Dundonald

This research aims to better understand the natural history of Congenital Myasthenic Syndromes CMS caused by mutations in the DOK7, MUSK, AGRN, or LRP4 genes. It evaluates disease activity by collecting clinical data and quality of life information from participants with these specific genetic mutations. The study is observational and involves participants aged 2 years and older diagnosed with CMS due to these mutations. Participants will attend up to four study visits where clinical assessments will be performed. These assessments include evaluating symptoms and quality of life using tools like the Quantitative Myasthenia Gravis QMG score and other standardized measures. The study collects both retrospective and prospective data on diagnosis, healthcare use, medications, and health status changes related to CMS over a period of up to 12 months. During the study, participants will undergo various evaluations including symptom scoring, questionnaires on daily living activities, fatigue, and health-related quality of life. Researchers will analyze changes from baseline in these measures to understand disease progression and impact. No investigational treatments are given, and the focus is on monitoring and documenting the condition. Participation may last up to 12 months with scheduled visits for data collection and assessments.

Researchers are evaluating the investigational drug omecamtiv mecarbil to see if it can lower the risk of serious effects related to heart failure, such as hospitalization, heart transplantation, or death, in patients with symptomatic heart failure and severely reduced ejection fraction. This phase 3 trial aims to assess both the effectiveness and safety of the drug compared to placebo in reducing cardiovascular events including death, heart failure events, left ventricular assist device implantation, cardiac transplantation, and stroke. Participants will be randomly assigned to receive either omecamtiv mecarbil or a placebo. Those in the omecamtiv mecarbil group will take an oral tablet twice daily at a dose based on their blood drug levels 25, 37.5, or 50 mg. The placebo group will receive matching tablets twice daily. The study will continue until at least 850 participants experience a heart failure event or cardiovascular death. An interim analysis will be performed when about 67% of these events have occurred. The total estimated participation duration is up to 3 years. During the trial, participants will be regularly monitored for cardiovascular events, hospitalizations, and other health outcomes. Researchers will measure the time to first cardiovascular death or heart failure event among other secondary outcomes such as stroke and overall survival. Safety will be carefully tracked throughout the study. Participants adherence to the study medication and health status will be assessed at scheduled visits over the course of the study.