Active clinical trials for "Thrombotic Microangiopathies"

This study will evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab administered by intravenous infusion to pediatric participants, from 1 month to < 18 years of age, with HSCT-TMA. The treatment period is 26 weeks, followed by a 26-week off-treatment follow-up period.

Thymoglobulin is widely applied as serotherapy in order to prevent acute graft-versus-host disease (GvHD) and graft rejection in patients undergoing non-Human Leukocyte Antigen (HLA)-identical hematopoietic stem cell transplantations (HSCT), with a delicate balance between prevention of GvHD and the promotion of immune reconstitution. Thymoglobulin is known as a drug with high pharmacokinetic (PK) variability. This variability influences drug exposure, which in turn determines the drug response of pharmacodynamics (PD). In order to maintain efficacy while reducing adverse effects of drugs across the entire age range, identification of the PK/PD relationships and the effect of growth and maturation on the different PK and PD parameters involved are crucial. The investigators hypothesise that a better knowledge of Thymoglobulin PK and its covariates would help to individualise dosage regimen and would improve clinical outcomes, such as GvHD and immune reconstitution. The investigators aim to build a population PK model of Thymoglobulin in order to study PK variability and its covariates. This model will help in optimizing dosage regimen in an individually way.

The purpose of this study is to evaluate the safety and efficacy of narsoplimab in pediatric patients with thrombotic microangiopathies (TMA) following hematopoietic stem cell transplant (HSCT).

This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ravulizumab in adult and adolescent participants with hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA). In Stage 1, an open-label, single-arm period, the dosing regimen will be confirmed. In Stage 2, participants will be randomized to receive either blinded ravulizumab plus best supportive care or matching placebo plus best supportive care. The treatment period is 26 weeks (open-label for Stage 1, and randomized, double-blind, and placebo-controlled for Stage 2) followed by a 26-week follow-up period.

Multicentre Study of nomacopan in Paediatric Haematopoietic Stem-Cell Transplant Associated Thrombotic Microangiopathy

The purpose of the study is to assess PK, Pharmacodynamics (PD), Efficacy and safety of pegcetacoplan in patients with TA-TMA after HSCT.

Ultomiris (Ravulizumab), is a monoclonal antibody that specifically targets terminal complement products and is proposed for the treatment of COVID-19 induced microvasculature injury and endothelial damage leading to thrombotic microangiopathy (TMA) causing acute kidney injury (AKI). Ravulizumab is to be used for participants with a confirmed diagnosis of COVID-19 who clinically or diagnostically present with deteriorating renal function. Ravulizumab causes immediate and sustained inhibition of the terminal complement cascade. The use of ravulizumab could ameliorate COVID-19 induced kidney injury due to TMA, shorten hospital stay, and improve the overall survival.

Haemolytic and Uraemic Syndrome (HUS) is a serious disease requiring rapid diagnosis and management. The atypical HUS diagnosis has been greatly improved by anti-CS antibody (Eculizumab) wich block alternative complement pathway activation. To rise treatment success, Eculizumab introduction should be as early as possible. In some secondary HUS (infection, drugs…) complement is also involved as "second-hit". To date, there is no tool to confirm complement involvement in a HUS at diagnosis stage. This study suggest to evaluate a therapeutic orientation test, in order to determine the complement implication in HUS diagnosis. The test evaluates the complement deposits on endothelial cell surface in vitro, compared to a normal human serum. In order to determine the test performance, first the positive or negative results will be compared to the HUS clinical evolution, treated or not by the clinician with Eculizumab. Second, the test results will be compared to the presence of alternative complement pathway regulation abnormalities.

Thrombotic microangiopathies (TMA) are defined as a triad combining mechanical hemolytic anemia, peripheral thrombocytopenia and ischemic organ damage. Mitomycin C is an alkylating agent used as chemotherapy in adenocarcinomas of the breast, lung, pancreas, rectum and anal carcinoma. Mitomycin-C-induced TMA (m-TMA) is a potentially serious complication of chemotherapy: its estimated incidence ranges from 4 to 15% and its mortality exceeds 70%, with an estimated median survival of 2 months. This can also be responsible for kidney failure, sometimes requiring hemodialysis. The time to onset of m-TMA varies from one week to 15 months after the last infusion and is believed to depend on the cumulative dose of mitomycin C. Eculizumab is a monoclonal antibody that binds to complement protein C5, blocking activation of the terminal complement pathway and formation of the membrane attack complex. This therapy has significantly changed the prognosis of patients with atypical hemolytic uremic syndrome (HUS), a disease in which complement activation plays a central role in TMA. Recently, a retrospective study suggested efficacy of eculizumab in TMA induced by gemcitabine, another chemotherapy, with normalization of platelets and LDH in 83% of patients, and partial or complete renal recovery in 67% and 17% of patients. These results provided arguments in favor of a potential benefit of complement-targeted therapies in TMA induced by certain chemotherapies. However, data on eculizumab in m-TMA remain extremely limited to date. The objective of this study is to describe the clinical, biological and histological presentation of patients with m-TMA and their evolution after treatment with or without eculizumab.

Hematopoietic stem cell transplant (HSCT) is an effective but toxic therapy and pulmonary morbidity affects as many as 25% of children receiving transplant. Early pulmonary injury includes diffuse alveolar hemorrhage (DAH), thrombotic microangiopathy (TMA) interstitial pneumonitis (IPS) and infection, while later, bronchiolitis obliterans is a complication of chronic GVHD associated with severe morbidity and mortality. Improved diagnosis and treatment of pulmonary complications are urgently needed as survival after HSCT improves, and as HSCT is increasingly used for non-malignant disorders such as sickle cell disease. Currently, there are large and important gaps in the investigator's knowledge regarding incidence, etiology and optimal treatment of pulmonary complications. Moreover, young children unable to perform spirometry are often diagnosed late, and strategies for monitoring therapeutic response are limited. This is a prospective multi-institutional cohort study in pediatric patients undergoing allogeneic (alloHSCT) or autologous hematopoietic stem cell transplantation (autoHSCT). Assembly of a large prospective uniformly screened cohort of children receiving HSCT, together with collection of biological samples, will be an effective strategy to identify mechanisms of lung injury, test novel diagnostic strategies for earlier diagnosis, and novel treatments to reduce morbidity and mortality from lung injury after transplant.