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Researchers are evaluating the safety and effects of a gene therapy called 4D-150 in adults aged 50 years and older with neovascular wet age-related macular degeneration AMD who are currently receiving anti-VEGF treatments and have shown a positive response. This Phase 12 trial includes a dose-escalation stage, a randomized controlled expansion phase, and additional cohorts to optimize steroid use and extend the population studied. The study also includes substudies to assess dosing safety in the opposite eye and to examine vector shedding. Participants receive a single injection of 4D-150 into the eye on Day 1 at assigned dose levels. Some participants receive aflibercept injections as an active comparator. Following the injection, participants are monitored monthly for 24 months to track safety and treatment effects. Those who receive 4D-150 enter a long-term follow-up period lasting up to five years to evaluate extended safety and the duration of the gene therapys activity. The substudies include one-time dosing in the contralateral eye and assessments of vector shedding, with safety monitored for one year and continued follow-up through five years. Throughout the study, participants undergo regular eye function and structure tests, including visual acuity and retinal thickness measurements using imaging technologies. Researchers track adverse events and the need for additional aflibercept injections, as well as changes in vision and retinal health. Participants must comply with study procedures and agree to use barrier methods during and after treatment to prevent fluid transmission. The study ensures comprehensive safety monitoring, with evaluations continuing for up to five years after treatment administration.

Researchers are investigating new treatments for neovascular age-related macular degeneration NVAMD, a condition that affects vision. This study aims to learn if a medicine called tiespectus also known as MK-8748 or EYE201 can treat NVAMD as well as the standard treatment called aflibercept. The trial is a pivotal Phase 23 study that compares these treatments in people newly diagnosed with NVAMD. Participants are randomly assigned to one of three groups one group receives a low dose of tiespectus, another receives a high dose of tiespectus, and the third group receives aflibercept. Those in the tiespectus groups get three initial injections every 4 weeks, then continue injections every 8 weeks until week 48, followed by treatments at intervals based on their individual response up to week 92. The aflibercept group receives three initial injections followed by injections every 8 weeks until week 92. During the study, participants are regularly assessed for changes in their best-corrected visual acuity using ETDRS letters from baseline to one year. Other evaluations include eye imaging to measure retinal thickness and monitoring for any adverse events up to approximately 96 weeks. The study lasts over one year with ongoing visits to track treatment response and safety.

This research investigates intravitreal EYE103 in adults with neovascular age-related macular degeneration NVAMD or macular edema caused by branch retinal vein occlusion BRVO. The trial is randomized and dose-masked, including four different patient groups to study different doses and combinations of EYE103, aiming to assess its effects in these eye conditions. Participants are divided into four cohorts treatment-naive NVAMD, incomplete responders IR with NVAMD as monotherapy, IR NVAMD combined with aflibercept, and treatment-naive BRVO. Each cohort randomly receives either a low or high dose of EYE103 via intravitreal injection. All receive three injections spaced 4 weeks apart the IR NVAMD combination group also receives aflibercept on Day 1. Assessments occur at each injection visit and some groups return 2 weeks post-injection for extra evaluations. During the 12-week study, participants undergo safety and efficacy assessments including vision tests using ETDRS charts, slit-lamp exams, fundoscopy, and imaging with spectral domain optical coherence tomography SD-OCT to measure retinal thickness. The studys main measure is the change in best-corrected visual acuity at Week 12. The trial also monitors retinal thickness and vision changes throughout. The Week 12 visit marks the studys end for all participants.

Researchers are evaluating the efficacy and safety of combining durvalumab and domvanalimab compared to durvalumab plus placebo in adults with locally advanced Stage III, unresectable non-small cell lung cancer NSCLC whose disease has not progressed after definitive platinum-based concurrent chemoradiotherapy cCRT. This Phase III, randomized, double-blind, placebo-controlled, international study aims to provide new insights into treatment options for this patient population. Participants will receive either durvalumab and domvanalimab or durvalumab plus placebo as intravenous infusions every four weeks, beginning on Day 1 and continuing for up to 12 months. The study includes two groups one receiving the combination of durvalumab and domvanalimab, and the other receiving durvalumab with a placebo. Both treatments are given through infusion to assess their effects on disease progression and safety. During the trial, participants will undergo regular assessments including monitoring progression-free survival for up to 8 years after randomization. Other measures include overall survival, response rates, duration of response, and various time-to-event outcomes related to disease progression and symptom deterioration. Researchers will also evaluate drug concentrations and immune responses approximately 12 weeks after the last dose. Participants can expect scheduled visits for infusions and evaluations as part of this long-term study.

Researchers are evaluating the long-term safety and tolerability of JNJ-81201887, given as an intravitreal injection a shot into the eye, in participants with Geographic Atrophy GA secondary to Age-related Macular Degeneration AMD. This study is a long-term extension of parent clinical trials where participants had previously received either low or high doses of JNJ-81201887 or a sham procedure. The goal is to monitor participants over an extended period to understand any lasting treatment effects or side effects. Participants entering this long-term extension study will not receive additional doses of the study drug or any new intervention as part of this trial. They previously participated in parent studies where they were treated with either low dose or high dose JNJ-81201887 or sham procedure. Some participants who were in the sham group of the parent study may receive open-label treatment outside this study before entering this extension. This study focuses solely on follow-up without new treatment administration. Throughout the study, participants will undergo regular assessments to monitor ocular and systemic safety. These include tracking treatment-emergent adverse events, clinical laboratory tests, retinal imaging, and eye examinations over up to five years. This extended monitoring aims to evaluate the long-term safety profile of the previous treatments. Participants will be followed with periodic visits and evaluations, with the total study duration extending until 2030.

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study. This trial focuses on patients with established atherosclerotic cardiovascular disease ASCVD or those at high risk for a first ASCVD event. The study aims to assess how AZD0780 compares to placebo in reducing the risk of major adverse cardiovascular events, also known as MACE-PLUS, over the course of the trial. Participants are randomly assigned to receive either oral AZD0780 once daily or a matching placebo once daily. The study continues until a primary analysis censoring date, which may be up to approximately 54 months from randomization. After this, a study closure visit will be conducted as the final visit for each participant. During the study, participants will be regularly monitored for cardiovascular events including heart attacks, strokes, urgent coronary revascularizations, and other related outcomes. Researchers will track the time to first occurrence of these events as the primary outcome. Safety and other secondary outcomes like all-cause mortality will also be assessed. The total participation time can last up to about 54 months, with ongoing evaluations throughout this period.

The trial investigates the corneal endothelial cells in adults aged 50 and older with neovascular age-related macular degeneration nAMD who are treated with the Port Delivery System PDS implant delivering ranibizumab. This Phase IV, open-label study aims to monitor changes in corneal endothelial cell density over time, comparing the treated eye with the fellow eye to evaluate the effects of this device-based treatment approach. Participants will have a PDS implant surgically inserted in the study eye, initially filled with ranibizumab before implantation. Following this, the implant will be refilled every 24 weeks. Supplemental intravitreal ranibizumab injections may be given if the participant stops study treatment, based on investigator discretion. The study monitors participants for at least 48 weeks, focusing on corneal cell changes and ocular safety events. During the study, participants undergo assessments including specular microscopy to measure corneal endothelial cell density and morphology at baseline and at weeks 24 and 48. Researchers will track ocular adverse events, device-related effects, and serious safety concerns throughout the approximately one-year follow-up. The study collects visual acuity data, imaging results, and historical treatment records to support evaluation. Participants remain under close observation to assess treatment impact and safety.

Researchers are comparing two chemotherapy treatment plans for patients with newly diagnosed intermediate-risk rhabdomyosarcoma, a type of soft tissue cancer. This phase III trial evaluates whether a higher dose chemotherapy over a shorter time Regimen A is better than a lower dose chemotherapy followed by maintenance treatment over a longer time Regimen B, both combined with standard surgery and radiation. The study also aims to assess survival rates, treatment side effects, and molecular features of the tumor. Participants are randomly assigned to one of two treatment groups. Regimen A involves multiple cycles of vincristine, dactinomycin, and cyclophosphamide given intravenously every 21 days, with possible surgery during week 12 and radiation treatments during specified cycles. Regimen B includes alternating cycles of vincristine, dactinomycin, cyclophosphamide, and irinotecan, followed by 24 weeks of maintenance chemotherapy with vinorelbine and oral cyclophosphamide. Both groups undergo imaging scans and biopsies as needed during treatment. Throughout the study, participants will have regular CT or MRI scans and blood tests, along with other procedures such as lymph node biopsies, bone marrow tests, and lumbar punctures to monitor disease status. After treatment, follow-up visits occur every 3 months for the first year, then less frequently up to 5 years to check for event-free survival and overall health. The trial also collects biospecimens for future research and evaluates treatment effects on fertility and quality of life.

This research aims to evaluate the effectiveness and safety of zanidatamab combined with a physicians choice of chemotherapy compared to trastuzumab combined with chemotherapy in treating adults with metastatic HER2-positive breast cancer who have either progressed on or cannot tolerate previous trastuzumab deruxtecan T-DXd treatment. Zanidatamab has shown promising results against various HER2-positive advanced tumors, including metastatic breast cancer, and may serve as a potential treatment option for these patients. The study also investigates patient-reported tolerability and physical functioning, as well as the pharmacokinetics and immune response to zanidatamab with chemotherapy. Participants will be randomly assigned to receive either zanidatamab or trastuzumab, each given by intravenous infusion alongside one of several chemotherapy options chosen by the physician eribulin, vinorelbine, gemcitabine, or capecitabine the latter is taken orally. Treatment will be administered according to the assigned group, and the study is open-label and multicenter, designed to compare these two treatment combinations in this patient population. During the study, participants will undergo regular assessments to monitor disease progression using imaging criteria RECIST version 1.1, evaluate survival, treatment response, and duration of response. Safety and side effects will be tracked through adverse event reporting and patient questionnaires on symptoms and physical function. Blood samples will be collected to study drug levels and immune reactions. Participants will be followed until disease progression, death, or for up to approximately 44 months for key outcomes, with overall survival monitored for up to about 80 months.

Researchers are evaluating the characteristics and outcomes of individuals with asthma across different levels of disease severity in routine clinical practice. The study aims to describe participants sociodemographic and clinical features, treatment patterns, disease burden, biomarkers, and both asthma-specific and general quality of life. This research includes both a cross-sectional analysis and a prospective follow-up to observe changes in disease progression over time. The study involves participants receiving standard asthma care, including treatment with varying doses of inhaled corticosteroids andor biologic therapies. Participants are grouped based on asthma control levels and biomarker status. The first part of the study collects baseline data cross-sectionally, while the second part follows participants prospectively to assess differences in asthma symptom control, treatment use, lung function, and comorbidities over a two-year period. Participants will be involved in scheduled data collection including patient and physician-reported outcomes, lung function tests, blood samples, and questionnaires assessing quality of life and symptom control. The study monitors treatment utilization and health resource use from the prior year and during follow-up visits at one and two years. The total participation period spans up to two years with ongoing assessment of disease characteristics and outcomes.