Periodic Reporting for period 3 - SUPPORT-E (SUPporting high quality evaluation of COVID-19 convalescent Plasma thrOughoutT Europe)
Okres sprawozdawczy: 2022-07-01 do 2023-06-30
Due to the lack of effective treatments for COVID-19, the need for new treatment strategies such as convalescent plasma has emerged during the pandemic. Initial controversial findings from research and the use of convalescent plasma from patients with COVID-19 (CCP) have highlighted the need to develop recommendations based on scientific and clinical knowledge derived from newly developed standardized tests and evaluation of data on CCP donors and recipients. In this context, the SUPPORT-E project was established, which aims to support high-quality clinical and scientific evaluation of CCPs. The main goals of the project, which uses, among other things, a special database created by the European Commission, are to help EU countries both in evaluating the effectiveness of a new therapeutic solution for dealing with the coronavirus pandemic, as well as in developing new strategies for dealing with possible future pandemics. SUPPORT-E will advance the current state-of-the-art by delivering 1) an assessment of the efficacy of CCP as a potential treatment of COVID-19, 2) the much-needed harmonised evidence-based recommendations derived from data on the use of CCP in clinical trials and monitored access programmes for COVID-19 patients in Europe. Further, standardised informative in vitro assays providing scientific insights that could support such recommendations will also be developed. SUPPORT-E hereby promotes and conducts data collection and analysis to identify factors that predict the therapeutic efficacy of CCP. The project also attempts to remove access barriers to anti-SARS-CoV-2 testing to support faster and more accessible donor screening and help direct the blood establishments (BEs) to begin prioritising plasma collections from COVID-19 convalescent donors and expedite the availability of these products. If CCP proves to be a valid therapeutic, the SUPPORT-E recommendations will ultimately serve as a critical tool to facilitate the implementation of a CCP approach across all EU Member States to combat COVID-19 infection.
The SUPPORT-E project is carried out through seven Work Packages to achieve the main project objectives:1) to support a high-quality CCP donation and a high-quality CCP evaluation in clinical trials and monitored access use programmes, 2) to deliver recommendations for the collection and use of CCP in EU member states to treat Covid-19 and recommendations for future outbreaks, and 3) to ensure EU wide adoptions of recommendations and project legacy. To achieve these objectives the SUPPORT-E consortium has evaluated the results of scientific articles on clinical and monitored access use of the CCP, defined the datasets for the development of the EU CCP database and analysed these data, worked on the analysis and comparison of the total and neutralizing anti-SARS-CoV-2 antibodies in CCP collected at different sites, analysed the utilisation of the CCP resource and developed a model to calculate the costs of a CCP collection programme. Results have provided evidence for the set of recommendations on CCP, a resource that could help tackle also novel pandemics in the future. All activities and results were continuously communicated to the professionals and public across the EU.
Due to the development of a pandemic, the emergence of new variants, and widespread vaccinations, a succession of findings related to the use of COVID-19 convalescent plasma (CCP) have emerged. This flow of information allowed the SUPPORT-E consortium to complete many of the project objectives. For some objectives, however, data on the clinical use of CCP including results of other randomised controlled trials which may only become available at a later stage of the project are needed.
Based on the identified knowledge gaps which are indispensable for addressing the effectiveness of CCP in COVID-19 patients with impaired immune systems/responses, the SUPPORT-E consortium decided to support a “Randomised Open-Label Trial of Convalescent Plasma Therapy in Clinically Vulnerable Individuals with Mild COVID-19” (COVIC-19) clinical trial within WP2 (ClinicalTrials.gov Identifier: NCT05271929). This ongoing randomised control study may provide substantial evidence to address these gaps combines several features:
• Early treatment with CCP (within 7 days after onset of symptoms in patients with mild COVID-19) (without need for hospitalisation for COVID-19)
• Administration of high-titre CCP exceeding a pre-specified threshold of anti-SARS-CoV-2 antibodies from super-immunized individuals (i.e. immunized by a SARS-CoV-2 infection and vaccinations).
• Treatment of vulnerable and in particular immunocompromised patients at high risk of progression to severe COVID-19.
• Analysis of virus variants causing the infection in the trial patients (by SARS-CoV-2 whole genome sequencing) and in-vitro studies on cross-neutralization of high-titre CCP from vaccinated, convalescent donors against these variants.
Due to the development of a pandemic, the emergence of new variants, and widespread vaccinations, a succession of findings related to the use of COVID-19 convalescent plasma (CCP) have emerged. This flow of information allowed the SUPPORT-E consortium to complete many of the project objectives. For some objectives, however, data on the clinical use of CCP including results of other randomised controlled trials which may only become available at a later stage of the project are needed.
Based on the identified knowledge gaps which are indispensable for addressing the effectiveness of CCP in COVID-19 patients with impaired immune systems/responses, the SUPPORT-E consortium decided to support a “Randomised Open-Label Trial of Convalescent Plasma Therapy in Clinically Vulnerable Individuals with Mild COVID-19” (COVIC-19) clinical trial within WP2 (ClinicalTrials.gov Identifier: NCT05271929). This ongoing randomised control study may provide substantial evidence to address these gaps combines several features:
• Early treatment with CCP (within 7 days after onset of symptoms in patients with mild COVID-19) (without need for hospitalisation for COVID-19)
• Administration of high-titre CCP exceeding a pre-specified threshold of anti-SARS-CoV-2 antibodies from super-immunized individuals (i.e. immunized by a SARS-CoV-2 infection and vaccinations).
• Treatment of vulnerable and in particular immunocompromised patients at high risk of progression to severe COVID-19.
• Analysis of virus variants causing the infection in the trial patients (by SARS-CoV-2 whole genome sequencing) and in-vitro studies on cross-neutralization of high-titre CCP from vaccinated, convalescent donors against these variants.
SUPPORT-E is advancing the current state-of-the-art by delivering the much-needed harmonized evidence-based recommendations derived from data on the use of CCP in clinical trials for COVID-19 patients in Europe. In addition, standardized informative in vitro assays providing scientific insights that could support such recommendations are also being developed within the project. SUPPORT-E offers an EU-wide collaboration between EU Member States, BEs and clinical centres to close the knowledge gap regarding the use of CCP in COVID-19 clinical trials and to ensure applicability of the recommendations for all EU Members States. The project represents the first European Union coordinated research effort on passive immunotherapy, sharing data and protocols in real-time and pooling efforts to speed up the validation of CCP as a valid therapeutic option while providing a basis for further optimization by combined approaches with other anti-viral treatments.