Periodic Reporting for period 2 - ECRAID-Prime (European Clinical Research Alliance on Infectious Diseases - PRIMary care adaptive platform trial for pandemics and Epidemics)
Période du rapport: 2023-06-01 au 2024-11-30
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:
- Extensive contact with pharmaceutical companies having promising compounds for the trial and with the JAAM, being responsible for rigorous evaluation of the compounds.
- Writing the master protocol for ECRAID-Prime and intervention-specific appendices for Nitric Oxide Nasal Spray, Saline and usual care.
- Selection of 8 countries from the existing European Primary Care research network, setting up agreements with the coordinating teams in those countries and offering master clinical trial agreements 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, and where needed interactions between those systems.
- Finalizing data management and sample management plans and instructions.
- Preparing the full submission package for ethical and regulatory approvals for 6 countries via the CTIS system; UK and Georgia will apply for these approvals via their routine structures.
- Obtaining full approvals to start the trial in UK, Belgium, Ireland, Germany, Spain, Poland and France.
- Three training meetings with the national coordinating teams (1 virtual, 1 in Utrecht, the Netherlands, 1 final training just before opening the trial).
- First 100 patients recruited in 2024.
- Selection of a third compound, LTX-109, and preparing for testing this compound in a phase 2A trial.
- Extensive contact with pharmaceutical companies having promising compounds for the trial and with the JAAM, being responsible for rigorous evaluation of the compounds.
- Writing the master protocol for ECRAID-Prime and intervention-specific appendices for Nitric Oxide Nasal Spray, Saline and usual care.
- Selection of 8 countries from the existing European Primary Care research network, setting up agreements with the coordinating teams in those countries and offering master clinical trial agreements 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, and where needed interactions between those systems.
- Finalizing data management and sample management plans and instructions.
- Preparing the full submission package for ethical and regulatory approvals for 6 countries via the CTIS system; UK and Georgia will apply for these approvals via their routine structures.
- Obtaining full approvals to start the trial in UK, Belgium, Ireland, Germany, Spain, Poland and France.
- Three training meetings with the national coordinating teams (1 virtual, 1 in Utrecht, the Netherlands, 1 final training just before opening the trial).
- First 100 patients recruited in 2024.
- Selection of a third compound, LTX-109, and preparing for testing this compound in a phase 2A trial.
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 three intervention-specific appendices, for nitric oxide nasal spray, for saline nasal spray and for usual care, with all 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. Network/Country team and site selection have been completed and contracting of many of the involved parties has been completed, and advanced training of national coordinating teams and their sites has been conducted. We have worked closely with the Joint Access Advisory Mechanism to review additional candidate interventions for ECRIAD-Prime, and LTX-109 is the next promising treatment to be implemented in ECRAID-Prime.
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. Beginning 2025, a site in Georgia will add to the recruitment potential.
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.
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. Beginning 2025, a site in Georgia will add to the recruitment potential.
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.