Bordeaux

Researchers are evaluating the effects of early apneic ventilation compared to usual care with ultra-protective lung ventilation in patients with severe acute respiratory distress syndrome (ARDS) who require venovenous extracorporeal membrane oxygenation (ECMO). This Phase 3, open-label, multicenter trial aims to examine whether early apneic ventilation can reduce lung injury, shorten ECMO duration, and lower mortality at 60 days in this critically ill population. Participants are randomized to receive either ECMO plus near apneic ventilation or ECMO plus ultra-protective lung ventilation. Near apneic ventilation is applied during the first three days of ECMO using BIPAP/APRV or pressure-controlled ventilation, with specific settings to maintain airway pressures and low respiratory rates. After three days, apneic ventilation may continue or standard ultra-protective ventilation is used. The ultra-protective lung ventilation group receives low tidal volume and pressure ventilation settings until ECMO weaning. Prone positioning during ECMO is allowed at the physician's discretion in both groups. Throughout the study, researchers monitor mortality, need for lung transplantation, ongoing ECMO support, and days alive without ECMO up to day 60. Participants undergo clinical assessments and ventilator management according to the assigned strategy. Consent procedures accommodate emergency inclusion with surrogate consent when needed, and follow-up includes evaluation of lung recovery and survival outcomes over the 60-day period.

Multiple sclerosis is a common inflammatory disease affecting the central nervous system and is a leading cause of physical disability in young adults. Spinal cord involvement occurs in about 90% of patients, causing symptoms like sensory loss, pain, spasticity, weakness, and bladder or bowel issues. Imaging of the spinal cord is important for diagnosis and prognosis, but it is challenging due to the spinal cord's location, small size, and movement. This study compares a new 3D OPTIMIZED WMN MPRAGE imaging sequence to conventional MRI sequences to see if it better detects spinal cord lesions in multiple sclerosis patients. Participants will undergo MRI scans at the cervical and thoracic spinal cord levels using both conventional sequences and the investigational 3D OPTIMIZED WMN MPRAGE sequence. At the cervical level, conventional scans include 2D sagittal T2 FSE, STIR, PSIR, and 3D MPRAGE sequences, alongside the new 3D OPTIMIZED WMN MPRAGE acquired in sagittal and axial views. At the thoracic level, conventional sequences include 2D sagittal T2 FSE, STIR, and 3D MPRAGE, compared with the 3D sagittal OPTIMIZED WMN MPRAGE. During the study, 60 patients with multiple sclerosis confirmed by McDonald 2017 criteria will have these MRI scans to compare lesion detection between sequences. Researchers will focus on lesions at the cervical spinal cord level as the primary outcome. Participants will provide informed consent, and safety and reproducibility of the new imaging technique will be assessed. The study aims to find if the new sequence can replace conventional imaging methods in clinical practice.

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 studying advanced renal cell carcinoma (RCC) that has returned after prior adjuvant therapy. The trial aims to find out if treatment with belzutifan and zanzalintinib helps patients live longer and delays disease progression compared to treatment with cabozantinib. This is a Phase 3 randomized study focusing on participants with recurrent advanced RCC who have previously received anti-PD-1/L1 therapy. Participants are randomly assigned to receive one of two oral drug regimens: either belzutifan combined with zanzalintinib, both taken once daily, or cabozantinib alone, also taken once daily. The study compares these treatments to assess their effects on disease control and overall survival. During the study, participants will be monitored for progression-free survival and overall survival for up to approximately 73 months. Researchers will evaluate how well the cancer responds to treatment and track any changes in health status over time. Safety and effectiveness of the treatments will be closely followed throughout the study period.

Researchers are evaluating the safety and effectiveness of ifinatamab deruxtecan (I-DXd) alone or combined with other treatments in people with metastatic castration-resistant prostate cancer (mCRPC). This study aims to understand how well patients tolerate the treatment, find a safe dose for combining I-DXd with other drugs, and measure prostate-specific antigen (PSA) levels during treatment. The study is part of a larger master screening protocol and includes patients with confirmed prostate adenocarcinoma who have progressive disease despite prior therapies. Participants receive treatments including I-DXd given through intravenous infusion, sometimes combined with other drugs such as docetaxel (IV), MK-5684, abiraterone, or enzalutamide (all oral). Before each I-DXd dose, patients take premedication to prevent nausea and vomiting. The study includes both a safety lead-in phase and an efficacy phase, with ongoing monitoring for side effects and tolerability. The combination therapies are carefully dosed and scheduled according to the study protocol. During the study, participants undergo regular assessments to monitor side effects, measure PSA response, and track any dose-limiting toxicities. Safety is closely followed, particularly during the first 21 days for combination treatments, and throughout up to 54 months for long-term outcomes. Researchers also observe if participants discontinue treatment due to adverse events. The study requires ongoing visits and evaluations to ensure participant health and collect data on treatment effects over time.

Researchers are evaluating new treatments for people with high-risk non-muscle invasive bladder cancer (HR NMIBC), a type of bladder cancer that has not spread to the muscle but has a high chance of worsening or returning. This cancer type may include carcinoma in situ (CIS), which is a flat, surface-level bladder cancer. The study aims to learn whether adding intismeran autogene (V940), a treatment designed to boost the immune system's attack on cancer, to the standard Bacillus Calmette-Guerin (BCG) immunotherapy can help people live longer without the cancer growing, spreading, or coming back. Participants will receive either the combination of V940 with BCG or BCG alone. BCG is given as a bladder instillation, while V940 is given as an intramuscular injection. The study is phase 2, open-label, and randomized. As of a 2026 amendment, outcome measures for a monotherapy arm of V940 are no longer primary or secondary. Treatment is focused on Cohort A, which includes people with high-risk non-muscle invasive bladder cancer who are BCG-naïve or meet specific recurrence criteria. During the study, participants will be monitored for event-free survival for up to approximately 5 years. Researchers will assess how long participants live without the cancer worsening or returning. The study includes regular evaluations, imaging, and safety monitoring. The total duration of participation depends on individual outcomes and follow-up but includes long-term observation to assess treatment effects and safety.

Researchers are studying a new treatment for HIV-1 infection that combines two medicines, islatravir and ulonivirine, taken once weekly. The goal is to see if this new study treatment works as well as the standard antiretroviral therapy (ART), which usually involves taking up to three medicines once or twice daily. This research also aims to learn about the safety and tolerability of the study treatment compared to the standard ART. The study compares the once-weekly combination of islatravir and ulonivirine with the standard daily treatment of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Participants will take either the study drugs or the standard drugs for 96 weeks. Some participants may receive matching placebos as part of the study design. The treatment is given orally as capsules or tablets according to the assigned group. Participants will be monitored throughout the study with regular assessments, including measuring the amount of HIV-1 virus in the blood to see if it is suppressed below 50 copies/mL at weeks 24 and 48. The study will also track any side effects or adverse events and whether participants stop the treatment due to these events. Overall, the study lasts about 96 weeks, with ongoing safety and effectiveness evaluations to understand how well the treatments work and how safe they are over time.

Researchers are studying TD001, an antibody-drug conjugate (ADC) that targets prostate-specific membrane antigen (PSMA), to evaluate its safety, tolerability, drug levels, and early anti-cancer effects in men with metastatic PSMA-expressing castration-resistant prostate cancer (CRPC). This first-in-human, open-label, multicenter Phase 1/2 trial includes a dose escalation phase to find recommended doses for Phase 2, followed by an expansion phase to further assess the treatment. Participants will receive TD001 through intravenous infusions at doses and schedules defined by the study protocol. Treatment continues until the disease progresses or another reason requires stopping. Multiple dosing schedules may be explored to optimize dose and administration for effectiveness and safety in this patient group. During the study, men will have their disease monitored through measurements of tumor lesions and prostate-specific antigen (PSA) levels. Safety is carefully tracked by recording any adverse events or serious side effects, as well as any treatment modifications or discontinuations due to side effects. The study also evaluates the maximum tolerated dose and recommended Phase 2 doses over estimated follow-up periods of 9 to 21 months to guide future research.

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.