Glasgow

Researchers are studying how the drug Filgotinib works to reduce pain in patients with moderate to severe active rheumatoid arthritis (RA). They focus on understanding pain pathways in the brain and how these relate to inflammation and nervous system sensitization. The study explores the role of brain connectivity and neurotransmitters linked to pain, especially pathways seen in conditions like fibromyalgia, to explain Filgotinib's rapid pain relief effects. This is an observational test-retest study where patients prescribed Filgotinib will be evaluated using advanced 7 Tesla MRI brain imaging. The research targets specific brain networks involved in pain processing, such as the Default Mode Network-insula and dorsal attention network-left inferior parietal lobule connections, along with measuring insular glutamate levels. These imaging assessments occur at baseline and after 12 weeks of treatment to observe changes in central nervous system pain sensitization. Participants will undergo brain MRI scans and be monitored for pain-related brain activity and inflammation markers over 12 weeks. The main outcomes include changes in brain connectivity and glutamate levels measured by MRI. Researchers will also assess clinical responses and safety during this period. The study involves adults aged 18 to 74 who have been prescribed Filgotinib for RA and can complete MRI procedures.

Researchers are evaluating new treatments for people with high-risk non-muscle invasive bladder cancer (HR NMIBC), a type of bladder cancer that has not spread to the muscle but has a high chance of worsening or returning. This cancer type may include carcinoma in situ (CIS), which is a flat, surface-level bladder cancer. The study aims to learn whether adding intismeran autogene (V940), a treatment designed to boost the immune system's attack on cancer, to the standard Bacillus Calmette-Guerin (BCG) immunotherapy can help people live longer without the cancer growing, spreading, or coming back. Participants will receive either the combination of V940 with BCG or BCG alone. BCG is given as a bladder instillation, while V940 is given as an intramuscular injection. The study is phase 2, open-label, and randomized. As of a 2026 amendment, outcome measures for a monotherapy arm of V940 are no longer primary or secondary. Treatment is focused on Cohort A, which includes people with high-risk non-muscle invasive bladder cancer who are BCG-naïve or meet specific recurrence criteria. During the study, participants will be monitored for event-free survival for up to approximately 5 years. Researchers will assess how long participants live without the cancer worsening or returning. The study includes regular evaluations, imaging, and safety monitoring. The total duration of participation depends on individual outcomes and follow-up but includes long-term observation to assess treatment effects and safety.

Researchers are evaluating sotatercept as a potential treatment for pulmonary arterial hypertension (PAH), a condition where blood vessels in the lungs thicken and narrow, causing high blood pressure in the lungs and overworking the heart. PAH symptoms include difficulty breathing and reduced ability to be active. Current standard treatments address symptoms but do not stop disease progression. This Phase 3 study focuses on the long-term safety and tolerability of sotatercept when added to standard PAH therapy. Participants in this long-term follow-up study receive sotatercept through subcutaneous injections every three weeks. Only individuals who completed prior sotatercept PAH studies without early discontinuation may join. This study continues the observation and assessment of participants over an extended period to learn about the effects and safety of sotatercept combined with background PAH treatments. During the study, participants will be regularly monitored for adverse events, treatment discontinuations, and the presence of anti-drug antibodies for up to approximately 90 months. Laboratory tests will evaluate blood components such as platelets, hemoglobin, creatinine, bilirubin, and liver enzymes. Changes from baseline in body weight, blood pressure, and electrocardiogram readings will also be tracked. The study involves adherence to visit schedules and compliance with study procedures to ensure comprehensive long-term safety data collection.

Researchers are evaluating the safety and effectiveness of ETX101, a gene therapy, in infants and children diagnosed with SCN1A-positive Dravet syndrome. This is a Phase 1/2, two-part, multicenter study including participants aged 6 months to under 36 months in Part 1A, 48 months to under 18 years in Part 1B, and 6 months to under 48 months in Part 2. Part 1A uses an open-label dose-escalation design, Part 1B is open-label, and Part 2 is a randomized, double-blind, sham delayed-treatment controlled study. ETX101 is a single dose gene therapy delivered through an intracerebroventricular injection. It uses a viral vector to increase the expression of the SCN1A gene, which is linked to Dravet syndrome. The study includes different age groups and designs to assess safety and response over varying durations and methods, including dose escalation and placebo control. Participants will be monitored for changes in seizure frequency from before treatment through up to one year after dosing, with assessments occurring between Week 5 and Week 52. The main outcome measure is the percentage change in monthly countable seizures. Safety and efficacy will be closely evaluated throughout the study, with follow-up visits to assess the participant’s condition and response to the gene therapy.

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.

Researchers are evaluating the safety and effectiveness of trontinemab in people aged 50 to 90 with early symptoms of Alzheimer's disease, ranging from mild cognitive impairment to mild dementia. This Phase III clinical trial focuses on those who show evidence of Alzheimer's pathology and have a recent history of cognitive decline. The study aims to measure changes in cognitive function over 72 weeks. Participants will be randomly assigned to receive either intravenous trontinemab or a placebo. The trial is designed as a double-blind, placebo-controlled study, meaning neither participants nor researchers know who receives the active drug or placebo. The treatment period lasts up to 72 weeks, during which participants will undergo various assessments to monitor their cognitive status and safety. During the study, participants will complete clinical tests including cognitive assessments and imaging such as MRI, PET scans, or cerebrospinal fluid analysis to confirm Alzheimer's pathology. A study partner will assist participants as needed. Researchers will track changes from the start of the study through week 72 using tools like the Clinical Dementia Rating. Safety monitoring and adherence to study procedures will also be closely observed throughout the trial.

Researchers are evaluating the efficacy, safety, and tolerability of zorevunersen in patients with Dravet syndrome, a condition marked by reduced levels of the Nav1.1 protein due to mutations in the SCN1A gene. Zorevunersen is an investigational antisense oligonucleotide designed to increase the expression of the sodium channel Nav1.1 protein by boosting the production of its messenger RNA. This Phase 3, multicenter, randomized, double-blind, sham-controlled study aims to assess the potential of zorevunersen for disease modification by measuring changes in major motor seizure frequency and other health outcomes. The study has two treatment periods. In Treatment Period 1, participants assigned to zorevunersen receive the drug by intrathecal administration on Day 1, Day 57, Day 169, and Day 281 with doses of 70 mg initially and then 45 mg later. The sham group undergoes a procedure mimicking drug administration without receiving the drug. In Treatment Period 2, those initially on zorevunersen receive 45 mg doses on Day 393, Day 477, and Day 589. Participants initially in the sham group are then given zorevunersen doses of 70 mg on Day 393 and Day 477, and 45 mg on Day 589. Participants will be closely monitored throughout the study with a primary focus on seizure changes measured at Week 28. Secondary assessments include behavior, cognition, clinical status, and quality of life. The study includes an initial 8-week baseline period and a 6-week observation period to confirm seizure frequency and stability of other treatments. Patients may continue to an open-label extension study to receive zorevunersen if eligible. The study involves children aged 2 to under 18 years and tracks safety and tolerability alongside efficacy outcomes.

Researchers are evaluating the safety and effectiveness of a new drug called BAY 3547926 in people with advanced liver cancer known as hepatocellular carcinoma (HCC) that expresses a protein called Glypican 3 (GPC3). This first-in-human study aims to find the best dose of BAY 3547926 and to understand how the body absorbs and processes the drug. The drug carries a radioactive agent that targets cancer cells, causing damage to them while limiting harm to nearby healthy tissues. The study includes four parts. In Part 1, participants receive increasing doses of BAY 3547926 alone to identify the safest and most effective dose. In Part 2, a larger group receives BAY 3547926 alone at the chosen dose. In Parts 3 and 4, BAY 3547926 is given in combination with other treatments. Another drug, BAY 3547922, which is an antibody conjugate without the radioactive label, is used as a preinjection in the study. During the study, participants undergo health check-ups, body scans, and provide blood and urine samples. Researchers also ask about symptoms and general well-being. They will monitor side effects, tumor response using standard criteria, and progression of cancer for up to 60 months after the first dose. The study assesses safety, tolerability, drug levels in the body, and anti-tumor activity over this period.

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.