Bristol

Researchers are evaluating vonoprazan, a drug taken once daily at 20 mg, in adults with eosinophilic esophagitis EoE, a condition characterized by a high number of eosinophils in the esophagus. The study aims to compare vonoprazan to a placebo to see how many participants achieve a peak eosinophil count below 15 eosinophils per high-power field after 12 weeks of treatment. This phase 2, randomized, double-blind study is sponsored by Phathom Pharmaceuticals, Inc. and involves adult participants who meet specific clinical and diagnostic criteria for EoE. Participants are randomly assigned to receive either vonoprazan 20 mg daily for 12 weeks followed by an additional 12 weeks at the same dose, or placebo for 12 weeks followed by 12 weeks of vonoprazan 20 mg daily. The study is conducted across multiple centers and includes a double-blind design to compare the safety and efficacy of vonoprazan against placebo initially and then evaluate continued treatment effects up to 24 weeks. During the trial, participants will be monitored through various assessments including esophageal biopsies to measure eosinophil counts, electronic diaries documenting dysphagia episodes, and endoscopic scoring for EoE severity. The main outcome is the number of participants achieving reduced eosinophil levels at week 12. Secondary assessments include changes in dysphagia days, endoscopic reference scores, and eosinophil counts from baseline to week 12. Safety and adherence will be tracked throughout the study period, with participant involvement expected for up to 24 weeks.

Researchers are evaluating ASP1002, an investigational drug, for adults with metastatic or locally advanced solid tumors that have high levels of a protein called claudin 4. The study aims to check the safety and tolerability of ASP1002 and to find suitable doses. Participants have cancers that have spread or are locally advanced and have previously been treated with standard therapies or have refused them. The study has two parts. In Part 1, small groups receive ascending doses of ASP1002 through weekly, biweekly, or triweekly intravenous infusions in treatment cycles lasting 21 or 28 days. Researchers record medical problems to determine appropriate doses. In Part 2, other groups receive the best doses found in Part 1. Treatment continues for up to two years unless medical issues, cancer progression, new treatments, participant choice, or missed visits occur. Participants will visit the clinic multiple times for health checks, including safety monitoring and reporting medical issues. Tumor status will be assessed regularly with CT or MRI scans. Tumor tissue samples will be collected during and optionally after treatment. After stopping treatment, participants have follow-up visits within 7 days, then at 1 and 3 months, with health monitoring continuing for up to a year after the last dose.

Researchers are evaluating the safety and effectiveness of SAR441566 in adults with moderate to severe Crohns Disease CD in this phase 2, multinational, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study. The main goal is to compare different doses of SAR441566 with a placebo to see how well they work in treating this condition. The study lasts up to 59 weeks, including screening, treatment, and follow-up phases. Participants will be randomly assigned to receive one of three doses of SAR441566 or a matching placebo, all taken orally as tablets. The treatment phase includes a 12-week double-blind induction period followed by 40 weeks of maintenance. After this, eligible participants may join an open-label period lasting up to 40 weeks, but the total time in maintenance and open-label cannot exceed 40 weeks. During the study, participants will undergo assessments for endoscopic response, clinical remission, and patient-reported outcomes using various scores like the Crohns Disease Activity Index CDAI. Researchers will monitor drug levels, safety events, and quality of life measures over time. The total participation includes a 4-week screening, 52 weeks of treatment, and a 2-week follow-up for those not entering the long-term safety study.

Researchers are evaluating SAR441566 in adults aged 18 to 75 years with moderate-to-severe ulcerative colitis UC in this Phase 2 multinational, randomized, double-blind, placebo-controlled study. The main goal is to assess how different doses of SAR441566 affect clinical remission in participants with active UC. The study includes a screening period of up to 28 days plus an additional 7 days if needed. Participants will receive one of three dose regimens of SAR441566 or a matching placebo, given orally as tablets. The study treatment period lasts up to 52 weeks, with a 12-week induction phase followed by a 40-week maintenance phase and a 2-week follow-up after treatment ends. An optional open-label period of up to 40 weeks is also offered to eligible participants not enrolling in a long-term safety study. During the study, participants will attend 12 visits in the main treatment period and up to 8 visits during the open-label phase. Researchers will monitor clinical remission using the modified Mayo Score at week 12 and evaluate other outcomes such as clinical response, endoscopic remission, patient-reported outcomes, and adverse events. Safety will be closely followed throughout the study, which may last up to 59 weeks in total for each participant.

Researchers are evaluating the effectiveness of the Change4Better C4B mobile app in reducing the severity of problem gambling compared to standard treatment as usual TAU. This study is a 6-month randomized clinical trial involving individuals with gambling disorder who are enrolled in or seeking treatment at outpatient facilities affiliated with Bettor Choice Gambling Treatment Programs or Kindbridge Behavioral Health. The study aims to assess the feasibility and efficacy of adding the C4B app, which is based on cognitive behavioral therapy, as a support tool alongside routine outpatient treatment. Participants will be randomly assigned to one of two groups one group will receive standard TAU, which includes individual or group therapy sessions tailored to their needs and usually lasts about one hour per week for 12 weeks. The other group will receive TAU plus access to the C4B mobile app, which teaches skills to manage gambling behaviors and cognitive distortions. Participants using the app will be instructed by staff on how to use it and encouraged to spend about 8 hours over 12 weeks completing modules and practicing exercises. Monthly follow-up continues for an additional 12 weeks, during which the app remains accessible. During the study, participants will be monitored for changes in gambling symptom severity from baseline to 6 months. Researchers will track app engagement through measures such as days used, topics completed, practice exercises, weekly usage, and total time spent. Participants will continue receiving usual outpatient care, and data will be collected through assessments and follow-ups conducted by the Yale research team. The total study duration for each participant is 6 months, starting from randomization.

Researchers are studying tulisokibart also known as MK-7240, a medicine designed to treat active, moderate to severe Crohns disease CD and ulcerative colitis UC. This extension study allows people who have already received tulisokibart in certain previous studies for CD or UC to continue in order to learn more about the long-term safety and how well people tolerate this medicine. The study is led by Merck Sharp Dohme LLC and is in Phase 3. Participants receive tulisokibart through injections under the skin. There are different groups receiving either low or high doses, with some doses given openly and others in a blinded manner where participants and researchers do not know which dose is given. This allows comparison of how different doses work and their safety over time. The study lasts up to approximately 378 weeks, which is about 7 years. During the study, participants are regularly monitored for any side effects and whether they stop treatment due to these effects. Researchers also assess disease symptoms such as remission rates using scores for Crohns disease and ulcerative colitis at week 364. Participants undergo clinical evaluations and safety checks throughout the study period. The goal is to understand the long-term effects and safety of tulisokibart while participants continue their usual care.

Researchers are investigating whether survodutide can improve liver function in adults diagnosed with non-alcoholic steatohepatitis NASH or metabolic-associated steatohepatitis MASH who also have cirrhosis and a body mass index BMI of 27 or higher, or 25 or higher for Asian participants. This phase III trial randomly assigns participants to receive either the medication survodutide or a placebo, with twice the chance of receiving survodutide. The study is double-blinded, meaning neither participants nor doctors know which treatment is given, to fairly evaluate the effects of the medication compared to placebo. Participants inject survodutide or placebo under the skin once a week and receive regular counseling to support diet and exercise changes. The study lasts up to 4.5 years, with frequent visits either in person or via video calls every 2, 4, or 6 weeks for about 17 months. After this period, visits occur every 3 months until the study concludes. This approach allows close monitoring of treatment effects and adherence. Throughout the study, doctors assess participants health, monitor for side effects, and regularly measure body weight. Liver health is evaluated using imaging techniques and blood tests at specific visits. Participants also complete symptom questionnaires. The main goal is to measure the time until certain serious liver-related events occur, while secondary goals include changes in liver fibrosis, liver stiffness, blood sugar levels, and body weight. This comprehensive evaluation helps determine the medications impact over the long term.

Researchers are evaluating whether a medicine called survodutide can help adults living with obesity who have a liver disease known as non-alcoholic steatohepatitis NASH or metabolic associated steatohepatitis MASH combined with moderate or advanced liver fibrosis. This phase III trial aims to find out if survodutide improves liver function and safety over a long period. Participants with other liver diseases or chronic alcohol intake are not eligible. The study has two parts. In the first part, participants are randomly assigned to receive either survodutide or a placebo, with twice the chance of getting survodutide. Both groups inject their assigned treatment under the skin once a week, with doses gradually increasing to a target level. All participants also receive counselling on diet and exercise. The second part focuses on how safe and effective survodutide is over time. Participants stay in the study for up to seven years, with regular visits either in person or through video calls. For about the first year, visits occur every two weeks, then every four weeks, then every six weeks. After the first year, visits alternate between in person and remote every three months. Doctors monitor participants health, body weight, and gastrointestinal effects. Liver health is checked using imaging methods and sometimes liver biopsies. Participants also complete questionnaires about symptoms and quality of life. The study measures whether survodutide helps improve liver disease compared to placebo.

Researchers are evaluating the best way to sample patients with known or suspected Barretts esophagus BE, a condition that increases the risk of esophageal adenocarcinoma, a type of esophageal cancer. The study compares the standard Seattle biopsy protocol to a newer method called wide area transepithelial sampling WATS3D. Early detection of precancerous changes called dysplasia is critical to prevent cancer, and this trial aims to determine which sampling method is more effective for identifying these changes. Participants undergo an upper endoscopy procedure using high-definition white light and electronic chromoendoscopy to detect visible abnormalities. They are randomly assigned to receive either the Seattle biopsy protocol, which takes tissue samples every 2 cm in four quadrants plus targeted areas, or the WATS3D brushings, which collect samples from every 5 cm segment of Barretts esophagus. Each participant receives both sampling methods in a randomized order during the same procedure. If results differ, a repeat endoscopy with the Seattle biopsy protocol is done to confirm findings. During the study, participants will have tissue samples examined by expert pathologists blinded to patient details and prior results. Researchers will assess the diagnostic yield of dysplasia and intestinal metaplasia up to one year after sampling. They will also monitor progression to dysplasia, cancer, need for treatment, and death. The study involves approximately 2700 participants across multiple centers and includes follow-up for up to five years to evaluate long-term outcomes and quality of life.

Researchers are evaluating VE303, a live biotherapeutic product made of eight nonpathogenic bacterial strains, for preventing recurrence of Clostridioides difficile infection CDI. This Phase 3, randomized, double-blind, placebo-controlled trial aims to assess the safety and rate of CDI recurrence eight weeks after treatment. The study includes participants with either recurrent CDI or primary CDI at high risk of recurrence, comparing VE303 to a placebo. Participants receive either VE303 or placebo capsules three times daily for 14 days, following 10 to 21 days of standard antibiotic treatment for CDI. VE303 capsules contain the active live bacteria, while placebo capsules contain inactive ingredients and look identical. The study is divided into two stages focusing on recurrent CDI and high-risk primary CDI populations. During the trial, participants are monitored for CDI recurrence over eight weeks, with assessments including stool sample testing and symptom tracking. The study evaluates the effectiveness of VE303 in preventing CDI from returning after initial antibiotic treatment, while monitoring participant safety. Total participation time includes the treatment period plus follow-up to week 8.