Charlottesville

Researchers are developing advanced four-dimensional magnetic resonance imaging (4D-MRI) techniques to create detailed moving images of the lungs and liver in adults. This technology aims to improve radiation therapy for cancer patients by accurately capturing tumor size, shape, location, and movement caused by breathing. The study focuses on enhancing treatment planning for lung and liver cancer by using better imaging methods that can precisely track tumor motion. The study involves creating ultra-quality 4D-MRI scans with high spatial and temporal resolution and minimal motion artifacts. Healthy volunteers and cancer patients will undergo these scans, which will be compared to current imaging methods like deformable image registration (DIR) and four-dimensional computed tomography (4D-CT). The research includes two parts: developing the imaging technique in healthy subjects and evaluating its performance in cancer patients receiving radiation therapy. Participants will have a single imaging session lasting up to two hours, during which image quality and motion modeling accuracy will be assessed. The study measures the quality of images produced and compares errors in motion estimation between 4D-MRI and existing methods. Safety and compliance with imaging protocols are monitored, and findings aim to support improved, personalized radiotherapy treatments for lung and liver cancer.

Researchers are evaluating the safety and effectiveness of tenapanor in adults with Chronic Idiopathic Constipation (CIC) in this 26-week phase 3 study. The study is randomized, double-blind, and placebo-controlled, involving multiple centers. It aims to compare three doses of tenapanor (5 mg, 25 mg, and 50 mg taken twice daily) against a placebo, with a focus on improving spontaneous bowel movements. Participants will first undergo a 2-week screening where their eligibility is assessed through medical history, physical exams, lab tests, ECG, and self-reported constipation symptoms using an electronic diary (eDiary). Eligible patients will then be randomly assigned to receive one of the three doses of tenapanor or placebo twice daily for 26 weeks. During this treatment period, patients will continue daily and weekly symptom reporting via the eDiary and attend regular safety visits at weeks 2, 4, 8, 12, 16, 20, and 26. After completing the 26-week treatment, patients enter a 4-week treatment-free safety follow-up period to monitor any adverse events. A final visit occurs at the end of this follow-up to assess safety. The main outcome measured is the durable complete spontaneous bowel movements response over 12 weeks. Overall, the study involves careful monitoring of symptoms, safety, and treatment effects over approximately 32 weeks.

Researchers are evaluating whether an investigational drug called OHB-607 can prevent Bronchopulmonary Dysplasia (BPD), a common chronic lung disease, in extremely premature infants. The study compares infants receiving OHB-607 alongside standard neonatal care to those receiving standard care alone to reduce the burden of this lung condition. This is a Phase 2b, multicenter, randomized, open-label study focused on safety and clinical efficacy. Participants will receive an intravenous infusion of OHB-607 from birth until reaching a postmenstrual age (PMA) of 29 weeks and 6 days. The study includes two arms: one group receives the investigational drug plus standard care, while the other group receives only standard neonatal care. The treatment period ends at 29 weeks plus 6 days PMA, after which infants are monitored. Throughout the study, researchers will track the incidence of severe BPD or death up to 36 weeks PMA, whichever occurs first. Assessments will include clinical evaluations and monitoring for safety and any side effects. The study also involves long-term follow-up to observe the infants' health outcomes beyond the treatment period. Participation involves consent from parents and collection of birth and medical history information.

Researchers are evaluating new treatment options for adults with locally advanced or metastatic colorectal cancer that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This study compares the safety and effectiveness of adding calderasib and cetuximab, both targeted therapies, to a standard chemotherapy regimen called mFOLFOX6. The goal is to see if this combination can help patients live longer without their cancer growing or spreading compared to current treatments that may include mFOLFOX6 with or without bevacizumab. The study has two parts. It involves treatment with calderasib taken as an oral tablet, cetuximab given according to standard procedures, and mFOLFOX6 chemotherapy combining oxaliplatin, leucovorin/levofolinate calcium, and 5-fluorouracil. Some participants may receive bevacizumab or a bevacizumab biosimilar as part of the comparison. The treatments are given following approved dosing schedules. This design allows researchers to assess the safety and tolerability of these drug combinations in treating this type of colorectal cancer with the KRAS G12C mutation. Participants will be monitored for side effects, treatment tolerability, and cancer progression over a period that may last up to about 44 months. Researchers will track outcomes such as how many participants experience dose-limiting toxicities or adverse events, how many stop treatment due to side effects, and progression-free survival time. Assessments include health evaluations, laboratory tests, and imaging to observe cancer status. This long-term follow-up aims to understand both safety and effectiveness of the treatment combinations.

Researchers are evaluating a new vaccine called V118C designed to prevent pneumococcal disease, which includes infections caused by the Streptococcus pneumoniae bacteria. This study focuses on toddlers and infants to understand the safety and tolerance of V118C. It is a Phase 1 trial that compares V118C to an existing pneumococcal vaccine called PCV20 in children. The study has two parts: Stage 1 involves toddlers aged 12 to 15 months who have already received three doses of PCV20 during infancy. Stage 2 involves infants around 2 months old who will receive four doses of V118C using a 3+1 schedule (three infant doses plus one toddler dose). Both vaccines are given by intramuscular injection. The study compares safety and immune response between V118C and PCV20. Participants will be monitored for immediate reactions within 30 minutes after vaccination and for local and systemic side effects up to 7 days post-vaccination. Unsolicited adverse events will be tracked up to 28 days, and serious or medically attended events will be assessed for up to 12 months after vaccination. The study aims to collect detailed safety and tolerability information over this period.

Researchers are evaluating new treatment options for women with relapsed high-grade serous ovarian cancer, a fast-growing cancer that starts in the cells covering the ovaries, lining of the belly, or fallopian tubes. This study focuses on people whose cancer has returned after prior platinum-based chemotherapy. The goal is to assess the safety, tolerability, and effectiveness of a new antibody drug conjugate called raludotatug deruxtecan (R-DXd), alone or combined with other anticancer treatments, in this patient group. The study has two parts: Part 1 is a dose escalation phase to find the recommended dose of R-DXd, and Part 2 is an expansion phase using that dose. R-DXd is given as an intravenous infusion on Day 1 of every 3-week cycle. Other treatments that may be given include carboplatin and paclitaxel (each up to 6 cycles), bevacizumab every 3 weeks, pembrolizumab up to 35 cycles, gemcitabine on Days 1 and 8 of each 3-week cycle, and pegylated liposomal doxorubicin every 4 weeks. Rescue medications to control side effects are also administered according to protocol. Participants will be monitored for adverse events, dose-limiting toxicities, and treatment discontinuations up to about 3 years. Researchers will measure cancer response using established criteria and assess safety through clinical exams, imaging, and laboratory tests. Eligibility includes having measurable disease and adequate health status. The study includes long-term follow-up to track treatment effects and safety outcomes over time.

Researchers are investigating new treatments for metastatic cervical cancer, which is cancer that has spread from the cervix to other parts of the body. This Phase 3 study aims to evaluate the safety and effectiveness of combining sacituzumab tirumotecan (sac-TMT), an antibody drug that targets cancer cells, with pembrolizumab and bevacizumab. The study seeks to find out if this combination can help people live longer or keep their cancer from worsening compared to standard treatments. The study has two parts. In Part 1, participants receive sac-TMT together with pembrolizumab and bevacizumab to assess safety. In Part 2, after standard initial treatment, those whose cancer does not progress will be randomly assigned to maintenance treatment with either pembrolizumab alone or sac-TMT plus pembrolizumab. Bevacizumab may be added during maintenance treatment based on the doctor's decision. All treatments are given through intravenous infusions, and participants may receive rescue medications to manage side effects before sac-TMT infusion. Participants will be monitored for adverse events and treatment tolerability over several months. The study measures include progression-free survival and overall survival, assessed by independent review. Safety and treatment continuation rates are tracked during Part 1 for up to approximately 66-69 months, while Part 2 outcome measures extend up to 48-60 months. Various assessments, including laboratory tests and evaluations of cancer status, will be performed throughout the study to understand treatment effects and participant well-being.

Researchers are evaluating the safety and effectiveness of Alpha DaRT-224, a novel treatment for patients with recurrent cutaneous squamous cell carcinoma who have not responded to standard therapies and are not candidates for surgery or standard radiation. This multicenter, pivotal, single-arm, open-label clinical study aims to determine the objective response rate and duration of response following treatment, as well as assess progression-free survival, overall survival, local tumor control, and quality of life. The treatment involves placing DaRT seeds, which contain a radium-224 source that releases alpha-emitting atoms, directly into the tumor. These seeds remain in the tumor for 14 to 21 days before being removed. The procedure is planned using radiotherapy parameters and monitored with volumetric imaging to ensure proper placement and coverage of the tumor. Participants will undergo evaluations including CT scans and blood tests before and during the study. Researchers will measure tumor response from day 14 through 52 weeks after treatment and monitor safety by tracking adverse events related to the device. The study also includes assessments of quality of life and long-term outcomes over several months. Participants are followed closely to document tumor changes, side effects, and overall health during the study period.

Researchers are evaluating the experimental antibody COM701 in participants with relapsed platinum sensitive ovarian cancer (PSOC). This trial aims to find out if COM701, given as a maintenance treatment, can delay the progression of ovarian cancer, delay the need for new anti-cancer treatments, and to assess its safety. The study is part of an adaptive-platform trial with multiple sub-studies, focusing initially on COM701 alone compared to a placebo. Participants are randomly assigned in a 1:2 ratio to receive either a placebo or COM701 via intravenous infusion every 3 weeks. The trial includes a double-blind, randomized, placebo-controlled design for the first sub-study. Future sub-studies will explore COM701 combined with other anti-cancer drugs. During the study, participants will visit the clinic every three weeks for treatment and monitoring. Health checks include physical exams, vital signs, ECGs, blood and urine tests, and pregnancy tests if applicable. Disease response will be assessed with CT or MRI scans and tumor marker tests using tumor tissue samples. The primary measure is progression-free survival, tracking time from randomization until disease progression or death, assessed up to two years.

Researchers are evaluating the efficacy, safety, and tolerability of zorevunersen in patients with Dravet syndrome, a condition marked by reduced levels of the Nav1.1 protein due to mutations in the SCN1A gene. Zorevunersen is an investigational antisense oligonucleotide designed to increase the expression of the sodium channel Nav1.1 protein by boosting the production of its messenger RNA. This Phase 3, multicenter, randomized, double-blind, sham-controlled study aims to assess the potential of zorevunersen for disease modification by measuring changes in major motor seizure frequency and other health outcomes. The study has two treatment periods. In Treatment Period 1, participants assigned to zorevunersen receive the drug by intrathecal administration on Day 1, Day 57, Day 169, and Day 281 with doses of 70 mg initially and then 45 mg later. The sham group undergoes a procedure mimicking drug administration without receiving the drug. In Treatment Period 2, those initially on zorevunersen receive 45 mg doses on Day 393, Day 477, and Day 589. Participants initially in the sham group are then given zorevunersen doses of 70 mg on Day 393 and Day 477, and 45 mg on Day 589. Participants will be closely monitored throughout the study with a primary focus on seizure changes measured at Week 28. Secondary assessments include behavior, cognition, clinical status, and quality of life. The study includes an initial 8-week baseline period and a 6-week observation period to confirm seizure frequency and stability of other treatments. Patients may continue to an open-label extension study to receive zorevunersen if eligible. The study involves children aged 2 to under 18 years and tracks safety and tolerability alongside efficacy outcomes.