Reims

This study is a multicenter, open label phase I dose escalation trial designed to define the Maximum Tolerated Dose (MTD) of 177Lu-DOTATATE in children with refractory or recurrent neuroblastoma. 177Lu-DOTATATE will be delivered intravenously for 2 cycles, 6 weeks apart. The duration of study participation of each patient will be 5 months.

Despite substantial progress made in the first- and second line mCRC settings, there are still unmet clinical needs for patients harboring BRAFV600E mutations, especially those with microsatellite stability (MSS) / proficient mismatch repair (pMMR) tumor. The overall survival and access to different treatment in the real-life setting are unknown. Moreover, patient prognosis remains poor and therapeutic resistance to combinations with BRAF inhibitors, is at present, nearly universal. Therefore, it seems essential to prospectively collect clinical and biological data about this rare mCRC subtype. These data will allow us to improve knowledge and to identify clinical and biological factors that could drive therapeutic decisions, predict resistance to treatments, and that are prognostic for survival. In this context, we designed this large, prospective, cohort study to collect clinical data and biological samples to be used for research but also to gather real-world clinical data concerning the treatments and the survival outcomes in patients with BRAFV600E mCRC. This collection of clinical and biological data (tumor tissue and blood samples) will allow us to identify predictive and prognostic biomarkers with several research work packages planned: i. To evaluate the circulating tumor DNA (ctDNA) during the metastatic first-, second-, and third-line treatment to: * Evaluate its positive and negative predictive value. * Identify molecular alterations preceding and explaining clinical resistance during BRAF/EGFR inhibition therapy and immunotherapy. ii. To evaluate BRAFV600E mCRC immune environment both at the tumor and blood level (immunomonitoring). iii. To study specific the dMMR/MSI BRAFV600E subgroup. Furthermore, the data collected will describe the therapeutic management of BRAFV600E mCRC patients in the routine-practice setting which will bring very useful data. The results of the COBRAF study could lay the groundwork to better understand BRAFV600E mCRC and to identify prognostic and predictive biomarkers helping the development of new therapeutic approaches in this population.

The cohort for inflammatory respiratory diseases: from phenotyping to personalised medicine (The PALMIRE project) is a monocentric study conducted at the University Hospital of Reims, France. Study Population : Adult patients (\>18 year-old) followed at the University Hospital of Reims and diagnosed with asthma, COPD, bronchiectasis, CF, PCD, and IPF will be considered for inclusion. Patients will sign an informed consent for inclusion. Exclusion criteria include "subjects protected by the law" as required by the French authorities. Control patients with no respiratory diseases after clinical and pulmonary function tests assessment will also be included. The expected number of patients included is 470 (Asthma, n=100; COPD, n=150; bronchiectasis, n=50; CF, n=60; PCD, n=30; ILD, n=30; controls, n=50). Inclusion will be conducted for 60 months from July 2025 to July 2030. Study Procedures: For all asthma, COPD, bronchiectasis, CF, PCD, and IPF patients included, data will be registered at inclusion, and at follow-up visits for 10 years. Patients will be followed-up as usual care with no specific therapeutic intervention. For control patients, data will be registered at inclusion with no follow-up. The recorded data will include demographics, history of respiratory disease and comorbidities, respiratory symptoms, results of lung function tests and CT-scan, microbiological and pathological features of respiratory sampling when performed. Data Analysis: Data will be registered in a centralized anonymized database. The characteristics of the patients will be described as mean and standard deviation for quantitative data and as number and percentages for qualitative data. Comparisons and associations between groups and variables will be analyzed by Student, Wilcoxon, Chi2, Fischer exact, and Spearman tests as applicable. A p\<0.05 will be considered as significant. Multivariate and longitudinal statistical models will be used to identify clusters of patients with shared endotypes. Machine learning approaches will be employed to integrate multi-omic data and generate predictive models for disease trajectories and treatment responses. Significance: This study should help better understand the pathogenesis and heterogeneity of chronic respiratory diseases by integrating the analysis of phenotypic and endotypic characteristics of patients.

This study is open to people with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF). They can only take part if they have completed treatment in a previous study with a medicine called nerandomilast or BI 1015550. The goal of this study is to find out how well people with pulmonary fibrosis tolerate long- term treatment with nerandomilast. The study also tests whether nerandomilast improves lung function and prolongs the time until symptoms get worse, participants need to go to the hospital, or die. Every participant takes nerandomilast as tablets for up to 1 year and 10 months. The participants may also continue their regular treatment for pulmonary fibrosis during the study. Participants visit their doctors regularly. During these visits, the doctors collect information on any health problems of the participants. Participants also regularly do lung function tests.

The aim is to describ rare primary hepatic cancers clinical, histological and radiological features, to obtain a biological tumor and blood collection, and to evaluate the efficacy of treatments received in clinical practice in order to determine optimal therapeutic sequences.

In this study, data from patients with INS will be recorded prospectively, regularly and systematically. The cohort will be composed of patients followed by pediatric nephrologists affiliated with the SNP. Metropolitan France, Reunion Island and Mayotte are the geographical areas concerned. It is planned to integrate other French overseas departments and territories, in particular the West Indies. This is therefore a prospective, multicenter, cohort follow-up study. The data will be centralized via a secure website dedicated to the study. Data will be obtained from: * Medical record data (hospitalization/consultations) as part of routine clinical follow-up for patients with active disease. This information will be medically validated and integrated into the database with the help of clinical research staff. * A telephone interview for annual follow-ups for patients whose absence of active disease no longer requires a systematic medical visit. This structured interview will be administered by telephone by the study's clinical research staff. * Self-administered or hetero-administered quality of life questionnaires (PEDS-QL), self-administered or hetero-administered treatment compliance questionnaires (Morisky's Score), and questionnaires on the aesthetic impact of treatments (Ferriman's Score). These questionnaires will be centralized and reported to the database by the study's clinical research staff.

The study population consists of children under 18 years-old when laying multi-brackets orthodontic treatment in the oral medicine department of Reims University Hospital. This population is distributed into 2 groups. The control group consists in children having completed their orthodontic treatment by December 2024, (n=30). The study group consists in children starting their orthodontic treatment during 2024 and benefiting from semi-annual oral prevention during four years-treatment. Moreover, their dentists and orthodontists will be able to access a digital communication tool to facilitate their exchanges. The number of patients in the study group will depend on the number of the patients in the control group. The study protocol was approved by a regulatory agreement of the RGPD (register of processing activities) of Reims University Hospital since 14/11/23. All data will be anonymized. These data correspond to those that are systematically and usually collected by professionals during the orthodontic treatment. They will be stored in a secure computer located in the oral medicine department. The aim of the study and clinical procedures will be explained to the parents and the children to obtain their informed consent. Data collected for control group at the treatment completion, an average of 4 years: put out the treatment: * Sex: Girl/Boy/Non-Registered * Date of birth (month/year) / age * Processing end date * Regular orthodontic appointment * Socio-Professional Category (PCS 2020 level 1 nomenclature: 6 levels INSEE) : farmers; artisans, traders and business leaders; executives and higher intellectual professions; intermediate professions ; employees ; workers * Decayed, missing and filled teeth index (DMFT Index) * ICDAS score (International Caries Detection and Assessment System) * Decays under dental restauration * Modified orthodontic plaque index (MOP Index) * Individual carious risk (based on HAS-France): * Regular brushing * Manual or electric brushing * Presence of snacking and soda * Taking long-term sweet or medication causing hyposialia * Presence of dental plaque visualized by dental plaque disclosing tablet * Presence of dental plaque visible without dental plaque disclosing tablet * Presence of enamel demineralization * Presence of caries lesions (dentin involvement) and/or reversible initial lesions (enamel involvement) * Serrated grooves in molars * Grooves treated by Sealent * Fluoride varnish * Presence of gingival hyperplasia Data collected for study group during each consultation before the orthodontic treatment and followed every 6 months, up to 4 years: * Appointment date * Sex: Girl/Boy/Non-Registered * Date of birth (month/year) / age * Regular follow-up with a dentist * Socio-Professional Category (PCS 2020 level 1 nomenclature: 6 levels INSEE) : farmers; artisans, traders and business leaders; executives and higher intellectual professions; intermediate professions ; employees ; workers * Decayed, missing and filled teeth index (DMFT Index) * ICDAS score (International Caries Detection and Assessment System) * Plaque Index Silness et Loe before treatment * Modified orthodontic plaque index (MOP Index) as soon as the treatment is applied * Molar Incisor Hypomineralization (MIH): degree of severity (moderate - severe), type of teeth affected (molars - incisors), number of teeth treated * Amelar abnormality: incisal dysplasia, number of teeth treated * Individual carious risk (based on HAS-France): * Regular brushing * Manual or electric brushing * Presence of snacking and soda * Taking long-term sweet or medication causing hyposialia * Presence of dental plaque visualized by dental plaque disclosing tablet * Presence of dental plaque visible without dental plaque disclosing tablet * Presence of enamel demineralization * Presence of caries lesions (dentin involvement) and/or reversible initial lesions (enamel involvement) * Serrated grooves in molars * Grooves treated by Sealent * Fluoride varnish * Presence of gingival hyperplasia * Need for prevention and/or care sessions

The total duration of the study is 76 weeks and consists of: Screening (up to 4 weeks), Treatment Period 1 (16 weeks, double-blind treatment with remibrutinib (Dose A or Dose B) or placebo, Treatment Period 2 (52 weeks, treatment with remibrutinib (Dose A or Dose B) and Safety Follow-Up (treatment-free follow-up for 4 weeks). Participants who prematurely discontinue study treatment (either during Treatment Period 1 or Treatment Period 2) are encouraged to remain in the study. Participants who do not wish to remain in the study will enter a 4-week Safety Follow-Up period.

The purpose of this study is to investigate the efficacy, safety, and tolerability of baxdrostat in combination with dapagliflozin, compared with placebo and dapagliflozin, in reducing the risk of the composite endpoint of ≥ 50% sustained decline in eGFR, kidney failure, HF events, or CV death in participants with CKD and HTN. This study consists of a 4-week dapagliflozin Run-in Period for participants untreated with SGLT2i at screening, and a double-blinded period where participants will receive either baxdrostat/dapagliflozin or placebo/dapagliflozin. Site visits will take place at 2-, 4-, 8-, 16-, 34, and 52-weeks following randomisation. Thereafter visits will occur approximately every 4 months. The study closure procedures will be initiated when the predetermined number of primary endpoint events is predicted to have occurred (N = 845) ie, the PACD. All randomised participants including any participants who have prematurely discontinued study intervention will be scheduled for a SCV within 6 weeks of the PACD. This period can be extended by AstraZeneca. In case of premature discontinuation of blinded study intervention, participants will continue in the study and receive dapagliflozin 10 mg, unless the participant meets dapagliflozin specific discontinuation criteria. Baxdrostat/placebo should not be administered without dapagliflozin: baxdrostat/placebo should be interrupted if dapagliflozin is interrupted (baxdrostat/placebo may be resumed with dapagliflozin, if dapagliflozin is resumed), and should be permanently discontinued if dapagliflozin is permanently discontinued. If study intervention is temporarily or permanently discontinued, the participant should remain in the study, and it is important that the scheduled study visits (including the PTDV for participants with permanent discontinuation of study intervention) and data collection continue according to the study protocol until the SCV.

This is a prospective, randomized (1:1 ratio), multicenter, comparative and phase II trial. Patients with unresectable advanced gastrointestinal stromal tumors (GIST) will be accrued after the failure of standard treatments (imatinib, sunitinib and regorafenib) : * For imatinib, failure is defined as disease progression * For sunitinib and regorafenib, failure is defined as disease progression and/or intolerance Randomization (1:1 ratio) will be stratified according to: * The tumor KIT (exon 11) mutational status: wild type or mutated STUDY TREATMENTS : During the treatment period (12 months maximum), all patients will receive either: * Imatinib per os 400 mg daily continuously associated with intravenous administrations of atezolizumab at the fixed dose of 1200 mg every 3 weeks (experimental arm) * Or imatinib alone, per os 400 mg daily continuously (control arm) The comparison between this two arms will allow to compare whether or not atezolizumab and imatinib is efficient for disease control, in terms of Progression-Free Survival improvement. STATISTICAL ANALYSIS : A total of 110 patients will be randomized (55 per arm). It is expected a 6-month PFS rate of 10% in the standard arm (imatinib alone). Thus, a 6-month PFS-rate of 30% is a clinically significant target for patient treated with imatinib associated to immunotherapy. An interim safety analysis is planned to be conducted after 6-month follow-up of the 12th patient has been randomized (approximately 6 patients by arm). PFS will be estimated using the Kaplan-Meier method, and will be described in terms of median PFS along with the associated 2-sided 95% CIs for the estimates. PFS distributions will be compared between the 2 study arms using a stratified Log-Rank test by tumor mutational status of KIT - exon 11 (stratification factors used for the randomisation). A statistical interim analysis will be conducted after 50 events (PFS). Predefined stopping rules for futility will be applied to state on the continuation of the trial. DATA ENTRY, DATA MANAGEMENT AND STUDY MONITORING : All the data concerning the patients will be recorded in the electronic case report form (eCRF) throughout the study. Serious adverse event (SAE) and Adverse Event of Specific Interest (AESI) reporting will be also paper-based by e-mail and/or Fax. The sponsor will perform the study monitoring and will help the investigators to conduct the study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local law requirements.