Dublin

Researchers are evaluating two different methods of pacing the heart in patients with slow heart rates (bradycardia). This multi-center randomized controlled trial, called PROTECT-HF, aims to compare the standard right ventricular pacing approach with a newer physiological pacing technique, which includes His bundle and left bundle area pacing. The study will enroll 2600 patients to assess differences in outcomes related to heart function and survival. Participants will be randomly assigned to receive either right ventricular pacing or physiological pacing through pacemaker implantation. The physiological pacing method may involve His bundle pacing or left bundle pacing, with biventricular pacing used if these are not possible. Both treatments will be performed at participating centers, with patients and outcome assessors blinded to the treatment allocation. A subgroup of 500 patients will also take part in an optional echocardiographic sub-study to observe heart changes over 24 months. During the study, participants will be monitored from the time of consent for up to 78 months. Evaluations will occur at the start and every six months afterward to track mortality and heart failure-related health events. Researchers will gather data on heart function, treatment effects, and safety. The main analysis will consider all patients as originally assigned, and additional analysis will assess those who received the assigned treatment.

Researchers are evaluating the safety of image-guided stereotactic ablative radiation therapy (IG-SABR) for patients with high-risk centrally located non-small cell lung cancer (NSCLC) tumors or a single pulmonary oligometastatic lesion that cannot be operated on. This phase II, non-randomized study aims to assess side effects and toxicities in patients receiving this precise high-dose radiation treatment. The study focuses on patients whose initial treatment plans do not meet certain dose criteria for tumors and surrounding tissues, ensuring careful dose delivery. The treatment involves delivering IG-SABR in 8 fractions, each with 7.5 Gy, using photon beams of 6-10 MV energy while respecting organ-at-risk constraints. The radiation targets 75% to 95% of the planning target volume (PTV) and 75% to 99% of the gross tumor volume (GTV). Respiratory monitoring and active management techniques are used during treatment to enhance precision. Optional translational sub-studies are available at participating centers to explore biomarkers through Raman spectroscopy and proteomic analysis. Participants will be closely monitored for toxicity weekly during treatment, then at 2, 4, and 8 weeks post-treatment, and at multiple intervals up to five years after treatment. Researchers will track the rate of severe treatment-related toxicities (Grade 3 or higher) up to one year following treatment. The study plans to enroll 60 patients over six years, with safety assessed continuously to halt enrollment if excessive toxicities occur.

Researchers are evaluating the safety, tolerability, and levels of the study drug SYX-5219 in healthy volunteers and people with moderate to severe atopic dermatitis (AD). This multi-part, Phase 1, first-in-human study includes participants aged 18 to 65 years. The study aims to understand how SYX-5219 behaves in the body and to assess its safety in different dosing scenarios, including single and multiple doses as well as food effects. The study is divided into three parts. Part 1 involves single ascending doses (SAD) and a food effect evaluation in up to 48 healthy volunteers, who receive oral capsules of SYX-5219 or placebo. Part 2 tests multiple ascending doses (MAD) in up to 24 healthy volunteers with multiple oral doses given over a treatment period. Part 3 enrolls up to 45 participants with confirmed active AD to receive SYX-5219 or placebo daily for up to 42 days. This part is conducted at multiple global sites. Participants will undergo safety and exploratory efficacy assessments during treatment and follow-up periods. Researchers will monitor adverse events from the date of consent through various time points depending on the study part, including up to 10 days after dosing in Part 1 and up to 56 days in Part 3. Assessments include laboratory tests, vital signs, ECGs, and clinical evaluations to gather information on safety, tolerability, and drug levels in blood and urine throughout the study duration.

Researchers are evaluating MDNA11, a long-acting "beta-only" recombinant interleukin-2 designed to activate immune cells that attack cancer while minimizing stimulation of cells that suppress immunity. This Phase 1/2 open-label study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of MDNA11 alone or combined with pembrolizumab in patients with advanced or metastatic solid tumors. The study includes dose-escalation and dose-expansion parts for both monotherapy and combination therapy with pembrolizumab. MDNA11 is given intravenously every two weeks with doses ranging from 0.003 to 0.6 mg/kg for monotherapy, while dose ranges for combination therapy are also evaluated. Treatment continues until progression, withdrawal, or loss to follow-up, with tumor assessments by CT or MRI every 8 weeks. Participants will undergo regular imaging scans every 8 weeks to monitor tumor response and safety assessments throughout the 24-month study. Researchers will track recommended doses for expansion, treatment-related adverse events, and overall safety. The study involves up to 115 patients across multiple sites and includes long-term monitoring for up to 24 months.

Researchers are studying advanced renal cell carcinoma (RCC) that has returned after prior adjuvant therapy. The trial aims to find out if treatment with belzutifan and zanzalintinib helps patients live longer and delays disease progression compared to treatment with cabozantinib. This is a Phase 3 randomized study focusing on participants with recurrent advanced RCC who have previously received anti-PD-1/L1 therapy. Participants are randomly assigned to receive one of two oral drug regimens: either belzutifan combined with zanzalintinib, both taken once daily, or cabozantinib alone, also taken once daily. The study compares these treatments to assess their effects on disease control and overall survival. During the study, participants will be monitored for progression-free survival and overall survival for up to approximately 73 months. Researchers will evaluate how well the cancer responds to treatment and track any changes in health status over time. Safety and effectiveness of the treatments will be closely followed throughout the study period.

Researchers are evaluating a new treatment called ifinatamab deruxtecan (I-DXd) for men with metastatic castration-resistant prostate cancer (mCRPC). This study compares I-DXd to chemotherapy to see if it helps people live longer overall and live longer without their cancer worsening. It is a Phase 3, open-label trial focused on patients who have progressed on prior therapies and have evidence of metastatic disease. Participants receive either I-DXd through an intravenous infusion every 3 weeks or docetaxel chemotherapy administered every 3 weeks. Prednisone tablets are also given daily as part of the treatment plan. Before each I-DXd dose, premedication is provided to help prevent nausea and vomiting using a combination of drugs such as corticosteroids and anti-nausea medicines. Treatment continues until disease progression, unacceptable side effects, or other reasons to stop. During the study, researchers monitor overall survival and how long patients live without their cancer progressing, for up to about 36 months. Participants undergo tumor tissue collection, scans, and assessments to track disease status and side effects. Safety is closely watched throughout treatment. The study includes men aged 18 and older with confirmed prostate cancer and metastatic disease who have previously received certain hormone therapies but no prior taxane chemotherapy for mCRPC.

Researchers are evaluating the safety and effectiveness of ifinatamab deruxtecan (I-DXd) alone or combined with other treatments in people with metastatic castration-resistant prostate cancer (mCRPC). This study aims to understand how well patients tolerate the treatment, find a safe dose for combining I-DXd with other drugs, and measure prostate-specific antigen (PSA) levels during treatment. The study is part of a larger master screening protocol and includes patients with confirmed prostate adenocarcinoma who have progressive disease despite prior therapies. Participants receive treatments including I-DXd given through intravenous infusion, sometimes combined with other drugs such as docetaxel (IV), MK-5684, abiraterone, or enzalutamide (all oral). Before each I-DXd dose, patients take premedication to prevent nausea and vomiting. The study includes both a safety lead-in phase and an efficacy phase, with ongoing monitoring for side effects and tolerability. The combination therapies are carefully dosed and scheduled according to the study protocol. During the study, participants undergo regular assessments to monitor side effects, measure PSA response, and track any dose-limiting toxicities. Safety is closely followed, particularly during the first 21 days for combination treatments, and throughout up to 54 months for long-term outcomes. Researchers also observe if participants discontinue treatment due to adverse events. The study requires ongoing visits and evaluations to ensure participant health and collect data on treatment effects over time.

Researchers are looking for ways to treat germinal center B-cell-like diffuse large B-cell lymphoma (GCB DLBCL). DLBCL is a fast-growing blood cancer that affects B-cells. GCB is a type of DLBCL that affects young B-cells that are still maturing. The goal of this study is to learn if more people who receive zilovertamab vedotin (MK-2140) and R-CHP have the cancer respond (go away) than those who receive polatuzumab vedotin and R-CHP.

Researchers are conducting a phase III randomized trial to evaluate the effectiveness of adjuvant cemiplimab immunotherapy in patients with surgically removed stage II-IIIA non-small cell lung cancer (NSCLC) who have not received prior platinum-based chemotherapy. The study focuses on patients whose tumors express PD-L1 at 1% or higher. The main goal is to measure disease-free survival, tracking the length of time patients remain free from cancer recurrence or death for up to about 59 months. Participants receive cemiplimab intravenously at 350 mg every 3 weeks for four cycles, followed by 700 mg every 6 weeks for six cycles, continuing until cancer relapse or unacceptable side effects occur. The treatment is compared to observation without additional adjuvant therapy. The study involves careful dosing schedules and monitoring to assess the impact of cemiplimab as a post-surgical treatment option. During the study, participants undergo brain imaging for staging, tumor PD-L1 testing, and regular pregnancy tests for women of childbearing potential. Researchers monitor disease recurrence and adverse effects throughout treatment and follow-up. Patients must meet specific health criteria, including recovery from surgery and adequate organ function, and agree to use contraception during treatment and for four months afterward. The total participation period includes treatment cycles and long-term follow-up to evaluate disease-free survival and safety.

Researchers are evaluating the safety and effectiveness of once-weekly subcutaneous doses of navepegritide compared to a placebo in adolescents aged 12 to 18 years with Achondroplasia. This Phase 2b clinical trial aims to measure Annualized Growth Velocity after 52 weeks of treatment to assess the impact of the drug on growth in these participants. Participants will receive either navepegritide at a dose of 100 micrograms per kilogram or a placebo injection once a week for 52 weeks. The study is randomized, double-blind, and placebo-controlled, ensuring that neither the participants nor the researchers know who is receiving the active drug or placebo during the treatment period. During the study, participants' growth will be closely monitored, including measuring their growth rate over the 52 weeks. Safety and efficacy assessments will be conducted throughout the treatment period. Participants will need to have documented genetic confirmation of Achondroplasia and provide past height measurements for comparison. The trial also includes careful monitoring for any side effects or safety concerns associated with the treatment.