Trials - Portfolio

In collaboration with 13 partners from 7 countries, Jena University Hospital is establishing the Antivirus Pandemic Preparedness EuropeAn pLatform (APPEAL), a European research initiative aimed at enhancing preparedness for future pandemics. This EU funded collaboration will establish a comprehensive program for the development of broad-spectrum antiviral drugs within a five year time frame ensuring drug affordability and accessibility to low income countries.

This research initiative aims to establish a platform for the identification of target proteins and their signalling pathways within host cells, utilising both computational and experimental approaches. Subsequently, potential drug candidates will undergo comprehensive testing in our laboratories, including cell culture and human-relevant 3D models. The most promising candidates will then advance to animal studies, and ultimately, validation in a clinical pilot study. The goal is to establish a comprehensive pipeline for the identification and validation of potential antiviral targets and associated drug candidates.

In addition, the scientists also aim to therapeutically activate target proteins that are identified as enhancers of cellular defence processes. For the most promising candidate, the safety and effectiveness of the lead compound will be evaluated in pre-clinical pilot studies.

Population: adult | Intervention type: Interventional Study

Best Antithrombotic Therapy in patients with acute Venous ThromboEmbolism while taking antiplatelets: the BAT-VTE randomised-controlled trial

Cardiovascular diseases are the leading cause of death and disability in Europe. Among them, venous thromboembolism (VTE) and atherosclerotic cardiovascular disease (ACVD) frequently coexist, requiring treatments with potentially conflicting effects. Anticoagulants (AC) are essential for managing the acute phase and preventing VTE recurrence, while antiplatelets (AP) reduce the risk of major adverse cardiovascular and cerebrovascular events in ACVD patients. However, combining AC and AP significantly heightens bleeding risk, making anticoagulant-related bleeding the leading cause of emergency admissions for adverse drug reactions.

Up to one in three patients treated for VTE receive concomitant AP therapy, yet evidence remains conflicting: some studies suggest a threefold bleeding risk increase, while others report improved cardiovascular protection. These discrepancies likely reflect confounding factors such as AP type, indication, or duration— leaving clinicians uncertain about the optimal benefit-risk balance in VTE patients with ACVD and leading to inconsistent practices.

Because VTE treatment protocols differ from those for atrial fibrillation—requiring DOAC loading followed by full-dose for at least six months—existing ESC guidelines cannot be extrapolated. Clinicians are thus left choosing between two strategies: continuing combined AC+AP therapy or switching to AC monotherapy. 

Given the lack of dedicated studies, a randomised trial is urgently needed to address this common clinical scenario. A de-escalation strategy appears feasible and of particular interest in patients with low arterial risk, and particularly in patients at high bleeding risk. We propose a randomized trial testing whether full-dose AC monotherapy reduces bleeding and improves net clinical benefit—defined as a composite outcome including clinically relevant bleeding, recurrent VTE, and major ischemic cardiovascular and cerebrovascular events—compared to combined AC+AP.

Population: Adult | Intervention type: Interventional

Heart failure (HF) is a chronic clinical condition involving up to 6.5 million people in Europe, the most frequent cause of hospitalization in adults with a 5-year mortality rate up to 70%. Several drugs positively modify the course of disease in the patients with HF with reduced ejection fraction (HFrEF), with a high level of evidence. Besides, the use of diuretics, the basic cornerstone of symptoms relief in HFrEF by targeting congestion, is supported by poor and outdated evidence. Congestion drives symptoms worsening leading to hospital admission. Clinical evaluation of congestion is often inaccurate and insensitive to detect interstitial or intravascular fluid overload, and thus insufficient to guide use of diuretics. Indeed, their use is inefficient, with studies showing that up to 70% of patients with chronic HFrEF show congestion despite diuretic therapy, the use of diuretics does prevent clinical events in patients discharged after an acute heart failure episode, and diuretics may represent a barrier to adherence to disease modifier therapies. An appropriate management of diuretic therapy is therefore crucial to overcome the risk of re-hospitalisation, manage patients symptoms, and achieve target guideline-directed medical therapy. To fill these gaps, BIOTOOL-CHF will 1) validate a set of qualified biomarkers estimating congestion, 2) define a multiparametric artificial intelligence-based score predicting congestion and prognosis, 3) develop a decision-making tool to manage congestion by diuretics, 4) develop a Point of Care companion diagnostic (CD) to assess biomarkers concentrations 5) set up a Strategy plan for industrial development and market access of the CD. This approach will support the definition of a framework to regulatory agencies and scientific societies to disseminate recommendations for a more efficient use of existing pharmaceuticals and allow a personalised strategy for the management of HFrEF, by using new tools and digital solutions.

Population: adult | Intervention type: Non-interventional

CARDIA is designed as non-IMP/non-MD clinical trial. The aim of the study is to compare the outcome of transhiatal extended gastrectomy with transthoracic esophagectomy as curative surgical therapy for patients with GEJ type II adenocarcinomas since nowadays both surgical strategies are in use with ambivalent results regarding oncological outcome, postoperative morbidity, and quality of life.

Population: adult | Intervention type: therapeutic procedural

ST-segment elevation myocardial infarction (STEMI) is the leading cause of death in Europe, posing significant social and economic burdens. Despite high mortality rates, revascularization strategies for STEMI have remained unchanged for over a decade, centering on primary percutaneous coronary intervention (PCI) with drug-eluting stents (DES). 

Despite advancements in DES technologies—such as reduced short-term target lesion revascularisation, stent thrombosis, and myocardial infarction—complications persist, with a 32.4% rate of cardiac events over 10 years after the index procedure. Drug-coated balloons (DCBs), which deliver antiproliferative drugs to the vessel wall without leaving a permanent scaffold, may reduce cardiac events and preserve vessel physiology, but their role in STEMI is unknown.

The COPERNICAN trial is a pragmatic, multicenter, randomized clinical study conducted in Spain, Italy, and France aimed to evaluate the safety and efficacy of a reduced stent strategy (DCB-based) compared to conventional DES-based revascularization for STEMI. Eligible patients will be randomised 1:1 to:

1. Study Group: coronary revascularisation with DCB.
2. Control Group: coronary revascularisation with DES.

The primary endpoint is target lesion failure (TLF), defined as cardiac death, myocardial infarction, or ischemia-driven revascularization. A total of 1,450 patients will be enrolled using a sequential design: 12-month non-inferiority followed by 3-year superiority testing. The trial is powered to detect non-inferiority with 1,272 patients (non-inferiority margin: 3.6%). An additional 178 patients will allow superiority testing, assuming a 3-year TLF rate of 11% with DES and 4 per cent absolute difference.

The COPERNICAN trial will be the first randomised clinical trial evaluating a change in the revascularization paradigm in patients presenting with STEMI by assessing the role of DCB-PCI.

Population: Adult | Intervention type: Interventional

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Progressive, relapsed and refractory paediatric low-grade glioma (pLGG) is a serious and potentially fatal disease for which there is currently no standard of care (SOC) after systemic frontline SOC treatments.​ pLGGs are a group of tumors that affect children, teenagers, and young adults. They are the most common tumors of the brain and spinal cord in young people.

pLGG is considered a chronic disease and patients with pLGG can suffer from significant damage to vital functions and long-lasting side effects throughout their lives.​

The EPILOGUE trial applies an intra-individual dose escalation concept to achieve the optimal tolerable dose for each patient for different (combination) treatment arms.​ The study design is an exploratory, open label, combination phase I/II umbrella trial of ulixertinib, tovorafenib, and vinblastine in pediatric patients with relapsed/refractory/progressive pLGG.​

Population: Paediatric | Intervention type: Interventional

EPILOGUE - Phase I/II combination umbrella trial in relapsed paediatric low-grade glioma (pLGG)​

Progressive/relapsed/refractory pLGG is a serious disease with a significant impact on quality of life and disease burden. Although it is a MAPK-driven single-pathway disease, targeted treatments have so far been associated with limited durability of response and rebound growth after treatment withdrawal. Our preclinical data demonstrate synergistic activity of dual targeting of the MAPK pathway at the level of RAF and ERK, as well as in combination with chemotherapy. These data provide a strong in vitro and in vivo rationale to evaluate ulixertinib in pLGG as single agent as well as in combination with tovorafenib and conventional chemotherapy (vinblastine).

This exploratory, multicenter, international, open label, combination phase I/II umbrella trial applies an intra-individual dose escalation concept to achieve the optimal tolerable dose for each patient for different (combination) treatment arms. The primary objectives are to determine safe starting doses in an intra-individual dose escalation regimen and to evaluate activity and safety of the treatment arms. Paediatric patients aged 6–21 years with refractory, relapsed, or progressive pLGG and the presence of a genetic activating RAF alteration, as assessed by molecular analysis, are eligible for this trial. Patients are randomised to three treatment arms:

• Arm 1: single-agent ERK inhibitor ulixertinib
• Arm 2: combination of ulixertinib and the type II RAF inhibitor tovorafenib
• Arm 3: combination of ulixertinib and vinblastine.

The maximum treatment duration is 12 cycles (1 cycle = 28 days), with the option for re-challenge in case of tumour rebound.

Population: Paediatric | Intervention type: Interventional

The objective of the study is to determine whether, among extremely low birth weight (ELBW - birth weight less than 1000g) infants, early targeted treatment with Paracetamol for patent ductus arteriosus (PDA), based on specific criteria and commencing between six to twelve hours of life, results in significant reduction of a combined primary outcome of periventricular and intraventricular haemorrhage (PIVH), necrotising enterocolitis (NEC) and death before discharge. The Trial design is a Phase 3 randomised, parallel-group, placebo-controlled trial.

Analysis will be carried out as intention to treat. For the analysis of the primary end point a mixed-effects logistic regression model will be used. The fixed covariates will be the treatment group and weight as a continuous variable. The centre will be included in the model as a random intercept (i.e. fixed + random effects = mixed effects), which will adjust for centre-specific variance. By this approach a precision and statistical power will be gained (with potential ability to describe smaller, but significant effects). The trial statistician will prepare a Statistical Analysis Plan.

A sample size of 218 infants is needed with 109 infants in each arm, (using corrected chi-square test and Fischer’s Exact test), to decrease the rate of our combined outcome from 32% to 15% (17% absolute reduction), with alpha 5% and 80% power.

Population: paediatric | Intervention type: therapeutic procedural

The overall aim of the PROACT EU-Response project is to prepare Europe for future diseases of epidemic or pandemic potential by strengthening and building upon existing networks of experts and civil society focused on clinical therapeutic platform trials within hospital inpatient settings across Europe.
This network will provide the capacity to pivot rapidly in the event of an outbreak to implement large, multi-country platform trials investigating drug efficacy and performance of diagnostic tools, with a strong patient and public involvement. The civil society and community at large are engaged in the planning of the trials as well as in designing specific activities concerning communication and information for the public about health threats and how to avoid disinformation, particularly during an epidemic or pandemic.
This project is led by ANRS-MIE, Inserm and Sorbonne University, as part of a consortium of 20 European countries and 23 partners, including many teams in biostatistics, clinical research and social sciences, as well as numerous associations and citizens' groups.
Population: adult | Intervention type: Interventional Study

The study will be a multi-national, multi-centre longitudinal observational study with the aim to evaluate the performance of the candidate digital endpoints of fatigue and sleep disturbance in the following neurodegenerative disorders (Parkinson’s disease and Huntington’s disease) and immune-mediated inflammatory diseases (Inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren’s syndrome). Healthy volunteers without symptoms of chronic fatigue or sleep disturbance will also be include as a comparative group.

Population: adult | Intervention type: therapeutic medical device

The aim of this trial is to determine preliminary activity of the combination treatment with nivolumab and entinostat in children and adolescents with high risk refractory/relapsed/progressive tumors harboring a high mutational load, high PD-L1 mRNA expression or focal MYC(N) amplification and explore activity in biomarker low tumors (low mutational load, low PD-L1 mRNA expression and non-MYC(N) amplified).

Population: paediatric | Intervention type: therapeutic medicinal product

The LEOPARD project stands as a pioneering effort in the field of liver transplantation (LT), uniting stakeholders across Europe to revolutionise organ allocation strategies for individuals with decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC).

Among patients currently listed for liver transplantation in Europe, mortality/drop-out on the waitlist averages 15-20% with large disparities across European countries. In recognition of the critical need to prioritise LT candidates based on mortality risk, particularly in the context of organ shortages, and the limitations of existing predictive models such as the Model for End-Stage Liver Disease (MELD) in accurately assessing this risk, there is a growing urgency for updated algorithms to refine organ offering schemes.

The LEOPARD project seeks to enhance liver transplantation outcomes by creating and validating an AI-based predictive algorithm, considering recently identified predictors, that surpasses current models in stratifying both DC and HCC patients by mortality/dropout risks on the waitlist. Additionally, the project will develop calculators for DC and HCC candidates to aid in patient prioritisation, as well as integrate predictive signatures from OMICs/radiomics to improve risk assessment accuracy.

At its core, the LEOPARD project aims to improve patient outcomes by ensuring timely transplantations, harmonising European prioritisation schemes, and advocating for equitable access to LT to significantly reduce mortality on the waitlist. 

Population: adult | Intervention type: interventional excluding health product

LIVERATION is a comprehensive, practical, and multinational clinical trial spanning six countries, with the objective of investigating if the enlargement of the ablated margin through radiofrequency can reduce the recurrence of Colorectal Cancer Liver Metastasis (CRLM) and enhance patient longevity.

Colorectal cancer (CRC) is the third most common tumour in men and the second in women, with an estimate of 1.9 million new cases worldwide (450K in Europe) and approximately 900,000 deaths in 2020. Hepatic metastases develop in approximately 50% of colorectal cancer cases.

The liver, in addition to being the most common site of metastases, is also the first and only area of spread in 30–40% of patients.Surgery is considered the gold standard treatment and the only potentially curative option for colorectal liver metastases (CRLM).

LIVERATION leverages a prospective pragmatic clinical trial coordinated by expert clinicians and surgeons on liver cancer that had achieved promising preliminary results: a reduction of cancer local recurrence by adding an additional coagulation of the margin (ACM) with radiofrequency (RF) ablation devices compared to conventional hemostatic techniques in a retrospective clinical trial.

The main aim of LIVERATION is to evaluate the real-world effectiveness of ACM after liver resection in order to decrease liver cancer recurrence through a pragmatic clinical trial.

Population: adult | Intervention type: therapeutic procedural

The major objective is to develop novel clinical endpoints for clinical trials with a regulatory and patient access intention in patients with intermediate age-related macular degeneration (iAMD). Additional objectives are to characterise visual impairment in iAMD and its progression, as well as identify risk factors for progression to late stage AMD.

Population: adult | Intervention type: non-interventional study

Venous thromboembolism (VTE) is a frequent and life-threatening disease. In 50% of cases, VTE occurs in the absence of any major risk factors (unprovoked VTE). In these patients, when anticoagulation is stopped after 3 months of anticoagulation, more than 35% will develop recurrent VTE. Consequently, international guidelines recommend to treat these patients “indefinitely”. However, such practice exposes them to a substantial increase risk of bleeding. Nevertheless, after several years of anticoagulation in all patients with unprovoked VTE, the risk of anticoagulant-related bleeding is expected to exceed the risk of recurrent VTE after stopping treatment.

In addition, extending anticoagulation indefinitely in all patients with unprovoked VTE exposes 65% of patients to an unjustified high risk of bleeding, who would never have experienced recurrent VTE after stopping treatment. In this setting, optimal duration and management of anticoagulation remains a pivotal and unresolved challenging issue which has the potential to markedly improve long-term prognosis of unprovoked VTE.

Based on quantitative and qualitative approaches, MORPHEUS will for the first time integrate (i) clinical, laboratory and imaging biomarkers (personalized medicine) and (ii) socio-anthropological markers (patient-centred model) into sets of prediction rules for optimizing anticoagulant management integrated in a shared decision-making process.

The ultimate goal of the European MORPHEUS project will be to develop and validate a time-dependent multi-component tool integrated in a shared decision-making process regarding anticoagulant treatment duration in patients with unprovoked VTE.

Population: adult | Intervention type: Non-interventional

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease (AID) involving 0.5 to 3/1000 persons. The disease affects exocrine glands leading to dryness of the eyes and the mouth and is associated with fatigue and limb pain. In 30% to 50% of the patients, systemic and extra-glandular manifestations may develop. The spectrum of extra-glandular
manifestations in pSS is broad and includes vasculitis, peripheral neuropathy, synovitis, kidney involvement and interstitial lung disease. Moreover, pSS patients have a 10 to 20-fold higher risk of developing B cell lymphomas, conferring shorter lifetime expectancy to these patients.
Whereas 10 new targeted-immunomodulatory treatments have been marketed for rheumatoid arthritis in the past 20 years, only one drug has been licensed for other systemic AIDs, such as pSS and systemic erythematous lupus in the same period. There are several factors that may hamper the development of successful drugs for AID. Being multi-organ, these AIDs are considerably heterogeneous among individuals both in terms of clinical manifestations and biological disturbances, with, as a consequence, great difficulty to set-up accurate composite clinical end-points sensitive to change and usable in clinical trials. In this project, our objectives are:
- To develop and assess sensitive clinical endpoints, for use in future clinical trials, able to evaluate response to drug treatments in patients with pSS with high disease burden and/or systemic involvement,
- To identify and evaluate discriminative biomarkers for stratification of pSS patients predictive of organ involvement and disease progression and thus available for inclusion in clinical trials,
- To set-up and perform an original multi-arm multi-stage clinical trial to validate the newly defined pSS endpoints and the identified biomarkers, by maximizing the chance of finding a difference between the placebo arm and the treated arm.

Population: adult | Intervention type: therapeutic medicinal product

The PARTUM Trial: A pragmatic non-inferiority trial comparing low-dose aspirin versus usual care low-molecular-weight heparin for postpartum VTE prevention

"Postpartum venous thromboembolism (VTE: deep vein thrombosis [DVT] or PE) carries significant morbidity, and PE is a leading cause of maternal mortality. Conversely, bleeding is a major cause of severe maternal morbidity. Postpartum VTE prevention strategies frequently include low-molecular-weight heparin (LMWH) injections despite little evidence. LMWH prophylaxis is overused in many countries and imposes cost, pain, and bleeding risk. There remains a critical and well-defined knowledge gap regarding the optimal prophylaxis strategy to prevent postpartum VTE.

The PARTUM trial will close this gap and is a non-inferiority randomised trial of 8,805 participants in 11 countries to assess if 6 weeks (wks) of low-dose aspirin (ASA) is non-inferior to usual care LMWH regimens to prevent VTE in postpartum patients at risk of VTE. We request funds to recruit 1,850 patients in 3 European countries.

Population: Adult | Intervention type: Interventional

Clinicaltrials.gov ID: NCT0649metaspins casino 4878

EU-PEARLDIVER is a multinational European platform trial for depression to rapidly and robustly assess the efficacy and safety of several therapies simultaneously. With this innovative trial design, new treatments can be added over time as they become available and treatments that turn out to be ineffective will be dropped.

The trial is designed to accommodate different types of drugs and may also include non-pharmacological treatments such as psychotherapy or non-invasive neuromodulation in the future. In a platform trial, several experimental treatments share a control group, which can help to make it faster, more efficient, and more patient-centric.

Population: Adults (18-70 years) with a treatments-resistant major depressive disorder | Intervention type: Interventional clinical trial under the EU Clinical Trials Regulation (CTR), using a platform trial design

PHOENIX is an EU Cancer Mission project dedicated to improving treatment options for children with high-risk cancers, including neuroblastoma and other aggressive paediatric solid tumours. Despite advances in cancer care, many children with relapsed or treatment-resistant disease still face poor outcomes and severe long-term side effects from existing therapies.

The project focuses on the clinical development of ibrilatazar (ABTL0812), an innovative oral anticancer therapy designed to target tumour cells in a potentially safer way than conventional chemotherapy while sparing healthy DNA. Building on promising preclinical and adult clinical data, PHOENIX will conduct the first-in-child multicentre Phase I/II clinical trial of ibrilatazar in combination with standard treatments and selected immunotherapies.

Alongside the clinical trial, PHOENIX integrates advanced biomarker research, personalised medicine approaches, and studies on social determinants of health to improve patient stratification, treatment monitoring, inclusiveness, and quality of care.

By bringing together 13 partners from 6 countries, including leading researchers, clinicians, patient organisations, and innovation partners across Europe, PHOENIX aims to deliver safer and more effective therapeutic options and create new hope for children and families affected by high-risk cancers.

PHOENIX is part of the EU Cancer Mission cluster “Diagnosis and Treatment – Innovative clinical trials for paediatric cancer.”

Population: Paediatric | Intervention type: Interventional

End stage renal disease (ESRD) causes high socioeconomic burden for citizens and the healthcare system in Europe. Kidney transplantation represents the treatment standard for ESRD. Graft rejection due to inadequate immunosuppression is the leading cause for chronic graft dysfunction and infectious disease due to reduced immune function is a major cause of death. Optimisation of immunosuppressive drugs is a crucial step to minimize the risk of infection and rejection and thereby prolonging patient and graft survival.

The peripheral blood copy number of the highly prevalent and non-pathogenic Torque Teno virus (TTV) is associated with the grade of the immunosuppression of the host. Non-interventional studies suggest superiority of TTV copy number guided immunosuppression compared to standard strategies.

To demonstrate the safety and preliminary efficacy of TTV-guided dosing of immunosuppressive drugs in kidney transplant recipients, a phase II clinical trial comparing infection and rejection rate between TTV-guided immunosuppression and the clinical routine strategy.

TTV allows for a comprehensive and personalised assessment of the function of the immune system. For the first time this novel and original approach will be tested in an interventional randomised and controlled setting.

The proposed project has the potential to reduce infection and graft rejection by 20% thereby significantly improving graft and patient survival of kidney transplant patients. The improved survival will reduce healthcare costs by ~€ 50 million in the EU per year. The project will serve as a proof-of-concept for TTV-based assessment of the immune system, with potential applications in solid organ transplantation, autoimmune and infectious disease and oncology.

The TTV Guide project also built information videos and information regarding the consent process and ethical legal social implication study that is integrated into the TTV Guide IT clinical trial. 

Population: adult | Intervention type: therapeutic medical device