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 for people 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. Evidence-based therapeutics for use in primary care 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 potentially 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. In the winter of 2022/23, respiratory viruses will be co-circulating and disease aetiology can’t be distinguished solely on clinical grounds. 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 might be included. 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 rapidly set up. Its goal is to test at least four candidate treatments, identifying suitability for inclusion in 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 overall goal of COMECT is to coordinate activities across Europe’s strategic adaptive platform trials (APTs) and cohort studies (CS) on infectious diseases (IDs) with epidemic or pandemic potential, by overseeing and facilitating dialogue, sharing of good practices, promoting collaboration and coordination across studies and providing updated information on initiatives and innovation in ID clinical research. COMECT will build on and strengthen existing networks and infrastructure. These include EU-funded coordination mechanisms and networks, namely the Trial Coordination Board (TCB), Joint Access Advisory Mechanism (JAAM), the Cohort Coordination Board (CCB), and the ECRAID Coordinating Comittee. COMECT will develop a visible, well-defined coordination mechanism to highlight Europe's capacity and competence as an attractive base for clinical research. COMECT will deliver: 1) an expanded, combined European coordination mechanism that will work on harmonizing research initiatives, exchange of good practices, and stakeholder engagement across ID clinical studies in outbreaks and during inter-epidemic phases. 2) a strengthened JAAM to support coordination through independent scientific assessment of compounds/vaccines and recommendations for APTs to evaluate the new compound in new or adapted platform trials. 3) the mapping of stakeholders and their respective activities relevant to APTs and CS 4) a harmonised approach cross-study identification, assessment, and reuse of participant-level data from European APTs and CS 5) coherent communications and stakeholder engagement across all activities 6) a sustainability plan for the continuation of activities beyond the funding period. COMECT will quickly adapt coordination efforts to a changing research landscape and to new ID threats. COMECT will operate in close collaboration with other emergency preparedness mechanisms, such as HERA, EMA, GLOPiD-R and the European Pandemic Preparedness Partnership.

Spontaneous healing of articular cartilage injuries is poor and untreated defects predispose to osteoarthritis. Current therapies, including innovative autologous cell-based treatments, cannot predictably and reproducibly restore cartilage structure and function. BIOCHIP will carry out a multicenter, prospective phase II clinical trial to treat knee cartilage injuries using engineered grafts based on autologous nasal chondrocytes (NC). As compared to typically employed articular chondrocytes, NC have a higher and more reproducible capacity to generate mature cartilage tissues. Importantly, molecular/mechanical characterization, large size animal studies and a phase I trial carried out by BIOCHIP partners have already shown the compatibility of NC upon implantation in a joint, with promising preliminary clinical results. BIO-CHIP’s specific objectives are: (1) To test the hypothesis that the maturation of NC-based cartilage grafts improves the clinical efficacy in the treatment of cartilage lesions (108 patients will be recruited to reach statistical significance) (2) To extend the range of clinical indications of NC-based grafts to so far untreatable pre-osteoarthritic lesions (‘kissing’ cartilage lesions in a sheep model) BIO-CHIP capitalizes on clinical experience of 4 reference centers for cartilage surgery, on established GMP manufacturing capacity and on preparation for commercial exploitation by a strong orthopedic device company. Demonstration of therapeutic efficacy of the new treatment will address a large clinical need (over 2 million cartilage defects/year worldwide), improve quality of life (reduce pain & disability in the young, delay prosthetic implants in the elderly), exploit a commercial opportunity (prospected revenues of up to 130 million €/year) and reduce healthcare costs (estimated 12,000€ healthcare savings/procedure). BIO-CHIP will consolidate the currently leading role of Europe in the development of cell-based cartilage regeneration strate

Colorectal cancer (CRC) ranks fourth in cancer deaths worldwide. Between 20% and 30% of patients with advanced CRC have liver metastases (CRLM). Liver cancer ranks second in cancer deaths worldwide, including hepatocellular carcinoma (HCC). Despite recent advances, liver resection offers the only chance of cure for patients with liver metastases. However, the recurrence rate of these tumours is high even after post-resection. The presence of positive margins in the remaining liver after resection correlates with increased local recurrence and decreased overall survival, the only factor where prognosis could be influenced by the performance of surgery. However, at present, the extent of an R-negative status remains debatable and varies widely from one publication to another. Currently, there are radiofrequency ablation studies that, based on preliminary retrospective human clinical trials, are able to correlate an additional coagulation of tumor margins with a reduction on local recurrence. However, there is no prospective and pragmatic controlled study that accurately measures this additional margin and its impact on oncological outcomes. The aim of LIVERATION is to conduct an ambitious, pragmatic multicenter clinical trial with 720 patients with CRLM and HCC at 24 clinical centres in 6 different countries to determine whether additional ablated margin produced by radiofrequency can decrease the recurrence rate and improve patient survival. We will also evaluate the patient-centredness of the intervention and its comparativeness with other therapeutic alternatives in terms of quality of life and patient experience in real-world settings. To this end, the consortium has been formed by highly experienced, highly qualified and multidisciplinary entities to carry out the project successfully. The results will not only have a major impact on a social and scientific level but also on an economic level for the EU. This action is part of the Cancer Mission cluster of projects on ‘Diagnosis and treatment’.

VISION-DMD aims to advance clinical development of the orphan drug VBP15 as a new therapy to revolutionise care for all patients with Duchenne muscular dystrophy (DMD) by 2020, in line with IRDiRC goals. DMD is an incurable, rare muscle wasting disease; boys progressively weaken, lose ambulation and death occurs by early adulthood. Corticosteroids (CS) are widely recognised to increase muscle strength and delay disease progression but global acceptance as standard of care is very variable due to severe side effects. VBP15 is an innovative steroid-like drug designed to retain or better CS efficacy and improve membrane stabilization with reduced or no side effects. VBP15 will increase the therapeutic window to slow disease progression and improve quality of life and lifespan for all DMD patients. Building on positive preclinical and Phase 1 results funded by government grants and international patient groups and based on FDA and EMA advice, VISION-DMD proposes a Phase 2 registration directed clinical programme aimed at an affordable therapy: Phase 2a will study the safety and tolerability of ascending doses of VBP15 in ambulant DMD boys; Phase 2b will demonstrate the efficacy and safety of two doses of VBP15 in young ambulant DMD boys. Both studies will be followed by extension studies for long term safety and efficacy data collection leading to cumulative exposure of up to 2100 drug months. The project proposes the Time to Stand Test as a highly relevant and reliable primary endpoint. Innovative exploratory serum biomarkers and novel wide scale MRI techniques will be used to investigate the VBP15 pharmacodynamics and the effect on muscle cellular pathology. VBP15 will meet the unmet need for better treatment for DMD with widespread acceptance and potentially be used in combination with stratified therapies as they are developed. The Consortium links the leading networks TREAT-NMD and CINRG with ECRIN-ERIC, for trial delivery and regulatory undertakings in Europe/US