Trials - Portfolio

A phase IIb, prospective, multicentre, double-blind, triplearm, randomized versus placebo trial, to assess the efficacy of a single injection of either 2 or 10 x 106 autologous adipose derived mesenchymal stromal cells (ASC) in the treatment of mild to moderate osteoarthritis (OA) of the knee, active and unresponsive to conservative therapy for at least 12 months.

Population: adult | Intervention type: therapeutic medicinal product

Prospective, randomized, placebo-controlled, multi-centric international phase IIb clinical trial. The target population consists of patients with cardiac structural remodelling with or without symptoms of heart failure (maximum NYHA II). The objective is to evaluate mirabegron (a new β3-specific agonist) over 12 months as add-on to standard treatment compared to standard treatment alone. Endpoints focus on cardiac remodelling: Quantitative indices of hypertrophy and left ventricle (LV) function, in addition exercise tolerance is investigated.

Population: adult | Intervention type: therapeutic medicinal product

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

This study is an adaptive, randomized, open clinical trial to evaluate the safety and efficacy of possible therapeutic agents in hospitalized adult patients diagnosed with COVID-19.

The study will compare different investigational therapeutic agents to a control group managed with the Standard of Care (SoC). There will be interim monitoring to allow early stopping for futility, efficacy, or safety and to introduce new therapies as they become available. If one therapy proves to be superior to others in the trial, this treatment will then become part of the SoC arm for comparison(s) with new experimental treatment(s).

This protocol, therefore, describes a randomised trial among adults (≥18) hospitalised for COVID-19 that randomly allocates them between the 2 arms (since June 29 2020): Standard of Care (SoC) alone versus SoC + remdesivir. Other arms can be added as evidence emerges from other candidate therapeutics.

Population: adult | Intervention type: therapeutic medicinal product

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

A randomised controlled, adaptive, multicentre Phase II protocol evaluating different booster strategies in individuals aged 75 years and older already vaccinated against SARS-CoV-2. Part B of this trial foresees testing of different vaccines as a 4th vaccination dose (second booster) for comparative assessment of their immunogenicity and safety against SARSCoV-2 wild-type and variants in the elderly, a usually neglected population.
Additional vaccines and extended follow-up visits can be added through amendments of this sub-protocol. As stated in the EU-COVAT master protocol, this trial, i.e., the EU-COVAT-1_AGED study, implements a specific safety monitoring strategy .

Population: adult | Intervention type: vaccine

The overarching objective is to evaluate anti-SARS-CoV-2 immune responses to different booster strategies in individuals already vaccinated against SARS-CoV-2. Specifically, this subprotocol will determine the need for, optimal timing of and immunogenicity of administering a 4th homologous vaccination dose against SARS-CoV-2 in the general population (18+ years) who have already been vaccinated with three doses of the BNT162b2 vaccine.

Population: adult | Intervention type: vaccine

The EU-SolidAct trial – European DisCoVeRy for Solidarity: An Adaptive Pandemic and Emerging Infection Platform Trial – is part of EU-RESPONSE, a pan-European research project involved with the rapid and coordinated investigation of medications to treat COVID-19 during the ongoing pandemic. The EU-SolidAct (EudraCT: 2021-000541-41; clinicaltrials.gov ID NCT04891133) is a multi-center, randomized, adaptive Phase 2 and 3 platform trial, the master protocol of which has been developed to evaluate potential treatments in hospitalised patients with COVID-19, the disease caused by the SARS-CoV2 virus (coronavirus). Under the trial, bemcentinib will be studied in up to 500 hospitalised COVID-19 patients. In support of the trial, BerGenBio will provide bemcentinib drug material and incremental funding of costs related to the bemcentinib sub-protocol. 

The first drug studied under the EU-SolidAct platform was baricitinib, marketed by Eli Lilly and Company, and is now under market authorisation evaluation by the EMA (European Medicines Agency) for use in hospitalised COVID-19 patients.  BerGenBio’s AXL inhibitor, bemcentinib, has been selected by an international expert group to be the second compound to be studied in the EU-SolidAct platform.

EU-SolidAct has established clinical sites in 15 countries. The trial is sponsored by Oslo University Hospital, Norway in collaboration with the Institut National de la Santé Et de la Recherche Médicale (Inserm), France and the not-for-profit intergovernmental organization European Clinical Research Infrastructure Network (ECRIN). The trial through the EU-RESPONSE project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101015736. Individual patient-level data will be made as public as possible while maintaining the integrity and privacy of the trial participants.

Population: adult

The EU-TRAIN project was formed by gathering reference kidney transplant centres in a fully operating European network including 12 partners. Our ambitious but realistic goals are: to provide clinicians with innovative and accessible tools for early prediction of individual risk of allograft rejection and transplant loss; to personalise clinical management and treatment and; to improve allograft outcomes.
This project will engineer a risk stratification system applied to kidney transplant patients by analysing the integration of several layers of data (clinical, histological, immunological data as well as gene expression and novel biomarkers) - the TRAnsplant Comprehensive Evaluator of Risk (EU-TRACER). EU-TRACER will be generated and validated in two dedicated studies including a randomised control trial.

Population: adult | Intervention type: non-interventional

This randomized trial is based on the hypothesis that the combined use of (1) biomarkers including non‐invasive biomarkers in peripheral blood and urine predicting anti‐donor immunological activation or quiescence, and high/low risk clustering using the transcriptional changes in allograft tissue samples using gene expression assessment and (2) interactive and actionable data analytics delivered at the bedside will promote safe clinical follow‐up of kidney transplant patients without the need for invasive surveillance allograft biopsies to assess allograft rejection in clinically stable kidney transplant patients. We therefore propose a with/without, European, multicenter, prospective randomized and biomarker‐guided trial.

Population: adult | Intervention type: therapeutic medicinal product

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 Huntingdon’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

ImmunAID is seeking to enable a rapid and accurate diagnosis across all the spectrum of SAID, in order to improve clinical management of SAID patients, through a graded approach:
- Identification and validation of novel Omics- and pathway-based diagnostic biomarkers, with a strong link to pathogenic pathways involved in autoinflammation, and likely to be considered as genuine “autoinflammation signatures”;
- Development of a robust clinical decision algorithm to assist physicians, having a progressive and targeted approach (triage process) when facing a patient with suspected SAID, and thus avoiding the prescription of a large number of costly and frequently inadequate diagnostic investigations in parallel;

The ImmunAID research will likely lead to the reorganization of SAID into a new comprehensive and pathogenesis-driven classification with strong clinical impact.

Population: adult & paediatric

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 objective of the LIVERHOPE project is to evaluate a novel therapeutic strategy for patients with cirrhosis based on a combination of rifaximin and simvastatin, targeting the main pathophysiological mechanisms of disease progression , namely the impairment in the gut-liver axis and the persistent hepatic and systemic inflammatory response. This dual therapeutic approach is supported by preclinical data showing excellent and very promising results.
LIVERHOPE will include two randomized double-blind trials (LIVERHOPE SAFETY and LIVERSHOPE EFFICACY) to investigate safety, tolerability and efficacy of combination of simvastatin plus rifaximin in patients with decompensated cirrhosis in six EU countries (285 patients will be enrolled in two trials in Germany, France, Italy, Spain, The Netherlands, and the United Kingdom). The expected impact is to halt progression to acute-on-chronic liver failure, the main cause of death, to decrease complications of the disease, to reduce hospital re-admissions, to improve cost-effectiveness of therapy.
The aim of the LIVERHOPE SAFETY trial is to assess the safety and tolerability of oral administration of simvastatin plus rifaximin in patients with decompensated cirrhosis.
The aim of LIVERHOPE EFFICACY is to assess the efficacy of the combination of simvastatin plus rifaximin in patients with decompensated cirrhosis to prevent ACLF development.

Population: adult | Intervention type: therapeutic medicinal product

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

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

Friedreich ataxia is a rare incurable and devastating disease. The clinical phenotype includes poor balance, impaired coordination, difficult articulation of speech and swallowing, distal weakness, deep sensory loss, visual and hearing impairment, but also heart failure, diabetes mellitus, scoliosis and foot deformities. Clinical manifestation normally starts around puberty. There is no cure or treatment that can slow down the disease which frequently results in severe disability by early adulthood. Friedreich ataxia is an inherited disorder caused by Frataxin deficiency. Nicotinamide (vitamin B3) was identified to increase Frataxin expression by an epigenetic mechanism in patients with Friedreich ataxia. This multinational study NICOFA will investigate randomized, placebo-controlled and double-blinded, whether high doses of nicotinamide are an effective treatment for Friedreich ataxia over a study period of two years. Study design and duration and number of patients to be included are based on our natural history data obtained in EFACTS (European Friedreich’s Ataxia Consortium for Translational Studies).

Population: adult & paediatric | Intervention type: therapeutic medicinal product

Spinal cord injury is a severe and devastating neurological disorder that leaves patients with permanent paralysis of the body. No treatment is available today to regenerate interrupted nerve fibers and repair the damaged spinal cord. The incidence of spinal cord injury is about newly injured 10’000 people per year in the EU, and due to an almost normal life expectancy more than 200’000 patients are living with a spinal cord injury in the EU. The impact on the individual quality of life is high, and social costs are enormous. Recent preclinical research in animal models succeeded to greatly enhance axonal sprouting, fiber regeneration and neuroplasticity following injuries of brain and spinal cord. These results warrant translation now to patients suffering from acute spinal cord injury. A previous phase I clinical study using intrathecal application of a nerve fiber growth promoting antibody against the growth inhibitory protein Nogo-A has shown in patients with complete spinal cord injury that this treatment is safe and well tolerated. The present study will enroll patients with various degrees of complete to incomplete acute spinal cord injury for a double-blind, placebo-controlled trial to test the efficacy of this antibody therapy to improve motor outcome and quality of life of tetraplegic patients. The enrollment of patients with different degrees of spinal cord injury is considered essential to reveal drug activity and eventual proof of concept in a broad patient population. Advancements in clinical trial design, improved prediction algorithms of clinical outcomes and development of surrogate markers (in cerebro-spinal fluid/serum and by neuroimaging) will allow for scrutinizing the effectiveness of this novel treatment in an unprecedented way. A positive outcome of this trial will represent a breakthrough for the future therapy of spinal cord injuries and beyond (traumatic brain injury, stroke, multiple sclerosis).

Population: adult | Intervention type: therapeutic medicinal product

This clinical trial involves two comparative analyses:

Comparison of efficacy in terms of superiority of hBM-MSCs + biomaterial (both experimental arms, low and high doses) versus iliac crest autologus graft (active comparator arm). The principal endpoint is bone consolidation at one year, defined as a combination of clinical and radiological improvements: radiological consolidation (considered as a new bone formation across the fracture site visible in 3/4 cortices, on at least 3/4 views, qualitative analysis) without pain (with and without weight bearing) and without further reoperation in the callus site.
Comparison of efficacy in terms of non-inferiority (target delta of 0.10 points) of low dose hBM-MSC+Biomaterial versus high dose of hBM-MSC+Biomaterial. The principal endpoint is the radiological consolidation, measured in a scale from 0 to 1, considering the mean consolidation of 0.6875 points (quantitative analysis).

Population: adult | Intervention type: therapeutic medicinal product

PAPA-ARTIS is a phase II trial to demonstrate that a staged treatment approach can reduce paraplegia and mortality dramatically. It can be expected to have both a dramatic impact on the individual patient's quality of life if saved from a wheelchair, and also upon financial systems through savings in; 1) lower costs in EU health care; 2) lower pay-outs in disability insurance (est. at 500k in Year 1), and; 3) loss of economic output from unemployment. Approx. 2500 patients a year in Europe undergo these high risk operations with a cumulative paraplegia rate of over 15%; therefore >100M per year in costs can be avoided and significantly more considering the expected elimination of type II endoleaks.

Population: adult

Elderly patients have a high risk of complications after stroke, such as infections or fever. This study aims to assess whether preventive treatment in the first four days of hospitalisation with ceftriaxone, paracetamol, and/or metoclopramide prevents the most common complications and reduce the risk of death or long-term disability compared to standard care alone.

Population: adult | Intervention type: therapeutic medicinal product

The PROOF project now seeks to demonstrate that NBHO (high-flow 100% oxygen at >45 L/min via a non-rebreather mask, or FiO2=1.0 for intubation/ventilation) reduces infarct growth from baseline to 24 hours compared to standard treatment if administered at 3 hours after onset of anterior circulation IS, in patients with proximal vessel occlusion and salvageable tissue at risk. The study is multi-center, adaptive phase-IIb, randomized, open-label with blinded-endpoint (PROBE design).

The primary efficacy criterion will be infarct growth from baseline to 24 hours. Secondary endpoints will be NIHSS 24h, categorical shift in the pre-stroke modified Rankin Score, QoL and cognition at day 90. Potential surrogate biomarkers, health economics and societal impacts will be assessed. If NBHO proves its neuroprotective potential in this selected population, phase-III trials in all IS patients may be undertaken. Considering its low costs and ease of use, NBHO may impact stroke care worldwide.

Population: adult | Intervention type: therapeutic medicinal product

The objective of this study is to identify the eligibility criteria for treatment with Li in BDI in terms of response, safety and tolerability.

Population: adult | Intervention type: therapeutic medicinal product

The primary outcome of this trial is to evaluate the effectiveness of intradiscal injection of bone marrow mesenchymal stromal/stem cells (BM-MSCs) in reducing chronic lower back pain (LBP) using the visual analog scale (VAS) and functional status (Oswestry scale) after 12 months of treatment, defining responders in case of at least 20% improvement in VAS or Oswestry scale at month 12 compared to a baseline with absolute change of 20 mm on a 100 mm scale.

Population: adult | Intervention type: therapeutic medicinal product

In Europe, Rare Eye Diseases (RED) are the leading cause of severe visual impairment/blindness (SVI/B) in children. This sensory disability with its accompanying psychological distress hugely impacts their lives and their families. Understanding this impact is key in care, shared decision making, developing therapies, and improving social integration. However, current tools to evaluate vision related quality of life (VR-QoL) disregard age and cultural differences, while we lack knowledge on what aspects of this impact are important at the individual child’s level. Instruments capable of yielding high-quality data, with broad applicability and regulatory compliance, remain to be developed.

SeeMyLife convenes a multidisciplinary team from 6 EU countries to generate data on the experience of these children. We will combine quantitative (QUAN) and qualitative (QUAL) data in a mixed methods research framework. QUAN data will be generated using standardized, validated VR-QoL questionnaires. QUAL data will be generated from a socio-anthropologic study including semi-directive interviews to address how their disability affects lives. The conclusions of the QUAN study, comparable across several countries, will be reinforced by the richness of the individual data collected during the QUAL study.

SeeMyLife will provide tools for RED children/teenagers’ self-report which will be used in clinical care and research as a new European standard, and the long-awaited knowledge about the patient’s position within his/her own life course and within his/her family and healthcare actors.

Population: paediatric | Intervention type: therapeutic medical device

Sesame is a European, multi-center, single arm, prospective, observational registry.
Sesame aims to demonstrate that use of SOFIA™/SOFIA™ PLUS catheter for direct aspiration as a first line treatment technique is fast, safe and effective in patients suffering an Acute Ischemic Stroke when assessed at 24 hours, discharge and 90 days after treatment. 250 patients will be enrolled. All patients will be followed for 90 days or until death.

Population: adult | Intervention type: therapeutic medical device

The overall aim of the randomised controlled trial SWEET (S&SEs: Prolonged effects on health, obesity and safety) is to investigate the efficacy and safety of combined (foods and drinks) and prolonged use of S&SEs—as part of a whole healthy ad libitum diet approach—in a population of overweight adults and children. The two primary outcomes on efficacy and safety will be assessed in adults by 1-year changes in body weight and 1-year changes in gut microbiota related to metabolic health outcomes, respectively. Secondary objectives concern effects on obesity-related risk factors such as fat mass, glucose metabolism and lipidemia as well as safety aspects such as allergenicity. Other outcomes include appetite sensations, food cravings, food preferences and preference for sweet taste.

Population: adult & paediatric | Intervention type: therapeutic medicinal product

This study is a post-market, multicenter, prospective, single arm observational registry that aims to collect performance and safety clinical data of NEOCEMENT (CE marked device) in the treatment of bone defects as part of routine clinical practice. The results of the Clinical Investigation shall be used as clinical evidence for clinical evaluation of the device aiming for submission to the new Medical Device Regulation (EU) 2017/745. This protocol does not include any new intended uses, new populations, new materials or design changes.

Population: adult | Intervention type: non-interventional medical device

TENSION is a prospective, open label, blinded endpoint (PROBE), European two-arm, randomized, controlled, post-market study to compare the safety and effectiveness of endovascular thrombectomy as compared to best medical care alone in the treatment of acute ischemic stroke patients with extended stroke lesions defined by an Alberta Stroke Program Early CT Score (ASPECTS) score of 3-5 and in an extended time window (up to 12 hours or unknown time of symptom onset). Up to 714 subjects will be randomized. Primary endpoint will be functional outcome assessed by the modified Rankin scale at 90 days post-stroke ("mRS shift analysis"). By this, TENSION will provide evidence of efficacy and safety of thrombectomy in an acute stroke population with uncertain benefit of endovascular stroke treatment.

Population: adult | Intervention type: therapeutic medical device

Purpose: To prospectively study the efficacy of Teriflunomide in extending the time to a seminal acute or progressive demyelinating event in a cohort of RIS subjects.
Rationale: RIS subjects are frequently exposed to disease modifying therapies despite the lack of scientific literature supporting the use of such treatments. Earlier treatment intervention may extend the time to the first acute or progressive clinical event resulting from CNS demyelination and reduce radiological progression. In addition, early treatment may result in more profound effects on reducing disability progression long-term.
Primary outcome: The primary outcome measure for this trial is the time to the first acute or progressive neurological event resulting from CNS demyelination.
Population: This study will include RIS subjects from the Europe who fulfill 2009 RIS Criteria.

Population: adult | Intervention type: therapeutic medicinal product

To define an optimal dosage of intravenous acetaminophen to close DA in EPI and thereafter to evaluate the consequence of early prophylactic acetaminophen treatment on mortality/morbidity at 36 weeks (w) of postconceptional age (PCA).

Population: paediatric | Intervention type: therapeutic medicinal product

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