Stuart

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 drug disitamab vedotin, alone or combined with pembrolizumab, to treat urothelial cancer that expresses HER2. This cancer is locally advanced, cannot be removed by surgery, or has spread to other parts of the body. The study aims to see how well the drug works and how safe it is for participants by monitoring side effects and treatment responses. Participants will receive disitamab vedotin through an intravenous (IV) infusion every two weeks. Pembrolizumab, when given, is administered by IV on the first day of each six-week cycle. The study includes several groups, called cohorts, each with different treatment histories and eligibility criteria. Treatment and evaluation may continue for about two years. During the study, participants will have regular tests including scans to measure tumor response, lab tests, heart function checks, and monitoring for adverse events. Researchers will also track drug levels in the blood and any changes in heart function. The study will assess confirmed tumor responses and safety outcomes over approximately two years, with close monitoring to understand how participants respond to the treatments and any side effects experienced.

Researchers are conducting a Phase 3, randomized, double-blind, placebo-controlled study to evaluate the safety and effectiveness of KarXT in men and women aged 55 to 90 years who have mild to severe Alzheimer's Disease with moderate to severe psychosis related to the condition. The main goal is to compare KarXT against a placebo by measuring changes in hallucinations and delusions using the Neuropsychiatric Inventory-Clinician (NPI-C) score. Participants will receive different doses of KarXT ranging from 20/2 mg to 66.7/6.67 mg daily or placebo capsules. The study is designed to compare the effects of KarXT with placebo in a parallel group format, maintaining the double-blind setup to ensure unbiased results. During the study, participants will be assessed at the start and end of treatment (up to 14 weeks) to evaluate changes in psychotic symptoms. They will undergo clinical scales such as the NPI-C and the Clinical Global Impression-Severity (CGI-S) scale. The study also requires imaging scans like MRI or CT to rule out other brain diseases. A study partner who has regular contact with the participant will be involved to support adherence and observation. Safety and efficacy will be monitored throughout the treatment period.

Researchers are investigating the effectiveness and safety of KarXT combined with KarX-EC in treating cognitive problems associated with mild to moderate Alzheimer's Disease. This phase 3 study focuses on patients diagnosed according to the National Institute on Aging and Alzheimer's Association criteria, targeting those with specific dementia stages and confirmed disease pathology. The goal is to assess whether this combination therapy can improve cognitive function in this population. Participants will receive either KarXT and KarX-EC together or a placebo, with doses given on specified days during the study. The study is randomized, double-blind, and placebo-controlled, meaning neither participants nor researchers know who receives the active treatment or placebo during the trial. The treatment period lasts up to 24 weeks to evaluate the effects of these medications on cognitive impairment. During the study, participants will be closely monitored through cognitive assessments including the Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 and the Clinician's Interview-Based Impression with caregiver input, both measured at 24 weeks. Caregivers play an important role by maintaining regular contact, reporting on the participant's condition, and helping with medication adherence. Safety and cognitive function will be regularly evaluated to understand the impact of the treatment over the study period.

Researchers are studying Benfotiamine, a drug that might delay or slow the symptoms of early Alzheimer's disease. This clinical trial is a randomized, double-blind, placebo-controlled study lasting 18 months, designed with a seamless phase 2A-2B approach involving 406 participants. The goal is to learn about the safety, effectiveness, and tolerability of Benfotiamine in people with early Alzheimer's disease. In phase 2A, about 150 participants will be randomly assigned to receive either 1200 mg/day Benfotiamine, 600 mg/day Benfotiamine, or a placebo. This phase aims to find the highest dose that is safe and well tolerated by measuring tolerability events up to 72 weeks. In phase 2B, all participants who received Benfotiamine will continue at the selected dose, and the study will evaluate the drug’s effect on cognitive function and daily living abilities over 72 weeks, while also monitoring longer-term safety and tolerability. Participants will attend clinic visits where cognitive and functional assessments will be done, including the Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 and Clinical Dementia Rating - Sum of Boxes. Blood tests for biomarkers and other safety monitoring will be conducted throughout the study. Participants will be followed for up to 72 weeks to assess changes in cognition, function, and tolerability of the treatment.

Researchers are investigating the safety and effectiveness of Accelerated Partial Breast Irradiation (APBI) using Stereotactic Body Radiation Therapy (SBRT) for women aged 50 to 100 with certain types of early breast cancer, including ductal carcinoma in situ and invasive ductal carcinoma. This multi-institutional, prospective, observational study will enroll 200 patients who have undergone breast conservation surgery and meet specific tumor and health criteria. Participants will receive a focused radiation treatment of 30 Gray (Gy) delivered in 5 separate doses (fractions) over 5 to 10 days using SBRT technology with real-time image guidance and motion tracking. The treatment involves placing fiducial markers to precisely target the tumor area. Two main SBRT delivery methods are used: gantry-based linear accelerator or CyberKnife robotic system, each with specific imaging and positioning protocols to ensure accurate treatment. During the study, patients will be followed for up to 5 years. Researchers will assess breast appearance using cosmetic scoring systems, track acute and late breast toxicities, and monitor overall safety. Regular imaging scans, clinical evaluations, and adverse event assessments will be conducted throughout the follow-up to evaluate treatment outcomes and patient well-being.

Researchers are evaluating the safety and effectiveness of AGN-193408 SR in people with open-angle glaucoma or ocular hypertension. This Phase 1/2 study includes different study designs such as an initial open-label dose escalation and later randomized, masked, parallel groups to compare treatments. The study focuses on participants with these eye conditions and aims to measure changes in intraocular pressure and monitor any treatment-related side effects over 36 months. The study uses an implant called AGN-193408 SR, which contains a preservative-free drug dispersed in a biodegradable polymer. The implant is inserted into the front chamber of the study eye using a preloaded applicator. Comparator treatments include topical eye drops of Lumigan 0.01% in the fellow eye and sham administrations using a needleless applicator that simulates the implant procedure. Vehicle eye drops are used for masking in certain cohorts. Treatment schedules vary by cohort, with daily evening eye drops starting from Day 1 in some groups. Participants will be involved in regular assessments to track intraocular pressure changes and any adverse events from baseline up to 36 months. Evaluations include eye exams, monitoring for side effects, and adherence to treatment protocols. Researchers will measure the main outcomes by comparing intraocular pressure at hour 0 from baseline to 36 months and counting participants who experience treatment emergent adverse events during this time frame. The study includes safety follow-up and long-term monitoring throughout the 3-year period.

Researchers are evaluating treatments for adults with intracerebral hemorrhage (ICH) who have high blood pressure. The study compares how quickly patients treated with intravenous clevidipine reach a stable systolic blood pressure (SBP) target within 60 minutes, compared to those treated with other intravenous antihypertensive medications such as nicardipine. The goal is to understand which treatment better controls blood pressure in acute stroke caused by bleeding in the brain. Participants will receive either IV clevidipine or an alternate IV antihypertensive regimen based on their hospital's standard care. Clevidipine dosing starts at 1-2 mg/hour and may increase quickly at first, then more gradually, with typical effective doses ranging from 4-6 mg/hour and a maximum recommended dose of 16 mg/hour. The alternate regimen usually involves IV nicardipine, starting at 5 mg/hour and increasing by 2.5 mg/hour until the blood pressure goal is reached, then lowering the dose as needed. Treatments are given as intravenous infusions following specific dosing guidelines. During the study, participants' blood pressure will be closely monitored, including measurements every 15 minutes. Researchers will assess neurological status using standard stroke scales and confirm brain hemorrhage size by CT scans. Participants will provide informed consent and agree to follow-up visits at 90 and 180 days after treatment. Safety and effectiveness outcomes, including blood pressure control and neurological function, will be tracked throughout the study period.

Researchers are evaluating if adding adjuvant chemotherapy (ACT) to ovarian function suppression (OFS) plus endocrine therapy (ET) improves invasive breast cancer-free survival (IBCFS) compared to OFS plus ET alone. This Phase III trial focuses on premenopausal women with early-stage breast cancer that is estrogen receptor (ER)-positive, HER2-negative, and has a 21-gene recurrence score between 16-25 for node-negative patients or 0-25 for patients with 1-3 positive nodes. The study addresses the need for better treatment options for younger women diagnosed with this type of breast cancer, as younger age is linked to worse outcomes despite standard therapies. Participants receive one of two treatments: either OFS combined with an aromatase inhibitor (AI) for five years or adjuvant chemotherapy followed by the same OFS plus AI regimen. The specific AI and GnRH agonist used, along with their dosing schedules, are chosen by the investigator, commonly including goserelin, leuprolide, or triptorelin administered monthly or every three months. Bilateral oophorectomy may be used instead of ovarian suppression if preferred. Endocrine therapy beyond five years is at the investigator's discretion. During the trial, participants will be closely monitored for invasive breast cancer-free survival over an 11-year period from randomization. Assessments include clinical evaluations, hormone receptor testing, tumor staging, and genetic recurrence scoring prior to enrollment. Safety and effectiveness data will be collected throughout the study, with particular attention to treatment side effects and long-term outcomes. The trial involves detailed eligibility screening and ongoing follow-up to ensure accurate measurement of the study's primary outcome.

Researchers are evaluating the safety and effectiveness of several perioperative treatment combinations involving Durvalumab with other drugs like Oleclumab, Monalizumab, AZD0171, Volrustomig, Rilvegostomig, and Datopotamab deruxtecan (Dato-DXd) alongside platinum-based chemotherapy in participants with resectable, early-stage non-small cell lung cancer (NSCLC). This phase II open-label study compares multiple treatment regimens to understand their impact on tumor response and safety outcomes in patients with stage IIA to IIIB NSCLC. Participants will be randomly assigned to one of seven treatment arms. Each arm includes neoadjuvant (before surgery) treatments combining different drugs with chemotherapy, followed by adjuvant (after surgery) treatments with selected drug combinations. Treatments are administered intravenously and include various drug combinations such as Oleclumab plus Durvalumab and chemotherapy, Monalizumab plus Durvalumab and chemotherapy, Volrustomig plus chemotherapy, Dato-DXd with Durvalumab and chemotherapy, AZD0171 plus Durvalumab and chemotherapy, Rilvegostomig plus chemotherapy, and Dato-DXd with Rilvegostomig and chemotherapy. Throughout the study, researchers will monitor participants from randomization through approximately 15 weeks after the first dose to measure how many achieve a complete tumor response. Safety will be tracked up to 90 days after the last dose and for up to about three years to record adverse events. Participants will undergo evaluations including tumor sample provision to check biomarkers, organ function tests, pulmonary assessments, and ongoing monitoring of any side effects or health changes during and after treatment to ensure safety and effectiveness.