Vaccine and Infection Research

Some people who had COVID-19 have persistent symptoms beyond 3 months after the infection. This is known as Long Covid. Long Covid is thought to affect around 2 million people in the UK. As many as seven out of ten adults don’t feel fully recovered from COVID-19 a year after leaving hospital. Currently there are no specific medications for Long Covid, and it is therefore a national priority to find effective treatments.  

This trial aims to investigate whether a medication called Tocilizumab will help patients with Long Covid feel better and improve their symptoms. Tocilizumab is in an anti-inflammatory medication. It has been used for many years to treat some types of arthritis and inflammatory diseases. Tocilizumab is currently being used to treat some patients admitted to hospital with COVID-19. We have previously shown that people with the worst health after COVID-19 had higher levels of inflammation.  We are testing whether treating patients with Long COVID and ongoing inflammation with Tocilizumab will help them feel better. This trial is comparing Tocilizumab with a placebo (‘dummy drug’). Approximately 152 participants will be asked to take part in this trial from approximately 15 UK hospitals. 

In order to understand if the treatment is effective, we would like to collect information from you including health questionnaires, tests of physical function, breathing tests, blood, urine and stool samples as well as collecting information from your medical notes. This will also enable us to compare information between those who are receiving Tocilizumab and those who receive the placebo (dummy drug).

Project Details
Principal Investigator: Dr. Nick Maskell
Planned End Date: 31/08/2025
Local Ref: 5613

Infection of the bloodstream with the bacterium Staphylococcus aureus (Staphylococcus aureus bacteraemia, SAB) is a serious infection that results in 15-30% (mortality lower in children but up to 5%) of affected patients dying within three months of acquiring the infection. Treatment of this infection requires patients to be hospitalised, treated with prolonged antibiotics through an intravenous line, and carefully examined for the occurrence of complications associated with this condition. At present, there are many treatment options in current use, with no clear agreement as to which of these is best. The SNAP trial aims to identify which treatment options for SAB results in the fewest patients dying within the first 90 days after an infection. 

In contrast to a conventional clinical trial, the SNAP trial will examine multiple different treatment options at once. Patients will be randomly assigned to different concurrent treatment options currently considered acceptable in routine medical care. The trial will adapt to accumulating trial evidence, on a regular basis, by removing treatment options found to be inferior, incorporating new treatment options, and ensuring that all patients in the trial receive the best treatments once they have been identified. Over time, we hope to determine the best combination of treatment options for patients with SAB.

Project Details
Principal Investigator: Ed Moran
Planned End Date: 31/12/2029
Local Ref: 5305

The global burden of hospital admissions due to respiratory viral illnesses is considerable across the lifespan. Treatment options are mainly supportive, with limited benefit to specific antiviral agents to date. Vaccination is the most effective public health measure currently available. Response to infection is variable, with some experiencing only mild symptoms that do not require admission, whilst others develop a severe response to infection and require higher level care. Rates of complications from respiratory viral infections appear comparable to influenza, suggesting greater attention needs to be focussed on non-influenza respiratory viral illness. 

The recent pandemic highlighted the need to link clinical care with research for more rapid translation of new treatment discoveries. The majority of winter pressures facing NHS acute trusts are as a result of acute respiratory viral infection. Whilst many patients recover without need for hospitalisation, a small proportion go on to develop severe disease. A better understanding of the natural history of acute respiratory viral infection and recovery will facilitate improved clinical management with the potential to identify options for intervention in those at risk of more severe disease, with resultant health economic benefits.

We aim to better understand the different responses between individuals to respiratory viral infections, and why some patients become more unwell than others. We hope to identify new ways to spot respiratory diseases. We want to recruit 2,000 volunteers to take part. 

Project Details
Principal Investigator: Jade King
Planned End Date: 31/12/2026
Local Ref: 5607 

We aim to find the shortest length of time we can give someone an antibiotic when they have a urinary tract infection (UTI) and still be able to treat that infection effectively. 

UTIs, which are infections of the bladder or the kidney, are among the most common infections treated with antibiotics and are far more common in women than men. Over four million prescriptions for UTIs are given to women in the UK every year. However, there is little evidence to help doctors decide how many days of antibiotic treatment are necessary. We think that one way to keep antibiotics working for patients and for the future is to reduce the amount we prescribe, so we need to use the shortest treatment duration which still ensures that the infection is properly treated. 

Bacteria can develop ways to avoid being killed by antibiotics, this is called resistance. We want to find out whether taking less days of antibiotics reduces the chances of the bacteria becoming resistant. We will do this by looking at the impact of the length of treatment on the bacteria in the bowels and also by looking at the bacteria causing any UTIs which occur after starting in the trial. We will also be looking at the cost effectiveness of the different treatment durations and the impact of your quality of life. The total length of the trial will be 36 months, your involvement will last for 6 weeks, and we will access your medical record 6 months after you join the study.

Project Details
Principal Investigator: Dr. Ankur Gupta Wright
Planned End Date: 31/07/2025
Local Ref: 5415

The purpose of RESTORATiVE303 is to see if the study drug, which is called VE303, is safe and effective in preventing you from having another episode of CDI. 

VE303 is an investigational drug that has 8 strains of live bacteria. “Investigational” means that VE303 is not approved for use in people diagnosed with CDI by the Medicines and Healthcare products Regulatory Agency (MHRA), European Medicines Agency (EMA), or any other regulatory authorities. 

The bacteria strains in VE303 are called “commensals.” Commensals are the type of bacteria that live in harmony with your body, without harming health. These specific bacteria are often found in the intestines of normal, healthy people. They were selected for inclusion in VE303 because they rarely infect humans (mostly in very weakened patients), they do not carry any toxins that can make you sick, and they are not known to carry any risk of creating or spreading resistance to antibiotics. 

If you are eligible and choose to take part in this double-blind, placebo-controlled study, you will be randomly assigned to 1 of 2 treatment groups. “Randomly assigned” means that you will be entered into the treatment group by chance (like flipping a coin). Neither you nor the Study Doctor can choose which group you will enter. “Double-blind” means that the Study Doctor, study staff, the study Sponsor, and you, will not know whether you are receiving VE303 or placebo. However, in case of an emergency, the Study Doctor or study staff can find out what study drug you are taking. If you are selected to enter the placebo group, the placebo capsules look just like the VE303 capsules, but do not have any live bacteria. The probability for random treatment assignment is 2:1, meaning that you have a two-out-of-three chance of getting VE303 as your treatment. 

You will be asked to take 3 capsules of the study drug, once per day for 14 days, starting within two days after the last dose of antibiotics for your current CDI episode. Once all participants complete the study, the results obtained in the two groups will be compared to see if VE303 is safe and if it is more effective than the placebo.

Project Details
Principal Investigator: Dr. Ed Moran
Planned End Date: 19/12/2025
Local Ref: 5496

Arboviruses are a group of viruses that are transmitted by arthropod insects such as mosquitoes, ticks and midges and cause diseases in humans. (Arthropod Borne Viruses= Arboviruses) They can cause a variety of different symptoms from high temperatures, skin rashes, pains in your muscles and joints, to internal bleeding (haemorrhage) and brain swelling (encephalitis). 

You may have heard of some of the more common infections such as dengue virus, chikungunya, west Nile virus, yellow fever and zika virus but there are many more. 

We are trying to understand why some people develop worse symptoms than others, also how initially and over time people’s immune systems respond to fight off these infections and how people feel after these infections. 

We are also aiming to produce a collection of blood samples and throat swabs from people who have had Arboviral infections which may be used to test new products being developed to diagnose, confirm or even treat Arboviruses. 

You have been invited to take part in this study because you either have been confirmed to have an Arboviral infection or your doctors strongly suspect you probably have an Arboviral infection given the symptoms and signs you have displayed in your recent illness together with your travel history. 

If you decide to take part your doctor will provide us with information regarding your recent illness and your general medical health. We will require you to donate blood samples, throat swabs and to complete a survey regarding your symptoms. This will be done now, in one month and six months.

Project Details
Principal Investigator: Dr. Alex May
Planned End Date: 01/12/2029
Local Ref: 5610

In the UK, TB is routinely treated with a combination of four medicines, this is referred to as 4-drug treatment. Most patients can successfully complete their treatment course without any problems. Unfortunately, in some cases, the treatment can begin to cause damage to the liver, this is called drug-induced liver injury (DILI). To protect the liver and encourage it to recover, the TB treatment is stopped. 

Once the liver has recovered doctors must decide how to restart TB treatment. There are two options that are used in the NHS. One is to re-introduce all 4 drugs again and complete 6 months of treatment, the other option is to re-introduce only 3 drugs, leaving out the drug pyrazinamide (Z), and complete 9 months of treatment.  

Some research suggests that leaving out pyrazinamide (Z), lowers the chance that a patient will experience another episode of DILI, it might be safer for the patient, and less disruptive to their TB treatment. 

The main purpose of the TB-DILI trial is to determine whether restarting TB treatment with only 3 drugs is safer for patients than restarting with 4 drugs. We will determine this by looking at how many patients on each treatment (restarted with 3 or 4 drugs) go on to experience a reoccurrence of DILI. Participants on the trial will be randomly assigned one of the two treatment options. We will also perform an investigation to see which of the treatment options is more cost-effective for the NHS. At the end of this trial, we hope to be able to advise the NHS on the best way that doctors should treat future TB-DILI patients. 

Project Details
Principal Investigator: Dr. Ankur Gupta Wright
Planned End Date: 30/08/2026
Local Ref: 5402

This study aims to find out if tozorakimab is safe and effective in treating severe viral lung infections with Acute Respiratory Failure (ARF). ARF is a condition in which your lungs have difficulty getting enough oxygen or removing carbon dioxide. 

Tozorakimab is a research drug and has not been approved by any health authority, except for use in research studies like this. Tozorakimab is a protein called an "antibody" designed to stick to and decrease levels of Interleukin-33 (IL-33), which is made in the lungs following viral infection. We would like to find out if tozorakimab can prevent the need for invasive mechanical ventilation (breathing support with a machine connected to a tube placed into the airway through the mouth or nose). 

Tozorakimab is an investigational study drug and has not been approved by any health authority, except for use in research studies like this. The experimental, or not fully tested parts of the study are the efficacy (how well the drug works) and safety of tozorakimab in participants hospitalised for viral lung infection requiring supplemental oxygen. 

Approximately 2,902 people will take part. The study is funded by AstraZeneca AB.

Project Details
Principal Investigator: Dr. David Arnold
Planned End Date: 30/04/2026
Local Ref: 5316

mRNA-1403 is a norovirus (NoV) mRNA-based vaccine candidate that is being developed for prevention of NoV-associated Acute Gastroenteritis (AGE).

Norovirus is one of the leading causes of AGE worldwide and is the leading cause of AGE in many countries that have implemented rotavirus vaccination, including the US. Currently, no licensed NoV vaccine is available for prevention of AGE caused by NoV. This Phase 3, randomized, observer-blinded, placebo-controlled, multicentre study will be conducted globally. The purpose of this Phase 3 study is to establish the safety and efficacy of mRNA-1403 vaccine in adults ≥18 years of age in support of licensure. Approximately 25,000 to 30,000 participants will be randomly assigned in a 1:1 ratio to receive a single injection of either 50 µg of mRNA-1403 or placebo. The total duration of study participation will be approximately 25 months.

Project Details
Principal Investigator: Dr. Ed Moran
Planned End Date: 28/01/2025
Local Ref: 5624