This is a multicentre,double blinded,randomised,active-controlled study of a novel vaccine SII-TCV(B) against typhoid and paratyphoid A infection,using a healthy adult participant controlled human challenge model of paratyphoid A infection compared with a licensed Vi-polysaccharide vaccine against typhoid infection (Typhim Vi). The aim is to assess the efficacy of SII-TCV(B) against S. Paratyphi A using the challenge model and to demonstrate the non-inferiority of the immune response to the S. Typhi component of SII-TCV(B),when compared to Typhim Vi. In total,192 participants will ...

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This is a platform trial testing the addition of experimental treatments to standard of care (SoC) with two randomised controlled trials called research comparisons. The platform design allows the addition of other research treatments into the structure following protocol amendment. The primary objectives of each comparison are to test whether survival and/or cancer outcomes can be improved by the addition of the research treatments to SoC in men with metastatic prostate cancer and starting long-term androgen deprivation therapy. Key secondary objectives ...

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This is a first-in-human Phase I, open-label, multicenter, dose-escalation and expansion study designed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary anti-tumour activity of RO7566802 as a single agent and in combination with atezolizumab in patients with locally advanced, recurrent, or metastatic incurable solid tumour malignancies. The study consists of a screening period of up to 28 days, a treatment period, a minimum follow-up period of 90 days after treatment, and survival follow-up. Patients will be enrolled in two stages: a ...

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We will use state-of-the-art imaging to look at heart disease in people with haemophilia. Haemophilia is an inherited disorder in which blood does not clot properly because of lack of a key ‘glue’ blood component (chemicals known as factor VIII or IX). People with haemophilia are 40% less likely to die of heart disease, but we don’t know why. Understanding heart disease in people with haemophilia is important because better treatments for haemophilia mean that these patients are now ...

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To evaluate the effect of AP01 100 mg given twice daily (BID) and AP01 50 mg BID compared to AP01 placebo (hereafter referred to as placebo) on lung function over 52 weeks in subjects with PPF B17: Secondary objective(s) To evaluate the effect of AP01 100 mg given twice daily (BID) and AP01 50 mg BID compared to AP01 placebo (hereafter referred to as placebo) on lung function over 52 weeks in subjects with PPF B18: Full inclusion criteria

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Design: A 2x2 factorial pragmatic open-label randomised controlled trial,with an embedded randomised double-blind parallel group trial Setting: 60 general ICUs in the UK Target population: Adult patients who are critically ill due to sepsis Inclusion criteria - Adult patients admitted to ICU due to suspected sepsis and expected to stay for at least 48 hours - Receiving intravenous antibiotics for suspected sepsis - Initial early fluid resuscitation complete - Acute organ dysfunction due to infection Additional criteria for GM-CSF subset - Mechanically ventilated - Receiving vasopressors/inotropes - Absolute lymphocyte count <1.2 ...

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Cytomegalovirus (CMV), the international leading cause of neurodevelopmental impairment from infection acquired during pregnancy, is estimated to affect over 4200 babies and cost over £750 million each year in the UK. CMV is a common virus usually causing mild infection in healthy individuals, however CMV can cause serious disease if it affects a baby during pregnancy. Only the most severely affected cases of CMV acquired in pregnancy tend to be identified by healthcare professionals because there is currently no screening ...

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People with any condition that affects the liver over a long period of time can develop cirrhosis. Conditions that can lead to cirrhosis include alcohol excess, liver steatosis (lipid or fat accumulation in the liver) and infection with hepatitis B and C. One concern about people with cirrhosis is that they are at increased risk of developing liver cancer. People with cirrhosis are recommended to have an ultrasound scan (USS) every 6 months (surveillance) so that if a cancer develops, ...

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Our musculoskeletal system is essential for movement and to give our body structure. The system is made up of bones (skeleton) and soft connective tissues (muscles, tendons, cartilage and ligaments )that enable the skeleton to move. These tissues contain cells that work together to help the tissue function and grow normally. Our musculoskeletal system changes continuously from infancy to adulthood, with each tissue type changing in both size and shape, and they become less effective at repairing themselves when injured. Our ...

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Parkinson's disease (PD) is the second commonest neurodegenerative disorder, affecting over 145,000 people in the UK. Initially, PD patients experience slowness of movements, limb stiffness, and tremor. With progressive loss of neurons over time, many patients start to experience balance and walking problems, and falls, which are resistant to currently available treatments. Falls can lead to fractures and nursing home admission, and can significantly shorten patients' life expectancy. In this pilot study, we will investigate the effects of spinal ...

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