Liverpool

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 whether an investigational drug called OHB-607 can prevent Bronchopulmonary Dysplasia (BPD), a common chronic lung disease, in extremely premature infants. The study compares infants receiving OHB-607 alongside standard neonatal care to those receiving standard care alone to reduce the burden of this lung condition. This is a Phase 2b, multicenter, randomized, open-label study focused on safety and clinical efficacy. Participants will receive an intravenous infusion of OHB-607 from birth until reaching a postmenstrual age (PMA) of 29 weeks and 6 days. The study includes two arms: one group receives the investigational drug plus standard care, while the other group receives only standard neonatal care. The treatment period ends at 29 weeks plus 6 days PMA, after which infants are monitored. Throughout the study, researchers will track the incidence of severe BPD or death up to 36 weeks PMA, whichever occurs first. Assessments will include clinical evaluations and monitoring for safety and any side effects. The study also involves long-term follow-up to observe the infants' health outcomes beyond the treatment period. Participation involves consent from parents and collection of birth and medical history information.

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 evaluating the safety, effectiveness, best dose, and how the body processes (pharmacokinetics) an investigational drug called BNT326. This study includes people with advanced solid tumors that are metastatic, recurrent, or have progressed after previous treatments. The investigation is divided into two parts: Part 1 tests BNT326 alone, and Part 2 studies BNT326 alone or combined with other immunotherapy drugs, including pumitamig (BNT327). Participants have specific tumor types like melanoma, non-small cell lung cancer, breast cancer, gastric cancer, colorectal cancer, and cervical cancer, among others. In Part 1, participants receive BNT326 by intravenous infusion in various groups based on cancer type and prior treatments. Part 2 involves BNT326 given alone or with pumitamig, also by intravenous infusion, in several defined cancer groups. Some groups are randomized to receive different dose levels or combinations to find the optimal treatment plan. The study includes a screening phase, treatment phase lasting up to 24 months or until progression or unacceptable side effects, a safety follow-up, efficacy follow-up, and long-term survival monitoring, totaling about 38 months for Part 1 and 48 months for Part 2. During the study, participants undergo regular assessments including measuring tumor response using RECIST criteria, monitoring for side effects and serious adverse events up to months after treatment ends, and measuring drug levels in the blood. Researchers track treatment interruptions or discontinuations due to side effects and evaluate dose-limiting toxicities. Tumor tissue samples are required before enrollment. Safety and effectiveness data are collected throughout treatment and follow-up periods to understand how well BNT326 works alone or combined and its safety profile.

Researchers are evaluating the safety, tolerability, and therapeutic effects of a combination treatment using BNT113 and pembrolizumab compared to pembrolizumab alone for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is positive for human papillomavirus 16 (HPV16+) and expresses the PD-L1 protein with a combined positive score of 1 or higher. This Phase II/III trial includes patients whose cancer cannot be treated with local therapies and who have not received prior systemic anticancer therapy for their current disease condition. The trial consists of two parts. Part A is a non-randomized Safety Run-In Phase to confirm the safety and tolerability of BNT113 combined with pembrolizumab at the selected dose. Part B is a randomized phase that compares BNT113 plus pembrolizumab against pembrolizumab alone as first-line treatment. Patients in Part A continue their treatment without randomization. Treatments are given by intravenous injection or infusion, and patients may receive either combination therapy or monotherapy for up to 24 months. There is also an optional pre-screening phase to test tumor samples for HPV16 DNA and PD-L1 expression before entering the main trial. Participants undergo regular assessments including tumor measurements based on RECIST 1.1 criteria confirmed by independent review. Researchers monitor treatment-emergent adverse events for up to 27 months in Part A and evaluate overall survival and progression-free survival for up to 48 months in Part B. Tumor tissue samples are collected before treatment to confirm eligibility. The study involves ongoing safety monitoring and efficacy evaluations throughout the treatment and follow-up periods.

Primary immune thrombocytopenia (ITP) is a condition in which the immune system mistakenly destroys platelets, the cells that help stop bleeding. This leads to a low platelet count, making it easier to bruise or bleed. The trial investigates the long-term safety, tolerability, and effectiveness of mezagitamab in adults with chronic primary ITP who have previously participated in certain mezagitamab studies. It also examines how the body processes mezagitamab over time. Participants who completed the previous mezagitamab studies TAK-079-3002 or TAK-079-1004 and meet specific criteria will receive mezagitamab as a subcutaneous injection during this continuation study. The study is open-label and multicenter, focusing on continued treatment based on protocol requirements. The medication is given under medical supervision, and participants return to the study clinic several times throughout the study. During their participation, individuals will undergo regular assessments including monitoring for treatment-emergent adverse events and serious adverse events up to approximately 108 weeks. Researchers will track safety by noting any adverse events that lead to permanent withdrawal from mezagitamab. The study includes physical evaluations, laboratory tests, and ongoing safety monitoring to understand how well participants tolerate the treatment and how effective it is over the long term.

Researchers are evaluating whether the drugs retatrutide and tirzepatide can prevent major adverse liver outcomes (MALO) in adults with metabolic dysfunction-associated steatotic liver disease (MASLD) who are at high risk. This Phase 3 trial enrolls about 4,500 adults with MASLD identified by non-invasive tests indicating an increased likelihood of developing serious liver problems. The study aims to understand how these treatments might affect liver health over time compared to a placebo. Participants will be randomly assigned to receive either retatrutide, tirzepatide, or a placebo, all given by subcutaneous injection. The study will last approximately 224 weeks, during which participants may attend 25 to 30 clinic visits for monitoring and assessment. After the main study, eligible participants can join an optional 2-year extension where all will receive either retatrutide or tirzepatide regardless of their original group. Throughout the trial, participants’ liver function and disease progression will be closely monitored through various health assessments. Researchers will track the time to the first major adverse liver event as the main outcome. Safety and health status will be evaluated regularly during clinic visits, ensuring thorough observation over the long study period.

Neuroblastoma is a common and serious childhood cancer that often leads to death, especially in high-risk cases where the cancer is harder to treat. This trial focuses on children aged one year and older with relapsed neuroblastoma, which means the cancer has come back or is resistant after initial treatment. The study aims to find better treatment combinations to improve survival, evaluate their safety and effectiveness, and learn more about the biology of relapsed neuroblastoma through biomarker research. This is a phase I/II international trial designed to potentially impact clinical practice and advance targeted therapies. Participants will be randomly assigned to one of two main treatment groups receiving combinations of drugs including dinutuximab beta, irinotecan, temozolomide, and bevacizumab, administered every three weeks for up to 12 cycles. A third treatment group with a more experimental combination is also available for a smaller number of patients to confirm dosing and safety before possibly expanding. The trial includes detailed drug regimens and allows for adjustments based on safety and effectiveness findings. During the study, participants will undergo various assessments such as imaging scans, blood tests, and bone marrow evaluations to monitor disease status and treatment effects. Researchers will track progression-free survival and observe any dose-limiting toxicities over up to five years after randomization. Biological samples will be collected to support research on neuroblastoma. Patient quality of life and safety will be closely monitored throughout the treatment and follow-up periods, which together may last up to eight years from enrollment.

Researchers are evaluating the effects of pelacarsen (TQJ230), given as a monthly injection under the skin, in people with mild to moderate calcific aortic valve stenosis. This study aims to see if pelacarsen can safely slow the progression of this heart valve condition compared to a placebo. The trial is a phase 2, randomized, double-blind, placebo-controlled study conducted at multiple centers. Participants will receive either pelacarsen 80 mg or a matching placebo once a month. Before starting the treatment, they must have elevated lipoprotein(a) levels and be optimally treated for existing cardiovascular risk factors. The study focuses on those aged 50 to under 80 years with mild or moderate calcific aortic valve stenosis. During the 36 months of participation, researchers will monitor changes in peak aortic jet velocity and aortic valve calcium score to assess disease progression. Safety, tolerability, and the impact of the treatment will be evaluated. Participants will undergo regular assessments, including laboratory tests and clinical evaluations, to track heart valve condition and overall health throughout the study.

Researchers are studying bleximenib, an investigational drug taken orally, to find the best dose for treating acute leukemia and to evaluate its safety and effectiveness. In Phase 1, they aim to identify the recommended Phase 2 dose (RP2D) through a dose escalation and expansion process. Phase 2 will focus on assessing how well bleximenib works at the recommended dose in participants with relapsed or refractory acute leukemia, particularly those with specific genetic alterations in KMT2A, NPM1, or NUP98/NUP214. The study involves administering bleximenib orally and includes different participant groups based on age and disease status. Phase 1 includes pediatric participants aged 2 to less than 18 years and adults 18 years and older with relapsed or refractory acute leukemia who have limited treatment options. Phase 2 focuses on adults over 18 with relapsed or refractory acute myeloid leukemia harboring KMT2A or NPM1 mutations. The trial monitors participants for dose-limiting toxicities, adverse events, and treatment tolerability over periods lasting up to nearly five years. Participants will undergo evaluations of safety, including the number and severity of adverse events and dose-limiting toxicities during the first cycle. The effectiveness measure in Phase 2 is the rate of complete remission or remission with partial blood count recovery. Throughout the study, participants will be assessed using laboratory tests, performance status scales, and pregnancy tests as applicable. Safety monitoring and long-term follow-up will continue for up to 4 years and 9 months to fully evaluate treatment effects and tolerability.