Plymouth

Researchers are evaluating the use of PET imaging with the radioligand 18FPI-2620 to detect tau protein deposits in people with Alzheimers 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 Alzheimers. 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 18FPI-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 Alzheimers 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 disease progression in adults with sporadic Cerebral Amyloid Angiopathy sCAA and Dutch-type Cerebral Amyloid Angiopathy D-CAA. This Phase 2 study aims to assess the safety, tolerability, and pharmacodynamics of ALN-APP in these patient groups. The study is sponsored by Alnylam Pharmaceuticals and includes a randomized, double-blind, placebo-controlled 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 an optional 18-month open-label extension will receive ALN-APP. The study involves two main periods the initial double-blind treatment phase followed by an optional open-label extension. During the study, participants will undergo brain MRIs to measure new cerebral microbleeds and other brain changes. Researchers will also assess cerebrovascular vasoreactivity using functional MRI and measure amyloid precursor protein levels in cerebrospinal fluid. Safety and adverse events will be monitored throughout the up to 50 months of participation, which includes screening, treatment, and safety follow-up.

Researchers are evaluating whether donanemab slows the progression of cognitive decline, which affects thinking, learning, memory, attention, and decision-making, as well as functional decline impacting daily activities. This study focuses on adults aged 55 to 85 who have early cognitive decline along with Lewy Body Dementia features and confirmed brain amyloid and alpha-synuclein pathology. The trial is a phase 2 treatment study sponsored by Eli Lilly and Company, lasting one and a half years per participant. Participants are randomly assigned to receive either donanemab or a placebo, both given as intravenous infusions. Donanemab is being studied to assess its effects compared to placebo in this population. The treatment period lasts for 52 weeks, during which participants receive regular infusions under medical supervision. During the study, participants will undergo various assessments including cognitive and functional tests such as the Clinical Dementia Rating - Sum of Boxes CDR-SB, Integrated Alzheimers Disease Rating Scale iADRS, and Alzheimers Disease Assessment Scale - Cognitive Subscale ADAS-Cog13. Brain imaging and cerebrospinal fluid analysis will also be performed to measure amyloid plaque levels and alpha-synuclein pathology. Safety and drug levels in blood will be monitored throughout, with participants being followed closely for one and a half years total.

Researchers are evaluating the addition of Saruparib AZD5305 to standard radiation therapy RT and androgen deprivation therapy ADT for men with high-risk or very high-risk localized or locally advanced prostate cancer who have a BRCA1 or BRCA2 mutation. The study aims to determine if Saruparib improves metastases-free survival compared to placebo when added to these treatments. This phase 3 trial involves approximately 700 adult male participants. Participants are randomly assigned to receive either Saruparib or a matching placebo alongside physicians choice of ADT, with or without abiraterone and prednisoneprednisolone, depending on their cohort. Cohort A includes those receiving RT and continuous ADT, while Cohort B includes participants receiving RT, ADT, and abiraterone. Saruparib and placebo are administered orally. Treatment continues with close monitoring throughout the study. Participants will undergo scans including CT or MRI, bone scans, and PSMA-PET after their planned RT to confirm eligibility and monitor disease status. They will be followed for survival and disease progression for up to approximately 11 years. Researchers will assess metastasis-free survival, overall survival, prostate cancer-specific survival, biochemical recurrence, physical function, and urinary symptoms. Safety and drug levels will also be monitored. An independent committee will review safety and efficacy regularly throughout the trial.

Researchers are evaluating the disease-free survival in participants with high-risk non-muscle-invasive bladder cancer HR-NMIBC who have previously received Bacillus Calmette-Gurin BCG treatment. This Phase 3 trial compares a new treatment called TAR-210 with the investigators choice of intravesical chemotherapy. The study focuses on participants with specific fibroblast growth factor receptor FGFR alterations and aims to find out which treatment better prevents cancer recurrence or progression after BCG therapy. Participants are randomly assigned to one of two groups. Group A will have TAR-210 inserted into the bladder starting on Day 1 and continuing for about 2 years. Group B will receive either mitomycin C or gemcitabine chemotherapy, chosen by the investigator, given once weekly for 4 to 6 weeks induction, followed by monthly maintenance doses for up to 1 year, with a possible second year of maintenance at the investigators discretion. All treatments are delivered directly into the bladder intravesically. During the study, participants will be monitored for up to 5 years to track disease-free survival and other outcomes such as recurrence-free survival, time to next intervention, disease worsening, progression, and overall survival. Researchers will also assess side effects, laboratory and vital sign changes, and quality of life using specific questionnaires. The study includes regular evaluations and safety monitoring throughout the participation period, which may last several years.

The trial investigates the efficacy and safety of TYRA-300 in adults with FGFR3 altered low-grade, intermediate-risk non-muscle invasive bladder cancer NMIBC. This Phase 2, multicenter, open-label study focuses on participants with specific tumor characteristics confirmed by diagnostic biopsy and who meet intermediate risk criteria according to updated guidelines. The study is designed to evaluate a new oral treatment option for this condition, providing important insights into its potential role in managing this cancer type. Participants receive TYRA-300 as a self-administered oral tablet daily in one of several dose groups 60 mg, 50 mg, or a dose to be determined. The study is randomized and open-label, with participants assigned to different dose cohorts to assess treatment effects. The treatment period and dose details are structured to monitor safety and response over time, allowing evaluation of how well the drug works in this patient group. Throughout the study, participants are monitored for efficacy and safety outcomes, including disease response at 3 months, duration and timing of any recurrence, recurrence-free survival at 12 and 24 months, and progression-free survival. Safety is assessed through adverse event monitoring up to 2 years. Participants undergo various clinical evaluations, including tumor assessments and laboratory tests, to track treatment effects and health status. The total study duration extends to September 2028, with ongoing follow-up to capture long-term outcomes and tolerability.

Researchers are comparing the rates of surgical and minimally invasive interventions, as well as any harms, in Medicare beneficiaries treated with the MILD procedure versus those treated with interspinous process decompression IPD for lumbar spinal stenosis with neurogenic claudication. This observational study uses Medicare claims data to follow patients for 24 months after their initial procedure starting from January 1, 2017. The purpose is to evaluate outcomes between these two types of procedures without requiring prior patient enrollment or consent. The study includes two groups patients who received MILD, which is a percutaneous image-guided lumbar decompression performed under fluoroscopic guidance through a dorsal approach to the spine, and patients who received IPD, a different device-based decompression procedure. Data on reoperations and complications will be collected for both groups over a 24-month follow-up period using Medicare claims. Enrollment continues until the sponsor decides to stop. Participants involvement is passive as the study uses existing Medicare claims data. Researchers will monitor rates of harms related to the initial procedure and subsequent surgical or minimally invasive interventions over two years. No direct patient visits or interventions are conducted, and the study is exempt from institutional review board oversight. The total study duration extends to December 2026, covering cases treated since early 2017.

Researchers are evaluating the effectiveness and safety of Dabogratinib TYRA-300 in people with low grade upper tract urothelial carcinoma, a type of cancer affecting the urinary tract. This Phase 2AB open-label study focuses on patients with FGFR3-positive tumors and aims to understand how well the drug works in reducing tumor presence within six months. Participants will receive daily oral doses of Dabogratinib at different strengths60mg, 80mg, or a dose to be determined. The study is randomized and involves multiple centers, with participants assigned to one of three dose groups to assess the drugs impact and safety. During the trial, participants will be monitored for response to treatment, including complete tumor response within six months and duration of response up to 36 months. Safety and kidney function will be observed for up to two years, alongside other measures like tumor resectability and renal preservation. The total participation duration spans until the studys completion in November 2030.

Researchers are evaluating LHP588 in people aged 55 to 80 with mild to moderate Alzheimers disease AD who have experienced mental decline in the past year and have an infection with P. gingivalis, a bacterium linked to dementia development. This randomized, double-blind, placebo-controlled Phase 2 study aims to assess the safety and effectiveness of LHP588 in slowing down or halting AD symptoms in participants with confirmed P. gingivalis infection and progressive cognitive decline. Participants will be randomly assigned to one of three groups a placebo group, a 25 mg LHP588 group, or a 50 mg LHP588 group. They will take the assigned oral capsules once daily in a fasted state for 48 weeks, with a 2-week dose increase period for the high dose group. The study includes a screening period of up to 12 weeks to confirm eligibility through tests including saliva sampling for P. gingivalis, blood tests for pTau217, cognitive questionnaires like MMSE, and brain MRI. After treatment, there is a 4-week safety follow-up to monitor overall health. Participants and their caregivers will attend at least 20 visits over the 64-week study period, plus at least one phone call for safety monitoring. Assessments include medical history, physical exams, saliva and blood samples, ECG, and cognitive and functional tests such as ADAS-Cog. Researchers will measure changes in cognition and daily functioning to evaluate the drugs impact. Caregiver involvement is required to assist with study participation and clinic visits throughout the trial.

Researchers are evaluating the Golazo4 Peripheral Atherectomy System in people with symptomatic infrainguinal peripheral arterial disease PAD. This prospective, multicenter, single-arm study aims to provide reasonable assurance of the safety and effectiveness of this device when used as intended. It involves up to 159 participants across multiple investigational sites in the U.S. who have PAD affecting their lower limbs. Participants will receive atherectomy treatment using the Golazo4 Peripheral Atherectomy System, a sterile, single-use percutaneous device designed for removing plaque from peripheral blood vessels. After treatment, participants will be followed and assessed for up to 6 months to monitor outcomes. The study focuses on safety and technical success during the procedure and tracks clinical success and adverse events during follow-up. Throughout the trial, participants will undergo assessments of blood flow, limb function, and complications related to the procedure. Researchers will measure freedom from major adverse events within 30 days, technical success during surgery, and longer-term outcomes such as vessel patency and limb health over 6 months. Participants progress will be monitored through clinical visits and evaluations to understand the treatments impact and safety.