Davis

Researchers are evaluating the safety and tolerability of a single dose of INS1201 given through intrathecal (IT) injection in ambulatory male children with Duchenne Muscular Dystrophy (DMD). This Phase 1 study focuses on males aged 2 to under 5 years, aiming to understand how the treatment is distributed in the body and monitor any side effects that arise during the 96-week follow-up. Participants will receive one IT injection of INS1201, a genetic therapy suspension. The study includes two parts based on age groups: Part 1 for children aged 3 to under 5 years and Part 2 for those aged 2 to under 3 years. There are no additional treatments or comparator groups, and the study is open-label, meaning both researchers and participants know the treatment given. Throughout the 96-week study, participants will be closely monitored for treatment-emergent adverse events to assess safety. Assessments will include motor function tests, vaccination status checks, and blood tests such as antibody levels against AAV9. The study requires participants to be able to walk independently and cooperate with motor assessments. Safety monitoring also involves echocardiograms and electrocardiograms to evaluate heart function.

Researchers are evaluating the safety and effectiveness of a drug called GSK4532990 in adults aged 18 to 70 who have alcohol-related liver disease. This Phase 2 study compares GSK4532990 to a placebo to better understand its impact on this condition, focusing on liver health and related symptoms. Participants will receive either GSK4532990 or a placebo during the study. The treatment is given under double-blind conditions, meaning neither the participants nor the researchers know who receives the drug or placebo. The study aims to find the appropriate dose and assess its effect on liver stiffness and disease severity over a period of up to 52 weeks. During the study, participants will be monitored for any side effects or serious health events for up to 8 weeks. Researchers will also track changes in liver stiffness using FibroScan and measure liver disease severity with a specific score at the start and after 52 weeks. Regular checks of vital signs, lab tests, and heart monitoring will be done to ensure safety throughout the study.

Researchers are conducting a Phase 3, global, randomized, open-label, multicenter trial to evaluate the safety and effectiveness of brelovitug (BJT-778) in treating chronic hepatitis delta virus (HDV) infection. The study aims to compare brelovitug treatment to delayed treatment in participants with chronic HDV infection. Approximately 80 participants will be enrolled and randomized into three groups to assess treatment outcomes. The study includes three arms: one group will receive brelovitug 300 mg by subcutaneous injection once weekly for 96 weeks; the second group will receive brelovitug 900 mg by subcutaneous injection once every 4 weeks for 96 weeks; the third group will initially delay treatment, attending clinic visits for 12 weeks, then start brelovitug 300 mg subcutaneously once weekly for 96 weeks. The study evaluates different dosing schedules and the effect of delayed treatment. Participants will be monitored for safety and efficacy, with the main outcome being the percentage of participants achieving a combined endpoint of virologic response and normalization of ALT levels at Week 24 compared to Week 12 in the delayed-treatment arm. The trial includes regular clinical visits, laboratory tests, and assessments over the treatment period to track response and safety. Total participation duration aligns with the 96 weeks of treatment after initial randomization or delay period.

Researchers are evaluating two methods for managing severe open tibia fractures that require multiple irrigation and debridement surgeries. This Phase III randomized controlled trial compares an antibiotic cement bead pouch with negative pressure wound therapy (NPWT), also called a Wound VAC, to determine which method better reduces complications. The study focuses on patients 18 years and older who have severe open tibia fractures treated with internal or external fixation. Outcomes will be assessed at 6 weeks, 3 months, and 6 months after surgery, with a primary focus on clinical status at six months using a composite measure including mortality, amputation, reoperation, and fracture healing. Participants will be randomly assigned in equal numbers to receive either the antibiotic cement bead pouch or NPWT following their first irrigation and debridement surgery. The antibiotic bead pouch involves placing antibiotic-laden cement beads in the wound, while NPWT applies negative pressure to the wound site. Both treatments are temporary wound management strategies used between multiple surgeries for open fracture care. The study includes a follow-up period with assessments to monitor wound healing and complications. During the study, participants will have follow-up visits at 6 weeks, 3 months, and 6 months post-fracture to evaluate their clinical status. Researchers will assess mortality, need for amputation, unplanned surgeries for wound problems or delayed healing, and fracture healing using a specialized functional index. An independent committee will review all outcomes and safety events. The total participation time spans from randomization through six months of post-surgery follow-up to capture key clinical results.

Researchers are evaluating the safety, feasibility, and effectiveness of prolonged automated robotic Transcranial Doppler ultrasonography (TCD) monitoring in critically ill patients with severe traumatic brain injury (TBI). This study involves multiple clinical sites with different levels of TCD experience and availability. The goal is to assess how well this technology works and how safe it is for patients with severe brain injuries. Patients will receive daily sessions of automated robotic TCD monitoring lasting up to 4 hours per day, for a minimum of 3 days and up to 5 days when possible. The monitoring uses a robotic TCD system with bilateral 2-MHz Doppler probes to measure blood flow velocity in both middle cerebral arteries. The robotic probes allow continuous recording with automated angle correction to keep the best position for accurate measurement. The study also collects feedback from bedside nurses and clinicians through surveys to evaluate safety and ease of use. During the study, researchers will monitor patient discomfort, any accidental movement or dislodgement of intracranial devices, and skin changes at probe sites. They will assess the quality of the temporal windows and the ability to properly isolate the middle cerebral arteries. Provider feedback on the safety and feasibility of long-term robotic TCD monitoring in this patient group will also be collected. The total monitoring and evaluation period spans 2 years, ensuring thorough assessment of this monitoring method.

The study includes 2 distinct parts: Part 1 and Part 2. In Part 1, an ascending-dose design will be utilized to enable evaluation of increasing doses in a stepwise manner. The objective for this dose escalation is to identify the dose of BE-101 required to achieve desired FIX activity 28 days after infusion. Upon identification of a safe and efficacious dose in Part 1, an expansion phase (Part 2) will initiate. The initial cohort in the Part 2 expansion (Part 2a) phase will include up to 6 adult participants to further characterize the safety and activity of BE-101 at the selected dose. Additional cohorts for adolescents and redosing for participants in Part 1 of the study will occur following data availability of Part 1. Up to 24 participants will be enrolled across Part 1 (up to 18) and Part 2a (up to 6). Consented participants will complete a screening period to assess eligibility and upon enrollment will undergo leukapheresis collection to support BE-101 manufacturing. Following administration, participants will be monitored for safety and clinical activity. The total duration of study participation is approximately 52 weeks post IV administration of BE-101.

Researchers are examining the effects of products containing Chardonnay marc from the Vine to Bar line on heart and metabolic health. The study aims to gather initial data to help design future dietary trials focusing on how Chardonnay marc intake influences markers of heart and metabolic health as well as the gut microbiome. This trial also explores the vascular response to cocoa flavanols beyond four hours after intake, targeting a six-hour window to capture the presence of microbial flavanol metabolites in the bloodstream. The study uses a crossover design involving up to five male participants aged 30 to 50 years with specific health criteria. Participants will consume different products including low and high flavanol cocoa powders, two servings of Vine to Bar chocolate, one serving of Vine to Bar chocolate, and Vine to Bar chocolate-covered almonds. Responses to these products will be measured at two and six hours after intake to assess vascular and metabolic effects. Participants will undergo assessments including the Framingham Reactive Hyperemia Index measured six hours post intake to evaluate vascular response. The study includes screening for eligibility based on blood flow response, body mass index, and medical history. Participants will be monitored for adherence to study protocols, and outcomes focus on metabolic and vascular health indicators after acute consumption of the test products.

Researchers are evaluating how to best recommend chemotherapy for patients with colon cancer after surgery by using the presence or absence of circulating tumor DNA (ctDNA) in the blood. This approach aims to identify microscopic residual tumor cells and may provide better risk prediction for cancer recurrence compared to traditional methods. The trial focuses on patients with Stage IIB, IIC, or III colon cancer who have undergone complete tumor removal. Participants will have their tumor tissue and blood tested centrally using the Signatera assay to determine ctDNA status. Patients without detectable ctDNA may avoid chemotherapy, while those with detectable ctDNA are considered at higher risk and will be randomly assigned to receive different chemotherapy regimens, including mFOLFOX6, CAPOX, or mFOLFIRINOX, given intravenously or orally over periods ranging from 3 to 6 months. The study includes initial screening, treatment, and possible second randomization for patients whose ctDNA status changes during monitoring. During the study, participants will undergo various assessments including blood tests, imaging scans, and performance evaluations to monitor their health and response to therapy. Researchers will track the time to ctDNA positivity and disease-free survival for up to 3 and 5 years, respectively. Safety and treatment effects will be closely observed throughout the study duration, ensuring thorough follow-up and monitoring for all participants.

Researchers are evaluating treatments for patients with metastatic kidney cancer to see if adding surgery to standard immunotherapy-based drug combinations improves outcomes. This phase III trial focuses on kidney cancer that has spread to other parts of the body. The study compares standard immunotherapy drugs, which help the immune system fight cancer, with or without the surgical removal of the kidney, known as nephrectomy. Doctors currently do not agree on whether surgery adds benefit when combined with these immunotherapy treatments. Participants first receive one of three immunotherapy-based drug regimens, including combinations of nivolumab, ipilimumab, pembrolizumab, avelumab, and axitinib, given through intravenous infusions and oral tablets over several weeks. After 10-14 weeks of this initial treatment, patients are randomly assigned to either continue immunotherapy drugs alone or to also have kidney surgery followed by the same drugs. Surgery may be done by different methods and must occur within 8 weeks of randomization. Axitinib is stopped at least 24 hours before surgery. During the study, participants undergo regular scans of the chest, abdomen, and pelvis to assess disease status. They are monitored for survival for up to 7 years after randomization, with follow-up visits every 3 months in the first year, then every 6 months for two years, and annually thereafter. Researchers also evaluate tumor response, surgical complications, and drug side effects. Specimens are collected for future research, and participants' health and treatment effects are closely followed throughout the study period.

Researchers are studying whether a natural product supplement can help increase collagen production when combined with collagen protein intake. The goal is to see if this supplement enhances the body's collagen synthetic response, which is important for connective tissue health. The study involves young healthy adults aged 18 to 30 years who will participate in this evaluation. Participants will be divided into two groups: one receiving the natural product supplement and the other receiving a placebo. Both groups will take their assigned supplement and perform load-bearing exercises daily for seven days. Blood samples will be collected before and one hour after supplement ingestion, and on the final day, blood will be drawn four hours after exercise to measure collagen protein synthesis. During the study, participants will have their serum isolated from blood samples to assess collagen synthesis using human engineered ligaments. The primary outcome measured is collagen protein synthesis over the seven-day period. This study monitors how the supplement and exercise together may affect collagen production over one week.