Annapolis

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 collecting data in a multicenter patient registry to observe outcomes in patients who undergo cryoablation of the intercostal nerves, known as cryoanalgesia, for managing pain after cardiothoracic surgery. This observational study aims to record both retrospective and prospective information from patients treated with this approach, focusing on post-operative pain relief. Participants include those who have been scheduled to receive or have already received cryoablation using the AtriCure Cryo Nerve Block Device Family or similar devices. The study monitors patients who used the device for post-operative pain management as well as comparable patients treated without cryoablation. During the study, researchers will gather data on the effectiveness and safety of the cryo nerve block for pain control from enrollment through five years after the surgical procedure. Participants outcomes are recorded to understand long-term pain management results. The registry is observational, so patients continue their usual care while their data is collected and analyzed.

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study. This trial focuses on patients with established atherosclerotic cardiovascular disease ASCVD or those at high risk for a first ASCVD event. The study aims to assess how AZD0780 compares to placebo in reducing the risk of major adverse cardiovascular events, also known as MACE-PLUS, over the course of the trial. Participants are randomly assigned to receive either oral AZD0780 once daily or a matching placebo once daily. The study continues until a primary analysis censoring date, which may be up to approximately 54 months from randomization. After this, a study closure visit will be conducted as the final visit for each participant. During the study, participants will be regularly monitored for cardiovascular events including heart attacks, strokes, urgent coronary revascularizations, and other related outcomes. Researchers will track the time to first occurrence of these events as the primary outcome. Safety and other secondary outcomes like all-cause mortality will also be assessed. The total participation time can last up to about 54 months, with ongoing evaluations throughout this period.

Researchers are evaluating the efficacy, safety, and tolerability of combining elecoglipron and dapagliflozin compared to each drug alone in adults with type 2 diabetes mellitus T2DM who have not achieved adequate control through lifestyle changes or other glucose-lowering medications. This Phase III study aims to better understand how these treatments work together in managing blood sugar levels in this population. Participants are randomly assigned to one of five groups two groups receive elecoglipron at different dose levels combined with dapagliflozin two groups receive elecoglipron at different dose levels combined with a placebo matching dapagliflozin and one group receives dapagliflozin alone with a placebo matching elecoglipron. All medications are taken orally once daily. The treatment period lasts 40 weeks, during which the effects of the drugs on blood sugar and other health measures will be monitored. Throughout the study, participants will have regular assessments of their blood sugar control, body weight, and blood pressure. Researchers will measure changes in Hemoglobin A1c HbA1c, fasting plasma glucose, and self-monitored blood glucose levels. Other outcomes include weight loss and the need for rescue medication. Safety and tolerability will be closely monitored. Participation in the trial lasts for 40 weeks, during which participants will attend scheduled visits for evaluation and medication monitoring.

Researchers are evaluating the effectiveness and safety of combining inavolisib with a cyclin-dependent kinase 4 and 6 inhibitor CDK46i and letrozole compared to placebo plus CDK46i and letrozole in adults with endocrine-sensitive PIK3CA-mutated hormone receptor-positive HR, HER2-negative advanced breast cancer. This phase III, randomized, double-blind study focuses on participants who have measurable disease and meet specific hormone receptor and HER2 status criteria. Participants are randomly assigned to receive either oral inavolisib once daily along with letrozole and CDK46i or placebo once daily with letrozole and CDK46i. The CDK46i is given on a schedule of either Days 1-21 or Days 1-28 of each 28-day cycle. The study includes parallel groups to compare these treatment combinations over time. During the study, participants will be monitored for progression-free survival, overall survival, response rates, duration of response, clinical benefit, and changes in pain, physical function, and global health status. Safety will be assessed by tracking adverse events and patient-reported treatment side effects using questionnaires. The study will follow participants for up to seven years, with regular evaluations to track disease status and quality of life.

Researchers are evaluating the combination of adagrasib, pembrolizumab, and platinum-doublet chemotherapy compared to placebo plus pembrolizumab and platinum-doublet chemotherapy in adults with previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer NSCLC carrying the KRAS G12C mutation. This Phase 3 trial aims to assess the efficacy, safety, and tolerability of these treatment combinations in this specific patient group. Participants will receive either adagrasib plus pembrolizumab combined with platinum-doublet chemotherapy or placebo plus pembrolizumab and platinum-doublet chemotherapy. Treatments involve specified doses administered on scheduled days, with the chemotherapy consisting of carboplatin or cisplatin along with pemetrexed. Participants are randomly assigned to one of the two study groups and treatments are blinded to ensure unbiased assessment. Throughout the study, participants will undergo regular evaluations including imaging scans to measure tumor response and progression-free survival, as well as assessments of overall survival. Safety is closely monitored by recording adverse events for up to 90 days after the last dose. Quality of life and symptom assessments are also conducted using validated questionnaires. The study duration includes follow-up for up to seven years to gather comprehensive data on treatment outcomes and participant health.

Researchers are evaluating STM-416, a drug studied for safety and tolerability in patients with recurrent high-grade papillary non-muscle-invasive bladder cancer NMIBC without carcinoma in situ CIS. This first-in-human, Phase 12a, multi-center study includes patients who have completed standard of care SOC and have visible recurrent disease, focusing on those undergoing transurethral resection of bladder tumor TURBT without perioperative intravesical chemotherapy. The study aims to determine the safety of STM-416 administered during surgery and to explore its effects alongside SOC therapy given afterward. The study has two parts. Phase 1 is an open-label, dose-escalation phase where up to six increasing doses of STM-416 are given intraoperatively in 3 to 6 patients per dose to assess safety and tolerability. Phase 2a is a randomized, single-blind, dose-expansion phase comparing two doses of STM-416 administered during TURBT followed by SOC therapy. All participants receive SOC treatment after surgery. The study plans to enroll about 30 patients in Phase 1, with additional participants in Phase 2a. Participants will undergo TURBT surgery with STM-416 treatment during the procedure, followed by SOC therapy. Researchers will monitor dose-limiting toxicities and adverse events for up to 90 days in Phase 1 and track recurrence-free survival for up to 24 months in Phase 2a. Pharmacokinetics and pharmacodynamics of STM-416 will be studied at various time points after administration. Overall, participants will be followed regularly to assess safety, treatment response, and disease recurrence as part of the study lasting up to two years.

Researchers are comparing the effectiveness of two different combinations of immunotherapy drugs with chemotherapy for adults with stage IV or recurrent non-squamous non-small cell lung cancer that has PD-L1 expression of 1% or higher. This phase 3, randomized study focuses on participants who have not previously received systemic treatment for advanced disease. The goal is to determine which combination better improves overall survival and other outcomes in this patient group. Participants will be randomly assigned to receive either Nivolumab plus Relatlimab combined with chemotherapy or Pembrolizumab combined with chemotherapy. The chemotherapy drugs used include Carboplatin, Pemetrexed, or Cisplatin, given in specified doses on scheduled days. Treatment is given as first-line therapy for their cancer, with dosing details managed throughout the study period. During the study, participants will undergo imaging scans like CT or MRI to measure disease status, and blood tests to monitor safety and side effects. The main outcome measured is overall survival over up to five years, along with progression-free survival, response rates, duration of response, and adverse events. Researchers will also assess symptoms related to lung cancer over two years. Participants are monitored regularly to track these outcomes and ensure safety throughout the study duration, which may last several years.

Researchers are conducting a Phase III, randomized, open-label multicenter study to evaluate the effectiveness and safety of giredestrant compared with fulvestrant. Both drugs are combined with the investigators choice of a CDK46 inhibitor palbociclib, ribociclib, or abemaciclib in participants with estrogen receptor-positive ER, HER2-negative advanced breast cancer who have become resistant to prior adjuvant endocrine therapy. Participants will be randomly assigned to one of two groups one group will receive giredestrant 30 mg orally daily on Days 1-28 of each 28-day cycle, while the other will receive fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1 and Day 1 of subsequent 28-day cycles. Both groups will also receive a CDK46 inhibitor chosen by the investigator, with dosing schedules depending on the specific inhibitor selected. Preperimenopausal women and men will receive a luteinizing hormone-releasing hormone LHRH agonist during treatment. Participants will be assessed for progression-free survival over up to 5 years, with additional measures including overall survival, response rates, duration of response, clinical benefit, and quality of life. Safety will be monitored through adverse event reporting, vital signs, and laboratory tests during treatment and up to 28 days after the last dose. The study is led by Hoffmann-La Roche and aims to provide detailed information on the treatments effects in this patient population.

Researchers are evaluating the safety and effectiveness of GDC-4198 alone and combined with giredestrant compared to abemaciclib combined with giredestrant in participants who have locally advanced or metastatic estrogen receptor-positive ER, HER2-negative breast cancer. This Phase IbII study focuses on participants who have previously experienced progression during or after treatment with a CDK46 inhibitor. The study aims to assess the safety, pharmacokinetics, and activity of these treatments in this population. Participants receive GDC-4198 orally, either alone or in combination with giredestrant at 30 mg daily, following a pre-defined dosing schedule during 28-day cycles until unacceptable side effects, disease progression, or loss of clinical benefit occurs. The study includes a Phase Ib dose-finding stage assessing safety and pharmacokinetics, followed by a Phase II stage that compares the activity and safety of GDC-4198 plus giredestrant against abemaciclib plus giredestrant, which is given orally at 150 mg twice daily with giredestrant 30 mg daily. During the study, participants undergo regular monitoring for adverse events, dose-limiting toxicities, and progression-free survival, with assessments lasting up to 36 months. Researchers measure response rates, clinical benefits, duration of response, overall survival, and plasma concentration of GDC-4198. Safety and activity data are collected throughout treatment cycles, with ongoing evaluations for up to three years to understand the long-term effects and recommended dosing.