Parkinson's disease clinical trials in Philadelphia

This study is referred to as the "umbrella master protocol" for pembrolizumab (MK-3475) in the treatment of non-small cell lung cancer (NSCLC). This pembrolizumab NSCLC umbrella master protocol uses a platform design and consists of this master screening study and additional substudies. Each substudy will enroll a different population of NSCLC participants.

The purpose of this international study is to evaluate long-term safety and effectiveness of Abbott deep brain stimulation (DBS) systems for all indications, including Parkinson's disease, essential tremor or other disabling tremor and dystonia.

Parkinson's Disease (PD) is the second most common of the age-related neurodegenerative disorders, affecting over 1,900 adults per 100,000 over the age of 80 in the US. The prevalence of sleep dysfunction in PD is estimated at nearly 80-90% which includes sleep fragmentation, insomnia, rapid eye movement (REM or dream sleep) Sleep Behavior Disorder (RBD), Restless legs syndrome (RLS), periodic limb movement, excessive daytime sleepiness, and sleep apnea. Sleep is vital to homeostasis, cognition, and nervous system repair. The dysfunctional sleep accompanying PD adversely affects both motor and non-motor symptoms, resulting in diminished quality of life for both patients and caregivers, including impairments in mood and behavior, and increased morbidity and mortality. Knowledge of sleep phenomenology and pathology in humans has largely been informed by analysis of non-invasive scalp electroencephalogram (EEG), and despite the profound importance of sleep, the underlying neural circuits important for controlling sleep and wakefulness in humans remain poorly understood. This study assesses whether adaptive stimulation of the Subthalamic Nucleus (STN) drives changes in sleep episode maintenance and improves sleep quality. Participants are adults with PD who experience inadequate motor symptom relief, and who have been offered implantation of a deep brain stimulator system targeting STN for the treatment of motor symptoms (standard-of-care). Prior to surgery, participant sleep patterns will be assessed with questionnaires and monitored with a non-invasive watch-like device. Approximately four months after implantation surgery, participants will each receive 2 1-week deep brain stimulation (DBS) treatments and 1 1-week control session with no DBS in random order. Sleep patterns will again be monitored during the treatments and compared to the patterns before surgery.

DESTINY-Endometrial01 will investigate the efficacy of first-line T-DXd + rilvegostomig (Arm A) and/or T-DXd+ pembrolizumab (Arm B) when compared to chemotherapy (carboplatin + paclitaxel) + pembrolizumab (Arm C), by assessment of progression free survival (PFS), as assessed by BICR, in participants with HER2-expressing (IHC 3+/2+), pMMR, primary advanced (Stage III/IV) or recurrent EC.

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) with or without chemotherapy in combination with vibostolimab (MK-7684), boserolimab (MK-5890), MK-4830, MK-0482, I-DXd, or HER3-DXd in treatment-naïve participants with advanced squamous or non-squamous NSCLC. This study is one of the pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

The goal of this Phase 2 clinical trial is to investigate the efficacy and safety of NEU-411 in men and women aged 40-80 years with early Parkinson's Disease (PD) who have predicted elevations in the activity of the "leucine-rich repeat kinase 2" ("LRRK2" for short) pathway based on their genetic profile. A DNA test will be used to identify the "LRRK2-driven" population with predicted elevation in the LRRK2 pathway.

The aim of this study is to contribute to and continue to sustain a repository of blood samples, nucleic acid (DNA and/or RNA) samples, family history information, and other demographic information from individuals with age-related neurodegenerative conditions, or their family members who may or may not be at risk for similar conditions. This study will continue to further expand research into the molecular and genetic basis of these diseases and their risk factors.

The current protocol is to determine the biodistribution, metabolism, excretion and brain uptake of 11C HY-2-15. The goal of this radiotracer is to quantify alpha-synuclein that is abnormally deposited in the brain of people with Multiple System Atrophy (MSA). The investigators will compare uptake in people with MSA with people with Parkinson disease (PD) and progressive supranuclear palsy (PSP) as well as healthy volunteers. This multicenter project funded by an NIH U19 grant, is centered at U Pennsylvania (Penn, Grant PI: Robert Mach) in collaboration with U Pittsburgh (Pitt) (not a clinical site), Yale U, U of California at San Francisco (UCSF) and Washington University in St. Louis (WU). The University of Pennsylvania will act as the sIRB for this multi-center human subjects project and participants will be recruited from all sites.

Development of a central repository for PD-related genomic data for future research.

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics (PK) of prasinezumab compared with placebo in participants with early-stage Parkinson's disease (PD) on stable symptomatic monotherapy with levodopa.

The study is a longitudinal, multi-center study to assess progression of \[18F\] AV-133 imaging in Prodromal PD participants. Participants will be followed for up to 24 months. Approximately 100 Prodromal participants will be recruited from up to 10 sites. Participants will be comprehensively assessed at baseline and follow up. Participants will undergo imaging assessments with \[18F\] AV-133 and clinical (motor, neuropsychiatric, cognitive and imaging and biomarker) assessments (conducted under the PPMI Clinical protocol).

The objective of this randomized, surgically controlled, double-blinded, Phase 2 study is to evaluate the safety and efficacy of AAV2-GDNF delivered to the putamen in subjects with moderate Parkinson's Disease.

The current protocol is to determine the biodistribution, metabolism, excretion and brain uptake of 11C-M503. The goal of this radiotracer is to quantify alpha-synuclein that is abnormally deposited in the brain of people with Parkinson's disease (PD). Investigators will compare uptake in participants with PD versus participants with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), as well as non-Parkinsonism volunteers. This multicenter project funded by an NIH U19 grant, is centered at U Pennsylvania (Penn, Grant PI: Robert Mach) in collaboration with U Pittsburgh (Pitt) (non-clinical site) Yale U, U of California at San Francisco (UCSF) and Washington University in St. Louis (WU). The University of Pennsylvania will act as the sIRB for this multi-center human subjects project and participants will be recruited from all sites.

This registry is a prospective, multicenter, international, single arm, observational post-approval registry with follow-up at 3, 6, and 12 months, and annually for 5 years. The proposed registry will enroll 60 subjects and will be conducted at approximately 10 centers worldwide.

This is an observational study in which data are collected and studied from Parkinson's disease patients who have movement symptoms despite taking standard Parkinson's medications. In observational studies, observations are made without any changes to the participant's healthcare or treatment plan. No investigational product will be administered in this study, as participants will be treated with the standard of care that medical experts currently consider most appropriate. Parkinson's disease (PD) is a condition that affects the brain and causes problems with movement and other body functions. The symptoms of Parkinson's disease can worsen over time. People with Parkinson's disease may experience shaking (tremor), slow movements, stiff muscles, trouble walking, and problems with balance. They can also have other symptoms, such as difficulty thinking clearly, changes in mood, or difficulty sleeping. Parkinson's disease mostly affects older adults, but it can happen to younger people too. There is no cure, but treatments can help manage the symptoms and improve quality of life. While doctors and researchers know that Parkinson's disease affects people in different ways and can worsen over time, there are still many things they don't fully understand-especially for people who experience movement symptoms despite taking their usual Parkinson's medicines. Earlier studies did not follow these patients long enough or collect all the important information needed. This study is being done to fill those gaps. The main purpose of this study is to better understand how Parkinson's disease changes over time in patients who experience movement symptoms while taking standard oral Parkinson's medications, what challenges patients and their care partners face, and how their treatments are working in real life. To do this, researchers will collect data on: * Sociodemographics (e.g. age, gender, race/ethnicity, insurance provider). * Medical history and vital signs (e.g. comorbidities, family history of Parkinson's, height, weight, blood pressure). * Medications and treatments (e.g. Parkinson's and non-Parkinson's medications and other treatments, rehabilitation therapy sessions, use of mobility assistance devices). * Movement symptoms (e.g. tremor, slow movement, balance). * Non-movement symptoms (e.g. cognition, mood, sleep, activities of daily living). * Molecular data (e.g. genetics, α-synuclein). * Burden of care (e.g. economic cost). Data will come from questionnaires or rating scales conducted by the doctor with the patient during study visits, diaries and logs completed by the patient, medical records, health insurance claims records, blood samples and skin biopsies, a digital device that records movement/non-movement symptoms, and questionnaires completed by the care partner. Data will be collected from December 2025 to December 2032. Each participant may be followed for up to 5 years.

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics/pharmacodynamics (PK/PD) of LY3962681 in healthy volunteers and patients with Parkinson's disease. The study consists of two parts, the Single Ascending Dose (SAD) study and the Multiple Ascending Dose (MAD) study. During the SAD portion of the study, healthy volunteers will receive a single dose of LY3962681 or placebo (artificial cerebrospinal fluid \[aCSF\]) administered intrathecally (into the spinal fluid). During the MAD portion of the study, patients with Parkinson's disease will receive two doses of either LY3962681 or placebo (aCSF) administered intrathecally (into the spinal fluid), 12 to 24 weeks apart. * The treatment period in the SAD study will be 1 day. The treatment period in the MAD study will be 2 dosing days, 12 to 24 weeks apart. * The follow-up period in the SAD study will be up to 52 weeks. The follow-up period in the MAD study will be up to 52 weeks after Dose 2.

The purpose of this study is to compare sacituzumab tirumotecan as a single agent, and in combination with pembrolizumab, versus Treatment of Physician's Choice (TPC) in participants with hormone receptor positive/human epidermal growth factor receptor-2 negative (HR+/HER2-) unresectable locally advanced, or metastatic, breast cancer. The primary hypotheses are that sacituzumab tirumotecan as a single agent and sacituzumab tirumotecan plus pembrolizumab are superior to TPC with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR) in all participants.

Researchers are looking for new ways to treat metastatic cervical cancer. Cervical cancer is cancer in the cervix, the lower part of the uterus (womb). Metastatic means the cancer has spread to other parts of the body. Researchers want to learn about giving the study medicine sacituzumab tirumotecan (also called sac-TMT or MK-2870) along with pembrolizumab and bevacizumab treatments. Sac-TMT is an antibody drug conjugate, which is a type of medicine that attaches to specific targets on cancer cells and delivers treatment to destroy those cells. The goals of this study are to learn: * About the safety of sac-TMT with pembrolizumab and bevacizumab, and if people tolerate them when given together, and * If people who receive sac-TMT and pembrolizumab, with or without bevacizumab, live longer overall or without their cancer getting worse as compared to those who receive standard treatment

Researchers are looking for new ways to treat people with proficient mismatch repair (pMMR) endometrial cancer (EC) that is advanced or recurrent. * EC is a type of cancer that starts in the tissues inside the uterus (womb) * pMMR indicates that certain normal proteins are present in the cancer cells * Advanced means the cancer has spread locally or to other parts of the body (metastatic) and cannot be removed with surgery * Recurrent means the cancer came back after surgery Sacituzumab tirumotecan (also known as sac-TMT) and pembrolizumab are the study medicines. Sac-TMT is an antibody drug conjugate (ADC). An ADC attaches to specific targets on cancer cells and delivers treatment to destroy those cells. The goal of this study is to learn if people who receive sac-TMT with pembrolizumab live longer and without the cancer getting worse compared to people who receive pembrolizumab alone.

The current protocol is to determine the biodistribution, metabolism, excretion and brain uptake of 18F-JSS20-183A. The goal of this radiotracer is to quantify 4Repeat Tau (4Rtau) protein that is abnormally deposited in the brain of people with a class of neurodegenerative diseases called tauopathies, such as Progressive Supranuclear Palsy (PSP), Corticobasal Syndrome (CBS), syndromes of genetic Frontotemporal Lobar Degeneration (genetic FTLD) as well as participants with Parkinson disease (PD), Alzheimer's Disease (AD) and healthy controls. This multicenter project funded by an NIH U19 grant, is centered at U Pennsylvania (Penn, Grant PI: Robert Mach) in collaboration with U Pittsburgh (Pitt), Yale U, U of California at San Francisco (UCSF) and Washington University in St. Louis (WUSTL). The University of Pennsylvania will act as the sIRB for this multi-center human subjects project and participants will be recruited from all sites.