Clinical Research Directory

A Study of TAK-755 in Participants With Congenital Thrombotic Thrombocytopenic Purpura

Thrombotic thrombocytopenic purpura (or TTP for short) is a condition where blood clots form in small blood vessels throughout the body. The clots can limit or block the flow of oxygen-rich blood to the body's organs, such as the brain, kidneys, and heart. As a result, serious health problems can develop. The increased clotting that occurs in TTP uses up the cells that help the blood to clot, called platelets. With fewer platelets available in the blood, bleeding problems can also occur. People who have TTP may bleed underneath the skin forming purple bruises, or purpura. TTP also can cause anemia, a condition in which red blood cells break apart faster than the body can replace them, leading to fewer red blood cells than in normal. TTP is caused by a lack of activity in the ADAMTS13 enzyme, a protein in the blood involved in controlling clotting of the blood. The ADAMTS13 enzyme breaks up another blood protein called von Willebrand factor that forms blood clots by clumping together with platelets. Some people are born with this condition, while others develop the condition during their life. Many people who are born with TTP experience frequent flare-ups that need to be treated right away. TAK-755 is a medicine that replaces ADAMTS13 and may prevent or control TTP flare-ups, called acute TTP events. The main aim of the study is to check for side effects of long-term treatment with TAK-755. Treatment will be given in 2 ways: 1. TAK-755 treatment given either every week or every other week to prevent acute TTP events from happening (the "prophylactic" cohort). 2. TAK-755 treatment given to control an acute TTP event when it happens (the "on-demand" cohort). Participants in the prophylactic cohort will receive treatment in the clinic or at home for up to approximately 3 years. They will visit the clinic at least every 12 weeks. Participants in the on-demand cohort will receive daily treatment for the acute TTP event until the flare-up has gotten better. They will have a follow-up visit at the clinic 4 weeks later.

A Study to Learn More About the Treatment of People With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Who Received Recombinant ADAMTS13 (rADAMTS13) as Part of the Early Access Program

Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare blood disorder that some people are born with. It is caused by inherited changes in the ADAMTS13 gene that reduce the body's ability to produce the ADAMTS13 enzyme. ADAMTS13 normally cleaves ultra-large multimers of a protein called von Willebrand factor (VWF). In cTTP, low ADAMTS13 activity allows these ultra-large VWF multimers to build up and promote blood clot formation in small blood vessels. These clots can restrict blood flow to vital organs and lead to serious complications. Recombinant ADAMTS13 (rADAMTS13) is a manufactured form of human ADAMTS13 designed to replace the missing enzyme and restore ADAMTS13 activity. This study aims to describe the impact of cTTP on participants before and after treatment with rADAMTS13. It will also evaluate participants' health outcomes after treatment and describe treatment patterns before and after rADAMTS13, including whether treatment was used to prevent or treat TTP episodes, how often it was given, the amount received, and others. In addition, the study will describe pregnancies and outcomes for the mother and baby before and during treatment with rADAMTS13. Only data already available in the medical records of the people who received rADAMTS13 through Takeda's early access program (EAP) for cTTP will be collected and reviewed in this study.

A Study of TAK-755 (rADAMTS13) With Little to No Plasma Exchange (PEX) Treatment in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)

This is a study of TAK-755 in adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP). The main aim of this study is to determine the percentage of participants with a clinical (Part 1) or platelet (Part 2) response without plasma exchange during the study. Participants who have an acute attack of iTTP will receive TAK-755 and immunosuppressive therapy during their stay at the hospital until they achieve a clinical response in Part 1 or platelet response in Part 2. Participants will also be treated with TAK-755 for an additional time of up to 6 weeks after the acute phase. In total, participants will stay in the study for approximately 3 months.

A Study in Children and, Adults With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Treated With Adzynma

Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare blood disorder that some people are born with. It is caused by a problem in a gene passed down from parents to children, which affects the body's ability to produce a enzyme called ADAMTS13. This enzyme helps to cut down a larger form of protein called von Willebrand Factor (VWF). People with cTTP have low levels of ADAMTS13. Without ADAMTS13, large forms of vWF build up and cause blood clots in small blood vessels. These clots can block blood flow to vital organs, causing serious health problems. Adzynma is a human ADAMTS13 protein made in the laboratory. It works the same way as natural ADAMTS13 does and may provide higher levels of ADAMTS13. The main aim of this study is to learn more about the risk of children and adults with cTTP treated with Adzynma developing antibodies that prevent Adzynma from working properly (called neutralizing antibodies) within 6 months after the first treatment and to understand the risk of allergic reactions within 7 days of the first treatment with Adzynma. Other aims are to better understand how safe treatment with Adzynma is over a longer period of time (called long-term safety) in children and adults with cTTP and to gather information about pregnancies and babies of women who have received Adzynma while pregnant. Only data already available in the medical records of the people who received Adzynma for the treatment of cTTP in normal clinical practice will be reviewed and collected during this study.

A Survey of Recombinant ADAMTS13 in Participants With Congenital Thrombotic Thrombocytopenic Purpura

This study is a survey in Japan of recombinant ADAMTS13 used to treat or to prevent participants with congenital thrombotic thrombocytopenic purpura (cTTP). The study sponsor will not be involved in how the participants are treated but will provide instructions on how the clinics will record what happens during the study. The main aim of the study is to check for side effects related from recombinant ADAMTS13 and to check if recombinant ADAMTS13 improves or prevents cTTP. During the study, participants with cTTP will take recombinant ADAMTS13 intravenous injection according to their clinic's standard practice. The study doctors will check for side effects from recombinant ADAMTS13 for 18 months.

Retrospective Epidemiological Study of Patients in the National Cohort of the French TMA Center

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disorder characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and ischemic organ damage due to microvascular thrombosis. It results from a severe deficiency in the von Willeband factor (vWF)-cleaving protease ADAMTS13, primarily caused by autoantibodies that inhibit its activity. This deficiency leads to accumulation of ultra-large vWF multimers, triggering pathological platelet aggregation and widespread microthrombi. iTTP typically presents with acute neurological symptoms (e.g., confusion, seizures, coma), cardiac events (e.g., myocardial infarction), and multiorgan dysfunction. Without prompt treatment-plasma exchange, immunosuppression, and the vWF inhibitor caplacizumab-mortality exceeds 90%. Survivors face long-term risks, including cardiovascular complications, cognitive impairment, and reduced life expectancy. The TWI-LIGHT protocol is a national retrospective epidemiological study coordinated by the French Reference Center for Thrombotic Microangiopathies (CNR-MAT). It aims to analyze long-term outcome in \>1,200 iTTP patients diagnosed between October 2000 and June 2024. The study leverages pseudonymized data from the CNR-MAT registry, collected via a secure REDCap database. Key Objectives: 1. Primary: Assess the impact of cardiovascular risk factors (e.g., hypertension, diabetes) and ADAMTS13 activity on life expectancy in iTTP survivors. 2. Secondary: * Evaluate disease burden in underrepresented groups (pregnant/postpartum women, children, elderly patients). * Analyze the influence of new therapies (caplacizumab, rituximab, recombinant ADAMTS13) on care pathways. * Identify prognostic factors and treatment practices. * Characterize neurocognitive outcomes and quality of life post-iTTP. Methodology: * Design: Non-interventional, retrospective (MR-004 compliance), using data from standard care. * Inclusion: Patients with confirmed iTTP (thrombocytopenia, hemolytic anemia, ADAMTS13 \<10%), diagnosed within the study period, and ≥1 year of follow-up. * Exclusion: Cancer-associated iTTP, severe sepsis, or patient opposition to data reuse. * Data Collection: Clinical, biological, and therapeutic variables from hospital/consultation records, including cardiovascular events, ADAMTS13 activity, and neurocognitive assessments. * Analysis: Kaplan-Meier survival curves and Cox regression models to identify risk factors for non-iTTP-related death. Expected Outcomes: * Prevalence of cardiovascular comorbidities and their correlation with ADAMTS13 activity. * Insights into iTTP subtypes (e.g., gestational, pediatric) and therapeutic efficacy. * Evidence-based strategies for personalized long-term management. Ethical Framework: * AP-HP-sponsored, with oversight from Sorbonne University's ethics committee. * Patients informed of data reuse with opt-out rights; data archived for 15 years. This landmark study will inform clinical guidelines, optimize survivor care, and address unmet needs in iTTP management through comprehensive, real-world data analysis.

Immunological Aspect of Thrombotic Thrombocytopenic Purpura (TTP)

The general objective of the proposed project is to characterise phenotypically and functionally ADAMTS13-specific memory B lymphocytes and autoreactive T lymphocytes, in particular follicular helper T lymphocytes, in the acute phase of the disease, but also during its progression after treatment. The aim is to highlight their contribution to the initial pathogenic process, their evolution under treatment, and also their involvement in patients who are refractory to immunosuppressive therapies and during relapses. The aim of this project is to identify early phenotypic or functional parameters that are predictive of relapse and that can be used for personalised optimisation of treatment to maintain remission.