Pozzilli

Researchers are evaluating the effects of pelacarsen (TQJ230), given as a monthly injection under the skin, in people with mild to moderate calcific aortic valve stenosis. This study aims to see if pelacarsen can safely slow the progression of this heart valve condition compared to a placebo. The trial is a phase 2, randomized, double-blind, placebo-controlled study conducted at multiple centers. Participants will receive either pelacarsen 80 mg or a matching placebo once a month. Before starting the treatment, they must have elevated lipoprotein(a) levels and be optimally treated for existing cardiovascular risk factors. The study focuses on those aged 50 to under 80 years with mild or moderate calcific aortic valve stenosis. During the 36 months of participation, researchers will monitor changes in peak aortic jet velocity and aortic valve calcium score to assess disease progression. Safety, tolerability, and the impact of the treatment will be evaluated. Participants will undergo regular assessments, including laboratory tests and clinical evaluations, to track heart valve condition and overall health throughout the study.

Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2), and Idiopathic Hypersomnia (IH) are rare sleep disorders causing excessive daytime sleepiness, making it difficult for people to stay alert during daily activities like school, work, or driving. NT1 often includes sudden muscle weakness called cataplexy triggered by strong emotions, while NT2 does not have cataplexy. People with IH feel tired even after long sleep and may have trouble waking up. This study aims to evaluate the safety, tolerability, and effects of ORX750, a drug designed to mimic orexin, a brain protein that helps keep people awake, in individuals with NT1, NT2, and IH. Participants will be randomly assigned to receive either ORX750 capsules or matching placebo capsules in this Phase 2a trial. The study will compare the drug against placebo to learn about its safety, how the body processes it, and its potential to reduce sleepiness and improve symptoms in these conditions. Participants must stop all other narcolepsy or hypersomnia medications and follow study requirements throughout the trial. During the study, researchers will monitor participants for treatment-related side effects, changes in laboratory tests, vital signs, heart electrical activity (ECG), and any suicidal thoughts or behaviors up to day 35. The main outcomes focus on safety and tolerability of ORX750. The study includes adults aged 18 to 65 years with specific diagnoses of NT1, NT2, or IH and tracks their response and health closely during the trial period.

Idiopathic Hypersomnia (IH) is a condition where adults feel very sleepy during the day, especially in the morning, even after getting plenty of sleep at night. They may find it hard to wake up and stay alert, affecting their ability to focus, think clearly, and carry out daily activities. This study is designed to evaluate the safety and tolerability of TAK-360, a drug that mimics orexin, a brain chemical that helps keep people awake, in adults with IH. Researchers also want to find out if TAK-360 helps improve wakefulness and determine the appropriate dose needed. Participants will be randomly assigned to receive either TAK-360 tablets or matching placebo tablets, which look the same but contain no active medicine. This study is a Phase 2 trial with a double-blind design, meaning neither the participants nor the researchers know who receives TAK-360 or placebo, to fairly assess the treatment's effects. The study focuses on finding the right dose of TAK-360 and monitoring its safety and tolerability. During the study, researchers will track treatment-emergent adverse events up to week 8 to evaluate safety. Participants will be monitored closely for how well they tolerate TAK-360 and any side effects. The study includes adults aged 18 to 70 years with a diagnosis of IH. Researchers will collect various health information to understand the drug's effects and ensure participant safety throughout the trial.

Researchers are evaluating the safety and tolerability of TAK-861 in people with narcolepsy type 1 (NT1) who have already been exposed to TAK-861 in earlier studies. The study also aims to observe improvements in symptoms such as excessive daytime sleepiness and the frequency of cataplexy episodes. This long-term extension trial continues from previous phase 2 and phase 3 trials and includes participants who completed those earlier studies. All participants in this trial will receive TAK-861 tablets. Those who were previously given a placebo in parent trials will be randomly assigned to a dose of TAK-861. The study plans to enroll up to 500 participants worldwide and will last approximately 5 years, or until the study is stopped or the drug is approved and launched. Participants will visit clinics multiple times, with some visits possibly done at home, and will have a follow-up check 4 weeks after their last dose. During the study, participants will be monitored for treatment-emergent adverse events from the time they consent until 4 weeks after their final dose, covering up to about 5 years. Researchers will assess safety and tolerability regularly through these visits and follow-ups. The focus is on identifying any side effects and understanding the long-term effects of TAK-861 in people with NT1.

Researchers are evaluating the bioequivalence of two subcutaneous formulations of ocrelizumab in adults with relapsing multiple sclerosis (RMS) or primary progressive multiple sclerosis (PPMS). This phase II study aims to compare a test formulation of ocrelizumab with the marketed reference formulation to understand if they behave similarly in the body. Participants include those diagnosed based on the revised McDonald criteria, with an Expanded Disability Status Scale (EDSS) score between 0 and 6.5. The study has two phases: a controlled phase where participants receive a single dose of either the test or reference ocrelizumab formulation, followed by a continuation phase where all participants receive the test formulation. Both treatments are administered subcutaneously according to the study schedule. The design is randomized, open-label, parallel group, and multicenter. During the study, researchers will monitor the body's response to the medication by measuring serum concentration levels, including the area under the concentration-time curve and maximum serum concentration over 12 weeks after dosing. Participants undergo screening and evaluations to confirm eligibility and safety. The study excludes those with recent anti-CD20 treatments, certain medical histories, or other conditions that might interfere with the study. The age range for participants is 18 to 65 years, and both genders are eligible.

Researchers are evaluating the effectiveness and safety of remibrutinib in adults aged 18 to 65 years with secondary progressive multiple sclerosis (SPMS). This Phase III study is randomized, double-blind, and placebo-controlled, designed to better understand how remibrutinib affects disability progression in SPMS patients over time. Participants will be randomly assigned to receive either oral remibrutinib tablets or matching placebo tablets during the Core Part of the study, which is event-driven and double-blinded. After this period, all participants may enter an Extension Part where they receive open-label remibrutinib treatment. This design allows researchers to compare remibrutinib against placebo and then monitor long-term effects when all participants receive the active drug. Throughout the study, participants will undergo regular assessments including MRI scans and clinical evaluations to track changes in disability using the Expanded Disability Status Scale (EDSS). The primary outcome measured is the time to confirmed disability progression over six months, with follow-up lasting up to approximately five years. Safety, tolerability, and other health parameters will also be closely monitored during both study phases.

This research aims to evaluate the long-term safety and tolerability of pelacarsen (TQJ230) in adults with established cardiovascular disease and elevated Lipoprotein(a) who have completed the parent trial CTQJ230A12301. The study is an open-label extension following the phase 3 parent study, providing participants continued access to pelacarsen after the initial trial. Participants will receive pelacarsen 80 mg by subcutaneous injection once a month during this open-label extension. The study is single-arm and multicenter, focusing on continued treatment with pelacarsen for up to 36 months after completion of the parent study. Throughout the study, participants will be monitored regularly to assess safety and tolerability, with particular attention to adverse events occurring up to 36 months. Researchers will collect data on health status throughout this period to understand the long-term effects of pelacarsen in this patient population.

Researchers are conducting a prospective and retrospective cohort study over about five years to investigate biomarkers related to synaptic damage in multiple sclerosis (MS). This study also includes control groups with other chronic neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and healthy subjects undergoing blood sampling or lumbar puncture for clinical reasons. The goal is to identify new biomarkers that may help define the course of MS and understand mechanisms underlying synaptic damage. Participants will provide blood and cerebrospinal fluid samples, which will be processed immediately after collection to isolate various components. The study will measure levels of microRNAs, cytokines, chemokines, growth factors, neuronal damage markers (such as tau proteins and neurofilaments), mitochondrial markers, and free d-amino acids. Synaptic changes will be assessed using an ex vivo chimeric model of MS and the patch-clamp technique. Genetic studies will identify specific gene variations associated with synaptic transmission alterations, clinical parameters, and biomarker levels. Participants will undergo lumbar puncture performed for diagnostic purposes. Researchers will analyze biological samples and perform genotyping to correlate biomarkers with disease features. The primary outcome is the identification of predictive biomarkers of synaptic damage using the ex vivo model. The study involves adult men and women aged 18 to 65 years diagnosed with MS, with monitoring of clinical and laboratory parameters. The study excludes those unable to consent, with altered blood counts, pregnancy or lactation, MRI contraindications, or other significant conditions.

Neurodegenerative disorders like Parkinson's disease (PD), Alzheimer's disease (AD), Frontotemporal dementia (FTD), and Amyotrophic Lateral Sclerosis (ALS) involve harmful buildup of misfolded proteins that affect nerve function and survival. Researchers aim to study protein structures in body fluids as potential markers to better understand these diseases. The study plans to gather a large group of patients and healthy individuals, using genetics and clinical data to find new circulating biomarkers linked to disease features and genetic profiles, and then validate these findings in brain tissue and nerve cell cultures. This observational study involves two main research centers collaborating. One center focuses on collecting samples, genetic testing, and analyzing protein complexes in cerebrospinal fluid (CSF) and plasma to identify changes related to disease and genetics. The other center collects patient samples and clinical data to detect and validate protein biomarkers, including their presence in brain tissue and their effects on nerve cells derived from stem cells. Participants will undergo genetic sequencing (whole genome and exome) and detailed clinical assessments specific to each disorder. Participants will be monitored over two years with evaluations of motor and non-motor symptoms, cognitive assessments, and genetic analysis. Researchers will analyze protein complexes in CSF and plasma, study their biological impact on dopaminergic neurons, and correlate findings with clinical and genetic information. The study measures outcomes such as disease progression scores and the identification of protein and genetic markers to improve early diagnosis, prognosis, and treatment approaches for neurodegenerative diseases.

Researchers are studying progressive multiple sclerosis (PMS), a condition where inflammation in the brain causes abnormal nerve communication, leading to worsening nerve damage and symptoms. The study focuses on a technique called transcranial static magnetic field stimulation (tSMS) that may help reduce nerve damage by balancing brain signals and promoting protective brain changes. This approach could slow down disease progression by improving nerve survival and function in patients with PMS. Participants will be randomly assigned to receive either real or sham tSMS in a double-blind, crossover design. Each patient will self-administer two daily sessions of tSMS, each lasting 60 minutes, over both sides of the primary motor cortex for 12 months total (6 months real and 6 months sham in random order). The real treatment uses special magnets applied via a helmet, while the sham treatment uses non-magnetic devices that look and weigh the same. Patients may perform the treatments at home or in a hospital outpatient setting. Throughout the study, patients will undergo clinical evaluations, including assessments of disability and motor function, before, during, and after each treatment phase. Researchers will also measure blood markers, brain excitability and plasticity, and brain imaging to monitor effects. Functional assessments will occur at baseline, midway, and after each stimulation period, totaling multiple evaluations to track changes over time and compare real versus sham stimulation effects.