Lysosomal Storage Disease

Researchers are evaluating the safety, tolerability, and pharmacodynamics of 4D-310, a gene therapy, in adults with Fabry Disease who have heart involvement. This open-label, dose-escalation trial includes adult males and females aged 18 to 65 years and aims to understand how the treatment works after a single intravenous dose. Fabry Disease is a condition that affects multiple organs, including the heart, and requires new treatment approaches. Participants receive one single intravenous administration of 4D-310 at different dose levels as part of the study. The trial includes several dose groups, with some dose levels no longer enrolling. The study is conducted across multiple centers and is designed to carefully monitor responses to the gene therapy over time. During the study, participants will be regularly assessed for safety by tracking any adverse events for one year following treatment. Researchers will also monitor how the body responds to the therapy through various evaluations. The total participation time includes screening, treatment, and follow-up visits to ensure thorough observation of treatment effects and safety.

Gaucher disease type 1 GD1 is caused by mutations in the GBA1 gene, leading to a deficiency in the enzyme glucocerebrosidase GCase. This deficiency results in the buildup of glucosylceramide GlcCer in various organs, including the liver, spleen, kidney, bone, lung, and brain, causing cells to change and leading to tissue and organ problems. Researchers are evaluating LY-M001, a gene therapy using an rAAV8 vector, which aims to deliver the GCase protein to liver cells after a single intravenous infusion to address this enzyme deficiency. This clinical trial includes two phases Phase I is a dose escalation study with three dose groups, starting at a lower dose and increasing to higher doses to assess safety. Participants receive a single intravenous infusion of LY-M001 at one of the specified doses. Phase II is a dose expansion study where the recommended dose from Phase I is given to more participants to further evaluate safety and efficacy. The study has a main period of 52 weeks following infusion and a long-term follow-up phase lasting from 53 weeks up to 5 years. Participants will undergo regular assessments including monitoring for adverse events, liver function tests, blood enzyme activity, blood counts, imaging of liver and spleen volumes, bone mineral density, and bone marrow evaluation. Safety evaluations also include electrocardiograms, vital signs, and laboratory tests. The study aims to track the effects of LY-M001 over time, with extended follow-up to gather long-term data on safety and treatment impact throughout the study duration.

Researchers are evaluating LY3884961, a genetic therapy delivered as a single intravenous infusion, in adults with peripheral symptoms of Gaucher Disease. This Phase 12, open-label, multicenter study aims to assess the safety and tolerability of different dose levels of LY3884961. The study includes dose-finding cohorts followed by an expansion cohort to better understand the therapys effects in this patient group. Participants will receive one dose of LY3884961 and will be monitored closely for 18 months to evaluate safety, tolerability, immune response, biomarkers, and treatment effects. The study may include up to three dose levels tested in small groups of patients, with an additional group enrolled afterward. The total study duration for each patient is about five years, including a screening period of up to 60 days. During the trial, participants will have regular evaluations including laboratory tests, imaging, and clinical assessments to track treatment-emergent adverse events and changes in spleen volume, platelet count, and relevant biomarkers. Researchers will also monitor the use and discontinuation of enzyme replacement or substrate reduction therapies. Long-term safety and immune response will be followed for up to 42 months after the initial 18-month period.

Researchers are evaluating the gene therapy FLT201 in adults with Gaucher disease Type 1 who have been on stable enzyme replacement therapy ERT or substrate reduction therapy SRT for at least two years. This Phase 3, non-randomized, multicenter study aims to confirm the efficacy and safety of FLT201 after participants stop their current treatments. FLT201 is an advanced therapy designed to address this rare genetic condition by delivering a gene using a recombinant adeno-associated virus vector. Participants receive a single intravenous infusion of FLT201 during the study. This gene therapy uses a replication-incompetent viral vector to introduce the therapeutic gene. The study includes only one treatment group and does not involve placebo or comparison arms. The primary treatment period focuses on evaluating FLT201s impact over one year after stopping prior therapies. Throughout the study, participants undergo regular assessments to monitor their health and treatment effects. Researchers evaluate the therapys efficacy by measuring clinical outcomes at one year. Safety is closely observed to identify any adverse effects. The total study duration extends to 2032, allowing long-term follow-up of participants responses and overall well-being.

This research is a global, multicenter, prospective observational registry studying patients with Pompe disease, including both late-onset LOPD and infantile-onset IOPD forms. It enrolls both untreated patients and those receiving approved therapies to better understand the long-term safety, real-world effectiveness, and quality of life impacts of treatments for Pompe disease. The study also aims to describe the natural history of untreated Pompe disease. Participants include groups receiving different enzyme replacement therapies such as Cipaglucosidase alfa with Miglustat, other approved ERTs like Alglucosidase alfa or Avalglucosidase alfa, as well as untreated individuals who are not on any medical therapy for Pompe disease. No experimental treatments are given as this is an observational study tracking real-world treatment use and outcomes. During the study, participant data on adverse events, treatment effectiveness, quality of life, and patient-reported outcomes will be collected over a period of at least five years. Researchers will monitor safety through the frequency of adverse events and serious adverse events. Participants health and treatment impacts will be regularly evaluated to provide long-term insights into Pompe disease management and outcomes.

Researchers are conducting a global prospective observational study involving women with Fabry disease who are pregnant or breastfeeding, along with their infants. The study aims to evaluate outcomes related to pregnancy and breastfeeding in women and infants who have been exposed to the drug migalastat. An unexposed group of women with Fabry disease may also be included for comparison. This study will collect data over a minimum of 10 years to gain comprehensive insights. The study includes two groups Cohort 1 consists of pregnant or breastfeeding women with Fabry disease who have taken at least one dose of migalastat during this time, while Cohort 2 includes similar women who have not been exposed to migalastat. Participants are reported voluntarily from any country by healthcare providers, patients, or secondary contacts. The Pregnancy Coordinating Center will follow the mothers through pregnancy and breastfeeding, and their infants up to one year old. Participants will have their pregnancies and infants monitored for various outcomes such as birth defects, miscarriage, fetal death, delivery complications, infant growth measurements, allergic reactions, hospitalizations, and mortality up to one year of age. Data collection includes monitoring major and minor birth defects, neurodevelopmental problems, jaundice, and serious adverse events in both mothers and infants. This long-term follow-up helps researchers understand the effects of migalastat exposure during pregnancy and breastfeeding.

Researchers are studying Gaucher disease to understand its long-term effects, evaluate how well treatments like enzyme replacement therapy ERT and substrate reduction therapy SRT work over time, and identify possible complications. This observational study involves reviewing health records of individuals with all three types of Gaucher disease to gather detailed information. The study is led by Dr. Kishnani at Duke University, a specialist in this condition. Participants health information will be collected systematically from medical records, both from Duke and other treating physicians. The study does not change the usual care patients receive. Researchers will monitor health status at least once a year, depending on when medical information becomes available from treating doctors. The study includes long-term follow-up to observe the course of the disease and treatment outcomes. During the study, researchers will document how Gaucher disease affects various body systems such as the nervous system, liver, and spleen over a period of 10 years. They will also record any adverse events related to ERT or SRT and track long-term complications. Participants will complete surveys and screenings every six months to a year to assess their health and neurological symptoms. This ongoing monitoring helps provide a comprehensive understanding of the diseases progression and treatment effects.

Researchers are conducting an observational study to better understand fucosidosis, a rare disease, its symptoms, and how it changes over time. The study aims to gather detailed information about the diseases natural history and progression, including patients who have or have not undergone stem cell transplant. There is currently no approved treatment for fucosidosis, so this study focuses on observing the condition without introducing new medications. The study is divided into two parts Part A involves collecting past medical data from up to 57 participants, and Part B involves following up with up to 31 participants prospectively, many of whom may also be in Part A. Participants will continue to receive their usual medical care throughout the study, with no additional treatments or interventions provided by the study team. Participants will provide medical history and health information that will be reviewed over time. The main focus is to track disease progression in individuals untreated by investigational products for up to four years. This includes gathering retrospective data and ongoing prospective observations to aid future research and potential treatment development. The study is expected to run until January 2031.

This observational study follows patients diagnosed with Pompe disease who are receiving or preparing to receive enzyme replacement therapy. The research aims to monitor long-term outcomes and the overall health of these patients over an extended period, providing valuable information about the disease progression and treatment experience. Participants will be observed prospectively without any investigational treatments assigned by the study. All enrolled individuals are those already receiving enzyme replacement therapy or preparing to begin it, and the study collects data on their health and treatment outcomes over time. During the study, patients will be regularly monitored for all-cause morbidities over a 10-year period. Researchers will collect health information to understand the long-term effects of enzyme replacement therapy in Pompe disease. Participation involves ongoing health assessments, and the study extends until December 2026, providing extensive long-term outcome data.

Researchers are conducting a large, multi-country observational study to assess the safety and effectiveness of pegunigalsidase alfa Elfabrio in patients with Fabry disease. This study includes patients who are currently treated with pegunigalsidase alfa in routine care and gathers data both retrospectively and prospectively. The study considers different patient groups such as those with Fabry-related heart disease, treatment-nave patients, and those transitioning from an earlier open-label extension study. The treatment being observed is pegunigalsidase alfa, administered through intravenous infusion as part of routine clinical care. Participants are grouped into cohorts based on their disease status and treatment history, including a cardiac cohort with Fabry-related heart involvement, a nave cohort who have not received prior Fabry treatment, and a long-term cohort of patients continuing from a previous clinical study. The study does not intervene in treatment but observes patients receiving this drug in real-world settings. Participants will be followed for up to four years, during which researchers will collect various clinical measurements such as kidney function estimated glomerular filtration rate, plasma lysoGb3 levels, heart structure and function via left ventricular mass index and cardiac biomarkers, and overall safety assessments. Data will be collected through routine clinical visits, imaging studies, and patient-reported outcomes. The study aims to provide comprehensive long-term information on the effects and safety of pegunigalsidase alfa in everyday clinical practice.