Belgium, Poland, and Sweden host fewer trials. This distribution suggests these countries have established expertise in stem cell transplantation and the treatment of related complications.
Three different investigational drugs are being tested across the four trials: narsoplimab, pegcetacoplan, and ravulizumab. Notably, ravulizumab is being studied in two separate trials, one for children and one for older patients, suggesting particular research interest in this complement inhibitor. All three medications work by targeting the immune system’s complement pathway, though through different mechanisms. Narsoplimab blocks the MASP-2 protein, pegcetacoplan inhibits the C3 protein, and ravulizumab acts as a complement inhibitor affecting blood vessel inflammation.
The trials vary in design, with most being open-label studies where all participants receive the active treatment, while one trial uses a placebo comparison. Treatment durations range from 24 weeks to one year, with extended follow-up periods to monitor long-term outcomes. All studies require participants to have received stem cell transplants within the past 12 months and to have confirmed diagnoses with specific blood test results and clinical signs.
