Pozzilli

This trial studies adults aged 50 to under 80 with mild or moderate calcific aortic valve stenosis and elevated lipoproteina levels. Researchers are assessing the safety, tolerability, and ability of pelacarsen TQJ230 given once monthly by injection to slow the progression of this heart valve condition. The study compares pelacarsen to a placebo in a randomized, double-blind design. Participants receive either pelacarsen 80 mg or a matching placebo as a subcutaneous injection monthly. They continue treatment and monitoring for up to 36 months to observe changes in heart valve narrowing and calcium buildup. The study also tracks lipoproteina levels and clinical heart-related events during this period. Throughout the study, participants will have regular assessments including imaging to measure aortic valve function and calcium score, blood tests for lipoproteina, and monitoring for safety. The main outcomes analyzed after 36 months include changes in valve jet velocity and calcium score, alongside clinical events. Participants remain under medical care while being observed for any effects of the study drug or placebo.

Researchers are evaluating orelabrutinib, a brain-penetrating BTK inhibitor, in adults with Primary Progressive Multiple Sclerosis PPMS. This phase 3, randomized, double-blind, parallel-group, multicenter study compares orelabrutinib to placebo to assess its efficacy and safety in treating PPMS. About 705 participants aged 18 to 60 years will be enrolled globally with a 21 randomization favoring orelabrutinib. Participants will receive either oral orelabrutinib or a matching placebo. Treatment will last approximately 30 to 60 months, with a minimum of 12 months on study drug. The study includes two groups one receiving orelabrutinib and the other receiving placebo, both administered orally. The trial design is intended to monitor long-term effects and progression. During the study, participants will undergo regular assessments including disability progression measured over 12 weeks and up to approximately 120 weeks. Evaluations include MRI scans to monitor lesions, timed walking and hand function tests, cognitive testing, and safety assessments such as monitoring adverse events. The study will closely follow participants for up to 5 years to understand the impact of the treatment on disease progression and safety.

Researchers are evaluating the safety, tolerability, and effects of ORX750 in adults with Narcolepsy Type 1 NT1, Narcolepsy Type 2 NT2, and Idiopathic Hypersomnia IH. These rare conditions cause excessive daytime sleepiness and affect daily activities such as school, work, and driving. The study aims to understand how ORX750, which mimics the brain protein orexin that helps maintain wakefulness, impacts sleepiness and other symptoms in these conditions. Participants will receive either ORX750 capsules or matching placebo capsules in a randomized, double-blind setup. The study assesses multiple groups those with NT1, NT2, and IH. The treatment and monitoring will occur over a period of up to 35 days, including evaluation of plasma drug levels and sleepiness measures. During the study, participants will undergo safety assessments including monitoring for adverse events, laboratory tests, vital signs, ECGs, and suicidal ideation screening up to day 35. Researchers will also measure sleepiness using the Maintenance of Wakefulness Test and the Epworth Sleepiness Scale. The total study duration for each participant is about five weeks, with careful observation of how the body processes ORX750 and its effects on daytime alertness.

Idiopathic Hypersomnia IH is a condition where adults feel extremely sleepy during the day, especially in the morning, even after sleeping a lot at night. This condition can cause difficulty waking up, trouble focusing, and symptoms like dizziness. Researchers are studying TAK-360, a drug that acts like orexin, a brain chemical that helps keep people awake. The study aims to understand how safe and tolerable TAK-360 is for adults with IH and to find the right dose to help with wakefulness. Participants in the study will be randomly assigned to receive either TAK-360 tablets or placebo tablets that look the same but contain no active medicine. Both treatments will be taken orally for 4 weeks. The study uses a double-blind design, meaning neither participants nor researchers know who receives the drug or placebo, to fairly evaluate the effects of TAK-360. During the study, participants will be monitored for safety and side effects up to 8 weeks. Researchers will measure changes in daytime sleepiness using the Epworth Sleepiness Scale and symptoms using the Idiopathic Hypersomnia Severity Scale at the start and after 4 weeks. The trial will also track any treatment-emergent adverse events. The total participation time may include screening, treatment, and follow-up assessments over several weeks.

Researchers are evaluating the safety and tolerability of TAK-861 in people with narcolepsy type 1 NT1. This study focuses on participants who have already been exposed to TAK-861 doses in previous clinical trials. The goal is to monitor how TAK-861 affects symptoms such as excessive daytime sleepiness and cataplexy episodes over a long period. All participants in this trial will receive TAK-861 tablets. Those who previously received a placebo will be randomly assigned to one of the TAK-861 dose groups. The study is a long-term extension conducted worldwide and is expected to last approximately five years or until the product is approved or the study is stopped. Participants may switch doses as needed and will attend multiple clinic visits, some of which can be done at home. Throughout the trial, participants will be regularly assessed for safety by tracking any treatment-emergent adverse events. Researchers will also measure changes in sleep latency, sleepiness scores, and cataplexy rates compared to baseline data from earlier trials. Follow-up assessments will take place four weeks after the final dose to monitor ongoing effects and ensure participant safety.

Researchers are evaluating the efficacy and safety of remibrutinib in patients with secondary progressive multiple sclerosis SPMS. This is a Phase III, randomized, double-blind, placebo-controlled, multi-center study involving approximately 1275 participants. The study aims to provide important data on remibrutinibs effect on disability progression in SPMS and includes both a Core Part and an Extension Part for further assessment. Participants are randomly assigned to receive either remibrutinib or a matching placebo as oral film-coated tablets during the Core Part. The Core Part includes double-blind treatment, followed by an Extension Part where all participants receive open-label remibrutinib tablets. Treatment is taken orally, and the study is event-driven, continuing until required endpoints are met. During the study, participants undergo regular assessments of disability progression using the Expanded Disability Status Scale EDSS, Timed 25-Foot Walk, 9-Hole Peg Test, and Symbol Digit Modalities Test, among others. Brain imaging and safety monitoring for adverse events are performed throughout up to approximately five years. Researchers track changes in brain lesions and atrophy, and follow participants for safety and treatment effects over time.

Researchers are evaluating clemizole HCl as an additional treatment for children and adults aged 2 to 55 years who have Lennox-Gastaut syndrome LGS, a condition characterized by seizures and abnormal brain activity. This Phase 3 trial aims to assess how well clemizole HCl works and how safe it is when added to existing treatments. The study is randomized, double-blind, and placebo-controlled to ensure reliable results. Participants will go through three main phases an Observational Period, a Double-Blind Period, and an optional Open-Label Extension. During the Double-Blind Period, participants receive either clemizole HCl or a placebo as an oral solution. Those who complete this phase may continue to receive clemizole HCl for up to three years in the Open-Label Extension Phase. Throughout the study, participants will be monitored closely with various assessments, including measuring seizure frequency using the CMMS-28 scale over up to 16 weeks. Researchers will also check global impressions of change, quality of life scores, and record any treatment-emergent side effects. The studys overall duration may last up to several years, allowing for long-term safety and effectiveness monitoring.

This study evaluates the long-term safety and tolerability of pelacarsen TQJ230 in people with established cardiovascular disease and elevated Lipoproteina who completed a previous related study. It is an open-label extension trial, meaning all participants receive the study drug without placebo comparison. The trial is sponsored by Novartis Pharmaceuticals and focuses on continued treatment after the completion of the parent study. Participants receive monthly injections of pelacarsen 80 mg subcutaneously for up to 36 months during this extension phase. This phase is designed to provide access to the study drug after the initial trial and to monitor participants closely. The study does not involve randomization or blinding, and all enrolled participants receive the active drug. During the study, participants will undergo regular assessments including monitoring for adverse events and cardiovascular events, as well as measuring Lipoproteina levels at baseline and several time points over 36 months. Safety and tolerability will be closely tracked throughout the treatment period. The total duration of participation corresponds to the length of the extension phase, up to three years.

This research aims to identify new biomarkers linked to synaptic damage in Multiple Sclerosis MS and to study the mechanisms that contribute to this damage. It involves both prospective and retrospective observation over about five years, analyzing blood and cerebrospinal fluid samples taken for diagnostic reasons. The study includes patients with MS, other chronic neurodegenerative diseases such as Amyotrophic Lateral Sclerosis, Alzheimers disease, Parkinsons disease, and healthy subjects as control groups. Participants undergo procedures including lumbar puncture and blood sampling to measure microRNAs, cytokines, chemokines, growth factors, neuronal damage markers like tau proteins and neurofilaments, mitochondrial markers lactate, and free d-amino acids. The study also evaluates synaptic changes using an ex vivo chimeric model of MS with patch-clamp techniques and conducts genotyping to find gene variants associated with synaptic transmission alterations and clinical parameters. Throughout the study, researchers monitor these biomarkers and genetic factors to predict disease progression and identify potential therapeutic targets. Participants provide samples for various laboratory analyses, including SNPs analysis, and clinical assessments such as the Expanded Disability Status Scale EDSS and disease activity indices. The studys main outcome is to identify predictive biomarkers using the ex vivo model, with secondary goals to find new therapeutic targets for MS.

Neurodegenerative disorders such as Parkinsons disease, Alzheimers disease, Frontotemporal dementia, and Amyotrophic Lateral Sclerosis involve the buildup of misfolded proteins that affect nerve cell function and survival. Researchers are studying protein complexes in body fluids as potential biomarkers to help with early diagnosis, prognosis, and treatment management of these disorders. This observational study aims to collect clinical, genetic, and biofluid data from patients and healthy individuals to identify and validate these biomarkers. Participants will undergo genetic testing including whole genome and whole exome sequencing to analyze DNA for variants related to their specific condition. Samples of cerebrospinal fluid CSF, plasma, serum, and blood cells will be collected for analysis. The study involves collaboration between two centers focusing on patient stratification, sample collection, bioinformatics, and biological validation using human brain tissue and neuron cultures derived from induced pluripotent stem cells. During the study, participants will be evaluated for motor and cognitive symptoms using clinical scales such as the Hoehn and Yahr score, MDS-UPDRS, MOCA, and others over two years. Researchers will analyze protein complexes in CSF and plasma and correlate findings with genetics and clinical data. The biological effects of identified protein complexes on neuron viability will also be assessed. Participant involvement includes clinical assessments, sample donations, and genetic testing, with ongoing monitoring throughout the study period.