Plymouth

Researchers are evaluating the use of PET imaging with the radioligand [18F]PI-2620 to detect tau protein deposits in people with Alzheimer's disease and healthy controls. This open-label, multi-center, non-randomized Phase 3 study aims to compare PET imaging results during life with brain tissue analysis after death to better understand tau pathology in Alzheimer's. The study is sponsored by Lantheus Biosciences Ltd. and focuses on diagnostic accuracy and safety of this imaging technique. Participants receive an intravenous injection of [18F]PI-2620 at a dose of 185 MBq ± 20%. The study involves a PET scan procedure that participants must tolerate, including lying still in the scanner. There are no randomized groups or placebo controls as this is an open-label study. The research compares the PET imaging findings with post-mortem brain autopsy results to evaluate the ability of this imaging to detect tau deposits accurately. During the study, participants undergo PET imaging and are monitored for their ability to tolerate the scan. Brain donation consent is required for post-mortem histopathological comparison. Researchers assess the diagnostic performance of the PET scan in correctly identifying tau-related pathology and Alzheimer's disease changes. The primary outcome focuses on the accuracy of visual assessment of PET images compared to autopsy findings, with follow-up continuing until study completion and an average of one year after death.

Researchers are evaluating the effects of ALN-APP on cerebral amyloid angiopathy (CAA), a condition affecting blood vessels in the brain. This study focuses on adult patients with sporadic CAA and Dutch-type CAA to understand how ALN-APP influences disease progression, safety, tolerability, and pharmacodynamics. The trial is sponsored by Alnylam Pharmaceuticals and involves a Phase 2 clinical trial design. Participants will receive multiple doses of ALN-APP or placebo administered intrathecally during a 24-month double-blind treatment period. Those who continue into the optional open-label extension period of 18 months will receive ALN-APP. The study includes two main periods: the initial double-blind phase and the optional open-label extension. During the study, participants will undergo brain MRI scans to measure new cerebral microbleeds, hemorrhagic events, and other disease markers over 24 months. Researchers will also assess cerebrovascular reactivity and concentrations of amyloid precursor proteins in cerebrospinal fluid. Safety will be monitored through adverse event tracking up to 48 months. Total participation, including screening and follow-up, may last up to 50 months.

Researchers are evaluating saruparib (AZD5305) combined with standard radiation therapy (RT) and androgen deprivation therapy (ADT) in men with high-risk or very high-risk localized or locally advanced prostate cancer who have a BRCA1 or BRCA2 gene mutation. The study aims to show saruparib's superiority compared to a placebo by measuring metastasis-free survival. This randomized, double-blind, placebo-controlled Phase III trial includes approximately 700 adult male participants with prostate adenocarcinoma and confirmed BRCA mutations. Participants will be randomly assigned to one of two groups: Cohort A includes those receiving saruparib or placebo with ADT (and abiraterone in Cohort B), after primary or salvage radiation therapy. Saruparib and placebo are given orally alongside standard ADT, with abiraterone and prednisone/prednisolone added for Cohort B participants. The study treatment is administered in cycles, and participants will be monitored for safety and effectiveness throughout the trial. During the study, participants will undergo scans including CT or MRI, bone scans, and PSMA-PET to confirm disease status. Researchers will assess metastasis-free survival over approximately 93 months and monitor overall survival up to about 11 years. Additional evaluations include progression-free survival, biochemical recurrence, urinary symptoms, physical function, and plasma drug concentrations. Safety will be closely monitored with an independent committee overseeing adverse events. Participants will be followed regularly until the study ends in 2036.

This trial investigates treatments for high-risk non-muscle-invasive bladder cancer in participants who have previously received Bacillus Calmette-Gue9rin (BCG) treatment. It compares disease-free survival between participants treated with TAR-210, a drug delivered inside the bladder, and those receiving intravesical chemotherapy chosen by their doctor. The study focuses on participants with certain FGFR gene alterations and aims to evaluate the length of time participants remain free of cancer signs or symptoms after treatment. Participants are randomly assigned to one of two groups. Group A receives TAR-210 inserted into the bladder on Day 1 and continues this treatment for about two years. Group B receives intravesical chemotherapy with either mitomycin C or gemcitabine, given once weekly for 4 to 6 doses as induction therapy, followed by monthly maintenance doses for up to one year, with an optional second year of maintenance at the doctor's discretion. Treatments are delivered directly into the bladder through a catheter. During the study, participants will be monitored regularly for up to five years to measure outcomes such as disease-free survival, recurrence-free survival, time to disease worsening, and overall survival. Assessments include safety evaluations using standard criteria, laboratory tests, vital sign checks, and quality-of-life questionnaires at multiple scheduled time points. Researchers will also track adverse events and changes in health status to assess the impact of treatments over time.

Researchers are evaluating the efficacy and safety of TYRA-300 in adults with low-grade, intermediate-risk non-muscle invasive bladder cancer (NMIBC) that has specific FGFR3 gene alterations. This Phase 2 multicenter study focuses on patients who have residual visible tumors and meet certain risk criteria, aiming to better understand treatment effects in this particular group. Participants receive self-administered oral tablets of TYRA-300 daily at doses of 50mg, 60mg, or a dose to be determined. The study is randomized and open-label, with three experimental dose cohorts. Treatment continues while monitoring for tumor response and safety over time. During the study, participants will undergo assessments including bladder mapping, tumor evaluations, and laboratory tests to monitor organ function and treatment effects. Researchers will measure tumor response at 3 months, duration of response, time to recurrence, recurrence-free survival, progression-free survival, and safety outcomes up to 2 years. Participants will be followed and monitored regularly throughout the study period.

Researchers are evaluating the outcomes of two treatments for lumbar spinal stenosis with neurogenic claudication (LSS with NC) in Medicare beneficiaries. This observational study compares the rates of surgical and minimally invasive interventions, as well as any harms, occurring within 24 months after receiving either the MILD procedure or Interspinous Process Decompression (IPD). The study uses Medicare claims data starting from patients treated on or after January 1, 2017, and continues enrollment until the sponsor stops it. The study groups include Medicare patients who underwent the MILD procedure, which involves a partial decompression performed under fluoroscopic image guidance through the removal of tissue and bone at the symptomatic spinal level. The control group consists of Medicare patients treated with Interspinous Process Decompression during the same enrollment period. Both groups are monitored for reoperation and harms for 24 months following their initial treatment. Participants are included based on Medicare claims with the study's NCT number, which automatically enrolls them without requiring prior consent. Researchers will analyze Medicare claims data to track surgical or minimally invasive interventions and any complications related to the initial procedure over two years. The study does not involve direct patient visits or interventions and is exempt from Institutional Review Board oversight. The total follow-up duration for outcome measurement is 24 months after the index procedure.

Researchers are evaluating the efficacy and safety of Dabogratinib (TYRA-300) in participants with Low Grade Upper Tract Urothelial Carcinoma (LG UTUC). This Phase 2A/B, multi-center, open-label study focuses on patients with confirmed low-risk LG UTUC, aiming to better understand the treatment's impact on this specific type of cancer. Participants receive Dabogratinib monotherapy in one of three dose groups: 60mg, 80mg, or a to-be-determined dose. The medication is taken daily as an oral tablet that participants self-administer. The study monitors participants over several months to assess response rates and other outcomes related to the treatment. Throughout the study, participants undergo regular assessments including genomic testing, imaging to identify marker lesions, and monitoring of blood and organ function. Researchers measure outcomes such as the proportion of participants achieving complete response within six months, safety and tolerability over two years, duration of response, renal preservation, and changes in tumor status. The study continues to observe participants for up to 36 months to evaluate long-term effects.

Researchers are evaluating whether brain MRI scans alone can effectively monitor small cell lung cancer compared to the combination of MRI scans with preventive brain radiation called prophylactic cranial irradiation (PCI). This phase III trial aims to see if using MRI surveillance alone can maintain overall survival and reduce side effects, potentially prolonging patients' lives. The study also looks at cognitive function, brain metastasis-free survival, and treatment toxicities. Participants are randomly assigned to one of two groups. One group receives PCI radiation therapy to the brain over two weeks along with scheduled MRI scans at 3, 6, 9, 12, 18, and 24 months. The other group only undergoes MRI scans at the same time points without PCI. Some patients in the PCI group may receive hippocampal avoidance radiation to spare cognitive function. During the study, participants undergo regular MRI scans and cognitive testing to track brain health and cancer spread. Researchers monitor survival rates, cognitive failure-free survival, brain metastases occurrence, and adverse events for up to two years after randomization. Blood samples may be collected for banking. The total follow-up includes multiple visits and assessments to evaluate the effects of MRI surveillance alone versus combined PCI and MRI monitoring.

This research aims to evaluate the use of the Erdafitinib intravesical delivery system in participants with non-muscle-invasive or muscle-invasive bladder cancer that have activating FGFR mutations or fusions. The study includes several parts: dose escalation to find the recommended Phase 2 dose, dose expansion to assess preliminary clinical efficacy, and further dose expansion to confirm safety and activity. The final phase focuses on assessing complete response in participants with intermediate-risk non-muscle-invasive bladder cancer, a condition where cancer cells are confined to the bladder's inner lining. Participants receive Erdafitinib delivered directly into the bladder through a specialized system designed to target localized bladder cancer while reducing side effects often seen with oral treatment. The study includes four parts: dose escalation to identify safe doses, dose expansion across different disease cohorts to evaluate safety and pharmacokinetics, RP2D dose expansion to further assess safety and preliminary activity, and a phase 2 expansion focusing on intermediate-risk NMIBC. Treatment is given according to disease type and dose level, with ongoing monitoring throughout. During the study, participants undergo screening, treatment, and follow-up phases lasting up to about 7 years and 4 months. Researchers monitor adverse events, dose-limiting toxicities, and clinical responses such as complete response rates and recurrence-free survival. Assessments include measuring Erdafitinib levels in plasma and urine, quality of life questionnaires, and tumor evaluations. Safety is closely tracked, and participants are regularly evaluated for treatment effects and disease status throughout the study period.

Researchers are evaluating LHP588 in people aged 55 to 80 who have mild to moderate Alzheimer's disease (AD) with progressive mental decline over the last year and a specific infection caused by P. gingivalis bacteria. This infection has been linked to dementia development, and the study aims to assess if LHP588, which targets this bacterium, can potentially help slow AD progression. The study follows strict criteria including AD diagnosis by established guidelines and evidence of infection through saliva tests. Participants will be randomly assigned to one of three groups: a placebo group, a group receiving 25 mg of LHP588 daily, or a group receiving 50 mg daily. Treatment is given orally once a day in a fasted state for up to 48 weeks, including a 2-week dose increase period for the higher dose group. The study includes a screening phase lasting up to 12 weeks to confirm eligibility, followed by a 4-week safety follow-up after treatment ends. Throughout the study, participants and their caregivers will visit the study center about 20 times over 64 weeks for assessments including cognitive tests like the ADAS-Cog, MMSE, saliva and blood samples, neuroimaging, physical exams, and safety monitoring. Caregiver participation is essential. Researchers will measure changes in cognition and daily functioning to evaluate the study drug’s effects. After treatment, participants will have safety follow-ups including a phone call and a final visit at week 52.