Warwick

This study is researching an experimental drug called odronextamab (referred to as study drug), in combination with lenalidomide. The study is focused on participants who have one of two types of cancer: follicular lymphoma (FL) or marginal zone lymphoma (MZL) that has come back after treatment (called "relapsed"), or did not respond to treatment (called "refractory"). FL and MZL are subtypes of Non-Hodgkin 's lymphoma (NHL). This study will be made up of two parts (Part 1 not randomized, Part 2 randomized - controlled). The aim of Part 1 of the study is to see how safe and tolerable the study drug is when used in combination with lenalidomide, in participants with FL or MZL, and to determine the dose of the study drug to be used in Part 2 of this study. This combination is considered "first-in-human" as it has not been tested as a combination treatment in humans before. The aim of Part 2, of the study is to assess how well the combination of the study drug and lenalidomide works compared to the combination of rituximab (called "the comparator drug") and lenalidomide. The combination of comparator drug and lenalidomide is the current standard-of-care treatment for relapsed/refractory FL and/or MZL. Standard-of-care means the usual medication expected and used when receiving treatment for a condition. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug in combination with lenalidomide * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects) * The impact from the study drug on quality-of-life and ability to complete routine daily activities

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm of the study is 7 years. Eligible patients must have intermediate-high or high risk of recurrence as defined by specified clinical and biologic criteria. Concurrent use of abemaciclib is permitted in both arms. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.

PRINCIPLE RESEARCH QUESTIONS The project will address a number key principal research questions largely based on two phases to the study. Phase/study 1 1. What percentage of disorder of consciousness patients assessed provide evidence of awareness using EEG-based BCI technology? 2. How does this differ from their clinical diagnosis/prognosis? 3. Does the EEG-based information complement or augment the clinical assessment and diagnosis process? 4. Do any of those participants who are diagnosed as being in a vegetative state (or MCS) show signs of awareness beyond the vegetative state based on the EEG-based detection of awareness protocol? Phase/study 2 1. Is it possible to train those participants who show clear signs of awareness, as indicated by significant brain activation during the initial assessment in study 1, to produce a more prominent and/or consistent response over a number of training sessions using BCI based training and feedback protocols? 2. Can a subset of the participants use BCI technology to communicate simple responses to questions at the end of the study or is there enough evidence to suggest that with further training over a longer period that the participant may use BCI technology as an alternative or an exclusive communication channel? 3. Does neurotechnology offer any other therapeutic benefits to patients, for example, a means of technology interaction that is movement independent and engaging brain areas otherwise not engaged? SECONDARY RESEARCH Q UESTIONS 1. Does the technology aid feedback/interpretation on assessment outcomes from consultants? 2. How might the experiment provide an opportunity for training others in the deployment of the technology in a clinical setting? 3. What types of BCI methods of feedback are best auditory/visual or both, musical or broadband noise, games or applications etc?

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.

This is a phase 2, multicenter, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study to assess vamifeport in adult participants with homeostatic iron regulator gene-related hereditary hemochromatosis (HFE-HH). The primary objective of the study is to assess the effect of vamifeport treatment on magnetic resonance imaging (MRI)-based liver iron concentration (LIC) in adult participants with HFE-HH.

The trial will be a phase III, randomised-controlled, multi-centre, international, open-label trial consisting of ruxolitinib versus best available therapy, where best available therapy is a choice of interferon alpha, any formulation permitted (IFN) or hydroxycarbamide (HC), and which will be elected by the Investigator prior to randomisation. There will be no cross-over either between arm A and B or between therapies on Arm B HC and IFN will be provided as best available therapy, IFN can include standard of pegylated-interferon at Investigators discretion.

Community-acquired pneumonia (CAP) that is of sufficient severity to require admission to an intensive care unit (ICU) is associated with substantial mortality. Patients with pneumonia who are being treated in an ICU will receive therapy that consists of many different treatments, as many as 20 or 30. These treatments act together to treat both the infection and its effects on the body. When treating a patient, doctors choose from many different treatments, most of which are known or believed to be safe and effective. However, doctors don't always know which treatment option is the better one, as individuals or groups of individuals may respond differently. This study aims to help doctors understand which treatments work best. This clinical study has been designed in a way that allows the information from patients already in the study to help new patients joining the study. Most studies aren't able to do that. REMAP-CAP has been designed to: * Evaluate multiple treatment strategies, at the same time, in the same patient. * Reach platform conclusions when sufficient data is accrued, rather than when a pre-specified sample size is reached * Utilise data that is already accrued to increase the likelihood that patients within the trial are randomised to treatments that are more likely to be beneficial * New questions can be substituted into the trial as initial questions are answered, meaning that the trial can be perpetual or open-ended * Interactions between interventions in different domains can be evaluated It is reasonable to presume that any pandemic respiratory infection of major significance to public health will manifest as life-threatening respiratory infection including Severe Acute Respiratory illness and severe Community Acquired Pneumonia (CAP) with concomitant admission to hospital, and for some patients, admission to an Intensive Care Unit (ICU). Previous pandemics and more localized outbreaks of respiratory emerging infections have resulted in severe CAP and ICU admission. Previous pandemics and outbreaks of emerging infectious diseases have outlined the urgent need for evidence, preferably from Randomized Controlled Trials (RCTs), to guide best treatment. However, there are substantial challenges associated with being able to organize such trials when the time of onset of a pandemic and its exact nature are unpredictable. As an adaptive platform trial that enrolls patients during the interpandemic period, REMAP-CAP is ideally positioned to adapt, in the event of a respiratory pandemic, to evaluate existing treatments as well as novel approaches.

This is a major pragmatic multi-centre prospective parallel group open RCT. It will be conducted in the UK, Australia and New Zealand, funding is being sought in several countries to expand recruitment internationally. The study is in 2 phases: the vanguard and main phase. Therefore the study will run an internal pilot to prove recruitment of the relevant number of participants during the initial 2 years. The over-arching aim is to determine whether early AVR results in better clinical outcomes and cost-effectiveness than a strategy of expectant management in asymptomatic patients with severe AS. The primary hypothesis is that early AVR or TAVI in asymptomatic patients with severe AS will result in a reduction in the composite primary outcome of cardiovascular (CV) death and hospitalisation for heart failure (HHF) when compared to the conventional approach of expectant management. Potential participants will be identified by a member of the clinical care team following diagnosis with severe AS. Participants will be screened for eligibility using pre-specified inclusion/exclusion criteria. Eligible participants will be provided with a written version of the participant information sheet detailing the exact nature of the study, what it will involve for the participant and any risks involved with taking part. Participants will be given at least 24 hours to consider the information and decide whether or not to take part. The study will randomise up to 2844 patients with severe asymptomatic AS to either allocated expectant management OR aortic valve replacement. Participants randomised to AVR will be placed on a waiting list with the aim that surgery will be performed within 3 months, dependent on local hospitals' waiting lists. Participants randomised to AVR will undergo routine tests/procedures which may include coronary angiography. If the outcome of the coronary angiography reveals coronary heart disease, the decision to perform CABG or PCI will be made by the responsible cardiac surgeon and cardiologist, in consultation with the patient. All analyses will be undertaken using the principles of intention-to-treat with participants analysed in the group they were randomised regardless of treatment received. EASY-AS is collaborating with the EVoLVeD study (Early Valve Replacement guided by Biomarkers of Left Ventricular Decompensation in Asymptomatic Patients with Severe Aortic Stenosis, Clinical Trials.gov NCT03094143). In centres where both EASY-AS and EVoLVeD are running, participants in EASY-AS will be offered the opportunity to take part in EVoLVeD. Funding has been granted by the British Heart Foundation (UK), Medical Research Future Fund (Aus) and Heart Foundation (NZ). The UK sponsor is the University of Leicester. Additional support and resources for the study will be provided by the participating Trusts and their corresponding Clinical Research Networks in the UK. The central co-ordination centre is the University of Leicester Clinical Trials Unit.