Uebigau Wahrenbruck

Researchers are evaluating whether the introduction of dedicated hospital-based HIV teams can improve HIV testing rates among patients with HIV indicator conditions across ten European countries. This real-world, multicenter, stepped-wedge cluster randomized effectiveness-implementation trial spans four years and involves hospitals in the Netherlands, Belgium, United Kingdom, Germany, Spain, France, Italy, Romania, Poland, and Ukraine. The study aims to address the current gap in HIV testing and improve early diagnosis by comparing testing rates before and after the implementation of HIV teams. The intervention involves creating local HIV teams led by HIV specialists, supported by nurses and data collectors. These teams focus on auditing and providing feedback to healthcare professionals to encourage HIV testing when indicated, reducing stigma, educating staff on HIV prevention and care, and improving linkage to local prevention services. The HIV teams use electronic health records to identify patients with HIV indicator conditions and integrate their activities into routine hospital care. Participants' data are collected retrospectively from routine care and prospectively at the healthcare professional level. Researchers measure changes in HIV testing rates, new HIV diagnoses, and variations across countries and specialties. They also assess the HIV diagnosis and care cascade, healthcare professionals' knowledge and stigma levels, and implementation outcomes such as resource use and cost-effectiveness. Monitoring includes feedback loops and evaluation of barriers and facilitators to implementation, aiming to improve HIV testing and care sustainability in hospitals.

Researchers are conducting a phase II, multicenter, open-label trial to investigate the combination of Fruquintinib and Tislelizumab in patients with microsatellite stable (MSS) or proficient mismatch repair (pMMR) metastatic colorectal cancer who do not have active liver metastases. The study aims to evaluate the effectiveness of this combination in comparison to a control treatment for this specific group of patients. Participants will be randomly assigned to one of two treatment groups. The experimental group will receive oral Fruquintinib (5 mg daily for 21 days in each 28-day cycle) along with intravenous Tislelizumab (400 mg every 42 days). The control group will be treated with oral Trifluridine/tipiracil (35 mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle) plus intravenous Bevacizumab (5 mg/kg every 14 days). Treatment continues until disease progression, unacceptable side effects, patient choice, or a maximum of 15 months. During the study, patients will undergo regular assessments including imaging to monitor disease status and safety evaluations. Follow-up will continue for up to 18 months after the last patient enrolls or until death, withdrawal, or loss to follow-up. The main outcome measure is the efficacy of Fruquintinib combined with Tislelizumab in this patient population over a 54-month period.

Researchers are studying a new treatment combination for adults with advanced breast cancer that is estrogen receptor positive, HER2 negative, and GRPR positive. The trial aims to find the recommended dose of the drug [177Lu]Lu-NeoB when given with ribociclib and fulvestrant to participants who have experienced early relapse after endocrine therapy or whose disease has progressed after endocrine therapy combined with a CDK4/6 inhibitor. This Phase 1 study includes a dose escalation part and a backfill part to assess safety, tolerability, and preliminary effectiveness. Participants will receive [177Lu]Lu-NeoB once every 28-day cycle for six cycles, ribociclib daily on days 1 to 21 of each cycle, and fulvestrant on specific days beginning at cycle 1. Pre- or perimenopausal women and men will also receive goserelin. The trial includes imaging with the radioactive agent [68Ga]Ga-NeoB at screening, possibly at cycle 2 day 15, and again 4 to 8 weeks after the last dose of [177Lu]Lu-NeoB to help locate cancer lesions. During the study, participants visit the clinic regularly for treatment, safety checks, and tumor assessments. Safety follow-up continues for 8 weeks after treatment ends, with extended monitoring every 12 to 24 weeks for up to 5 years to track side effects, adverse events, and treatment interruptions. Researchers will closely observe any dose-limiting toxicities and evaluate overall safety and effectiveness throughout the study period.

Researchers are conducting a phase III randomized trial to evaluate the effectiveness of adjuvant cemiplimab immunotherapy in patients with surgically removed stage II-IIIA non-small cell lung cancer (NSCLC) who have not received prior platinum-based chemotherapy. The study focuses on patients whose tumors express PD-L1 at 1% or higher. The main goal is to measure disease-free survival, tracking the length of time patients remain free from cancer recurrence or death for up to about 59 months. Participants receive cemiplimab intravenously at 350 mg every 3 weeks for four cycles, followed by 700 mg every 6 weeks for six cycles, continuing until cancer relapse or unacceptable side effects occur. The treatment is compared to observation without additional adjuvant therapy. The study involves careful dosing schedules and monitoring to assess the impact of cemiplimab as a post-surgical treatment option. During the study, participants undergo brain imaging for staging, tumor PD-L1 testing, and regular pregnancy tests for women of childbearing potential. Researchers monitor disease recurrence and adverse effects throughout treatment and follow-up. Patients must meet specific health criteria, including recovery from surgery and adequate organ function, and agree to use contraception during treatment and for four months afterward. The total participation period includes treatment cycles and long-term follow-up to evaluate disease-free survival and safety.

Researchers are evaluating the safety, effectiveness, best dose, and how the body processes (pharmacokinetics) an investigational drug called BNT326. This study includes people with advanced solid tumors that are metastatic, recurrent, or have progressed after previous treatments. The investigation is divided into two parts: Part 1 tests BNT326 alone, and Part 2 studies BNT326 alone or combined with other immunotherapy drugs, including pumitamig (BNT327). Participants have specific tumor types like melanoma, non-small cell lung cancer, breast cancer, gastric cancer, colorectal cancer, and cervical cancer, among others. In Part 1, participants receive BNT326 by intravenous infusion in various groups based on cancer type and prior treatments. Part 2 involves BNT326 given alone or with pumitamig, also by intravenous infusion, in several defined cancer groups. Some groups are randomized to receive different dose levels or combinations to find the optimal treatment plan. The study includes a screening phase, treatment phase lasting up to 24 months or until progression or unacceptable side effects, a safety follow-up, efficacy follow-up, and long-term survival monitoring, totaling about 38 months for Part 1 and 48 months for Part 2. During the study, participants undergo regular assessments including measuring tumor response using RECIST criteria, monitoring for side effects and serious adverse events up to months after treatment ends, and measuring drug levels in the blood. Researchers track treatment interruptions or discontinuations due to side effects and evaluate dose-limiting toxicities. Tumor tissue samples are required before enrollment. Safety and effectiveness data are collected throughout treatment and follow-up periods to understand how well BNT326 works alone or combined and its safety profile.

Researchers are evaluating the safety, tolerability, and therapeutic effects of a combination treatment using BNT113 and pembrolizumab compared to pembrolizumab alone for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is positive for human papillomavirus 16 (HPV16+) and expresses the PD-L1 protein with a combined positive score of 1 or higher. This Phase II/III trial includes patients whose cancer cannot be treated with local therapies and who have not received prior systemic anticancer therapy for their current disease condition. The trial consists of two parts. Part A is a non-randomized Safety Run-In Phase to confirm the safety and tolerability of BNT113 combined with pembrolizumab at the selected dose. Part B is a randomized phase that compares BNT113 plus pembrolizumab against pembrolizumab alone as first-line treatment. Patients in Part A continue their treatment without randomization. Treatments are given by intravenous injection or infusion, and patients may receive either combination therapy or monotherapy for up to 24 months. There is also an optional pre-screening phase to test tumor samples for HPV16 DNA and PD-L1 expression before entering the main trial. Participants undergo regular assessments including tumor measurements based on RECIST 1.1 criteria confirmed by independent review. Researchers monitor treatment-emergent adverse events for up to 27 months in Part A and evaluate overall survival and progression-free survival for up to 48 months in Part B. Tumor tissue samples are collected before treatment to confirm eligibility. The study involves ongoing safety monitoring and efficacy evaluations throughout the treatment and follow-up periods.

Researchers are evaluating the safety and effectiveness of trontinemab in people aged 50 to 90 with early symptoms of Alzheimer's disease, ranging from mild cognitive impairment to mild dementia. This Phase III clinical trial focuses on those who show evidence of Alzheimer's pathology and have a recent history of cognitive decline. The study aims to measure changes in cognitive function over 72 weeks. Participants will be randomly assigned to receive either intravenous trontinemab or a placebo. The trial is designed as a double-blind, placebo-controlled study, meaning neither participants nor researchers know who receives the active drug or placebo. The treatment period lasts up to 72 weeks, during which participants will undergo various assessments to monitor their cognitive status and safety. During the study, participants will complete clinical tests including cognitive assessments and imaging such as MRI, PET scans, or cerebrospinal fluid analysis to confirm Alzheimer's pathology. A study partner will assist participants as needed. Researchers will track changes from the start of the study through week 72 using tools like the Clinical Dementia Rating. Safety monitoring and adherence to study procedures will also be closely observed throughout the trial.

Researchers are evaluating the safety and potential benefits of VHB937 in people aged 50 to 85 years with early Alzheimer's disease, including those diagnosed with Mild Cognitive Impairment due to Alzheimer's or mild Alzheimer's disease. This Phase II, multicenter, randomized, double-blind, placebo-controlled study aims to assess how VHB937 affects memory, thinking abilities, daily activities, and brain changes, while also studying how the body processes and responds to the treatment. The study includes an initial 72-week double-blind phase followed by an extension period. Participants will receive either VHB937 solution for infusion or a placebo solution through infusion during the 72-week double-blind phase. The study compares these two groups to evaluate the effects and safety of VHB937 in early Alzheimer's disease. After the double-blind phase, participants may continue in an extension period for further observation. Treatment involves regular infusions under controlled conditions throughout the study. During the study, participants and their study partners will attend visits for assessments including memory and cognitive tests, evaluations of daily functioning, brain imaging, and biomarker analysis from cerebrospinal fluid or PET scans. Researchers will monitor safety, record any side effects, and track changes using the Clinical Dementia Rating scale (CDR) over 72 weeks. The study requires a reliable partner to accompany participants to visits, and overall participation includes monitoring during treatment and the extension phase to thoroughly assess VHB937's effects and safety.

Researchers are investigating two psychotherapy programs, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) and Behavioral Activation (BA), for adults with persistent depressive disorder (PDD) who have treatment-resistant depression. This study aims to compare the effectiveness of these therapies over 16 weeks in inpatient settings, including acute and continuation treatment phases. It also explores factors that influence treatment results and the reasons why these therapies may work differently for individuals. The trial includes a long-term follow-up 48 weeks after treatment to evaluate lasting effects and assesses cost-effectiveness to inform healthcare decisions. Participants will receive either CBASP or BA therapy delivered through structured sessions during a 5-week inpatient phase and a subsequent 6-week outpatient continuation phase. Both therapies include multiple weekly individual and group sessions, nurse contacts, and exercise therapy during inpatient care, followed by weekly group therapy during outpatient treatment. Alongside psychotherapy, all participants will receive algorithm-based antidepressant medication adjusted according to clinical guidelines to optimize treatment. Throughout the study, participants undergo regular assessments, including the Hamilton Depression Rating Scale (HDRS-24), to measure changes in depression symptoms over 16 weeks. Researchers will also analyze moderators such as childhood maltreatment and genetic factors and mediators like interpersonal problems or activity levels to understand treatment mechanisms. The study involves comprehensive monitoring of symptom changes, therapy adherence, and safety over the treatment and follow-up periods, aiming to improve personalized care for this challenging patient group.

PeriPREVENT is a prospective, multi-centre, controlled, open-label, 1:1 randomized superiority trial with two parallel groups. In the intervention group patients will undergo a routine peripheral angiographic intervention (PVI) using a maximally contrast medium sparing strategy with an automated CO2 injection system including iodinated CM as bailout option in case of insufficient image quality or patient's intolerability of CO2 angiography. The control intervention is routine PVI using iodinated contrast media (CM) as standard of care. All patients are followed up until 12 months after the PVI.