Wellington

Researchers are investigating new treatments for high-risk, early-stage breast cancer, specifically targeting two types triple-negative breast cancer TNBC and hormone receptor-low positiveHER2-negative breast cancer. These cancers are characterized by low or no HER2 protein and low hormone receptor presence. The study aims to evaluate if adding sacituzumab tirumotecan sac-TMT to pembrolizumab and chemotherapy can better reduce cancer cells in tumors and lymph nodes and improve the length of time patients live without cancer progression compared to pembrolizumab with chemotherapy alone. Participants in this trial receive one of two treatment plans. One group gets sacituzumab tirumotecan intravenously every two weeks plus pembrolizumab every three weeks for 12 weeks, followed by pembrolizumab with carboplatin and paclitaxel for another 12 weeks. After 3 to 6 weeks, surgery and optional radiation therapy take place, followed by pembrolizumab for about 28 weeks. Participants with remaining disease may receive additional treatments chosen by their doctors, including olaparib, capecitabine, doxorubicin, epirubicin, or cyclophosphamide. The other group receives chemotherapy drugs carboplatin and paclitaxel with pembrolizumab initially, then pembrolizumab with cyclophosphamide and doxorubicin or epirubicin, followed by surgery, optional radiation, and pembrolizumab for about 28 weeks, with similar additional options for residual disease. During the study, participants undergo core needle biopsies, receive intravenous infusions of study drugs, and have surgery and possible radiation therapy. Researchers assess outcomes such as the percentage of participants with no detectable cancer cells at surgery pathological complete response, event-free survival up to about 92 months, and overall survival up to nearly 10 years. Quality of life and side effects are monitored through questionnaires and adverse event tracking. The study lasts several years, with various assessments throughout treatment and follow-up periods to gather comprehensive data on treatment effects and safety.

Researchers are evaluating the safety and effectiveness of a once-daily oral medication called AP1189, at a dose of 100 mg, compared to a placebo in participants who have respiratory insufficiency expected to be caused by respiratory viral infections such as SARS-CoV-2, Influenza A or B, or RSV. This study is a Phase 2, randomized, double-blind, placebo-controlled trial aiming to include 96 hospitalized participants. The goal is to assess AP1189 as an add-on treatment to the standard care provided for these respiratory infections. Participants will be randomly assigned in equal numbers to receive either AP1189 tablets or matching placebo tablets once daily for 14 days, alongside their standard of care treatment. The study monitors participants during this 14-day treatment period to evaluate treatment outcomes and safety. During the study, participants will be assessed for a composite outcome including death, need for invasive mechanical ventilation or ECMO, cardiovascular organ support, or new renal failure within 28 days. The study includes clinical evaluations, oxygen saturation measurements, and safety monitoring during and after treatment. Overall participation lasts at least 28 days to capture these outcomes and monitor participant health.

Researchers are evaluating the maximum safe and tolerated dose of Levetiracetam LEV for treating neonatal seizures. This Phase IIb, open-label dose-escalation study aims to determine if higher doses of LEV than currently used can improve seizure control in newborns. The study includes infants at risk or confirmed to have neonatal seizures of mild to moderate severity, with continuous video EEG monitoring used to assess seizure activity and control. Participants initially receive a 60 mgkg dose of LEV. If seizures persist after this dose, they are randomized to either receive higher doses of LEV 90 mgkg, 120 mgkg, or 180 mgkg in increments or treatment with Phenobarbital PHB at 20-40 mgkg. Maintenance treatment with PHB may continue for five days either intravenously or orally if tolerated. The study includes three phases, with Phase 3 expanding to neonates with more severe seizure burden if earlier phases show efficacy. Throughout the study, participants are monitored with continuous EEG reviewed by neurophysiologists to assess seizure control over 24 hours and changes in seizure burden during the two hours after treatment. Safety, pharmacokinetics, seizure freedom rates, adverse events, and long-term outcomes up to eight years are evaluated. The study also assesses new technology for neonatal seizure detection. Participation may last several years due to extended follow-up for long-term outcomes.

Researchers are studying chronic post-surgical pain CPSP in children aged 0 to 16 years who undergo common pediatric surgeries such as laparoscopic appendicectomy, scrotal exploration, orchidopexy, hypospadias repair, and circumcision. The study aims to understand how often CPSP occurs, its risk factors, and its effects on childrens physical, emotional, and social well-being. This observational study will collect information through questionnaires from before surgery up to one year after surgery. Participants will be grouped based on the type of surgery they receive elective surgeries including circumcision, hypospadias repair, orchidopexy, or laparoscopic appendicectomy, and emergency surgeries including laparoscopic appendicectomy or scrotal exploration. The study observes these groups without providing treatments, focusing on collecting data about their pain experiences and related factors over time. Children and their families will complete questionnaires at six different times before surgery, on Day 2 after surgery, at 3 to 4 weeks, 3 to 4 months, and 10 to 12 months post-surgery. These questionnaires assess pain levels, function, anxiety, and other factors. Researchers will track the prevalence of chronic post-surgical pain at 10 to 12 months and identify potential risk factors to help improve future care and guidelines for children at risk of long-term pain.

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 efimosfermin alfa in adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis MASH and stage F2 or F3 liver fibrosis. The study aims to assess the safety and effectiveness of efimosfermin alfa compared to a placebo in resolving steatohepatitis and improving liver-related clinical outcomes. This Phase 3 trial is randomized, double-blind, and placebo-controlled, focusing on participants with specific liver conditions and metabolic syndrome components. Participants are assigned to one of three groups two groups receive different dose levels of efimosfermin alfa, while the third group receives a placebo. Treatments are given under controlled conditions, and the study follows a parallel design. The trial monitors participants at set intervals over a course of 52 weeks, with some outcomes tracked up to 48 months to evaluate long-term effects on liver fibrosis and steatohepatitis. During the study, participants undergo liver biopsies to confirm diagnosis and assess changes. Researchers evaluate improvements in fibrosis stage, steatohepatitis resolution, and various liver function measurements using imaging and blood tests. Safety is monitored by tracking adverse events and laboratory abnormalities. Quality of life and other health indicators are also assessed throughout the study, which lasts several years to capture both short- and long-term outcomes.

This trial focuses on elderly patients aged 80 years or older, or those 75 years and older who are considered frail, with untreated diffuse large B-cell lymphoma DLBCL and related lymphoma subtypes. The study is a phase III, randomized, open-label, multicenter trial conducted in several countries including Sweden, Norway, Finland, Denmark, Italy, Australia, and New Zealand. It aims to compare the standard chemotherapy regimen R-miniCHOP with an experimental treatment R-pola-miniCHP, where vincristine is replaced by polatuzumab vedotin, to assess differences in outcomes for this patient population. Participants will be randomly assigned to one of two treatment groups. One group will receive R-mini-CHOP consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone over six 21-day cycles. The other group will receive R-pola-mini-CHP, which includes rituximab, cyclophosphamide, doxorubicin, prednisone, and polatuzumab vedotin instead of vincristine, also given over six 21-day cycles. Both treatments last approximately 18 weeks. The study includes a screening period lasting up to 4 weeks before treatment begins. During the study, participants will be followed for up to 36 months after completing treatment to monitor progression-free survival over two years. Researchers will evaluate disease progression and safety outcomes through regular assessments during and after the treatment period. Participants will provide informed consent and undergo evaluations including health status and disease measurements to ensure eligibility and monitor treatment effects throughout the trial.

Researchers are conducting a randomized, double-blinded, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, immunogenicity, and exploratory clinical activity of BBT002. This study includes healthy adults and patients with chronic obstructive pulmonary disease COPD or chronic rhinosinusitis with nasal polyps CRSwNP. BBT002 is being developed as a potential treatment for these conditions and is administered via intravenous or subcutaneous injection. The study involves several parts where participants receive either single or multiple doses of BBT002 or placebo. Healthy volunteers receive both single and multiple doses, while patients with COPD or CRSwNP receive multiple doses. The study is designed with a sequential model and includes multiple treatment arms comparing BBT002 to placebo across these groups. Participants will undergo safety and lab assessments including monitoring for adverse events, vital signs, physical examinations, ECG readings, and laboratory tests for up to 141 to 169 days after the first dose depending on the study part. Pharmacokinetic parameters and immunogenicity through anti-drug antibody development will be evaluated at specified timepoints. The total duration includes follow-up periods to monitor safety and treatment effects.

Researchers are evaluating the safety, tolerability, recommended Phase 2 dose, and preliminary effectiveness of BGB-11417 alone and combined with azacitidine in adults with acute myeloid leukemia AML, myelodysplastic syndrome MDS, or MDSmyeloproliferative neoplasm MPN. The study includes participants with these myeloid cancers to better understand treatment responses and potential drug interactions. Participants receive BGB-11417 orally on a 28-day cycle, with dosing schedules varying between 10, 14, 21, or 28 days, depending on the cohort. Azacitidine is given intravenously or subcutaneously for 7 days in combination with BGB-11417 for certain groups. A subset of participants with AML and MDS also receive a modified second cycle to explore interactions with posaconazole, which is given orally for 8 days during this cycle. Some participants with MDS and relapsedrefractory AML in China receive BGB-11417 monotherapy. Throughout the study, participants are monitored for dose-limiting toxicities, adverse events, and response rates including remission and hematologic improvements over approximately 24 months. Blood samples are collected to measure drug levels and interactions during specific cycles. Participants health and responses are assessed regularly to evaluate safety and preliminary efficacy, with follow-up continuing until study completion or withdrawal.

Heart attacks occur when a blood clot blocks the hearts blood vessels, stopping blood flow to the heart muscle. This trial focuses on patients with ST-elevation myocardial infarction STEMI and looks at how microcirculatory damage can be measured using the Index of Microcirculatory Resistance IMR. The study aims to find out if treating patients with impaired microcirculatory perfusion using low-dose intracoronary thrombolytic therapy can reduce heart muscle damage and improve clinical outcomes. Participants who have had a heart attack and undergone angioplasty will have their IMR measured. Those with an IMR above 32 will be randomly assigned to receive either low-dose tenecteplase a clot-dissolving drug or a placebo sterile water administered directly into the coronary artery. Patients with lower IMR will be followed in a registry. The treatment is given as an intracoronary infusion over 3 minutes. Cardiac enzymes, MRI scans, and other heart function tests will be done at various time points. During the study, participants will have heart enzyme tests at hospital admission and discharge. Those in the randomised group will receive cardiac MRI scans at discharge and six months later. Follow-up visits will occur at 30 days, then 6, 12, and 24 months after discharge to monitor heart function, rehospitalisation, and mortality. The main outcomes measured include cardiovascular death, heart failure rehospitalisation, heart attack size, and bleeding events, with safety and efficacy monitored closely throughout the study period.