Pontoise

EFC18419 is a multinational, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 study with 3 treatment groups. The purpose of the study is to evaluate the efficacy, safety and tolerability of 2 dosing regimens of itepekimab compared to placebo as add-on therapy to intranasal corticosteroids (INCS) in male and female participants with chronic rhinosinusitis with nasal polyps (CRSwNP) aged 18 years of age and older. Study details include: * The study duration per participant (4-week screening, 52-week treatment, 20-week safety follow-up) will be up to 76 weeks. For participants transitioning to the LTS18420 study, the study duration will be 56 weeks. * The treatment duration will be up to 52 weeks. * The number of visits will be 9 site visits and 20 phone/home visits.

Elritercept (KER-050) is a recombinant fusion protein being studied to increase red blood cell production by inhibiting the signaling of a subset of the transforming growth factor beta (TGF-ß) family of proteins.

BACKGROUND Non-muscle infiltrating bladder tumors are a cancerous pathology with an estimated incidence of 13,000 new cases/year in France. ¾ of new cases are diagnosed at a stage where the cancer is of limited extension to the urothelial mucosa and/or its underlying chorion (non-muscle-invasive bladder cancer NMIBC). The management and follow-up of NMIBCs are performed according to the best practice recommendations issued by the Cancer Committee of the French Urology Association. The risk of recurrence at 1 and 5 years for NMIBC has been estimated in clinical trials to be between 15%-61% and 31%-78%, respectively, depending on grade, stage, number, size, frequency of previous recurrence and presence of carcinoma in situ. In this context, patients should have regular endoscopic examinations to ensure the absence of tumor lesions inside their bladder. Urine cytology pathology is recommended for the detection of recurrence of NMIBC. However, the negative predictive value of this examination does not allow it to be substituted for bladder endoscopy, as the risk of not recognizing a bladder tumor, especially of low grade, is too high. To date, no urinary biomarker has been shown to be clinically useful and their use is not recommended for the non-invasive detection of endovesical tumor recurrence. Urine sampling is recommended prior to bladder endoscopy for follow-up of NMIBC to ensure urine sterility (CBEU) and to perform urine cytology in patients with high-grade NMIBC and/or carcinoma in situ. The observational study of the clinical validity of the negative and positive predictive values of the biomarkers in a population of patients followed for a bladder tumor previously characterized is able to demonstrate the possibility of postponing the realization of the cystoscopy according to the tumoral characteristics and the treatments received by the patients. OBJECTIVES The main objective of the research will be to evaluate the diagnostic performance of biomarkers available in France, performed on a urine sample and providing a binary result (positive: probable presence of a tumor recurrence; negative: probable absence of a tumor recurrence) to the result of the bladder endoscopy performed as part of the routine care for the follow-up of NMIBC: determination of the negative and positive predictive values of biomarkers. The secondary objectives will be to describe the anatomopathological characteristics, the pathological history and the treatments received in the population, as well as analyze demographic and regional disparities in the treatment profiles of these diseases. MATERIAL AND METHOD When the patient is included in the study, medical data relating to the patient's pathology, including all previous treatments, will be entered into the register, as well as the name and result of the biomarker carried out before the resection (biopsy). At each follow-up endoscopic examination scheduled in the patient's personalized care plan, the investigating urologist will record its date and endoscopic findings (white light bladder fibroscopy). The name and result of the urine test will also be recorded by the urologist. The performance of the test will be evaluated from these data by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) and by means of an analysis of variance (ANOVA) to explore possible differences within the test by tumor grade and stage, and according to previous endovesical treatments received. The inclusion target is 8000 patients in France over a 3-year period.

The goal of this clinical trial is to learn about the variability of HGI (Hemoglobin Glycation Index) over time in patients living with diabetes using a continuous glucose monitoring.

Prematurity in itself, whether simple or associated with intrauterine growth retardation, continues to be a real public health problem. In addition to gestational age at birth, the presence of co-morbidities can affect the morbidity and mortality of premature babies, as well as the length of hospital stay. Advances in neonatal care and the involvement and skills of parents in the care of premature infants have led to a considerable reduction in mortality among these patients. According to the latest recommendations published in November 2022 by the WHO, and thanks to changes in the criteria for discharging these patients in recent years, the same applies to low-birthweight infants. The early and well-planned discharge of premature babies is currently the subject of a great deal of study and research. According to these studies, it has been shown that the essential criteria for this discharge are the physiological capacities and skills of these vulnerable patients (thermoregulation, autonomous feeding and breathing, etc.). Essential care, parental support and home visits by qualified health workers (PMI, HAD, etc.) are also essential. Premature birth has a real impact on the economic consequences in several countries. Infants small for gestational age had longer hospital stays, were more likely to be admitted to an intensive care unit and were more likely to be hospitalised in the first year of life, resulting in higher costs. It is against this backdrop that the NOVO hospital is proposing to evaluate the impact of discharging babies weighing less than 2 kilos. To do this, the investigator will base his study on the short-term and long-term outcome of newborns weighing less than 2 kilos who were discharged from the NOVO hospital's neonatology department between 2012 and 2024.

The study will capture post-marketing safety data on patients treated with eculizumab or ravulizumab. Additionally, the study will collect information on the progression of disease in all patients.

The overall objective of this study is to define the differential characteristics of autoimmune T and B lymphocytes across individuals with T1D, other forms of diabetes or autoimmunity, and no disease. The hypothesis is that the characterization of the autoimmune T and B lymphocytes involved in T1D development may allow us to clarify the pathophysiological mechanisms of disease and to identify novel biomarkers for diagnostic, prognostic and therapeutic follow-up applications.

Intensive combination therapies have revolutionised the management of solid neoplasms, hematologic malignancies, and acquired-immune-deficiency syndrome. These intensive strategies are based on the need to obtain rapid control of disease activity to afford the chance of stable full remission and avoid irreversible complications. The same goal applies to management of RA. Because current therapeutic strategies may fall short of these target goals and fail to improve quality of life in some patients, novel approaches are needed to improve outcomes. RA is a complex disease involving numerous cell types and inflammatory mediators of innate and adaptive immune systems. The investigators are aware that most of combination bDMARD strategies have been associated with little or no incremental benefit in efficacy compared to single-biologic therapy. However, our study will target mechanisms that differ from those in previous studies. Strategies that simultaneously target different pathways involved in the pathogenesis of RA may enhance treatment responses in patients with RA. Of note, baricitinib does not directly block signalling downstream of TNF, even if an indirect effect on TNF production is likely to occur. Targeting multiple inflammatory cytokines in combination may lead to more effective treatment and enhanced clinical responses in patients with RA compared to the current second-line strategies. The different mechanisms of action of baricitinib and anti-TNF, should ensure the efficacy of the combination. No concurrent trial evaluating similar strategies is registered at ClinicalTrial.gov.

Multicentre randomized non-inferiority trial comparing cotrimoxazole to standard antibiotic therapy for enterobacterial VAP. Selection of patients will be done by physicians in ICU. All clinically suspected VAP will be confirmed with a lung sample (preferably bronchoalveolar lavage or protected distal specimen, otherwise endotracheal aspiration). Patients with a microbiologically confirmed VAP due to an Enterobacteriaceae susceptible to cotrimoxazole and at least one antibiotic of the empiric antibiotic therapy (based on international recommendations) will be included. After written informed consent, they will be randomized (1:1), using a computer-generated randomization scheme of various-sized blocks, stratified by presence of septic shock at VAP diagnosis and by presence of COVID-19 pneumonia on ICU admission, through a centralized 24 hours internet service (CleanWEB™) to cotrimoxazole, or best standard of care (either a beta-lactam or a fluoroquinolone), after randomization for a total duration of 7 days (including empiric initial appropriate treatment). Posology and modalities of antibiotic administration will be optimized based on most recent recommendations for ICU patients. Because antibiotic therapy will be variable in the control group, single or double blind is not appropriate. Daily follow-up until death or ICU discharge or day 28 will be performed (vital status, antibiotic therapy, new infection, Clostridium-difficile infection). Clinical (arterial blood gas, temperature, haematology, tracheal secretions) and radiological cure (chest X-ray) will be assessed at Day 7. Systematic MDR bacteria screening will be performed weekly and at ICU discharge. Vital status will be assessed at day 90. Alive patients leaving ICU before 90 days will be contacted by phone (if discharge at home) or by interview at hospital (if transferred in a different ward). Assessment of the clinical and radiological cure by an independent committee (1 specialist in infectious disease and 1 intensivist), blinded of the randomization arm (PROBE methodology).

This study is designed as a multicenter, randomized, parallel groups, open-label, phase 3 study in subjects with untreated newly diagnoses Multiple Myeloma eligible for ASCT. 824 patients will be enrolled in this study from approximately 70 study sites. The 2 parts in the Treatment Phase are described below. Part 1: Induction/ASCT/Consolidation Phase (1:1 Randomization) After the screening period, patients will be randomly allocated (1:1) to either: * Arm A (standard of care arm): standard induction therapy with 4 cycles of D-VRd, followed by HDCT (Melphalan) + ASCT, D-VRd consolidation therapy * Arm B (experimental arm): standard induction therapy with 4 cycles of D-VRd, followed by elranatamab and lenalidomide consolidation therapy. Part 2: Maintenance Phase (1:1 Re-randomization) Patients will be re-randomized (1:1) and will enter the Maintenance Phase upon completion of consolidation therapy. * Arm C (standard of care arm): lenalidomide * Arm D (experimental arm): elranatamab