Koln

The study is a multi-center, prospective, single arm study designed to evaluate the safety and performance of the Cardiovalve Tricuspid Valve Replacement System

The #aware.hiv Europe study is a real-world, multicenter, stepped-wedge cluster randomized, effectiveness-implementation trial designed to evaluate whether the introduction of dedicated HIV teams in hospitals can improve HIV testing rates among patients presenting with HIV indicator conditions across ten European countries. Study Design: The study employs a stepped-wedge design, whereby clusters of hospitals transition sequentially from a control phase (routine care) to an intervention phase. All patient data are collected retrospectively from routine care, while prospective data are gathered at the healthcare professional level. The project spans four years and involves hospitals from the Netherlands, Belgium, United Kingdom, Germany, Spain, France, Italy, Romania, Poland, and Ukraine. This design allows for comparison of HIV testing rates and related outcomes before and after the implementation across different settings and time points. Intervention: The core intervention involves the establishment of hospital-based HIV teams. Each team is led by an HIV specialist and supported by nurses and data collectors. Their responsibilities include: Identification and Surveillance: Screening routine electronic health records for HIV indicator conditions using predefined ICD-10 codes and verifying cases that warrant HIV testing. Audit \& Feedback: Providing targeted recommendations to treating physicians when an HIV test is indicated but has not been performed, thereby prompting action. Education \& Training: Delivering training sessions to healthcare professionals to improve their knowledge and attitudes towards HIV testing, prevention, and care. Enabling Environment: Implementing digital solutions and other support mechanisms to streamline testing processes, reduce stigma, and enhance overall guideline adherence. Linkage to prevention: Improving linkage to the locally available preventive services. The intervention is intended to integrate seamlessly into routine hospital care, thereby reinforcing existing guidelines while addressing the current diagnostic testing gap. Endpoints and Outcome Measures: Primary Endpoint: The change in HIV testing rate among patients diagnosed with HIV indicator conditions before and after the implementation of HIV teams. Key Secondary Endpoints: The change in the incidence of new HIV diagnoses among patients with HIV indicator conditions. Variations in HIV testing rates across different countries, medical specialties, and types of indicator conditions, as well as over time. Assessment of the cascade of HIV diagnosis, including the proportion of patients identified with an indicator condition, the offer and acceptance of HIV testing, and documented reasons for non-testing. Evaluation of the cascade of HIV care and prevention, including linkage to HIV care, achievement of viral suppression, and referral and uptake of preventive services. Changes in healthcare professionals' knowledge, attitudes, and levels of stigma towards HIV. Implementation outcomes such as fidelity of HIV team activities, resource utilization, cost-effectiveness, and sustainability of the intervention. Analysis of contextual factors, barriers, and facilitators impacting the implementation process, using established frameworks like CFIR and RE-AIM. Impact: By introducing HIV teams and systematically monitoring their effect on HIV testing practices, the study aims to enhance early HIV diagnosis and improve patient outcomes. The findings will contribute to evidence-based guidelines and may promote the adoption of similar interventions across European healthcare settings, ultimately reducing HIV-associated morbidity, mortality, and transmission rates. This project not only addresses a critical diagnostic gap in HIV care but also provides valuable insights into the effective implementation of complex interventions in routine clinical practice.

The study comprises of a dose escalation part and, a concurrent backfill part. 1. The dose escalation part will estimate the RD of \[177Lu\]Lu-NeoB in combination with ribociclib and fulvestrant; four provisional dose levels are planned to be tested: 100 millicurie (mCi) (initial dose), 150mCi, 200 mCi and 250mCi in cohorts of 3 to 6 participants. After inclusion of each cohort of 3 to 6 participants, the incidence rate of DLTs will be compared to the pre-defined toxicity rate boundaries to decide whether the next cohort will receive a lower, higher or same dose or whether the trial will be terminated. 2. The backfill part will allow enrollment to a previously cleared dose level (during escalation part) in order to obtain additional safety, tolerability as well as preliminary efficacy data. During the backfill part, the cumulative incidence rate of DLTs will also be compared to the pre-defined toxicity rate boundaries to determine if escalation should be restarted from a lower dose level. 3. The recommended dose (RD) will be determined considering all available data from the escalation and backfill part. During screening, study participants will receive the investigational imaging agent \[68Ga\]Ga-NeoB. An additional administration of the \[68Ga\]Ga-NeoB will be performed potentially at Cycle 2 Day 15, and within 4-8 weeks from the last administration of \[177Lu\]Lu-NeoB for a positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI). Study treatment will include \[177Lu\]Lu-NeoB on day 1 of each 28-day cycle (+ =\< 3 days) for 6 cycles, ribociclib (once daily; days 1 to 21 in a 28-day cycle) and fulvestrant (C1D1, C1D15, C2D1 and every 28 days thereafter) until disease progression. Pre- and perimenopausal women and men will additionally receive goserelin on day 1 of every cycle. During the treatment period participants will be required to attend a site visit approximately every 28 days, on the first day of each cycle (as well as on C1D2, C1D3, C1D8, C1D15, C2D15, C3D3 and C5D3), to undergo study treatment administration, dosimetry and safety assessments. Tumor assessments are performed every 8 weeks until month 18, every 12 weeks until month 36 and as clinically indicated thereafter, until disease progression. After study treatment discontinuation, participants will be followed up for safety for 8 weeks after their last study treatment administration. Beyond the initial 8 weeks of safety follow-up, all participants will be followed up every 12 weeks until month 36 and every 24 weeks thereafter until month 60 for a total of 5 years from the participant's enrollment in the study, or until death, lost to follow-up, or withdrawal of consent (WoC), whichever occurs first. The end of study is defined as the date of the last visit, scheduled procedure or follow up (or date of death, WoC or lost to follow up, whichever occurs first) of the last participant in the study globally, or at 5 years from the date of the last participant enrolled, whichever occurs earlier.

Researchers are looking for other ways to prevent severe illness from COVID-19. COVID-19 is a virus that most often causes mild flu or cold-like symptoms. However, people with certain health conditions or other factors have a high risk (chance) of getting severely ill from COVID-19, which can require a hospital stay or lead to death. Some people who are high risk for severe illness may be unable to take certain treatments for COVID-19 because they are not available to them, or they take other medicines that may react with a treatment and cause an unwanted effect. Molnupiravir (MK-4482) is a study medicine designed to stop the COVID-19 virus from copying itself in the body (multiplying). The goal of this study is to learn if molnupiravir prevents severe illness from COVID-19 more than placebo in people who are high risk.

CLDN6 CAR-T is used as a general term to refer to CLDN6 CAR-T cells from the manual and automated manufacturing processes. The trial consists of two parts. The trial began using a manual CLDN6 CAR-T production process. Part 1 is a CLDN6 CAR-T dose escalation in lymphodepleted patients until the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of CLDN6 CAR-T are defined. Dose escalation with CLDN6 CAR-T cells from the automated manufacturing process follows an accelerated titration design, as opposed to the classical 3+3 trial design used for the dose escalation with CLDN6 CAR-T manufactured with the manual process. In addition, an optional de-escalation dose level may be explored to further evaluate clinical safety and efficacy of CLDN6 CAR-T manufactured with the automated process. Part 2 is a vaccine-modulated dose escalation using a bifurcated design until the MTD and/or RP2D of CLDN6 CAR-T + CLDN6 RNA-LPX are defined. The trial started with a CLDN6 encoding uridine containing RNA formulated in lipoplexes (CLDN6 uRNA-LPX). In order to optimize CAR-T cell persistence in patients, an alternative RNA-LPX, CLDN6 modRNA-LPX, will be tested once the RP2D dose for CLDN6 CAR-T ± CLDN6 RNA-LPX is identified. The planned trial duration per patient in the main trial is 25 months. Patients exposed to genetically engineered therapies may be at risk of delayed adverse events. Therefore, after patients complete or prematurely discontinue participation in the main trial, they will be asked to participate in a long-term follow-up (LTFU) trial to assess long-term safety and efficacy for up to 15 years. Patients will be asked to re-consent to participate in this LTFU period.

Researchers want to learn if V940 with pembrolizumab can stop advanced melanoma from growing or spreading. Melanoma is a type of skin cancer. Advanced means the cancer has spread to other parts of the body and cannot be removed with surgery. A standard (or usual) treatment for advanced melanoma is immunotherapy. Immunotherapy is a treatment that helps the immune system fight cancer. V940 is a study treatment designed to help a person's immune system attack their specific cancer. Pembrolizumab is an immunotherapy. The goal of this study is to learn if people who receive V940 with pembrolizumab live longer without the cancer growing or spreading than people who receive placebo with pembrolizumab. A placebo looks like the study treatment but has no study treatment in it. Using a placebo helps researchers better understand the effects of a study treatment.

The primary objective of the NOA-18/IMPROVE CODEL trial is to show superiority of an initial CETEG treatment followed by partial brain radiotherapy (RT) plus PCV (RT-PCV) at progression over partial brain radiotherapy (RT) followed by procarbazine, lomustine and vincristine (PCV) chemotherapy (RT-PCV) and best investigators choice (BIC) at progression for sustained qOS. An event with respect to a sustained qOS is then defined as a functional and/or cognitive deterioration on two consecutive study visits with an interval of 3 months, tolerating a deviation of at most 1 month. Assessments are done with 3-monthly MRI, assessment of the NANO (Neurologic assessment in neuro-oncology) scale, HRQoL, and KPS (Karnofsky performance status) and annually cognitive testing. Secondary objectives are evaluation and comparison of the two groups regarding secondary endpoints (short-term qOS, PFS, OS, complete and partial response rate). The trial is planned to be conducted at 21 NOA (Neurooncology Working Party of the German Cancer Society) study sites in Germany.

The study will consist of two parts (Parts A and B). Part A will be a randomized, double-blind, placebo-controlled, single ascending dose, first-in-human study part. Part A will enroll people living without HIV (PLWOH). Four cohorts are planned in Part A (Cohorts A1, A2, A3, and A4). Cohort A1 will evaluate one dose of BNT351 administered subcutaneously (SC). Cohorts A2 to A4 will evaluate three different doses of BNT351 administered intravenously (IV). For each cohort, participants will be randomized to BNT351 or placebo. Part B will be single-dose, open-label, proof-of concept study part. Part B will enroll PLWH. Part B comprises of a single cohort (Cohort B1) and will be non-randomized. The study will start with recruitment into Part A. Part B will be opened after review of safety data from Part A. In Part A, for each participant, there will be an \~4-week screening period, one dose of BNT351 or placebo, and an \~38-week follow-up period. In total, Part A will last up to \~42 weeks per participant. In Part B, for each participant, there will be an \~4-week screening period, one dose of BNT351, and an up to 8-week observation period with HIV viral load assessments, after which combination antiretroviral therapy (cART) will be started. Overall, participants will be followed for \~38 weeks after IMP administration and in total, Part B will last up to \~42 weeks per participant.

An open-label, controlled, multi-site, interventional, 2-arm, Phase II/III trial of BNT113 in combination with pembrolizumab vs pembrolizumab monotherapy as first line treatment in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing programmed cell death ligand-1 (PD-L1) with combined positive score (CPS) ≥1. This trial has two parts. Part A, is an initial non-randomized Safety Run-In Phase to confirm the safety and tolerability at the selected dose range level of BNT113 in combination with pembrolizumab. Part B, is a randomized part to generate pivotal efficacy and safety data of BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy in the first line setting in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing PD-L1 with CPS ≥1. Patients included in the Safety Run-In Phase of the trial (Part A) will not be randomized to Part B and will continue on-trial treatment (BNT113 plus pembrolizumab) within Part A. For Part B, an optional pre-screening phase is available for all patients where patients' tumor samples may be submitted for central HPV16 DNA and central PD-L1 expression testing prior to screening into the main trial. Patients will be treated with BNT113 in combination with pembrolizumab or with pembrolizumab monotherapy for approximately up to 24 months.

The purpose of this study is to assess the efficacy and safety of trontinemab in participants with early symptomatic Alzheimer's disease (AD) (mild cognitive impairment \[MCI\] to mild dementia due to AD).