Work plan

WP1 will be coordinated and managed by GUF and supported by executive committees and board members. WP1 will ensure that COVend’s objectives are achieved and the collaboration with other initiatives are added value to the project. WP2 and WP3 focus on the preparation and the testing of the promising therapeutic candidate FX06. WP4WP5 and WP6 are complementary in that they develop tools (biomarker profile incl. endothelial cell behaviour and AI-based predictive models for decision support) to prove and enhance the benefits of FX06 and thereby offer an individualised therapy. WP7 will develop the early HTA model to assess the cost effectiveness and the social and economic implications of the new therapy. Finally, WP8 will ensure proper dissemination of project results to expert and non-expert audiences (i.e., researchers, healthcare funders, patients, patient advocacy groups and policy makers).

Lead: GUF

The main objectives of WP1 are to ensure an efficient and effective project management. It will:

  • Ensure effective project coordination, including organisation, communication, and administration.
  • Implement timely financial and scientific, technological and management reporting.
  • Assess risks and implement mitigation measures.
  • Manage data, intellectual property (IP) to promote innovation and ensure legal compliance.
  • Align the project with complementary research initiatives.

Lead: F4

The main goal of WP2 is to set up and perform all prerequisites necessary for the conduction of a large scale ph IIb/III clinical study in moderate COVID-19 patients in several European countries. More specifically, we will:

  • Prepare and start the manufacturing of GMP grade API (active pharmaceutical ingredient) FX06.
  • Prepare and start fill and finish of clinical study material (IMP and placebo) for a randomized, multi-centre multinational ph II clinical study.
  • Prepare storage, labelling, release and distribution of clinical study material.
  • Set up and validate an analytic method to determine plasma levels in rat.
  • Perform a 4-weeks toxicity and toxicokinetic study in rat.

Lead: GUF/Fraunhofer

The main goal of WP3 is to conduct the multicentric clinical study in min. 8 European countries to provide data regarding safety and efficacy of FX06 in treatment of mild/moderate COVID-19. WP3 starts with study design, preparation of study documents, submission to ethical committees and competent authorities followed by data collection and verification leading to data analysis and display of results. Throughout the study patient recruitment will be followed at the study sites and investigators will be monitored closely to provide valid and true data and ensure patients’ safety. Support and overview of Sponsor (F4) will be provided by regular study reports, meetings and approval processes for essential documents. More specifically, we will:

  • Prepare study protocol and other study material as Informed consent form, IMP related documents, CTA document for submission.
  • Select experienced sites for patient recruitment and collect qualification documents.
  • Submit study in participating countries at ethical committee and competent authorities.
  • Set up and validate electronical data capture system (eCRF) and data base for collection of study data.
  • Perform close-out at study site after recruitment and data collection has been finished, provide data cleaning and query processes to ensure validated data for data base closure.
  • Analyse collected and validated data statistically, report the results in final end report and publish data

Lead: Fraunhofer/GUF

Applying OMICs technologies the main goal is to deeply characterise the molecular profiles in the blood of COVID-19 patients treated with FX06 versus. placebo over time (longitudinal). Doing that we will also provide information about plasma protein levels requested as secondary endpoints in WP3. New identified molecules (proteins, lipids, metabolites) involved into FX06 activity will be validated in WP5. The OMICs-derived data will be analysed in WP6 by machine learning and KI, integrated into modelling approaches. More specifically, we will::

  • Measure and analyse the proteomic, metabolomics and lipidomic profiles in the patients’ longitudinally collected blood samples using State-of-the-Art on-site established technology providing profound insight in disease and FX06 therapy mechanisms. Contribute to the COVID-19 data portal by providing rich OMICs data sets.
  • Identify novel biomarkers to characterize COVID-19 (risk, prognosis) as well as FX06 therapy (efficacy prediction, treatment response) to support clinical decision making (precision medicine).

Lead: UCD

There is accumulating evidence that SARS-CoV-2 does not only infect pulmonary epithelial, but also endothelial cells (ECs). The endothelium is also involved in thrombotic events and acute pulmonary embolism associated with COVID-19. Endothelial damage is key in facilitating a cytokine storm like we see with COVID-19 and protecting the vasculature may be critical for tackling the acute respiratory infection, organ failures (heart, liver, kidney) and thromboembolism, which are the most severe complications of COVID-19. FX06 has turned out to be a good candidate for this, since it protects against ischemia/perfusion injury in pre-clinical models of myocardial infarction and endothelial leakage-mediated shock. For SARS-CoV2 infection some key inflammatory response mediators have recently been discovered, namely IL-6, M-CSF, IL-1α, IL-1β (COVID-19-triggered cytokines). Specifically, we aim:

  • To investigate the influence of COVID-19-triggered cytokines on apoptosis/necrosis and immunological activation as well as transendothelial permeability of pulmonary endothelial cells (ECs) under steady-state and flow/shear stress conditions (Months 1-18).
  • To test the efficacy of FX06 to protect against any adverse virus-mediated effects (Months 19-36).
  • In silico modelling of transcriptional cellular host response networks in pulmonary ECs using an integrated machine learning approach (Months 13-24)

Lead: TAU

The main goal of WP6 is enable and carry out data analytics and modelling towards personalised decision support for FX06 in treatment of moderate COVID. WP6 interacts closely with WP3 and WP4, using their collected data to generate new information to create multi-variate / multi-modal profiles of patients, study possible side effects and patient state dynamics over time. WP6 will deliver knowledge, and implement this in algorithms, that serve as basis for decision support for personalised FX06-based intervention planning. Furthermore, the results of WP6 will feed into the activities of WP7, allowing to access the (cost-effectiveness) of delivered decision support approaches. Specifically, we will:

  • Prepare data sets, combined with knowledge in the form of guidelines and rules, that serve as input for modelling research and development, and provide data processing and data anonymization.
  • Define clinical meaningful questions and use cases that truly benefit from decision support models.
  • Define protocols for validating the models.
  • Develop personalised decision support models, building on wider efforts in the research community and enhancing that with COVend knowledge – particularly: novel profiling approaches using unsupervised and semi-supervised learning, dynamic multi-variate time-series modelling. Document models so that they can be used also in future R&D effort for other types of interventions.
  • Implement, deploy and make available the models for both the data science research community as well as clinical community (who have different demands with respect to information representation).
  • Validate the models independently and disseminate findings.

Lead: UMCG

The main goal of WP7 is to evaluate FX06 from a health economic perspective and identify relevant policies and barriers affecting feasibility of implementation. Given the clinical benefit that will result from the clinical study, can FX06 be considered good value for money within a hospital, within the healthcare system, and for society as a whole? Cost-effectiveness will be determined relative to relevant comparators in close collaboration with WP2 and EMA. More specifically, we will:

  • Provide an overview of reimbursement/payment policies applied for intramural therapies in each of the participating countries.
  • Perform an analysis to identify barriers for uptake of FX06 and how these may differ between participating countries.
  • Develop a health-economic model which incorporates costs and outcomes of FX06 projected over the longer term.
  • Determine the cost-effectiveness of FX06 relative to relevant comparators (e.g. antibody therapy), including sensitivity and scenario analysis.
  • Construct a hospital-level budget impact tool for FX06.

Lead: accelCH

The main goal of WP8 is to raise awareness about COVend and to achieve a wide outreach of the project results. We will:

  • Define and plan the dissemination and communication strategy in a multi-stakeholder outreach plan.
  • Deliver cross-media communication activities to raise awareness for the potential COVend therapy.
  • Disseminate the scientific and technological results to the scientific community and health care stakeholders.
  • Exploit the commercial and non-commercial opportunities of COVend outcomes and results to stakeholders interested in the further use and development of results.

Lead: GUF

The main goal of WP9 is to to ensure compliance with the ‘ethics requirements’ set out in this work package