Case study: Delivering commercial Urgent Public Health Research: Synairgen
The treatment candidate
The UK trial infrastructure and support enables smaller companies like ours to operate on that same international platform... It has truly enabled us to hit the ground running, and for the UK to shine.
COVID-19 is a global threat and there is an urgent need to assess new treatments and vaccines. According to the World Health Organisation, around one in five people who contract COVID-19 experience breathing difficulties caused by severe lower respiratory tract (LRT) illness. Synairgen, a small British biotech company, is trialling a new treatment to investigate if it can safely and effectively prevent and treat respiratory illness which is associated with COVID-19.
The treatment in question, known as SNG001, is an experimental medicine. In 2018 Synairgen commenced a phase II trial investigating if this treatment can help reduce exacerbations caused by cold or flu viral infections in patients with Chronic Obstructive Pulmonary Disease (COPD). Richard Marsden, CEO of Synairgen, explains the science behind the treatment:
“It is an inhaled form of interferon beta (IFN-beta) - a protein that is produced naturally by the human body. When we get a viral infection it triggers an immune response and our bodies begin to release interferon beta. This protein helps coordinate the body’s antiviral defences. If we don’t make enough interferon beta then we may struggle to overcome the viral infection.
“Some viruses, like the SARS-CoV-2 virus that causes COVID-19, can trick the immune system and suppress production of interferon beta. This is part of the virus’ strategy as it helps the virus to evade the immune system. There is also evidence suggesting that a deficiency of interferon beta production by the lung could be one of the reasons why older COVID-19 patients, and those with some co-morbidities, are more susceptible to developing severe respiratory illness.
“In the lab interferon beta has been shown to protect cells from infection with a broad range of respiratory viruses, including highly pathogenic coronavirus strains, such SARS-CoV-2. So we know we have quite a strong candidate for an effective treatment.”
Expediting the trial
Having already accessed NIHR support for the earlier COPD study, Synairgen knew exactly where to go to rapidly deliver a new study named SG016. Richard Marsden continues:
“This is the second trial we have delivered with NIHR support and, because the treatment is already in trials, we were able to go straight into a placebo controlled trial. With support from the NIHR Respiratory TRC, we learned how to deliver a trial in hospitalised COVID-19 patients, at a time when the clinical infrastructure was under huge strain.”
NIHR Translational Research Collaborations (TRCs) are ready-formed networks of the UK’s leading universities, NHS trusts and research centres which carry out early phase translational research and tackle experimental medicine challenges in selected therapeutic areas. These collaborations are set-up to support and work with the life sciences industry, charities and other funders and partners. They provide access to networks of internationally recognised investigators in the UK's leading centres of excellence. Nour Merzouki, Collaborations Operations Manager for the NIHR Respiratory TRC, describes how the TRC supported Synairgen’s COVID-19 study proposal:
“The Respiratory TRC has 10 member sites linked to the NIHR Biomedical Research Centres (BRCs). We provide scientific advice on a proposed study, help shape the protocol, and coordinate the collective response for prioritisation of, and participation in clinical trials for our member sites.
“Synairgen’s nebulised IFN study was one of the first studies we supported for COVID-19 - it came to us at the beginning of March. The TRC members evaluated and provided a collective view on the protocol and implementation of the trial. We also supported and coordinated involvement of BRC sites across the TRC respiratory network. This contributed to dosing in patients within a few weeks of the TRC being approached by Synairgen. Five TRC sites supported the study, plus a number of other sites.”
In parallel the NIHR Clinical Research Network, which supports the planning, set-up and delivery of clinical research in England, expedited the process of adding the study to the NIHR Portfolio and validating the study costing template. Carolina Parás is the Industry Operations Manager for Wessex Local Clinical Research Network (LCRN) – one of 15 LCRNs that cover the whole of England. She explains why this is a crucial step in the study set-up process:
“The LCRN leading on the study (usually where the Chief Investigator site is located) will perform a quality check or ‘validation’ of the study-specific costing. The validation ensures that all protocol required procedures, investigations and tasks are included in the template and highlights areas where additional activities may be required for inclusion to capture all the study delivery requirements for the site. This validation is required prior to Health Research Authority (HRA) Approval and an application for the NIHR Clinical Research Network Portfolio is required before the validation can take place. Working with the national Clinical Research Network Coordinating Centre, we were able to complete both tasks, on behalf of the company, within 48 hours.”
The UK’s system-wide approach to prioritising Urgent Public Health Research became fully operational during March and includes HRA and the Medicines and Healthcare Products Regulatory Agency (MHRA) among others. Both HRA Approval and MHRA Approval were expedited for the Synairgen study and acquired in 11 and four days respectively. Richard Marsden comments on the rapidity of study set-up:
Within a few weeks we opened the study and were heading towards our recruitment target. This is a tremendous achievement which could not have happened without the collaborative effort we are seeing in the UK.
“Having one place to submit study details to trigger the study support and set-up process was really helpful. The speed that we received MHRA approval and ethics approvals through HRA was remarkable. Within a few weeks we opened the study and were heading towards our recruitment target. This is a tremendous achievement which could not have happened without the collaborative effort we are seeing in the UK. This includes the MHRA, the HRA and the research infrastructure provided by the NIHR.
“Then, having already made connections through the NIHR Respiratory TRC, we were able to quickly and easily engage many of the same sites to deliver this COVID-19 study such as: Leicester, Nottingham, Belfast, Manchester, Southampton and Oxford. We are also delivering the study at sites in Bradford, Birmingham and Hull – which have also been excellent. It’s brilliant to have these top-flight sites on board, and when I say ‘top-flight’ we are talking about some of the top sites internationally for this type of research.”
The study, which is a double blind placebo controlled study of SNG001, accomplished its target of recruiting 100 patients in approximately seven weeks. But as the volume of new COVID-19 cases in the UK began to decrease, and the number of active COVID-19 trials increased, recruitment became more challenging. Carolina Parás explains:
“The NIHR Clinical Research Network provides a performance monitoring service and about three weeks after the study had opened we noticed that recruitment to the Synairgen trial began to slow. This was because a number of other COVID-19 studies were gathering momentum and becoming quite high profile, particularly the RECOVERY trial. In response, we arranged calls with my counterpart colleagues in the other LCRN regions where the Synairgen study was taking place and colleagues at the Clinical Research Network Coordinating Centre. We agreed a strategy which included reaching out to the relevant research delivery teams and reiterated that all COVID studies were high priority, including the Synairgen study. This helped to boost recruitment and now all 100 participants have been recruited in a matter of weeks. That is an exceptional achievement for a commercial, interventional trial, in the middle of a pandemic.”
Extending the trial into the community
In addition to the participant recruitment efforts, a second part of the trial was being planned using a decentralised delivery model investigating the use of SNG001 in patients in the home setting. Richard Marsden explains:
“Getting SNG001 into at-risk patients early in the course of the infection was always one of our objectives. This part of the trial is now underway and it has taken a very novel trial design to accomplish this. We worked in collaboration with Wessex LCRN and the Clinical Trials Unit at the University of Southampton to plan and set-up this very novel, virtual, home-dosing extension as part of the same SG016 trial of SNG001.
“Patients at high risk of severe lower respiratory tract illness - over 65 year olds, and over 50s with a co-morbidity - will be dosed in their home environment early in the course of the disease; by this we mean within 4 days of symptoms first developing. We will happily accept an NHS test result for coronavirus, but we are also setting up our own virus testing facilities to analyse swabs quickly. We have a contract with a seven days-a-week pharmacy service (Ringwood Pharmacy); and we have built a team of remote working ‘virtual’ doctors and nurses who will conduct all trial visits by video conference. This means that the patient doesn’t need to leave their home for the ‘virtual’ trial visits, and the researchers do not need to be exposed to infected patients.
“Interested patients will firstly discuss the trial with a trial doctor in an online consultation. Patients can enter the trial if they already have a positive test result, for example from an NHS testing centre. Alternatively, in some localities, we will arrange for a swab testing kit to be delivered by courier to the patient’s home. Those patients will need to self-swab under the supervision of a ‘virtual nurse’ while the courier waits to take the packaged swab to the lab for testing. Eligible patients who test positive for SARS-CoV-2 will receive a box containing SNG001 or placebo, the aerosol delivery device, pulse oximeter, thermometer, and other consumables required for the trial. All doses will be supervised and all endpoints will be assessed via video call.”
Professor Nick Francis is the Deputy Chief Investigator of the trial. He explains the thinking behind the extension of the trial:
“If SNG001 is able to protect patients’ lungs, especially later in the course of this infection, it will be a major breakthrough - which is desperately needed. For this part of the study we are targeting patients within 40 miles of Southampton, over the age of 65 or those over 50 with a comorbidity, who have had COVID-19 symptoms for less than four days. People in this area can find out more about the trial by visiting www.covidtrialathome.com.”
Switching from recruiting hospitalised, confirmed COVID-19 patients across the country, to recruiting patients who a) need testing, b) are at home in the community and c) within a 40 mile radius of Southampton, requires a completely different approach. Fortunately, provision of local knowledge, expertise and intelligence is one of the unique selling points of the NIHR Clinical Research Network’s geographically distributed model. Martine Cross, Primary Care Delivery Manager, describes how Wessex LCRN provided study set-up support locally:
“Firstly we used our local intelligence to advise the Synairgen team on the most suitable GP practices to set up as sites within the study’s catchment area. As a result, three GP practices were set up as research hubs for the study based on their substantial experience and strong track record of timely delivery of commercial studies. Feasibility searches were then carried out on General Practice IT systems - EMIS and SystmOne - by the Wessex LCRN General Practice locality leads to inform the decision making around the recruitment methodology. In parallel, other logistical issues such as how we achieve the most efficient supply of the Investigational Medicinal Product (IMP) were being considered in the planning conversations.”
The NHS, combined with the NIHR research infrastructure, make the UK is a unique place to deliver clinical research and many countries will be looking to the clinical evidence generated here for solutions to beat the global COVID-19 challenge. In the UK (as of 8 March) over 925,000 participants have joined COVID-19 trials and a total of 92 studies have been prioritised as Urgent Public Health Research. This includes commercial studies being run by large global life science companies. In addition, other platform studies such as the RECOVERY trial and the REMAP-CAP trial which have an academic base, are enabling life science global companies, large and small, to rapidly test new treatments and compounds. The NIHR has been a major enabler in the rapid set-up and delivery of these trials. Richard Marsden concludes by reflecting on the global perspective:
“Synairgen is a small company, especially when compared to some of the global pharmaceutical and biotech giants like AstraZeneca, Roche, Novartis and Gilead which are currently spearheading some of the international COVID-19 clinical trials. The UK trial infrastructure and support enables smaller companies like ours to operate on that same international platform. That’s what is so unique about the UK’s research infrastructure. It has truly enabled us to hit the ground running, and for the UK to shine. Without this whole system approach we would not be performing as well as a country.”
Trial update: 20 July 2020
Synairgen announced positive results from its Phase II double-blind placebo-controlled trial of inhaled interferon beta, SNG001, in hospitalised COVID-19 patients. Patients who received SNG001 were more than twice as likely to recover (defined as ‘no limitation of activities’ or ‘no clinical or virological evidence of infection’) over the course of the treatment period compared to those receiving placebo in both the ITT population (HR 2.19; p=0.017) and the PP population (HR 2.29; p=0.033). Read more on the results from its Phase II double-blind placebo-controlled trial of inhaled interferon beta Synairgen's website.
Trial update: 28 January 2021
Since this article was written, in June 2020, the home study arm of the SG016 trial, investigating SNG001 in patients in the home setting, has successfully reached its recruitment target. This was a smaller, pilot study and the next step will be to assess the data. Depending on the results, this trial may be expanded in the future.
Following the original SG016 trial, investigating SNG001, Synairgen has commenced a Phase III randomised placebo-controlled trial of SNG001 in hospitalised COVID-19 patients, named SG018. The trial is a randomised, placebo-controlled study being conducted in approximately 20 countries enrolling a total of 610 COVID-19 patients.This trial has also been awarded Urgent Publich Health status in the UK and is being supported by the NIHR.
- On 4 May 2020 BBC Panorama featured NIHR-supported Urgent Public Health COVID19 studies. The programme includes interviews with Prof Tom Wilkinson, Chief Investigator for Synairgen's SNG001 trial and Richard Marsdan CEO of Synairgen.
- Further information on how to conduct commercial COVID-19 research in the UK
Learn how life science companies can access Government support to expedite and deliver commercial COVID-19 research in the UK.