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 conducting a Phase 1/2, multicenter, open-label study to evaluate the safety and tolerability of LY3884961 in adults with peripheral manifestations of Gaucher Disease. The study focuses on finding the right dose of LY3884961, a gene therapy delivered as a single intravenous infusion. The trial aims to assess safety, immune response, biomarkers, and efficacy over time in patients who have specific genetic variants and have been on enzyme replacement or substrate reduction therapy. The study includes up to three dose-finding groups, each with three patients, followed by an expansion group of up to six patients. Patients receive one dose of LY3884961 and are monitored closely. The total participation time is about five years, with an initial 60-day screening period. During the first 18 months after dosing, detailed evaluations of safety, immune response, biomarkers, and efficacy take place, followed by an extended 42-month follow-up focusing on safety and selected measures. Participants will undergo regular assessments including monitoring for adverse events, blood tests for platelet counts and Gaucher disease markers, and imaging to evaluate spleen volume. Researchers will track treatment-emergent adverse events and serious adverse events for five years. The study also monitors whether patients can reduce or stop their enzyme replacement or substrate reduction therapies. Long-term follow-up helps ensure ongoing evaluation of safety and treatment effects throughout the study duration.

Researchers are evaluating the safety and effectiveness of FLT201 gene therapy in adults with Gaucher disease Type 1 who have been stable on enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) for at least two years. This Phase 3 study aims to confirm the benefits and safety of FLT201 after patients stop their current treatments. FLT201 is a gene therapy designed to address this rare genetic condition. Participants will receive a single intravenous infusion of FLT201, which is an advanced therapy investigational medicinal product (ATIMP). The therapy uses a special virus vector to deliver genetic material aimed at treating Gaucher disease Type 1. The study is non-randomized and conducted at multiple centers, focusing on adult patients who have maintained stable blood counts and have been on continuous treatment with ERT or SRT for at least two years. During the study, participants will be closely monitored for one year to evaluate the treatment's effects and safety. Researchers will assess the efficacy of FLT201 through various clinical measurements, including blood tests to monitor hemoglobin and platelet levels. Safety evaluations will be ongoing throughout the study. The total duration of participation is at least one year following the gene therapy infusion, with detailed follow-ups to track outcomes and any potential side effects.

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 disease's progression and treatment effects.

This research aims to better understand fucosidosis, a rare disease, by studying its natural history, symptoms, and how it progresses over time. The study collects information from people diagnosed with fucosidosis without providing any new treatments, relying only on the usual medical care. The findings may help design future studies and treatments for this condition. The study includes two parts: Part A gathers past medical data from up to 57 participants, while Part B involves ongoing data collection from up to 31 participants, most of whom may have participated in Part A. No investigational drugs or therapies are given during the study. Participants will provide information through medical records and ongoing observations, helping researchers evaluate how fucosidosis progresses over up to four years. The study team will monitor disease changes and collect data to improve understanding, without altering the participants’ usual care. The study is expected to continue 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.