Benaguasil, Spain

A Study of Guselkumab in Participants With Fistulizing, Perianal Crohn's Disease

HEM ISMART-D: Trametinib + Dexamethasone + Chemotherapy in Children with Relapsed or Refractory Hematological Malignancies

HEM-iSMART is a master protocol with sub-protocols. The overarching objective is that introducing targeted therapy using a biomarker driven approach for treatment stratification may improve the outcome of children with R/R acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) It is characterized by a shared framework that allows for the investigation of multiple IMPs and generate pivotal safety and efficacy evidence within the sub-protocols to establish and define the benefits and risks of new treatments for children with R/R leukemia. Sub-Protocol D within HEM-iSMART, is a phase I/II, multicenter, international, open-label clinical trial designed to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of trametinib in combination with dexamethasone, cyclophosphamide and cytarabine in children, adolescents and young with R/R ALL and LBL. Patients with actionable alterations in the RAS-RAF-MAPK pathway will be eligible for sub-protocol D including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del.

Clinical Study of Antibody-Drug Conjugate MYTX-011 in Subjects With Non-Small Cell Lung Cancer

The study will be conducted in 2 parts. Part 1 will assess the safety and tolerability of MYTX-011 and identify the dose to be studied in Part 2. Part 2 will include subjects with NSCLC with cMET overexpression or MET amplification/exon 14 skipping mutations, populations with a current unmet medical need.

Randomised Open Label Trial of Hypertonic Saline and Carbocisteine in Bronchiectasis (CLEAR)

Mucus hypersecretion is a clinical feature of BE. This mucus-retention aids bacterial infection that can lead to pulmonary exacerbations, which further develops the "viscous cycle" of mucus-retention, infection, inflammation and tissue damage. Mucoactive drugs target this cycle by potentially increasing the ability to expectorate sputum and/or decrease mucus hypersecretion. The current guidelines indicate that mucoactives in combination with airway clearance may be considered to enhance sputum expectoration in BE, but the evidence to support their use is limited. Furthermore, evidence for the effectiveness of hypertonic saline (HTS) and carbocisteine is insufficient to recommend them within the management of BE. However, EMBARC/BRONCH-UK data show that BE centres do prescribe mucoactives. This is important because adherence to therapies in BE in general is low, decreases as the number of prescribed medications increases, and is also related to poorer patient outcomes, including the number of pulmonary exacerbations and quality of life. Therefore, it is essential that only those drugs that are effective should be prescribed for patients with BE. There are cost considerations associated with mucoactives, and there is a risk of polypharmacy side effects. Unlike BE, relatively strong evidence exists to favour the use of both HTS and carbocisteine within other respiratory conditions. Therefore, this trial will answer important clinical questions about whether similar benefits can be demonstrated in BE by using a pragmatic design to explore the specific effects of mucoactive agents, and directly support, or refute, more targeted use of these drugs. Patients will be randomised to one of four treatment groups: (i) standard care and twice daily nebulised HTS (6%), (ii) standard care and carbocisteine, (iii) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (iv) standard care alone.

PRIMUS 001: A Study Looking at Two Different Chemotherapy Regimens in Patients With Metastatic Pancreatic Cancer

PRIMUS 001 is a multicentre, randomised, open label, two arm, phase II interventional trial with pre-clinical and translational work including in-depth molecular profiling and biomarker discovery/development. The primary objective is to look at the efficacy of FOLFOX-A compared to AG in all comers and in a biomarker positive group using progression free survival.

Clinical and Immunogenetic Characterization of Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR)

Giant cell arteritis (GCA), also known as temporal arteritis, is the most common form of primary systemic vasculitis, with up to 75,000 cases a year identified in the EU and US. It occurs almost exclusively in people over the age of 50 years and is considered to be a medical emergency. If not treated with high-dose glucocorticoids immediately, the thickening of the inflamed blood vessel wall can cause irreversible visual loss or stroke. GCA can lead to significant morbidity across a variety of systems, due to both the disease, and complications of treatment. Diagnosis may be confirmed with a temporal artery biopsy, imaging (e.g. USS/CT/MRA/PET-CR) or based on clinical signs (e.g. erythrocyte sedimentation rate) and symptoms (e.g. a new headache, jaw claudication, visual disturbances, temporal artery abnormality such as tenderness or decreased pulsation) . Polymyalgia rheumatica (PMR) is characterised by inflammatory limb-girdle pain with early morning stiffness, and a systemic inflammatory response demonstrated by elevated inflammatory markers. The UK GCA Consortium is a multi-centre observational study, the main arms of which recruit prospective (participants with suspected GCA) and retrospective cohorts (participants with confirmed GCA diagnosis). Analysis of data collected on these cohorts will help achieve the primary aim of finding genetic determinants of GCA and PMR susceptibility, in order to yield novel insights into disease pathogenesis. Secondary aims, and their associated analyses, are as follows: - Phenotype: characterising GCA and PMR subtypes, based on clinical features; imaging; cells; subcellular fractions and molecules in the circulation and/or arterial tissue; genetic/epigenetic/transcriptomic/proteomic or metabolomics factors, including next generation sequencing (whole exome sequencing) of selected cases. - Life impact: determining what aspects of the disease and treatments affect patients' quality of life, as assessed by patient-reported outcomes. - Long-term outcomes: characterising prognosis of GCA and PMR - both effects of the disease and its treatment - by longitudinal follow-up through electronic linkage to health records. - Exploratory analyses: exploring the potential role of environmental factors and co-morbidities on phenotype and outcomes. - Diagnosis, prognosis: improving diagnosis of GCA and PMR, and identifying factors that predict diagnosis, such as diagnostic clinical features, and prognostic and diagnostic biomarkers. - Disease activity: monitoring participants who commence a synthetic or biological disease-modifying anti-rheumatic drug (s/bDMARD). Finding a biomarker for GCA and PMR disease activity, which might be clinically useful in helping to optimise steroid and s/bDMARD treatments for individual patients.

Natural History of Duchenne Muscular Dystrophy

Study duration from FPFV: Q1 2019 to LPLV: Q3 2023 Primary Ojectives: - To assess the natural disease course using standardized and disease appropriate evaluations over a period of 6 to 36 months in a cohort of young male subjects aged from 5 to 9 years at inclusion and diagnosed for Duchenne Muscular Dystrophy (DMD). - To record a baseline period prior to the setup of an AAV gene therapy dose escalation phase I/II First in Man clinical study. Secondary Objectives: - To identify clinical, imaging and/or laboratory parameters that could be predictive indicators of the disease course in DMD, within the selected range of age. - To identify the best outcome measure(s) for further clinical trial assessments.

A Safety, Pharmacokinetic and Clinical Activity Study of NUC-7738 in Patients With Advanced Solid Tumours and Lymphoma