Harlow

Researchers are investigating new treatments for rheumatoid arthritis (RA), a condition where current therapies like methotrexate (MTX) may not fully control symptoms for many people. This Phase 2b study evaluates a medicine called tulisokibart to see if it can better reduce RA symptoms in individuals already taking MTX. The trial aims to determine if one or more doses of tulisokibart work better than a placebo, which looks like the medicine but contains no active drug. The study includes a 12-week period where participants receive either tulisokibart or a placebo by subcutaneous injection while continuing their MTX treatment, which can be given by injection or orally. Following this, there is a long-term extension lasting 116 weeks, composed of a 44-week main extension and a 72-week optional extension, to further assess the medication's effects and safety over time. Participants will undergo assessments to measure treatment response, including the American College of Rheumatology 20% response criteria at week 12 to gauge symptom improvement. Throughout the study, researchers will monitor for safety and effectiveness, with evaluations extending through the long-term extension periods, totaling over two years of participation.

Researchers are evaluating new treatments for men with prostate cancer that has spread to other parts of the body and still responds to hormone therapy. This Phase 3 trial compares two additional therapies with the best standard care to see if they slow cancer spread and improve survival. Participants from diverse backgrounds across multiple UK hospitals are involved, and the study is managed by University College London. The trial has two main comparisons. In Comparison S, participants receive either standard care alone or with added targeted high-dose radiotherapy (Stereotactic Ablative Body Radiotherapy or SABR) aimed at metastatic lesions. In Comparison P, participants receive standard care alone or with a radioactive drug (177Lu-PSMA-617) that targets prostate cancer cells. Standard care includes long-term hormone-reducing therapy and may include other approved medications or treatments. Treatments are given according to specific schedules: SABR is delivered in 3-5 sessions over 1-2 weeks, while 177Lu-PSMA-617 is given in up to three 6-week cycles. Participants are randomly assigned to either standard care or the new treatment with equal chance. During the study, participants undergo regular scans and tests to monitor cancer and side effects. Doctors track treatment safety and may stop treatment if side effects become serious or participants choose to stop. The main outcome measured is overall survival, with final results expected around 5 to 7 years after the first patient starts treatment. Participants' health status and response to treatment are closely observed throughout the study period.

Researchers are evaluating the effectiveness and safety of combining inavolisib with a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) and letrozole compared to placebo plus CDK4/6i and letrozole. This study focuses on participants with endocrine-sensitive PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. It aims to assess treatment outcomes in the first-line setting for this specific breast cancer type. Participants will be assigned to receive either oral inavolisib once daily or a matching oral placebo once daily. All participants will also receive a CDK4/6 inhibitor on either Days 1-21 or Days 1-28 of each 28-day cycle, along with daily oral letrozole. This randomized, double-blind study will compare these two treatment combinations to monitor differences in disease progression and safety. Throughout the study, researchers will evaluate progression-free survival from the time of randomization until disease progression or death, up to 7 years. Participants will undergo assessments including tumor measurements by RECIST criteria, performance status evaluations, and monitoring of blood and organ function before treatment begins. Safety and efficacy will be closely observed during treatment, aiming to provide detailed long-term data on the study therapies.

Psoriatic arthritis (PsA) is a chronic inflammatory condition that affects the joints and skin in people with psoriasis. This study aims to evaluate how well zasocitinib (TAK-279) works in adults with active PsA, considering their prior treatment experiences with specific medications. The study is a Phase 3 trial that compares zasocitinib to a placebo in participants who have or have not been treated with biologic medicines. Participants will receive either zasocitinib tablets or a matching placebo. The study is randomized, double-blind, and placebo-controlled. Treatment will continue with monitoring over a period of up to 60 weeks to assess the effects and safety of zasocitinib. During the study, participants will undergo assessments of joint and skin symptoms, including tender and swollen joint counts and evaluations of psoriatic skin lesions. Researchers will measure how many participants achieve a significant improvement in their arthritis symptoms by Week 16. Safety and response will be monitored throughout the study period, with detailed follow-up visits and evaluations to understand the treatment's impact over time.

Researchers are investigating the combination of lasofoxifene and abemaciclib compared to fulvestrant and abemaciclib to treat women and men with locally advanced or metastatic estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-) breast cancer that has an ESR1 mutation. This phase 3 study includes patients who have previously received treatment with ribociclib or palbociclib and aims to evaluate the effectiveness, safety, and tolerability of these treatment combinations. Participants will be randomly assigned to receive either oral lasofoxifene at 5 mg daily combined with oral abemaciclib 150 mg twice a day, or intramuscular fulvestrant 500 mg on specific days followed by monthly doses plus oral abemaciclib 150 mg twice daily. The treatment schedules are designed to compare how well these combinations work in managing the cancer. During the study, participants will be closely monitored for progression-free survival over approximately three years. Researchers will assess the cancer's response to treatment, track any side effects, and evaluate safety and tolerability. Regular evaluations and follow-ups will ensure comprehensive data collection to understand the impact of these therapies on advanced breast cancer.

Researchers are evaluating the effects of two different default dialysate sodium concentrations, 137 mmol/l and 140 mmol/l, on major cardiovascular events and death in adults receiving maintenance haemodialysis. This pragmatic, cluster-randomised, open-label study takes place in real-world dialysis sites and aims to compare the outcomes associated with these sodium levels over an extended period. The study focuses on patients with end-stage kidney disease undergoing regular haemodialysis treatment. Dialysis sites are randomly assigned to use either a default dialysate sodium concentration of 137 mmol/l or 140 mmol/l for at least 90% of dialysis sessions at that site. All other care practices continue as usual based on local standards. The study plans to recruit sites over 5 to 7 years, with individual follow-up lasting roughly 2 to 5 years. Site participation requires consent, while individual patient consent may be waived or offered an opt-out option. Participants will be monitored for major cardiovascular events and death, with the primary outcome measuring the time until the first such event occurs. Data collection methods are implemented across participating dialysis units, focusing only on in-center or satellite dialysis patients where applicable. The study's duration depends on the occurrence of endpoints, with an average follow-up of about 5 years anticipated per participant.

Researchers are evaluating the safety and effectiveness of a drug called PF-07220060 combined with letrozole compared to other approved treatments (palbociclib, ribociclib, or abemaciclib with letrozole) in adults with breast cancer that is hormone receptor-positive and HER2-negative. This cancer has spread locally or to other parts of the body and has not been treated with systemic anti-cancer therapy for advanced or metastatic disease. The study is a Phase 3, open-label, randomized trial involving multiple centers. Participants will be randomly assigned to receive either PF-07220060 plus letrozole or the investigator's choice of one of the approved CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib) combined with letrozole. The treatments are given as drugs with letrozole serving as endocrine therapy. The study compares these treatments in terms of how well they control the cancer and their safety profiles. Participants will visit the study clinic regularly for monitoring during treatment. Researchers will assess how long participants live without their disease worsening or dying from any cause, which is the main outcome measured up to about four years. The study team will monitor each participant's health and response to treatment through these visits to gather information about treatment effects and safety.

Researchers are evaluating the effectiveness and safety of inavolisib combined with fulvestrant in adults with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer. This study focuses on patients who have previously been treated with cyclin-dependent kinase inhibitors and whose disease has progressed. The study is a Phase II, randomized, open-label trial designed to compare two dose levels of inavolisib when combined with fulvestrant. Participants will receive inavolisib and fulvestrant following specific schedules outlined in the study protocol. The trial involves comparing different doses of inavolisib combined with fulvestrant in this patient population. All treatments are administered as drugs, with dosing and administration details managed according to the study guidelines. During the study, researchers will monitor participants for objective response rate and treatment-emergent adverse events over approximately two years. Participants will undergo evaluations for disease status using standard criteria and will be assessed regularly for safety and treatment effects. The study requires participants to complete patient-reported outcomes and comply with all study procedures throughout their involvement.

Researchers are investigating colorectal cancer (CRC) patients with newly diagnosed stage I, II, and III cancers to evaluate whether mutations in circulating tumor DNA (ctDNA) can predict disease relapse earlier than current methods. This study includes two parts: Part B focuses on analyzing tumor tissue, serial blood samples, and clinical data to detect minimal residual disease (MRD) and predict relapse, while Part C is a randomized study comparing ctDNA-guided adjuvant chemotherapy to standard care in high-risk stage II or III CRC patients post-surgery. In Part B, the study collects serial blood samples from patients who have undergone potentially curative surgery to detect and quantify ctDNA, aiming to identify MRD and predict relapse. Part C randomizes patients after surgery into two groups: one receiving standard adjuvant chemotherapy and the other receiving ctDNA-guided chemotherapy, where those testing ctDNA negative may have chemotherapy reduced. The goal is to assess if ctDNA-guided treatment can safely reduce chemotherapy use without compromising disease-free survival. Participants will undergo tumor tissue collection, blood sampling at multiple time points, and clinical assessments over several years. Researchers will monitor ctDNA levels and clinical outcomes, measuring disease-free survival up to 3 to 6 years. Safety and treatment effects will be evaluated, with follow-up visits to track relapse and treatment response. Total participation includes long-term monitoring for relapse prediction and chemotherapy guidance.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease that causes scarring, leading to coughing and breathlessness. Many people with IPF also have reflux disease, where stomach acid may enter the lungs and cause damage. This research is evaluating whether using proton pump inhibitors (PPIs), medicines that reduce stomach acid like lansoprazole, can slow the progression of IPF. The study is a phase 3 clinical trial involving 298 IPF patients from about 37 UK hospitals to determine if treating with PPIs affects IPF outcomes and cough, reflux, and sleep symptoms. Participants will be randomly assigned to take either lansoprazole 30 mg capsules or matching placebo capsules twice daily, about 12 hours apart, for 12 months. They will be asked to start weekly home breathing tests using equipment provided, and some with a cough will use a device to count coughs over 24 hours. Questionnaires on cough, breathlessness, sleep, and general health will be completed. A sub-study involves additional cough and sleep monitoring sessions. Participants may reduce the dose if side effects occur. Throughout the study, participants will complete home spirometry assessments weekly, provide blood samples for safety checks at set intervals, and answer questionnaires at 3, 6, 9, and 12 months. Visits may be remote or in person. Researchers will monitor medication adherence, medical history changes, and side effects. The main outcome measured is the change in lung function, specifically forced vital capacity, 12 months after randomization. Additional blood samples may be collected for future research with consent.