Wellington

Researchers are investigating new treatments for people with high-risk, early-stage breast cancer, specifically targeting triple-negative breast cancer (TNBC) and hormone receptor (HR)-low positive/HER2-negative breast cancer. These types have little or no HER2 protein and involve hormones like estrogen or progesterone. The study aims to evaluate if the addition of sacituzumab tirumotecan (sac-TMT), a targeted therapy, combined with pembrolizumab and chemotherapy can improve outcomes compared to pembrolizumab with chemotherapy alone. Participants receive treatments including sacituzumab tirumotecan, pembrolizumab, and chemotherapy drugs such as carboplatin and paclitaxel, all given by intravenous infusion. Rescue medications like antihistamines, acetaminophen, dexamethasone, or steroid mouthwash may be used as needed. The study is randomized and open-label, comparing sac-TMT followed by chemotherapy plus pembrolizumab to chemotherapy and pembrolizumab without sac-TMT. During the study, researchers will monitor participants up to about 30 weeks to assess the percentage of people with no remaining cancer cells at surgery. They will also follow participants for up to approximately 92 months to track event-free survival, meaning time without cancer growth, spread, or return. Participants will undergo imaging, clinical assessments, and laboratory tests to evaluate treatment effects and safety throughout the study.

Researchers are studying the optimal dosing of Levetiracetam (LEV) to treat neonatal seizures, focusing on determining the maximum safe and tolerated dose. The study hypothesizes that the best dose of LEV for neonatal seizures is significantly higher than 60 mg/kg. This Phase IIb, open-label dose-escalation study includes a randomized control component comparing higher doses of LEV to phenobarbital (PHB), the standard care. The study targets neonates with mild to moderate seizure burden initially, and may expand to more severe seizures in later phases to ensure the results are broadly applicable. Neonates diagnosed with or at risk for seizures will start with continuous video EEG monitoring to confirm seizures. All enrolled infants first receive 60 mg/kg of LEV. If seizures persist 15 minutes after this dose, infants are randomized to receive either increased doses of LEV (in 30 mg/kg increments up to 150 mg/kg total) or PHB at 20-40 mg/kg, given intravenously or orally over five days. The study uses a continual reassessment method to find the highest safe dose and includes phases that may escalate dosing based on efficacy results. During the study, participants undergo continuous EEG monitoring reviewed by neurophysiologists to assess seizure control within 24 hours and changes in seizure burden over 2 hours post-treatment. Researchers will also study the pharmacokinetics of high-dose LEV and evaluate a neonatal seizure detection technology. Safety and seizure control are closely monitored, with criteria to discontinue or add PHB if needed. Participation duration depends on seizure control and treatment response, with ongoing monitoring for adverse events.

Researchers are studying the prevalence, risk factors, and effects of chronic post-surgical pain in children aged 0 to 16 years undergoing common pediatric surgeries such as laparoscopic appendicectomy, scrotal exploration, orchidopexy, hypospadias repair, and circumcision. The study aims to understand how factors like parent and child anxiety, existing pain, and acute post-operative care relate to the development of chronic pain over time. This knowledge will help improve care and reduce the risk of long-term pain in children after surgery. The study involves completing questionnaires at six different times, starting before surgery, then at Day 2, 3-4 weeks, 3-4 months, and finally 10-12 months post-surgery. These questionnaires assess pain levels, function, and related factors. The study is conducted across multiple international centers and focuses on both elective and emergency surgeries. Participants will be involved in providing information through these questionnaires over about one year. Researchers will measure outcomes like the presence of chronic pain 10-12 months after surgery. The study will also monitor the impact of chronic pain on children's quality of life, emotional well-being, and social functioning. Families unable to complete follow-up surveys or those with language barriers may not participate, ensuring accurate and complete data collection.

Researchers are conducting a phase III randomized, open-label, multicenter trial across several countries including Sweden, Norway, Finland, Denmark, Italy, Australia, and New Zealand. The study focuses on elderly patients with untreated diffuse large B-cell lymphoma (DLBCL), defined as patients aged 80 years or older, or those aged 75 years or older who are considered frail based on a simplified Comprehensive Geriatric Assessment. The trial aims to compare the effectiveness of two treatment regimens in this population. Participants are randomly assigned to receive either the standard R-miniCHOP treatment or an experimental R-pola-miniCHP regimen where vincristine is replaced with an immunoconjugate, polatuzumab vedotin. Both treatments involve cycles of drugs including rituximab, cyclophosphamide, doxorubicin, and prednisone, administered over 18 weeks. The trial includes a screening period lasting up to 4 weeks, followed by the active treatment phase, and then a follow-up period lasting up to 36 months after treatment completion. Throughout the study, participants will be monitored to measure progression-free survival over 2 years as the primary outcome. The study involves regular assessments including clinical evaluations and safety monitoring. Enrollment began in the first quarter of 2020, with the last patient visit expected by the first quarter of 2027, allowing for long-term observation of treatment effects and patient outcomes.

Researchers are evaluating the safety, tolerability, recommended Phase 2 dose, and early effectiveness of the drug BGB-11417 used alone and combined with azacitidine in adults with certain blood cancers, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myelodysplastic/myeloproliferative neoplasm (MPN). This study is conducted in Phase 1b and Phase 2 to find the best dose and assess responses in these myeloid malignancies. Participants receive BGB-11417 orally in cycles of 28 days, with dosing schedules of 10, 14, 21, or 28 days depending on the study part. Azacitidine is given intravenously or by injection for 7 days, and posaconazole is taken orally for 8 days during the second cycle only. There are different study parts including dose finding and expansion phases, with treatments adjusted accordingly. During the study, participants are monitored for dose-limiting toxicities and treatment-emergent side effects over about 24 months. Researchers also measure the rates of complete remission and overall response in different patient groups. Blood samples are collected to study drug levels, and safety is closely observed throughout the treatment cycles. The study lasts up to two years to evaluate the effects and safety of these therapies in patients with these blood cancers.

Researchers are investigating the effects of low-dose intracoronary thrombolytic therapy in patients who experience ST-elevation myocardial infarction (STEMI), a type of heart attack caused by a blood clot blocking the heart's blood vessels. The study focuses on patients with impaired microcirculatory perfusion, identified by an elevated Index of Microcirculatory Resistance (IMR) after angioplasty. This damage to the heart's small vessels is linked to worse clinical outcomes, and the trial seeks to determine if dissolving clots inside the coronary artery can reduce this damage and improve patient outcomes. After patients receive angioplasty and a drug-eluting stent, their IMR is measured. Those with IMR above 32 are randomly assigned to receive either low-dose tenecteplase, a clot-dissolving drug, or a placebo of sterile water directly into the coronary artery. Patients with IMR 32 or below are monitored in a registry. The tenecteplase dose is one-third of the systemic weight-based dose, infused intracoronarily. Cardiac MRI scans are performed 3-7 days after the procedure and again at 6 months for randomized patients, with follow-up visits scheduled at 30 days, 6, 12, and 24 months. Throughout the study, participants undergo cardiac enzyme tests and clinical assessments. The primary outcomes measured include rates of cardiovascular death and rehospitalization for heart failure at 24 months, as well as the size of the heart attack and bleeding within the heart muscle at 6 months. The study carefully monitors safety and treatment effects through imaging and clinical follow-up to evaluate whether low-dose tenecteplase can improve long-term heart function after STEMI.

Researchers are investigating whether sacituzumab tirumotecan alone or combined with pembrolizumab can treat triple-negative breast cancer (TNBC). This phase 3 study compares these treatments to chemotherapy chosen by the physician, aiming to see if participants live longer or have longer periods without cancer growth or spread. The study focuses on people with previously untreated locally recurrent unresectable or metastatic TNBC with low PD-L1 expression. Participants receive sacituzumab tirumotecan through intravenous infusion alone or with pembrolizumab, also given intravenously. The study compares these to treatment options including paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin. Pre-medications like antihistamines, acetaminophen, and steroids are given before sacituzumab tirumotecan infusions to help reduce side effects. The trial evaluates safety and effectiveness over several months. Throughout the study, researchers monitor participants up to about 39 months for progression-free survival and up to about 61 months for overall survival. Participants undergo regular assessments to track cancer status and side effects. The study includes careful safety monitoring, and participants must meet specific health criteria to join. The total time in the study and follow-up depends on each participant's response and health status.

Researchers are conducting a multi-center, global, randomized, double-blind, placebo-controlled Phase 2b trial to evaluate the effectiveness, safety, and tolerability of IMVT-1402 in adults with Graves' disease who remain hyperthyroid despite antithyroid drug treatment. The study focuses on participants aged 18 to 75 years who have this diagnosis and are still experiencing hyperthyroidism. Participants will receive either IMVT-1402 or a placebo for 26 weeks. The study includes two dosing regimens of IMVT-1402: Dose 1 administered for 26 weeks and Dose 2 also administered for 26 weeks. The placebo group will receive treatment for the same duration. The treatments are given as drugs, and the study is designed to keep both participants and researchers unaware of which treatment is assigned. During the study, researchers will monitor participants to see how many achieve normal thyroid function (euthyroid) and remain off antithyroid drugs by Week 26. Participants will be assessed regularly to evaluate safety, tolerability, and treatment effects. The involvement includes following the assigned treatment and attending scheduled visits for evaluations. The total participation time corresponds with the 26-week treatment period.

Researchers are comparing the effectiveness of two treatments for participants with stage IV or recurrent non-squamous non-small cell lung cancer (NSCLC) who have PD-L1 expression of 1% or higher. This phase 3, randomized, open-label study focuses on first-line treatment options and aims to evaluate overall survival over up to five years for participants with PD-L1 levels between 1% and 49%. The trial involves participants with measurable disease and good performance status who have not received prior systemic therapy for advanced disease. The study compares a combination of Nivolumab and Relatlimab plus chemotherapy against Pembrolizumab plus chemotherapy. Chemotherapy drugs include Carboplatin, Pemetrexed, and Cisplatin, administered at specified doses on scheduled days. Participants are randomly assigned to receive either the Nivolumab and Relatlimab combination with chemotherapy or Pembrolizumab with chemotherapy as their initial treatment. Treatment schedules and doses are defined but not detailed here. Participants will be closely monitored throughout the study, which may last up to five years. Researchers will assess overall survival as the primary outcome, along with regular imaging tests like CT or MRI to measure disease status. Eligibility screening includes assessing PD-L1 levels, performance status, and other health factors. Safety monitoring and follow-up will continue to evaluate treatment effects and participant well-being during and after treatment.

Researchers are evaluating the safety, tolerability, pharmacokinetics, immunogenicity, and pharmacodynamics of two different dose levels of solrikitug compared to placebo in people with Chronic Obstructive Pulmonary Disease (COPD). This Phase 2 study includes participants who have had COPD for at least 12 months and have elevated blood eosinophil levels. The trial aims to understand how solrikitug affects blood eosinophil counts and other health measures related to COPD. Participants will be randomly assigned to receive either low-dose solrikitug, high-dose solrikitug, or a placebo. These treatments are given by subcutaneous injection at the study site over a 12-week period. After treatment, there is a 16-week follow-up period to monitor participants for any lasting effects or safety concerns. During the study, participants will have regular assessments including lung function tests, blood tests to measure eosinophil counts, and evaluations of COPD symptoms. Researchers will monitor safety and tolerability closely throughout the treatment and follow-up periods. The total time commitment for participants covers the 12 weeks of treatment plus the 16 weeks of follow-up, totaling 28 weeks.