Glasgow

Researchers are investigating how the medicine Filgotinib works to relieve pain in patients with moderate to severe active rheumatoid arthritis RA. This study focuses on understanding two main factors influencing pain relief brain pathways linked to central nervous system sensitization seen in fibromyalgia, and the inflammation surrounding joints and related immune signals. The study aims to clarify why Filgotinib may provide faster pain relief compared to other treatments by examining these mechanisms. Participants prescribed Filgotinib will be observed using advanced 7 Tesla MRI brain imaging to measure changes in brain connectivity and glutamate levels associated with pain processing. The study will assess Filgotinibs impact on both central nervous system pain pathways and peripheral inflammation over periods of up to 12 weeks. This observational test-retest design does not involve altering prescribed treatments but focuses on detailed imaging and biological assessments. During the study, participants will undergo brain MRIs and evaluations of joint inflammation through ultrasound and blood tests measuring cytokines and chemokines. They will also complete questionnaires on pain, fatigue, anxiety, sleep, and cognitive function. Researchers will monitor changes in these measures at intervals up to 12 weeks to understand how Filgotinib affects pain and related symptoms. Total participation time aligns with the 12-week observation period.

Researchers are evaluating new treatment options for people with high-risk non-muscle invasive bladder cancer HR NMIBC, a type of bladder cancer that affects the inner lining of the bladder but has not spread to the muscle or beyond. This includes carcinoma in situ CIS, a flat form of bladder cancer limited to the bladders surface. The study aims to find out if adding intismeran autogene, an immune system-targeting treatment, to the standard Bacillus Calmette-Guerin BCG therapy can improve outcomes for people with HR NMIBC by helping the immune system attack the cancer more effectively. Participants are assigned to different groups. One group receives both intismeran autogene by intramuscular injection every three weeks for nine doses along with BCG treatment given once weekly for six weeks, followed by additional weekly doses at later weeks. Another group receives BCG alone on the same schedule, while a third group receives only intismeran autogene. The study compares these treatments to see if the combination improves survival without cancer growth, spread, or return. During the study, participants will be monitored for up to approximately five years to track event-free survival, recurrence-free survival, overall survival, and other outcomes. Researchers will also evaluate adverse events and treatment tolerability. Follow-up includes assessments at regular intervals to observe disease status and safety. The total participation time may last several years to gather long-term data on treatment effects.

Researchers are investigating new treatments for Pulmonary Arterial Hypertension PAH, a condition where the blood vessels in the lungs thicken and narrow, causing high blood pressure in the lungs and making it difficult for the heart to work properly. PAH can lead to breathing difficulties and reduced activity levels. While current treatments help manage symptoms, they do not stop the disease from progressing. Sotatercept is a study medicine designed to target specific proteins involved in PAH, and this long-term follow-up study aims to assess its safety and tolerability when used alongside standard PAH treatments over an extended period. Participants who have completed previous sotatercept PAH studies may join this open-label follow-up study. Those from blinded studies will start sotatercept at 0.3 mgkg by subcutaneous injection every three weeks and may increase to 0.7 mgkg. Participants from unblinded studies will continue their current dose and may also increase to 0.7 mgkg. The study focuses on monitoring sotatercept use combined with background PAH therapy to observe long-term effects. Throughout the study, participants will undergo regular assessments including tracking adverse events, laboratory tests for blood and chemistry markers, body weight, blood pressure, and electrocardiograms up to approximately 7 years. Additional measurements include walking distance tests, heart function markers, and risk scores related to PAH. Safety monitoring and tolerance to the medication will be closely observed over time to better understand sotatercepts long-term impact in managing PAH.

Researchers are evaluating ETX101, an investigational gene therapy delivered via AAV9, in infants and children with Dravet syndrome caused by SCN1A gene mutations. This study, called ENDEAVOR, includes participants from 6 months up to less than 18 years old and aims to assess the safety and effects of ETX101 on seizure frequency and developmental outcomes. The trial includes multiple parts with different age groups and study designs to understand its impact comprehensively. The study has three parts Part 1A is an open-label dose-escalation phase for children aged 6 to less than 36 months, testing up to four dose levels of ETX101. Part 1B is an open-label phase for participants aged 48 months to less than 18 years, evaluating a single dose level. Part 2 is a randomized, double-blind, sham delayed-treatment control study for children aged 6 to less than 48 months, where participants are assigned in a 21 ratio to receive ETX101 or a sham procedure with delayed treatment. During participation, children will be monitored for changes in seizure frequency from before dosing to 52 weeks after treatment. Researchers will also assess cognitive and adaptive behavior development using standard scales like Bayley-4 and Vineland-3. Safety and efficacy will be closely observed through clinical evaluations, with follow-up lasting up to a year post-dosing to measure treatment outcomes and monitor health.

Researchers are evaluating the safety, effectiveness, best dose, and how the body processes BNT326 when used alone or combined with other immunotherapy drugs in adults with advanced solid tumors. These tumors are either metastatic, recurrent without further treatment options, or have relapsed after previous therapy. The study includes patients with different types of advanced cancers such as melanoma, lung cancer, breast cancer, gastric cancer, colorectal cancer, and cervical cancer. In Part 1, participants receive BNT326 alone across several cancer-specific groups, including cutaneous melanoma, non-small cell lung cancer with or without specific mutations, rare melanomas, advanced tumors, and cervical cancer. Part 2 evaluates BNT326 alone or combined with another immunotherapy drug called pumitamig. Participants are assigned to different dose levels, sometimes randomly, depending on their cancer type and group. The study includes a screening period, treatment for up to 24 months or until progression or other reasons, and follow-up periods. During the study, participants undergo assessments including tumor tissue sampling, monitoring of treatment side effects, blood tests to measure drug levels, and evaluations of tumor response and survival. Safety is closely followed up to 42 or 90 days after treatment ends, with longer-term monitoring for up to 38 months Part 1 or 48 months Part 2. Participants overall response rates, adverse events, and pharmacokinetics are key outcomes. The study is sponsored by BioNTech SE and includes open-label, adaptive design across two phases.

Researchers are evaluating the safety, tolerability, and effectiveness of BNT113 combined with pembrolizumab compared to pembrolizumab alone as a first treatment for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma HNSCC that tests positive for human papillomavirus 16 HPV16 and expresses the protein PD-L1. This Phase IIIII trial includes patients whose tumors have a combined positive score of 1 or higher for PD-L1. The study is designed to generate important safety and efficacy data for these treatments in this patient group. The trial consists of two parts Part A is a non-randomized safety run-in phase to confirm the safety and tolerability of BNT113 with pembrolizumab. Part B is a randomized phase comparing BNT113 combined with pembrolizumab versus pembrolizumab alone. Treatments are given by intravenous injection or infusion. Patients may receive treatment for up to 24 months. An optional pre-screening phase allows tumor samples to be tested centrally for HPV16 DNA and PD-L1 expression before entering the main trial. Participants will undergo regular assessments including monitoring for treatment-emergent adverse events, overall survival, and progression-free survival for up to 48 months. Researchers will also measure response rates and duration, disease control, and any dose adjustments due to side effects. Patients provide tumor tissue samples before treatment and are monitored closely throughout the study period. The trial aims to collect comprehensive data on safety, treatment effects, and patient outcomes over this extended follow-up.

Researchers are evaluating the safety and effectiveness of trontinemab in people aged 50 to 90 years who have early symptomatic Alzheimers disease, ranging from mild cognitive impairment to mild dementia. The study is a phase III trial designed to compare trontinemab with a placebo to better understand its impact on cognitive decline in Alzheimers patients. Participants will be randomly assigned to receive either intravenous IV trontinemab or an IV placebo. The study is double-blind, meaning neither the participants nor the researchers know who receives the drug or placebo. Treatment and monitoring will continue for 72 weeks, during which various cognitive and biological measures will be assessed. Throughout the study, participants will undergo regular assessments including cognitive tests like the Clinical Dementia Rating, Sum of Boxes CDR-SB, and the Mini-Mental State Examination MMSE. Brain imaging scans such as amyloid and tau PET scans, as well as MRI, will be used to observe changes in brain pathology. Researchers will also monitor safety by tracking adverse events, infusion reactions, and the presence of antibodies against trontinemab. Participants will be supported by a study partner and will be closely followed during the entire study period.

Researchers are evaluating the effects of zorevunersen, an investigational antisense oligonucleotide medicine, in children with Dravet syndrome, a rare epilepsy disorder caused by reduced Nav1.1 protein due to SCN1A gene mutations. This Phase 3, global, randomized, double-blind, sham-controlled study aims to assess the safety, tolerability, and potential to modify the disease by increasing Nav1.1 protein levels from the nonmutant gene copy. The study also measures changes in seizure frequency, behavior, cognition, clinical status, and quality of life. Participants are randomly assigned to one of two groups for Treatment Period 1, lasting about 52 weeks either receive zorevunersen or undergo a sham procedure without drug administration. Zorevunersen is given by intrathecal injection at specific days and doses during this period. After Treatment Period 1, all eligible patients enter Treatment Period 2, where everyone receives zorevunersen at defined intervals and doses. Patients may also join an open-label extension study if they meet criteria after the main study. Throughout the study, patients will be monitored regularly to assess seizure changes at weeks 28 and 52, as well as adaptive behavior using the Vineland-3 scale. Safety and tolerability are closely followed with standardized evaluations. The study lasts at least 84 weeks, including both treatment periods. Researchers aim to understand how zorevunersen may impact major motor seizures and overall functioning in children with Dravet syndrome.

Researchers are studying a new drug called BAY 3547926 to learn about its safety and effectiveness in people with advanced hepatocellular carcinoma HCC, a type of liver cancer that has a protein called Glypican 3 GPC3. This is the first time BAY 3547926 is being tested in humans. The study aims to find the best dose of the drug and understand how it is absorbed and distributed in the body. BAY 3547926 is an antibody linked to a radioactive substance called actinium-225. This radioactive agent is delivered directly to the cancer cells, where it emits radiation that can kill the cancer cells while limiting damage to nearby healthy tissues. The study includes four parts Part 1 tests different doses alone to find the safest and most effective dose, while Parts 2, 3, and 4 will give this dose either alone or combined with other treatments to more participants. Participants will undergo regular health check-ups, body scans like CT or MRI, blood and urine tests, and answer questions about their health and symptoms. The study will closely monitor side effects, tumor response using RECIST 1.1 criteria, and how long the benefits last. Follow-up will continue for up to 60 months after the first dose to evaluate safety and effectiveness outcomes.

Primary immune thrombocytopenia ITP is a condition where the immune system mistakenly destroys platelets, leading to a lower platelet count and increased risk of bruising or bleeding. This research aims to evaluate the long-term safety, tolerability, effectiveness, and how the body processes mezagitamab in adults with chronic primary ITP. Participants who previously took part in related mezagitamab studies TAK-079-3002 and TAK-079-1004 are invited to join this continuation study. Eligible participants will receive mezagitamab injections under pre-specified criteria and as needed, based on their clinical condition and the investigators judgment. This on-demand treatment may be repeated multiple times during the study. The study is an open-label, phase 3 trial that monitors participants over an extended period with repeated dosing as required. Participants will visit the study clinic multiple times for assessments throughout the study, which may last up to approximately 108 weeks. Researchers will monitor treatment-emergent adverse events, platelet response duration, use of other ITP medications, and the presence of antibodies against the drug. Blood samples will be collected to measure drug levels and immune responses. Safety and effectiveness will be closely followed, including any need for rescue therapies.