Brighton And Hove

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 exploring new treatments for women with relapsed high-grade serous ovarian cancer, which is a fast-growing cancer starting in ovarian cells, the lining of the belly, or fallopian tubes. The study evaluates raludotatug deruxtecan R-DXd, a type of antibody drug conjugate, combined with other therapies, to understand safety, tolerability, and cancer response. This includes women with platinum-sensitive and platinum-resistant recurrent ovarian cancer who have had prior treatments. The study has two parts Part 1 involves gradually increasing doses of R-DXd combined with chemotherapy drugs like carboplatin, paclitaxel, bevacizumab, or pembrolizumab to find a recommended dose. Part 2 uses this recommended dose to further assess treatment effects. Participants receive intravenous infusions every three weeks, with chemotherapy cycles lasting up to about four months and pembrolizumab up to two years. The combinations vary depending on cancer sensitivity and treatment history. Participants undergo regular treatment visits where cancer response and side effects are monitored. Tumor tissue samples are collected before treatment. Researchers track adverse events, dose-limiting toxicities, and how long the cancer responds to treatment. The study lasts up to approximately three years, allowing for long-term safety and effectiveness assessments, with ongoing evaluation of participants health throughout the trial.

Researchers are evaluating the effectiveness and safety of an investigational drug called BNT323 also known as DB-1303 compared with standard chemotherapy in women with recurrent endometrial cancer. The study includes two groups based on the level of HER2 protein in the tumor Cohort 1 with HER2 levels 1 or 2 who have been previously treated with immune checkpoint inhibitors, and Cohort 2 with HER2 level 3. The study aims to understand how well BNT323 or chemotherapy controls cancer progression and how the drug affects patients immune response and quality of life. Participants in Cohort 1 will be randomly assigned to receive either BNT323 or chemotherapy drugs such as doxorubicin, paclitaxel, or docetaxel. In Cohort 2, participants will receive BNT323 alone. Treatments are given intravenously and continue until the cancer progresses, unacceptable side effects occur, or consent is withdrawn. The study includes screening, treatment, safety follow-up, efficacy follow-up, and a long-term survival follow-up lasting up to about 53 months. During the study, participants will undergo regular assessments including tumor evaluations, safety monitoring, and quality of life questionnaires. Researchers will measure progression-free survival in Cohort 1 and tumor response rate in Cohort 2. Safety is monitored by tracking adverse effects and drug levels in the body. Participants can expect to be followed for up to 53 months after treatment to assess long-term outcomes and survival.

Researchers are evaluating the efficacy and safety of combining durvalumab and domvanalimab compared to durvalumab plus placebo in adults with locally advanced Stage III, unresectable non-small cell lung cancer NSCLC whose disease has not progressed after definitive platinum-based concurrent chemoradiotherapy cCRT. This Phase III, randomized, double-blind, placebo-controlled, international study aims to provide new insights into treatment options for this patient population. Participants will receive either durvalumab and domvanalimab or durvalumab plus placebo as intravenous infusions every four weeks, beginning on Day 1 and continuing for up to 12 months. The study includes two groups one receiving the combination of durvalumab and domvanalimab, and the other receiving durvalumab with a placebo. Both treatments are given through infusion to assess their effects on disease progression and safety. During the trial, participants will undergo regular assessments including monitoring progression-free survival for up to 8 years after randomization. Other measures include overall survival, response rates, duration of response, and various time-to-event outcomes related to disease progression and symptom deterioration. Researchers will also evaluate drug concentrations and immune responses approximately 12 weeks after the last dose. Participants can expect scheduled visits for infusions and evaluations as part of this long-term study.

Researchers are evaluating the safety and effectiveness of oral brepocitinib in adults with lichen planopilaris, a condition affecting the scalp. This Phase 23 trial aims to understand how well this medication works compared to a placebo in treating active and symptomatic lichen planopilaris. The study is sponsored by Priovant Therapeutics, Inc. and uses a randomized, double-blind design to ensure reliable results. Participants are randomly assigned to receive either oral brepocitinib or a placebo. The study is conducted in parallel groups, with neither the participants nor the researchers knowing who receives the active drug or placebo. The treatment period lasts 24 weeks, during which the participants take the assigned oral medication. The main goal is to measure improvement in the Investigator Global Assessment IGA score by Week 24. Throughout the study, participants will be regularly monitored for safety and symptom changes. Researchers will assess the proportion of participants who achieve significant improvement in their IGA scores at Week 24 and track changes in symptom severity using a numerical rating scale. The total study duration extends until July 2029, allowing for thorough evaluation of treatment effects and safety over time.

Researchers are evaluating whether less frequent dosing of pembrolizumab after six months of standard treatment is safe and effective for patients with advanced non-small cell lung cancer NSCLC. Pembrolizumab, an immunotherapy targeting the PD-1 receptor, has improved outcomes in NSCLC, but current dosing every six weeks for up to two years may result in overtreatment. This UK phase III trial aims to find if reducing dose frequency can maintain effectiveness while improving quality of life and lowering costs. Participants who have received six months of pembrolizumab, with or without chemotherapy, and plan to continue treatment will be randomized to receive pembrolizumab intravenously every six weeks control or every twelve weeks initially. If the 12-week dosing is found to be not less effective, additional groups receiving doses every nine, fifteen, and eighteen weeks will be included. Patients who experience disease progression while on reduced frequency dosing can return to the standard six-week schedule. Throughout the study, participants will be monitored for overall survival at 18 months from randomization, along with other outcomes such as progression-free survival, response rate, duration of response, and adverse events over two years. The study involves regular hospital visits for treatment and assessments, and the results may lead to safer, more convenient treatment options for NSCLC patients. The total participation time varies depending on individual treatment and follow-up schedules.

Researchers are evaluating the use of dual long-acting broadly neutralising antibodies bNAbs, 3BNC117-LS and 10-1074-LS, in adults living with HIV who started antiretroviral therapy ART early during primary HIV infection. This phase II randomized, placebo-controlled, double-blinded trial aims to determine whether these antibodies can control HIV replication when ART is paused. The study includes adults aged 18 to 60 years who have been on suppressive ART for at least 12 months. Participants will be randomly assigned to one of two groups one receiving ART plus infusions of the dual long-acting bNAbs followed by a monitored interruption of ART, and the other receiving ART plus placebo infusions followed by ART interruption. Those in the placebo group will later receive the bNAbs and undergo a second interruption of ART. The study will monitor the time to viral rebound after stopping ART, with treatment resumption and further monitoring as needed. During the study, participants will attend regular visits for blood sampling, assessments, and close monitoring of viral load to detect HIV rebound. Researchers will evaluate how long it takes for the virus to return after stopping ART, up to 20 weeks. Participants must comply with study procedures, including follow-up visits and blood tests, and will be monitored for safety throughout the study, which continues until viral rebound or study completion.

Researchers are evaluating the combination of bleximenib, venetoclax VEN, and azacitidine AZA compared to placebo with VEN and AZA in treating adults with newly diagnosed Acute Myeloid Leukemia AML who have mutations in the NPM1 or KMT2A genes. This Phase 3 study focuses on participants who are not eligible for intensive chemotherapy due to age or other health conditions. The goal is to understand how these treatments work in this specific AML population. Participants receive treatment in 28-day cycles, either with bleximenib plus VEN and AZA or placebo plus VEN and AZA. Bleximenib, VEN, and placebo are taken orally, while AZA is given intravenously or under the skin. Treatment continues until disease progression or unacceptable side effects occur. During the study, participants will be monitored for response to treatment including complete remission and overall survival for up to over four years. Researchers will track event-free survival, duration and timing of remission, transfusion independence, and other health outcomes. Safety is also closely observed through adverse events and lab tests. Participation involves regular visits for treatment and assessments over the study period.

Researchers are evaluating camizestrant against standard endocrine therapy for patients with ER-positive, HER2-negative early breast cancer who have an intermediate or high risk of disease recurrence. These patients must have completed locoregional therapy and at least 2 to 5 years of standard adjuvant endocrine therapy. The study is a Phase III open-label trial focused on improving outcomes for these patients over a long-term period. Participants are randomly assigned to receive either camizestrant orally or continue with the standard endocrine therapy chosen by their investigator, which may include aromatase inhibitors exemestane, letrozole, anastrozole or tamoxifen. Treatment in each group lasts for 60 months. The study allows prior use of CDK46 inhibitors and includes a follow-up period extending up to 10 years from the last patient randomization. During the study, participants will undergo regular assessments to monitor invasive breast cancer-free survival and other outcomes such as invasive disease-free survival, distant relapse-free survival, overall survival, and safety. Researchers will also evaluate symptoms like joint pain, hot flushes, and vaginal dryness using specific scales, along with quality of life measures and pharmacokinetics. Safety monitoring continues up to 28 days after the last dose, and participants remain under observation for up to 10 years total.

Researchers are evaluating elacestrant compared to standard endocrine therapies in adults with node-positive, Estrogen Receptor-positive ER, HER2-negative early breast cancer who are at high risk of cancer returning. The study focuses on those who have had prior endocrine therapy and aims to measure how well elacestrant may prevent invasive breast cancer recurrence over five years. Participants are randomly assigned to receive either 345 mg of elacestrant daily for five years or continue their prior standard endocrine therapy, which may include an aromatase inhibitor anastrozole, letrozole, or exemestane or tamoxifen. The trial is open-label, meaning both participants and researchers know which treatment is given. During the study, participants will have regular assessments to monitor cancer recurrence, survival, side effects, and quality of life. Evaluations include questionnaires on health status and physical functioning at baseline, six months, and annually for up to five years. Safety is tracked through adverse event reporting up to five years plus 28 days. The total participation duration can last up to five years with ongoing monitoring and data collection.