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Researchers are evaluating the combination of CGT9486 and sunitinib compared to sunitinib alone in patients with locally advanced, unresectable, or metastatic Gastrointestinal Stromal Tumors GIST. This Phase 3, open-label international trial involves multiple parts, including dose confirmation, drug interaction assessments, and efficacy comparisons. The study also includes substudies focusing on drug-drug interaction potential and first-line treatment in patients with specific genetic mutations KIT exon 9. Approximately 482 patients will participate across these parts.

Researchers are studying the outcomes of two surgical methods for treating perilunate dislocations, a serious wrist injury. This research aims to compare the clinical and X-ray results between a new internal brace technique using a 4-anchor construct and the traditional Kirschner wire K-wire method. The study also seeks to identify the types and rates of complications associated with each technique, such as pain, numbness, weakness, and range of motion loss. Participants in this observational study have already undergone surgery for perilunate dislocations using either the standard K-wire fixation or the new internal bracing method. Researchers will follow these patients from enrollment through two years after their surgery, monitoring recovery and complications. The study does not involve additional treatments but focuses on collecting data about the surgical outcomes of the two fixation techniques. During the study, participants will undergo clinical functional assessments and complete the Quick DASH questionnaire to measure arm disability. Researchers will track specific complications and their frequency over the two-year follow-up period. The study is led by Bryan D Brown, MD, and aims to improve understanding of surgical options for perilunate dislocation recovery and long-term wrist function.

Researchers are studying treatments for locally advanced or metastatic colorectal cancer mCRC that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This trial aims to evaluate if adding the targeted therapies calderasib and cetuximab to the standard chemotherapy regimen mFOLFOX6 can provide better outcomes compared to mFOLFOX6 with or without bevacizumab. The study focuses on the safety and tolerability of these combinations and whether they can help people live longer without their cancer growing or spreading. Participants will be assigned to one of two groups. One group will receive calderasib orally, cetuximab every two weeks, and mFOLFOX6 chemotherapy including oxaliplatin, leucovorin or levofolinate calcium, and 5-fluorouracil every two weeks. The other group will receive mFOLFOX6 chemotherapy with or without bevacizumab every two weeks, based on the investigators decision. Treatments will continue until certain stopping criteria are met. During the study, participants will be monitored for side effects and treatment tolerance, with regular assessments of cancer progression. Researchers will measure outcomes such as dose-limiting toxicities, adverse events, progression-free survival, and overall survival. Quality of life will also be evaluated through questionnaires. The study may last up to several years, with monitoring continuing for safety and effectiveness throughout the treatment period and follow-up.

Researchers are investigating new treatments for extensive-stage small cell lung cancer ES-SCLC, a type of lung cancer that has spread widely within the lungs or to other parts of the body. This study evaluates the combination of two study medicines, gocatamig and I-DXd ifinatamab deruxtecan, with or without standard chemotherapy and immunotherapy. The research aims to understand the safety and tolerance of these combinations and whether they can shrink or eliminate tumors in people with ES-SCLC. Participants are assigned to one of several treatment groups. Some receive gocatamig and I-DXd during maintenance after completing standard chemotherapy and immunotherapy, while others receive these study medicines during both induction and maintenance phases. Additional groups receive gocatamig and I-DXd followed by gocatamig and atezolizumab, or standard treatment with carboplatin, etoposide, and atezolizumab followed by atezolizumab maintenance. Treatments are given intravenously and continue until disease progression or other study-specified criteria. During the study, participants will have regular assessments to monitor safety, side effects, and treatment response, including scans to measure tumor size and laboratory tests to evaluate drug levels and immune response. The study will track adverse events, treatment tolerability, and cancer control over up to approximately 58 months. Participants health status and responses to the treatments will be closely observed throughout this period, with periodic evaluations to understand long-term effects and outcomes.

Researchers are evaluating new treatment options for people living with HIV-1 Human Immunodeficiency Virus Type 1 who have not been treated before. The current standard treatment, antiretroviral therapy ART, involves taking multiple medicines daily and may cause other health problems. This study aims to compare a new study ART combining two medicines, islatravir and ulonivirine, taken once a week, against the standard daily ART to see if it works as well and is safe and tolerable. Participants will receive one of several treatments for 96 weeks the study ART with islatravir and ulonivirine taken once weekly, the standard ART with bictegraviremtricitabinetenofovir alafenamide BICFTCTAF taken once daily, or combinations involving placebos matching these treatments. The study includes two phases Phase 2 which is open-label, and Phase 3 which is double-blind and randomized. During the study, participants will have regular assessments including measuring the amount of HIV-1 RNA in their blood and monitoring for adverse events and medication tolerance. Researchers will evaluate how well the treatments control the virus and affect immune cells over 24, 48, and 96 weeks. Safety monitoring will continue for about 102 weeks. The total study duration for participants is up to 96 weeks of treatment plus follow-up.

Researchers are evaluating MK-2214, a study treatment designed to slow brain changes in people with early Alzheimers disease AD. AD is a form of dementia that causes memory loss, communication difficulties, and challenges in decision-making, affecting daily tasks. This phase 2 trial aims to determine if MK-2214 slows the spread of tau protein in the brain compared to a placebo, as well as to assess the safety and tolerability of MK-2214. Participants will be randomly assigned to receive either MK-2214 or a placebo through intravenous IV infusion every 4 weeks during the study. The study uses a parallel design with quadruple masking to compare the effects of the study drug versus placebo over a period of up to approximately 23 months. Both groups receive infusions on the same schedule to maintain the studys integrity. During the study, participants will undergo brain scans including positron emission tomography PET to measure tau protein levels and other assessments such as cognitive and daily living function tests. Researchers will monitor adverse events and treatment discontinuations throughout the study, which lasts up to about 26 months. These assessments help determine the impact of MK-2214 on disease progression and safety in individuals with early AD.

Researchers are evaluating new medicines to prevent HIV-1 Human Immunodeficiency Virus Type 1 infection. This Phase 3 clinical study aims to determine if taking the drug MK-8527 once a month can prevent HIV-1 infection as well as or better than the standard daily pre-exposure prophylaxis PrEP. The study also assesses the safety and tolerance of MK-8527 in participants. Participants are randomly assigned to one of two groups. One group receives 11 mg of MK-8527 once monthly along with a daily placebo pill matching FTCTDF. The other group receives a daily dose of FTC245 mg TDF and a monthly placebo matching MK-8527. This treatment period lasts for approximately two years, followed by an additional 28-day period where all participants receive open-label FTCTDF daily. During the study, participants will undergo regular monitoring to check for HIV-1 infection and any adverse events. Researchers will track the number of participants who acquire HIV-1, experience side effects, or stop treatment due to side effects over the two-year period. Safety and adherence assessments will be conducted to evaluate the study treatments. The total participation time includes the two-year treatment phase plus the 28-day follow-up with open-label FTCTDF.

Researchers are evaluating molnupiravir, an oral medicine designed to stop the COVID-19 virus from multiplying, to see if it can prevent severe illness from COVID-19 in people at high risk of disease progression. The study focuses on adults with confirmed COVID-19 infection who are at increased risk due to age, medical conditions, or other factors. This is a Phase 3 randomized, placebo-controlled, double-blind clinical trial led by Merck Sharp & Dohme LLC. Participants will be randomly assigned to receive either molnupiravir or a matching placebo. Those in the molnupiravir group will take 800 mg orally every 12 hours for 5 days, totaling 10 doses. The same dosing schedule applies to the placebo group. Some participants may also receive remdesivir as part of standard care if clinically appropriate. During the study, participants will be monitored for up to 29 days to assess outcomes such as hospitalization, death, or medically attended visits related to COVID-19. Safety will be evaluated by tracking adverse events and discontinuation due to side effects. Researchers will also measure symptom relief, viral RNA levels, and other health indicators. The study is expected to continue until January 2031.

Researchers are studying pulmonary arterial hypertension PAH, a condition where lung blood vessels become thick and narrow, causing high blood pressure in the lungs and making it hard for the heart to work. PAH can cause difficulty breathing and limit activity. While standard treatments help symptoms, they do not stop the disease from worsening. This research focuses on sotatercept, a targeted therapy aimed at specific proteins involved in PAH, to learn about its long-term safety and tolerability when added to usual PAH treatments. Participants in this long-term follow-up study, who previously took part in certain sotatercept trials, may continue receiving sotatercept by subcutaneous injection every three weeks. Those coming from blinded studies start at 0.3 mgkg with possible increases up to 0.7 mgkg, while those from unblinded studies continue their current dose with possible titration to 0.7 mgkg. The study monitors participants over an extended period to assess continued effects alongside their usual PAH therapy. During the study, participants will have regular assessments including monitoring for adverse events, blood tests for blood components and chemistry, body weight, blood pressure, and ECG readings. Researchers will also evaluate exercise capacity, heart function markers, and risk scores related to PAH. The study aims to follow participants for up to approximately 7 to 8 years to understand long-term safety, treatment tolerability, and health changes while using sotatercept with standard PAH care.

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.