TACTIC-E trial to test whether a simple microbe could be an effective treatment for COVID-19

As part of a new trial led by Cambridge University Hospitals and supported by NIHR Cambridge Biomedical Research Centre, a microbe will be used to treat severe COVID-19 in an experimental drug known as EDP1815. Developed by Evelo Biosciences, EDP1815 is a naturally occurring microbe that has been isolated from the small intestine of a human donor.

EDP1815 works by communicating with immune cells in the small intestine, which in turn communicate with other immune cells around the rest of the body. Via the gut immune cells, EDP1815 can broadcast a message to the immune cells in other organs to reduce production of the chemical messengers, known as cytokines, that cause inflammation (and damage to organs), while encouraging anti-inflammatory messages instead. Most importantly, EDP1815 does not affect cytokines known as type-1 interferons, which are essential allowing people to recover from infection. In this manner, the drug may support an immune response that is ‘just right’ – reducing harmful immune responses while supporting the immune system to clear the virus.

One of the key reasons for selecting EDP1815 for this study is its safety profile, which means it will be safer to use in many of the vulnerable groups that are at greater risk of COVID-19 complications. It is not absorbed into the body, and only persists while the patient continues on the drug.

EDP1815 is being tested as part of a newly launched trial, known as TACTIC-E, which has been designed to test experimental drugs that may treat COVID-19, as well as investigating whether combinations of drugs that are already in use for other conditions can be effective. As with similar trials, such as TACTIC-R and RECOVERY, further treatments can be added as they are identified. Each of the treatments will target as yet unexplored aspects of COVID-19, offering the chance to quickly test new treatments as well as shedding new light on how SARS-CoV2 causes such severe disease in some people.

A second arm of TACTIC-E aims to reduce the damage seen in the lungs of patients with severe COVID-19, using a combination of ambrisentan and dapagliflozin (both manufactured by Astra Zeneca), which are licensed for pulmonary hypertension (elevated pressure in the lungs) and type 2 diabetes respectively. People with cardio-metabolic diseases (such as obesity, type 2 diabetes, heart failure or kidney disease) are known to be at higher risk of serious complications from COVID-19.

Ambrisentan helps to relax the arteries within the lungs, improving blood flow and oxygen pick up as well as having an anti-inflammatory effect. Dapagliflozin, when used together with ambrisentan could help counteract changes in fluid distribution that ambrisentan can cause. Researchers also believe that dapagliflozin may have further beneficial effects for COVID-19 treatment, due to its ability to support heart and lung function by balancing glucose and sodium in the blood.

The TACTIC-E trial will recruit patients admitted to hospital with COVID-19 who are at risk of entering the second stage of COVID-19 disease, which occurs around the second week following infection. It is during this phase that immune damage and severe respiratory symptoms begin to develop, and researchers believe that the treatments being tested in the trial will be most effective during this period.

It is anticipated that fewer than 500 patients per arm will be needed to assess the effectiveness of each treatment, but as the number of people with COVID-19 continues to decline across the United Kingdom, there are plans to open the TACTIC-E trial in nations where infections remain high. This will ensure that researchers can quickly understand whether or not these treatments are effective.

TACTIC-E Principal Investigator and Consultant Clinical Pharmacologist at Cambridge University Hospitals NHS Foundation Trust (CUH) Dr Joseph Cheriyan, said “COVID-19 is a complex disease that affects people in different ways and we are going to need a range of treatments in our armoury to be able to beat it.

“On the Cambridge Biomedical Campus, we are uniquely placed to work in the NHS alongside academia and industry to bring early phase drugs into circulation, potentially making a massive difference to the lives of many, many people.

“We have brought all this experience to bear with TACTIC-E. We will be trialling treatments that a panel of independent experts consider most likely to work, which are either already licensed, or known to have excellent safety, and observe them very closely to see what happens in order to identify successful drugs early on.”

Professor Ian Wilkinson, Director of the Cambridge Clinical Trials Unit, and Professor of Therapeutics at the University of Cambridge said “As we enter the next phase of the COVID-19 pandemic, Cambridge is proud to play a role in the rapid evaluation of potential treatments.

“The TACTIC-E trial has been carefully designed to swiftly detect effectiveness of potential treatments using small numbers of patients. It has a strong focus on collecting high quality data to confirm safety and effectiveness, enabling our manufacturing partners to gain the necessary approvals for widespread international use.”

The trial is led by the Cambridge University Hospitals NHS Trust and is supported by the NIHR Cambridge Biomedical Research Centre. Funding and drug supply for the trial has been provided by Astra Zeneca and Evelo Biosciences.