Bad Schwalbach, Germany

Prospective, Multicenter Cohort Study on Primary Biliary Cholangitis

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease. The course of the disease is characterized by a slow destruction of bile ducts, and progressive cholestasis. Prognosis depends on the development of cirrhosis and its complications. Ursodeoxycholic acid (UDCA) has been established as standard therapy for PBC and improves patients' long-term outcome. However, UDCA is not a uniformly effective drug, and the prognosis of PBC patients insufficiently responding to treatment is markedly worse. For patients with suboptimal treatment response to UDCA obeticholic acid (OCA) as newly approved medication (OCALIVA®) is available as second line treatment. Due to the low prevalence and the slowly progressive course of the disease it is very difficult to investigate the prognosis of subgroups of PBC patients or to evaluate the effectivness of therapeutic interventions on clinical outcomes. Therefore, several national or international registries (UK-PBC Consortium or the Global PBC Study Group) were founded to better characterize the clinical course of PBC patients. Since in Germany a registry for PBC does not exist, the German PBC Cohort is being implemented as observational study to collect data on treatment progress and success in clinical routine that reflects real world conditions in Germany as closely as possible. The effectiveness and safety/tolerability of PBC treatment options (UDCA as standard therapy and second-line treatment options like OCALIVA in case of inadequate UDCA treatment response) will be evaluated. In approximatly 40 sites in Germany routine data is collected. There are no specifications for the diagnosis, therapy and monitoring of the PBC patients. The documentation of the routine data is carried out alongside with guideline recommended treatment intervals of the patients. Furthermore, a critical criterion for the German PBC Cohort study is the involvement of a sufficient number of gastroenterology specialized practices and outpatient clinics that have consciously not been selected based on the strict specifications of a clinical trial and which provide routine treatment for PBC patients. In addition, patient access is designed to be open. Data will be collected on patient groups that represent a majority of the PBC patients in Germany, but who are not being investigated in clinical trials.

Glymphatic Pathway in Brain Imaging

To investigate the contrast enhancement in different brain compartments. Until recently, it had been assumed that Gadolinium-based contrast agents do not cross the blood-brain barrier, but delayed imaging revealed signal increase in a number of compartments in the CSF (the perilymph of the inner ear, the internal auditory canal, the Meckel's cave, the suprasellar cistern, the ambient cistern and anterior eye compartment). These findings suggested, that Gadolinium-based contrast agents (GBCA) penetrate into the CSF through the choroid plexus and the aqueous chamber of the eye. MRI has provided the evidence of presence of meningeal lymphatic vessels in human and non-human primates for central nervous system waste clearance. It has been demonstrated that heavily T2-weighted fluid-attenuated inversion recovery (hT2w-FLAIR) MRI detects even very low concentrations of GBCA in the CSF. The aim of our study is to find specific enhancement patterns in various cerebral compartments in correlation with specific diseases and procedures such as radiation, surgery and drug application in delayed gadolinium imaging. Only patients with a clinical indication for GBCA will be included in this prospective study. Before enrollment, each patient will have provided written informed consent of participation and publication prior to inclusion to the observational study. The scan will be performed as baseline before intravenous contrast administration of a single dose of gadoteric acid 20 minutes and 120 minutes after contrast administration. Whole-brain image stacks will be analyzed on patient basis. Regions of interest for signal intensity measurements will be drawn in various cerebral fluid spaces, the size of the region of interest will depend on the target structure. The following structures should be measured: lateral and central aqueous chamber and vitreous body of the eye, distal optic nerve sheath, Meckel's cave, lateral ventricles and basal cisterns. Data will be expressed as mean values +/- one-fold standard deviation (SD). The normality of data distribution will be assessed using Levene's test. Data showing a Gaussian distribution will be evaluated by an analysis of variances (ANOVA) with a post-hoc analysis. Estimated sample size is around 30 patients in the control and the experimental group. Cases with missing or unavailable data will be excluded.

European Disease Registry on Retinopathy of Prematurity (ROP)

Clinical Study of Fianlimab in Combination With Cemiplimab Versus Pembrolizumab in Adolescent and Adult Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma

Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients

This is a prospective, multicenter, phase IV, one-arm, open-label clinical trial investigating patients treated with ribociclib and standard of care endocrine therapy for hormone receptor positive (HR+) / human epidermal growth factor receptor negative (HER2-) advanced breast cancer in the first therapy line. Patients eligible for this trial will receive on-label ribociclib according to Summary of Product Characteristics (SmPC) and as well as the specified inclusion/exclusion criteria. The survival rates for progression-free survival (PFS) and overall survival (OS) at month 12 are the co-primary objectives. Quality of life and toxicity are secondary objectives. Additionally, there is a comprehensive biomarker discovery and validation program included into the study. A total of 1000 patients are planned to be enrolled into this trial in 75 trial sites in Germany. Biomarkers will be evaluated before, during and after treatment or at progression. A comprehensive biospecimens sampling will be done to enable translational research projects and evaluation of potential biomarkers within circulation tumor desoxyribonucleic acid (ctDNA), circulating tumor ribonucleic acid (ctRNA), formaldehyde-fixed paraffin-embedded tissue (FFPE) tissue, Serum, Plasma and circulating immune cells

Perioperative Management Evaluation in Patients With CIED

Background: The number of worldwide implanted cardiac electronic devices (CIED) is increasing continuously. On the other hand, the number of (more and more complex) surgical and catheter based interventions in this population is increasing as well. Recommendations for peri-operative management are often based on older data from case reports and small collectives. Data especially in particular subpopulations is limited. Objective: The study aims to evaluate the peri-operative management and outcome of patients with implanted CIED undergoing non-CIED related surgery or catheter interventional procedures (ablation) in clinical routine. Data from the study are expected to provide evidence for recommendations improving perioperative management and device programming. Study design: bi-center, non-randomized, observational registry, retrospective data-collection, on-going prospective patient enrollment, descriptive statistics Centers: Klinikum Fuerth (dep. for Heart and Lung disease, section for clinical electrophysiology), Klinikum Nuernberg (dep. for Heart surgery). Patients and methods: Primary endpoint: number and type of peri-operative adverse device related events (ADE) - all complaints, adverse events and adverse device effects will be documented and classified according to the ISO/DIS 14155 - Clinical Investigation of medical Devices in Human Subjects - Good Clinical Practices with respect to their relationship to the surgical or catheter intervention and [Stark NJ. A New standard for medical device adverse event classification. J of Clinical Research Best Practices 2009; 5(12): 1-7]. Secondary endpoints: pre-interventional data (patient characteristics, data from CIED interrogation); peri-interventional data (type of surgery/intervention, anesthesiology techniques, any AE), post-interventional data (data from post-interventional CIED interrogation, need for reprogramming / device revision). Subpopulations: cardiac surgery, vascular surgery, catheter ablation, ICD and mode of therapy inhibition, CRT, automatic features Inclusion criteria: patients with implanted CIED undergoing non-CIED related surgical or catheter-based procedure, peri-procedural CIED interrogation, age >18 years Exclusion criteria: no implanted CIED, no data from peri-procedural CIED interrogation available. Patient enrollment: retrospectively from the clinical records beginning from 2008, further on-going prospective inclusion Data acquisition: Data will be collected in CRF´s from the patient's history, the computer based clinical information system / clinical records and data records from CIED interrogations Sample size: For the observational study, there is no pre-specified sample size. Data from more than 500 patients undergoing > 700 interventions are expected. Data security: Study related data are collected by the study investigators in an anonymous clinic-internal data-base, that is password protected. All investigators have to provide valid GCP training. Risk estimation: the study is observational and descriptive with anonymized data collection/analysis and therefore adds no risk to the study population

IMA401 TCER® in Recurrent and/or Refractory Solid Tumors, Alone or in Combination With a Checkpoint Inhibitor

A Study to Assess Disease Activity in Adolescent and Adult Participants With Atopic Dermatitis Who Receive Oral Upadacitinib Tablets in a Real-World Setting

A Study to Investigate the Mechanistic Effects of Dapagliflozin Alone or in Combination With Balcinrenone, Compared to Balcinrenone and Placebo on Body Fluid and Electrolyte Handling and Energy Metabolism in Participants Over 50 Years of Age With Chronic Kidney Disease.

The Nuremberg site will perform metabolomics analyses and evaluation of metabolic longevity switches in erythrocytes; participants will be randomly allocated to 1 of the 4 treatment arms, with n=20 participants per arm. All participants in Nuremberg will undergo 3 study visits: at baseline, day 3 (to study the early effect of the intervention) and at day 28 (for the late metabolic effects). An additional safety study visit will take place at day 7+/-1. A follow-up visit will take place at day 28 +/- 7 after the last dose. Study procedures: medical examination, height, weight, blood pressure (BP), heart rate (HR), 24h urine collection and analysis, venous blood sampling. This site will prepare venous blood samples for metabolomic analysis and will perform the erythrocyte isolation protocol for the assessment of erythrocyte metabolism. The Marseille site will conduct an imaging sub-study to evaluate tissue sodium and water content, and muscle energy metabolism before and after the study intervention; participants will be randomly allocated to 1 of the 4 treatment arms, with n=10 participants per arm. All participants in Marseille will undergo 2 study visits: at baseline (before starting the intervention) and after 28 days of treatment. An additional safety study visit will take place at day 7+/-1. A follow-up visit will take place at day 28 +/- 7 after the last dose. Study procedures: medical examination, height, weight, blood pressure, heart rate, 24h urine collection and analysis, venous blood sampling, MRI scans. During each of the study visits at baseline and day 28 the participants will undergo 2 MRI scans: a 23Na MRI scan for the assessment of tissue sodium storage and water content at ultra-high field (7T MRI) and a spectroscopy scan for the assessment of muscle energy metabolism (phosphorus spectroscopy at 3T). The total duration of the scans at each study visit will be approximately 2h. A maximum of 150 participants will be assigned to investigational intervention, to account for a 20% drop-out rate after initiation of the investigational intervention. A total of 120 participants (30 per arm) would be needed to complete the study. Enrolled means participants' or their legally acceptable representatives' agreement to participate in a clinical study following completion of the informed consent process. Potential participants who are screened for the purpose of determining eligibility for the study, but do not participate in the study, are not considered enrolled, unless otherwise specified by the protocol. A participant will be considered enrolled if the informed consent is not withdrawn prior to participating in any study activity after screening. Participants in this study will be randomized into one of the 4 treatment arms: 1. Balcinrenone 150 mg (n=30) 2. Balcinrenone 150 mg + Dapagliflozin 10 mg (n=30) 3. Dapagliflozin 10 mg (n=30) 4. Placebo (n=30) For each group, 20 participants per group will complete the study in Nuremberg (total n=80) and 10 participants per group will complete the study in Marseille (total n=40). No dose modification, neither for dapagliflozin nor for balcinrenone, is planned during this study. To ensure a dose interval of about 24 hours, the medication should be taken every day in the morning. If a dose is missed by more than 12 hours, that dose should be skipped and the next dose should be taken as scheduled. No double doses should be taken. Because of the short treatment duration in this study (28 days) no temporary discontinuation can take place, as this can affect the metabolic phenotype at day 3 and day 28. Therefore, if a participant needs to discontinue the study intervention, this participant will be withdrawn from the study and replaced. Treatment duration will be 28 days, up to a maximum of 32 days to allow for scheduling flexibility. A follow-up visit will take place approximately one month (28 days +/-7 days) after the end of the intervention period. The screening visit may take place anytime within 4 weeks prior to Baseline visit. Therefore, the estimated total study duration for each participant, including screening and follow-up is 2 to 3 months.

IMA402 T Cell-Engaging Receptor Molecule (TCER®) in Recurrent and/or Refractory Solid Tumors

The study will be conducted in two phases: - Phase Ia: Dose escalation/de-escalation - Phase Ib: Dose extension - Phase II: Dose extension in selected Indication-specific extension cohort(s) (ISEC)