Asheville

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 1/2 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 therapy’s 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 studying intravitreal EYE103 in people with neovascular age-related macular degeneration (NVAMD) or macular edema after branch retinal vein occlusion (BRVO). This phase 2 randomized, dose-masked trial includes four patient groups, with participants randomly assigned to receive either a low or high dose of EYE103. Some groups include treatment-naïve participants, while others involve incomplete responders, including a group receiving EYE103 combined with aflibercept, a standard anti-VEGF medication. Participants will receive three injections of EYE103 in the study eye, spaced four weeks apart. Those in the combination therapy group will receive an additional aflibercept injection on the first day. The study will be conducted in sequential cohorts, with each group receiving their assigned treatment dose. Participants will have safety and effectiveness assessments at each injection visit, with some returning two weeks post-injection for extra evaluations. During the study, participants will undergo vision tests using the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart and eye examinations such as slit-lamp biomicroscopy, fundoscopy, and spectral domain optical coherence tomography (SD-OCT) to measure retinal thickness. The main outcome is the change in best-corrected visual acuity at week 12. The study concludes at the week 12 visit, which marks the end of participation for all enrolled individuals.

Researchers are evaluating the safety and effectiveness of pulsed field ablation (PFA) therapy for treating persistent atrial fibrillation (PersAF) that does not respond to medication. This study compares two approaches: PFA targeting the pulmonary veins plus electrographic flow (EGF) identified extra-pulmonary vein sources, and PFA targeting the pulmonary veins plus the left atrial posterior wall. The goal is to see if the new method with EGF mapping is at least as effective as the standard approach in managing symptoms of PersAF. Participants will be randomly assigned to one of two groups. The control group will receive pulmonary vein isolation (PVI) plus posterior wall ablation (PWA) using PFA, with EGF mapping performed but not used for treatment decisions. The treatment group will receive PVI plus ablation of active sources identified by EGF mapping. The FARAPOINT catheter may be used for narrow posterior wall channels if found. All subjects will undergo mapping and ablation with devices including the FARAPULSE PFA system and Opal HDx mapping system. Ablation procedures and mapping will be performed according to protocol. During the study, participants will be monitored for safety up to 60 days and effectiveness up to 365 days after treatment. Follow-up will include assessments to track heart rhythm and symptoms, with the use of a LUX-Dx insertable cardiac monitor for continuous monitoring. Participants must be able to comply with follow-up visits and device usage instructions. The study aims to capture data on safety outcomes and measure how well the ablation controls atrial fibrillation over one year.

Researchers are evaluating the safety and effectiveness of combining durvalumab with domvanalimab compared to durvalumab with a placebo in adults who have locally advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) that has not worsened after platinum-based concurrent chemoradiotherapy. This Phase III, randomized, double-blind, placebo-controlled international study aims to understand if adding domvanalimab improves outcomes in this patient group. Participants will receive either durvalumab plus domvanalimab or durvalumab plus placebo as intravenous infusions every four weeks, starting on Day 1, for up to 12 months. The study includes two groups: one receiving the experimental combination and the other receiving durvalumab with placebo. The treatment phase spans a maximum of one year. During the study, participants will be closely monitored through various assessments including tumor tissue analysis and performance status evaluations. Researchers will measure progression-free survival up to 8 years after randomization as the main outcome. Additional outcomes include overall survival, response rates, duration of response, and safety markers. The study involves long-term follow-up to assess durability of outcomes and treatment effects.

This research aims to assess the long-term safety and tolerability of JNJ-81201887, a medicine given by injection into the eye, in people with geographic atrophy secondary to age-related macular degeneration. The study includes participants who were previously treated in earlier clinical studies of this medicine. The main goal is to monitor any eye or systemic side effects and abnormal findings over up to five years. Participants who received low or high doses of JNJ-81201887 in earlier studies, as well as those initially given a sham procedure who may have later received the medicine, will join this extension study. No new treatments or injections will be given during this long-term study. It is designed as a randomized, triple-masked phase 2 trial to carefully observe participants over time. During the study, participants will have regular eye examinations, retinal imaging, and laboratory tests to check for any changes or adverse events related to the earlier treatment. Researchers will track ocular and systemic treatment-emergent adverse events for up to five years. Participants will be involved throughout this period with scheduled visits to monitor their condition and safety status consistently.

Researchers are evaluating the effect of AZD0780, an oral PCSK9 inhibitor, compared with a placebo in reducing the risk of major adverse cardiovascular events plus (MACE-PLUS) in adults with established atherosclerotic cardiovascular disease (ASCVD) or at high risk for a first ASCVD event. This phase 3, randomized, placebo-controlled, and double-blind study aims to assess the time to first MACE-PLUS event over up to approximately 54 months from randomization until the primary analysis censoring date. Participants will be randomly assigned to receive either oral AZD0780 once daily or an oral placebo once daily. The study includes a parallel-group design with two arms: the experimental AZD0780 group and the placebo comparator group. After the primary analysis censoring date, a study closure visit will be scheduled as the final visit for each participant. During the study, participants will be monitored for the occurrence of cardiovascular events including myocardial infarction, stroke, urgent coronary revascularization, cardiovascular death, major adverse limb events, and all-cause mortality. Researchers will assess these events through regular follow-up visits up to approximately 54 months. The study includes detailed safety monitoring and outcome evaluations to understand the effects of AZD0780 compared to placebo in this population at risk for cardiovascular events.

Researchers are evaluating corneal endothelial cells in people with neovascular age-related macular degeneration (nAMD) who are treated with the Port Delivery System (PDS) refilled every 24 weeks. This Phase IV study is open-label and multicenter, aiming to assess changes in corneal endothelial cell density and other eye health measures in participants receiving this treatment. Participants will have the PDS implant surgically placed in the study eye at the beginning of the study. The implant is filled with a ranibizumab solution before insertion and then refilled every 24 weeks. Supplemental ranibizumab injections may also be given if needed. The study monitors the participants during the treatment period, which lasts up to approximately one year. During the study, participants will undergo exams including specular microscopy to measure corneal endothelial cell density, visual acuity tests, and other eye health assessments at baseline, 24 weeks, and 48 weeks. Researchers will track any serious or special ocular adverse events, device effects, and other safety outcomes. Participants are followed closely to understand the effects of the PDS implant and treatment on eye structures over time.

This research aims to evaluate the effectiveness and safety of zanidatamab combined with a physician's 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 studying two combination treatments as front-line therapies for adults with stage IV or advanced stage IIIB/C nonsquamous non-small cell lung cancer (NSCLC) that carries a KRAS p.G12C mutation and is negative for PD-L1. This phase 3 trial compares progression-free survival and overall survival in participants receiving either sotorasib with platinum doublet chemotherapy or pembrolizumab with platinum doublet chemotherapy. The goal is to evaluate which treatment combination may better manage this specific lung cancer type. Participants receive one of two treatment combinations: sotorasib taken orally with carboplatin and pemetrexed, or pembrolizumab given intravenously with carboplatin and pemetrexed. These therapies are administered as front-line treatments. The study is randomized and open-label, meaning participants are assigned to a treatment group by chance and both participants and researchers know which treatment is given. During the study, participants will be monitored regularly for disease progression and survival over approximately 2.5 years. Additional assessments include quality-of-life questionnaires focusing on symptoms like dyspnea, cough, and chest pain, as well as physical function and global health status up to week 12. Safety is evaluated by tracking adverse events, vital signs, and laboratory test changes throughout the study, which may last up to about 5.5 years including follow-up. Participants receive care under medical supervision while contributing to important research on lung cancer treatment.

Researchers are evaluating a fixed-dose combination of lifitegrast and perfluorohexyloctane eye drops to study their effects on signs and symptoms of dry eye disease. This Phase 2, randomized, double-masked, parallel-group, active-controlled, multicenter study aims to assess the safety and efficacy of treatments administered twice daily over four weeks. The study includes adults aged 18 and older who have experienced dry eye disease symptoms for at least six months. Participants will be assigned randomly to one of six groups receiving either the lifitegrast/perfluorohexyloctane combination, lifitegrast alone, perfluorohexyloctane alone, or a placebo vehicle. All treatments consist of topical ocular drops administered twice daily for four weeks. The study compares the combination therapy with individual drugs and placebo to evaluate their effects on dry eye disease. During the study, participants will undergo assessments including corneal fluorescein staining to measure changes from baseline over 29 days. Researchers will monitor signs and symptoms of dry eye disease at screening, baseline, and throughout the treatment period. Participants are expected to follow all trial instructions and attend visits for evaluations to track treatment impact and safety.