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 several European countries to provide data regarding safety and efficacy of FX06 in the treatment of patients with mild/moderate ARDS related to COVID-19 or other aetiologies. 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.
• In collaboration with GUF, TAU, and MiDA, provide a GDPR compliant data collection and transfer infrastructure to collect and share the eCRF and multiomic data among all relevant partners
• Set up sites for start of recruitment providing training for site and coordinate study sites throughout the study including monitoring of patient data to provide verification of study data, supervise compliance to study protocol and regulations and ensure patients’ safety
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• 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 multiomic technologies, we will provide information about plasma protein levels requested as secondary endpoints in WP3.  Further, we aim to identify and follow up on major biomarkers  in the blood of patients treated with FX06 versus placebo over time (longitudinal). Newly identified molecules involved in FX06 activity will be validated in WP5. The omics-derived data will be analysed in WP6 by machine learning and AI and integrated into modelling approaches. More specifically, we will:

• Measure and analyse the multiomic profiles in the patients’ longitudinally collected blood samples using State-of-the-Art on-site established technology providing insight into the mechanism of FX06 therapy.
• Contribute to relevant data portal for ARDS related to COVID-19 or other aetiologies by providing multiomic data sets.
• Identify biomarkers to characterize the FX06 therapy in ARDS related to COVID-19 or other aetiologies 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 fatal 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 does not belong to any known drug class and targets the host response via the endothelium, which is affected directly and indirectly by the virus. FX06 may be an innovative promising therapy to improve endothelial dysfunction, capillary leak, arterial oxygenation, and lung function and, thus possibly able to improve disease severity and prevent progression. In the restructured clinical study, we will investigate the molecular mechanism of FX06.  Specifically, we aim:

• To investigate the influence of 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.
• To test the efficacy of FX06 to protect against any adverse virus-mediated effects.
• In silico modelling of transcriptional cellular host response networks in pulmonary ECs using an integrated machine learning approach.

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 mild to moderate ARDS related to COVID-19 or other aetiologies. 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 harmonisation for pseudonymised data provided by partners.
• Define clinically 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. interventions.
• Implement, deploy and make available the models for both the data science research community as well as clinical community.
• Validate the models independently and disseminate findings.

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 (T8.1).
• Deliver cross-media communication activities to raise awareness for the potential COVend therapy (T8.1).
• Disseminate the scientific and technological results to the scientific community and health care stakeholders (T8.2).
• 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