Leeds

Researchers are evaluating two different pacing methods for patients with slow heart rates, called bradycardia. This study compares the common right ventricular pacing approach with a newer physiological pacing method that includes His bundle and left bundle area pacing. The trial aims to better understand how these pacing techniques affect patient outcomes, including mortality and heart failure morbidity, in a large group of 2600 patients. Participants will receive a pacemaker implant and be randomly assigned to either right ventricular pacing or physiological pacing. The physiological pacing may involve His bundle pacing or left bundle pacing, but if these are not successful, biventricular pacing will be used. A subgroup of 500 participants will take part in an optional echocardiographic sub-study to assess heart function changes over a 24-month period. Throughout the study, patients will be assessed at baseline and every six months after randomization, with follow-up lasting up to 78 months. Researchers will monitor outcomes such as mortality, heart failure events, device-related safety issues, patient quality of life, symptoms, and pacemaker-derived data like arrhythmias and activity levels. The echocardiographic sub-study will measure specific heart function changes to understand pacing-induced cardiomyopathy. Participants involvement includes implantation, regular follow-up visits, questionnaires, and optional imaging assessments.

Researchers are investigating CGT9486, also known as bezuclastinib, in an open-label Phase 2 study for patients with Advanced Systemic Mastocytosis AdvSM. This includes those diagnosed with Aggressive Systemic Mastocytosis ASM, Systemic Mastocytosis with an Associated Hematologic Neoplasm SM-AHN, and Mast Cell Leukemia MCL. The study aims to evaluate the safety, effectiveness, pharmacokinetics, and pharmacodynamics of bezuclastinib in this patient population. Participants will receive bezuclastinib tablets orally, taken continuously in 28-day cycles. The study is divided into two parts Part I focuses on identifying effective and tolerable dosing exposures over 18 months, while Part II evaluates the drugs efficacy by measuring objective response rates and confirming the exposure-response relationship, also over 18 months. Additional assessments include effects on mutation allele burden, serum tryptase levels, histopathologic changes, spleen and liver volume, and safety monitoring. During the study, participants will undergo various clinical evaluations, including laboratory tests, imaging to monitor organ size changes, and assessments of disease response and progression. Researchers will track adverse events and pharmacokinetic profiles throughout the 18 months. The study involves continuous monitoring of participants to understand the treatments impact on survival and disease progression over this period.

Researchers are evaluating the safety, efficacy, and optimal dosing of a combination of two investigational treatments, BNT323 trastuzumab pamirtecan and BNT327 pumitamig, in people with advanced breast cancer. This includes those with hormone receptor-positive or -negative, HER2-positive, HER2-low, HER2-ultralow, HER2-null breast cancer, or triple-negative breast cancer. The study is a Phase III multi-site, open-label trial with a focus on advanced breast cancer treatment options. The study has two parts. Part 1 involves dose escalation of BNT323 combined with BNT327 to determine the recommended Phase 2 dose using six different dose levels. Part 2, which begins after Part 1 completion, includes dose optimization and exploratory cohorts. Cohort 1 in Part 2 uses randomization into four treatment arms, including combination therapy at different doses and monotherapies of either BNT323 or BNT327. Other cohorts receive the recommended dose without randomization. Participants will undergo assessments including tumor scans and cardiac function tests, with monitoring for side effects and tumor response up to 36 months. Researchers will track dose-limiting toxicities and treatment-emergent adverse events during early treatment cycles and monitor objective response rates and disease control over time. Safety and efficacy data will be collected through scheduled visits and tumor assessments during and after treatment to evaluate the study drugs effects and tolerability.

Researchers are evaluating the combination of BNT324, a B7-H3 antibody-drug conjugate, with BNT327, a bispecific antibody targeting PD-L1 and VEGF, in participants with advanced, metastatic, or relapsed small cell lung cancer SCLC and non-small cell lung cancer NSCLC. This multi-part study aims to find safe doses, optimize treatment, assess preliminary effects, and confirm clinical efficacy in different lung cancer groups. The study includes participants with confirmed lung cancer who have measurable disease and meet specific health criteria. Participants will receive intravenous infusions of BNT324 combined with BNT327 in a dose escalation design to establish two recommended dose levels RP2D and RP2D-1. The study has two parts Part 1 focuses on dose finding in NSCLC and SCLC Part 2 compares these doses in treatment-naive and relapsed lung cancer cohorts, with some randomized groups. Additional participants may join at the optimal dose to further evaluate safety and effectiveness. Participants will undergo screening, followed by treatment, safety follow-up, and long-term survival monitoring. Researchers will assess dose-limiting toxicities, adverse events, treatment interruptions, and response rates using standardized criteria. Outcomes include objective response rate, disease control, progression-free survival, duration of response, and overall survival, with evaluations continuing up to 87 months. Safety is closely monitored during and after treatment, and participants health status is regularly assessed.

Researchers are evaluating the safety, tolerability, and therapeutic effects of BNT113 combined with pembrolizumab compared to pembrolizumab alone as a first-line treatment for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma HNSCC positive for human papilloma virus 16 HPV16 and expressing the protein PD-L1 with a combined positive score of 1 or higher. This is an open-label, multi-site, Phase IIIII clinical trial consisting of two parts an initial safety run-in phase and a randomized phase. In the safety run-in phase Part A, patients receive BNT113 in combination with pembrolizumab to confirm safety and tolerability at selected dose levels. The randomized phase Part B compares BNT113 combined with pembrolizumab against pembrolizumab monotherapy. Treatments are given by intravenous injection or infusion and continue for up to 24 months. An optional pre-screening phase allows tumor samples to be tested for HPV16 DNA and PD-L1 expression before the main trial screening. Participants will be closely monitored throughout the study. Assessments include safety evaluations, tumor response, and survival outcomes such as overall survival and progression-free survival. Tumor tissue samples must be provided for testing. Researchers will measure treatment-emergent adverse events, response rates, duration of response, and disease control. The study may last up to 48 months, with ongoing safety and efficacy monitoring during and after treatment.

Researchers are evaluating the safety and optimal dose of BNT329, an investigational drug, in people with advanced solid tumors that express the tumor marker CA19-9. The study also aims to assess how well BNT329 works by measuring participant responses and how long the tumor remains stable without growth or spread. Additionally, the study will examine how BNT329 moves through and affects the body. The trial includes up to four parts. Parts A and B focus on increasing doses to study safety and tolerability in participants with various advanced cancers expressing CA19-9 who have not responded well to previous treatments. Part C may be added if safety or effectiveness concerns arise, involving pre-dosing with a CA19-9 targeting antibody before BNT329. Part D tests two selected dose levels in participants with pancreatic ductal adenocarcinoma PDAC who have received prior treatment. Treatment is given as intravenous infusions every 2 or 3 weeks depending on the study part. Participants undergo screening, followed by treatment for up to two years, an end-of-treatment visit, two safety follow-ups, and a survival follow-up until death, withdrawal, or study end. Throughout the study, researchers monitor side effects, dose adjustments, tumor response, and survival. Blood samples will be collected to study drug levels and immune responses. Safety and effectiveness will be assessed up to 36 months from first dose.

Researchers are evaluating BGB-16673, an oral drug, in adults with various types of B-cell malignancies such as marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, Waldenstrm macroglobulinemia, diffuse large B-cell lymphoma, and Richters transformation. This study includes Phase 1 dose finding and safety expansion, followed by Phase 2 expansion cohorts to determine recommended doses and further assess safety and efficacy. The study is divided into several parts, starting with Phase 1 dose escalation to find safe dosage levels, including monotherapy dose escalation and safety expansion in selected doses. Phase 2 involves expansion cohorts where participants receive the recommended doses identified in Phase 1 for further safety and efficacy evaluation. Some cohorts include participants who have not received prior BTK inhibitors, and Japanese participants are also enrolled to assess safety. Treatments are orally administered. Participants will undergo regular assessments including monitoring for adverse events, disease response, and drug concentration levels in the blood at various time points. Researchers will measure outcomes such as overall response rate and progression-free survival over approximately three years. Safety and tolerability will be closely tracked, and quality of life questionnaires will be completed at scheduled intervals. Participation may last several years, including follow-up periods to monitor long-term effects.

Researchers are evaluating AZD8421 alone and in combination with targeted anti-cancer drugs in patients with ER HER2- advanced breast cancer and metastatic high-grade serous ovarian cancer. This first-in-human study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AZD8421, both as a single treatment and combined with other therapies, in participants previously treated for these cancers. The study includes two main treatment modules AZD8421 monotherapy to determine a recommended dose in patients with specific advanced breast and ovarian cancers, and AZD8421 combined with camizestrant and CDK46 inhibitors in advanced breast cancer patients. Participants receive these treatments in cycles, with safety and response monitored closely. The study uses a sequential model to evaluate these approaches. Participants will undergo various assessments including clinical lab tests, vital signs, ECGs, and tumor measurements to monitor treatment effects and safety throughout the study, which includes an approximately 18-month safety follow-up. Researchers will track dose-limiting toxicities, adverse events, response rates, tumor changes, and pharmacokinetic profiles during treatment and follow-up periods.

Researchers are studying an experimental drug called ALN-CFB for adults with Paroxysmal Nocturnal Hemoglobinuria PNH who continue to have anemia despite treatment with a complement component C5 inhibitor. This study aims to evaluate the safety, tolerability, and initial effectiveness of ALN-CFB compared to a placebo. The study also examines how ALN-CFB affects levels of Complement Factor B protein in the blood and how the drug is processed in the body. Participants will receive either ALN-CFB or a placebo in a randomized, double-blind manner. The study includes a single-ascending dose escalation design to find the appropriate dosing. The protocol will be updated after initial data analysis to describe further parts of the study. Treatment duration and dosing schedules are defined by the study protocol. During the study, participants will undergo regular evaluations including blood tests to measure drug levels and Complement Factor B concentrations, and will be monitored for side effects for up to 365 days. Researchers will assess the occurrence and severity of treatment-emergent adverse events. The study spans several years, with the primary completion expected in late 2029 and final completion by mid-2031.

Primary immune thrombocytopenia ITP is a condition where the immune system mistakenly destroys platelets, leading to a lower number of platelets and increased risk of bruising or bleeding. This Phase 3 study evaluates the long-term safety, tolerability, and effectiveness of mezagitamab in adults with chronic primary ITP. The study also investigates how the body processes mezagitamab over an extended period. Participants who completed previous mezagitamab studies TAK-079-3002 or TAK-079-1004 will be invited to join this continuation trial. Eligible participants may receive mezagitamab injections on demand, with treatment courses repeated as needed based on specific criteria and the investigators clinical judgment. The treatment is administered subcutaneously. During the study, participants will visit the clinic several times for assessments. Researchers will monitor safety by tracking treatment-emergent adverse events, and evaluate effectiveness through platelet response and remission rates. Measurements of drug levels and antibodies will also be taken. The study may last up to approximately 108 weeks, allowing detailed long-term follow-up.