University Paris - Sud and Lille University Hospital Center | Date: 2015-04-16
The invention relates to an isolated monoclonal antibody that specifically binds to the D4 domain of VWF, competes for binding to VWF D4 domain with ADAMTS13 and partially inhibits ADAMTS 13 -mediated degradation of VWF. More particularly, the invention relates to an isolated monoclonal antibody comprising a heavy chain wherein the variable domain comprises at least one CDR having a sequence selected from the group consisting of SEQ ID NO: 3 for H-CDR1, SEQ ID NO: 4 for H-CDR2 and SEQ ID NO: 5 for H-CDR3 and a light chain wherein the variable domain comprises at least one CDR having a sequence selected from the group consisting of SEQ ID NO: 7 for L-CDR1, SEQ ID NO: 8 for L-CDR2 and SEQ ID NO: 9 for L-CDR3. Antibodies of the invention are presented to be useful in for the prevention or the treatment of bleeding episodes, such as bleeding episodes occurring in patients with aortic stenosis or patients with ventricular assist devices (VAD).
Morschhauser F.A.,Lille University Hospital Center
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013
Obinutuzumab (GA101), a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, was superior to rituximab in human diffuse large B-cell lymphoma (DLBCL) and mantle-cell lymphoma (MCL) xenograft models. In phase I of our study, obinutuzumab (GA101) exhibited encouraging activity but no clear dose-response relationship, and few patients had aggressive histologies. The efficacy and safety of two doses of obinutuzumab (GA101) were explored in our randomized phase II trial in patients with heavily pretreated DBLCL and MCL. Patients were randomly assigned to receive eight cycles of obinutuzumab (GA101) either as a flat dose of 400 mg for all infusions (days 1 and 8 of cycle 1; day 1 of cycles 2 to 8) or 1,600 mg on days 1 and 8 of cycle 1 and 800 mg on day 1 of cycles 2 to 8. Forty patients were enrolled: 21 patients in the 400/400-mg treatment arm (DLBCL, n = 10; MCL, n = 11) and 19 patients in the 1,600/800-mg arm (DLBCL, n = 15; MCL, n = 4). End-of-treatment response was 28% (32% and 24% in the 1,600/800-mg and 400/400-mg study arms, respectively). Best overall response rates were 37% in the 1,600/800-mg arm and 24% in the 400/400-mg study arm (DLBCL, eight [32%] of 25 patients; MCL, four [27%] of 15 patients). Five (20%) of 25 rituximab-refractory patients exhibited treatment response, including four of 12 in the 1,600/800-mg group. The most common adverse events were infusion-related reactions (IRRs), which were manageable. Three patients had grade 3/4 IRRs. Grade 3/4 neutropenia was seen in only one patient. Obinutuzumab (GA101) 1,600/800 mg achieves early steady-state concentration and clinical activity with an acceptable safety profile in relapsed/refractory DLBCL and MCL, supporting further exploration.
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-14-2015 | Award Amount: 5.78M | Year: 2016
Asbestos is one of the major occupational carcinogens. The European Union has an extensive history of protecting workers and consumers against asbestos and even adopted a resolution 2012/2065(INI) on asbestos related occupational health threats and prospects for abolishing all existing asbestos last year. Although asbestos is banned, it is still massively present in the built environment. Millions of workers & consumers in the EU were, and still are, for many years exposed to asbestos fibres, despite all measures. Inhalation of even very low quantities of asbestos fibres tremendously increases the risk of developing Malignant Mesothelioma (MM). The IARC reported 8.100 MM deaths in 2010 in the EU. Despite all EU actions, MM incidence is still increasing. MM is a highly fatal disease with a poor median survival time from first signs of illness to death around 12 months despite aggressive treatments. To date there is no curative therapy for MM. MM is considered as an extremely therapy-resistant disease. Chemotherapy consisting of a combination of pemetrexed and cisplatin is considered standard of care with a median survival increase of 3 months (9-12 months). The department of pulmonary diseases of the Erasmus MC, Rotterdam, The Netherlands, in collaboration with international partners, have developed a promising personalised immunotherapy for MM with very limited adverse effects. The first clinical results show a considerably prolonged average survival with limited adverse events (24 months, twice as long). The EMA and the FDA granted this therapy Orphan Designation: autologous dendritic cells pulsed with allogeneic tumour cell lysate for the treatment of malignant mesothelioma (EU: 16 January 2014 - EU/3/13/1229; FDA US: 06 May 2014). The objective for the project is to deliver the scientific & registration package for market approval by the EMA of a novel immuno therapeutic approach to treat MM. This includes the execution of a phase II/III clinical trial.
Lille University Hospital Center | Date: 2014-01-27
A device enabling food bolus flow between two stomas, said device having a pump forming means (3), said pump forming means (3) having an entry opening and an exit opening and being suitable for sucking food bolus through said entry opening and releasing it through said exit opening. The device further includes: first watertight connection means (11) suitable for connecting said entry opening to a upstream stoma (S1) located on a patients abdominal wall; second watertight connection means (1) suitable for connecting said exit opening to a downstream stoma (S2), located on said patients abdominal wall; said pump forming means being able to be activated by a user and suitable for being mounted on a patients body, particularly on said patients abdomen, in such a manner that once said device is mounted onto said patients abdomen, food bolus flow can circulate from said upstream stoma (S1) to said downstream stoma (S2) outside of said patients abdomen.
Lille 2 University of Health, Law and Lille University Hospital Center | Date: 2014-11-25
The system comprises: a bundle of light fibers (11) connected to a light-emitting source (8), and both transmitting light inside the light fiber and emitting light toward a treatment volume (V), a temperature-modifying system attached to the bundle of light fibers (11) to modify temperature in the treatment volume (V).
Lille University Hospital Center | Date: 2014-09-04
The present invention relates generally to the fields of reproductive medicine. More specifically, the present invention relates to methods and kits for determining the human sperm quality.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.2.2-1 | Award Amount: 7.88M | Year: 2012
Alzheimers disease (AD) is an ever-increasing public health concern among the aging population and is the most common form of dementia affecting more than 15 million individuals worldwide and around 5 million Europeans. The direct and indirect costs of AD and other dementias amount to more than 440,000 million each year (www.alz.org, 2010). Even modest therapeutic advances that delay disease onset and progression could significantly reduce the global burden of the disease and the level of care required by patients. While there are symptomatic-based drug therapies available for AD, these medications do not prevent the disease process itself. There is therefore an imperative to develop new treatments for AD that have disease modifying effects. This double-blind placebo controlled study will test the efficacy and safety of nilvadipine in 500 subjects with mild to moderate AD over a treatment period of 18 months. There is a strong scientific rationale for this study: Nilvadipine, a licensed calcium channel enhances A clearance from brain and restores cortical perfusion in mouse models of AD. Nilvadipine is safe and well tolerated in AD patients and clinical studies with this medication have shown stabilization of cognitive decline and reduced incidence of AD, pointing to both symptomatic and disease modifying benefits. Male and female patients with mild to moderate AD aged between 50 and 90 with a range of medical morbidities and frailty will be included in the study. If this trial is successful, nilvadipine would represent an advance in the treatment of AD patients and would have a major impact on the health and social care costs incurred in Europe by this neurodegenerative disorder. Furthermore, the creation of the NILVAD network will support future clinical trials and research innovation in AD across Europe.
MON4STRAT - Therapeutic Beta-Lactam Monitoring for Stratified Treatment of hospital-acquired pneumonia, improved dose-dependent efficacy, decreased treatment duration, and prevention of emergence of resistance
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.1-2 | Award Amount: 7.86M | Year: 2014
Stratified clinical treatment interventions meeting patient-specific efficacy (pharmacodynamics) while at the same time lowering the risk of emergence of drug resistance (EDR) and minimizing adverse effects are particularly needed in Hospital-acquired and Ventilator-Associated pneumonia [HAP/VAP] where morbidity, mortality and health care costs remain high. -lactam antibiotics are at the cornerstone of most effective treatments of HAP/VAP, but dosage adaptations remain difficult because available models (i) focus mainly on efficacy (neglecting EDR and dose-related side effects) and (ii) are derived from population data which imperfectly fit individual patients needs due to large, rapid and difficult-to-predict variations of blood levels. Current methods for monitoring -lactam blood levels are slow and require complex instruments not usable at bed-side. Yet, generating easily, rapidly and cost-effectively real data usable at the patients bed-side should improve outcomes of -lactam treatments. This is what 3 out of the 11 partners of the MON4STRAT consortium have recently developed (patent pending). Thus the objective of the Project is to integrate both (i) state-of-the-art PK/PD and EDR profiles AND (ii) real-time/patient-specific free -lactam blood levels monitored at the patients bed-side according to the patented assay for developing and implementing a new approach to (i) stratify the HAP/VAP patients according to their specific response, (ii) to propose immediately applicable dose adjustments during treatment and thus (iii) to improve efficacy while reducing risk of EDR or adverse effects. The MON4STRAT approach will be validated through a prospective, multicentre, randomized clinical trial with150 adults. Its applicability in paediatrics will be tested through an observational study with 70 children/neonates. Being generic in nature, MON4STRAT will be replicable to other infectious conditions.
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.4.2-1 | Award Amount: 14.96M | Year: 2012
The consortium led by UKER and EuroHYP, the European Stroke Research Network for Hypothermia, proposes a large, multicentre clinical trial which will assess mild hypothermia as a novel treatment for ischemic stroke. Stroke is the second cause of death world-wide and the second cause of lost disability-adjusted life years in high-income countries. Stroke incidence rises exponentially with age, so its social and economic burden will grow with the ageing of the European population. Current treatment options for the 80 to 85% of all strokes due to cerebral ischaemia - around. 900,000 events in Europe every year, or one every 40 seconds - are extremely limited. Systematic review of experimental studies suggests that hypothermia is the most promising intervention identified to date. Therapeutic cooling is effective in reducing ischaemic brain injury following cardiac arrest, and hypothermia is therefore considered by experts the most promising treatment for patients with acute ischaemic stroke, next to reperfusion strategies. The EuroHYP-1 trial is a pan-European, open, randomised, phase III clinical trial which will assess the benefit or harm of therapeutic cooling in 1500 awake adult patients with acute ischaemic stroke. In addition to efficacy and safety, the economic impact of therapeutic hypothermia will be assessed, along with several sub-studies involving imaging, ultrasound, and biomarker methods. The investigators involved in the EuroHYP-1 consortium are leading European experts in statistical design and analysis, therapeutic hypothermia, imaging, health economics, ultrasound, biomarkers, and trial execution (implementation and monitoring). Moreover in addition to these academic experts the consortium also involves European patient and family advocacy groups and small and medium-size enterprises, and the joint endeavours of this extended team will ensure the successful enrolment of patients at eighty hospitals across 25 countries in Europe.
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-13-2014 | Award Amount: 8.26M | Year: 2015
Parkinsons disease (PD) is a major, chronic, non-communicable disease and the 2nd most frequent neurodegenerative disorder worldwide. Excess iron is primarily detected in the substantia nigra pars compacta, where dopaminergic neurons are exposed to high levels of oxidative stress produced by mitochondrial disorders and dopamine metabolism. Our previous preclinical, translational and pilot clinical studies demonstrated that novel iron chelation therapy with the prototypic drug deferiprone (DFP) (i) induces neuroprotection in cell models of PD via a powerful antioxidant effect, (ii) reduces regional siderosis of the brain, (iii) reduces motor handicap via inhibition of catechol-o-methyl transferase, and (iv) slows the progression of motor handicap in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model and in early PD patients. This project now seeks to demonstrate that conservative iron chelation therapy with moderate-dose DFP (30 mg/kg/day) slows the progression of handicap in de novo PD patients while not affecting systemic parameters. The 9-month, parallel-group, randomized, placebo-controlled, multicentre trial will be followed by a 1-month wash-out period. The primary efficacy criterion will be the change in motor and non-motor handicap scores on the Total Movement Disorders Society Unified Parkinsons Disease Rating Scale to identify disease-modifying and symptomatic effects. The secondary efficacy criterion will be the change in score between baseline and 40 weeks (i.e. probing the disease-modifying effect only). Potential surrogate radiological and biological biomarkers, health economics and societal impacts will be assessed. 17 national, European and international research and innovation activities will be linked with the project. The study results should prompt academic and industrial research on iron chelation as a disease-modifying treatment in neurodegenerative diseases.