Periodic Reporting for period 3 - ECRAID-Prime (European Clinical Research Alliance on Infectious Diseases - PRIMary care adaptive platform trial for pandemics and Epidemics)
Berichtszeitraum: 2024-12-01 bis 2025-11-30
European citizens affected by COVID-19 have been well-served by landmark clinical trials in hospitals that have found treatments that save many lives. However, there are fewer opportunities in the community to contribute to the urgent mission of finding treatments that speed recovery, and reduce the need for hospital admission in the first place. In addition to SARS-CoV-2 other respiratory viruses will co-circulate like influenza, respiratory syncytial virus, other coronaviruses and others. There are not many evidence-based therapeutics to treat patients infected with these viruses in the primary and community care setting. Therapeutics for use in this setting have the potential for considerable reach and impact on individual suffering and functioning, as well as on the sustainability of health services. ECRAID-Prime, a European Adaptive Platform Trial (APT) of therapeutics for patients with COVID-19 and COVID-like-illness in primary care will build on many years of EU investment in infrastructure for primary care trials and a mature primary care research network that has pioneered novel, efficient, platform clinical trial designs. Disease aetiology of respiratory viruses can’t be distinguished solely on clinical grounds when patients consult their general practitioner. Treatments with potentially broad antiviral activity will be most beneficial if started early in the disease trajectory. For those treatments patients with syndromic COVID-like-illness will be included in the trial. For virus-specific agents, a rapid point-of-care test will be done as part of the inclusion process.
ECRAID-Prime, with a focus on early phase studies of safety and efficacy of exciting candidate treatments for COVID-19 and COVID-like-illness will be set up in eight countries. Its goal is to test four candidate treatments, identifying suitability for progression to the next phases of research, and so leading to critical additions to the primary care therapeutic armamentarium against COVID-19 and COVID-like-illness. ECRAID-Prime will additionally help complete the vison for a lasting, integrated, comprehensive and sustainable European clinical research preparedness and response capacity, Ecraid, that will provide a full, integrated suite of international priority clinical trials in intensive care units, hospital wards, and now in primary care as well.
ECRAID-Prime, with a focus on early phase studies of safety and efficacy of exciting candidate treatments for COVID-19 and COVID-like-illness will be set up in eight countries. Its goal is to test four candidate treatments, identifying suitability for progression to the next phases of research, and so leading to critical additions to the primary care therapeutic armamentarium against COVID-19 and COVID-like-illness. ECRAID-Prime will additionally help complete the vison for a lasting, integrated, comprehensive and sustainable European clinical research preparedness and response capacity, Ecraid, that will provide a full, integrated suite of international priority clinical trials in intensive care units, hospital wards, and now in primary care as well.
The first phase of the project focused on setting up all organizational, legal, logistical, ethical and regulatory necessities for the adaptive-platform ECRAID-Prime trial. The main achievements were:
- Establishment of the JAAM, which was responsible for a rigorous evaluation of potential compounds, and selected four, of which three are evaluated in the trial.
- Writing the master protocol for ECRAID-Prime and intervention-specific appendices for Nitric Oxide Nasal Spray, Saline, usual care and LTX-109 (Phase 2A).
- Selection of 8 countries, setting up agreements with the national coordinating teams (NCTs) in those countries and (supporting) contracting for their recruiting sites.
- Development of all data management structures: a data-capture system (CASTOR), randomisation system (ALEA), system for transferring personal data (YourResearch), sample management system, central monitoring system, and where needed interactions between those systems.
- Obtaining full approvals to start the trial (NONS, Saline, usual care) in the UK, Belgium, Ireland, Germany, Spain, Poland, France and Georgia and to start the LTX-109 study in Belgium, Ireland, Poland, Spain: in Georgia still under review. Obtaining approvals for a decentralized recruitment strategy in the UK.
- Patient recruitment ongoing in 39 sites, in total 514 in the NONS/Saline/usual care and 22 in the LTX-109 study.
- Monitoring and data cleaning ongoing to prepare for the first interim analysis.
- Establishment of the JAAM, which was responsible for a rigorous evaluation of potential compounds, and selected four, of which three are evaluated in the trial.
- Writing the master protocol for ECRAID-Prime and intervention-specific appendices for Nitric Oxide Nasal Spray, Saline, usual care and LTX-109 (Phase 2A).
- Selection of 8 countries, setting up agreements with the national coordinating teams (NCTs) in those countries and (supporting) contracting for their recruiting sites.
- Development of all data management structures: a data-capture system (CASTOR), randomisation system (ALEA), system for transferring personal data (YourResearch), sample management system, central monitoring system, and where needed interactions between those systems.
- Obtaining full approvals to start the trial (NONS, Saline, usual care) in the UK, Belgium, Ireland, Germany, Spain, Poland, France and Georgia and to start the LTX-109 study in Belgium, Ireland, Poland, Spain: in Georgia still under review. Obtaining approvals for a decentralized recruitment strategy in the UK.
- Patient recruitment ongoing in 39 sites, in total 514 in the NONS/Saline/usual care and 22 in the LTX-109 study.
- Monitoring and data cleaning ongoing to prepare for the first interim analysis.
ECRAID-Prime is an intricate study aimed at addressing a crucial gap in clinical trial capability within Europe. It is of utmost importance to enhance research capacity for prompt implementation and continuous evaluation of therapeutics for infectious diseases, including pandemic and epidemic infections, through a multi-country approach that enables therapeutic trials in the community. A community-based platform for trial capability aligns best with this requirement. However, designing, gaining approval for, establishing and implementing such a trial is a complex and challenging endeavour. It took 2 years to get full ethical and regulatory approval for the ECRAID-Prime master protocol and the first three intervention-specific appendices, with all the accompanying patient-facing materials and other trial related documents and systems, such as case report forms, databases, data and sample management plans, and the statistical analysis plan. With an approved master protocol, trial documents and procedures in place and team experience, it only took 2 months to have the 4th ISA approved. Moreover, with master agreements with NCT organisations and sites in place, initiating the LTX-109 evaluation was not hampered by legal procedures.
To be able to bring the trial to the intended use group population, a decentralized recruitment approach was approved and set up in the UK. This essential step was taken as patients with respiratory illness are increasingly advised to stay at home and not consult their clinician, which will even be reinforced more during a next pandemic. With the UK as prime example and with ICH-GCP and the EMA endorsing these strategies, ECRAID-Prime’s ambition is to implement alternative recruitment strategies in more countries.
In November 2024, the first patient was recruited into the trial in France and sites in all other countries, UK, Ireland, Belgium, Spain, Germany and Poland opened for recruitment. By the end of the third reporting period, 514 participants have been enrolled in the NONS/Saline/usual care and 22 in the LTX-109 evaluation.
These advancements have brought us significantly closer to achieving the urgently needed capability for Europe, which stands as a crucial component of our research efforts and, indeed, our preparedness for pandemics and epidemics. The main impact thus far from ECRAID-Prime is, therefore, a well-organised, recruiting primary care research infrastructure in eight countries, thereby adding to epidemic and pandemic preparedness.
To be able to bring the trial to the intended use group population, a decentralized recruitment approach was approved and set up in the UK. This essential step was taken as patients with respiratory illness are increasingly advised to stay at home and not consult their clinician, which will even be reinforced more during a next pandemic. With the UK as prime example and with ICH-GCP and the EMA endorsing these strategies, ECRAID-Prime’s ambition is to implement alternative recruitment strategies in more countries.
In November 2024, the first patient was recruited into the trial in France and sites in all other countries, UK, Ireland, Belgium, Spain, Germany and Poland opened for recruitment. By the end of the third reporting period, 514 participants have been enrolled in the NONS/Saline/usual care and 22 in the LTX-109 evaluation.
These advancements have brought us significantly closer to achieving the urgently needed capability for Europe, which stands as a crucial component of our research efforts and, indeed, our preparedness for pandemics and epidemics. The main impact thus far from ECRAID-Prime is, therefore, a well-organised, recruiting primary care research infrastructure in eight countries, thereby adding to epidemic and pandemic preparedness.