Fabry 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.

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 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.

Researchers are evaluating a gene therapy called AAV9-GLB1 for treating Type I and Type II GM1 gangliosidosis, a rare and fatal disorder that destroys nerve cells due to a deficiency in the enzyme beta-galactosidase. This trial aims to test if the gene therapy can help improve symptoms related to these types of GM1 gangliosidosis. The study is a Phase 1/2 non-randomized trial focusing on safety and effectiveness in children ranging from 6 months to 12 years old, sponsored by the National Human Genome Research Institute (NHGRI). Participants will receive a single intravenous infusion of the AAV9-GLB1 gene therapy at doses determined in stages. In Stage 1, different groups of Type I and Type II subjects will receive varying doses to assess safety. Immune system modulation drugs such as rituximab, sirolimus, methylprednisolone, and prednisone will be given before and after gene therapy to reduce immune reactions. Participants will stay at the study site for 8 to 10 weeks initially and may remain for additional safety monitoring after infusion. Stage 2 will administer the dose selected based on Stage 1 data, with further assessments planned. During the study, participants will undergo many tests including blood and urine tests, heart and hearing assessments, ultrasounds, EEGs, lumbar punctures, MRIs, bone scans, IQ and speech tests, and neurological exams. Central line placement and skin biopsies may also be done. Follow-up visits will occur at 3 and 6 months after treatment, then every 6 months for 2 years, and again at 3 years, with yearly visits for 2 more years in an extension study. Researchers will monitor safety, brain development, neurological function, motor skills, and immune responses throughout the study period.

Researchers are conducting a study to systematically screen newborns in the Normandy region for lysosomal storage diseases such as Mucopolysaccharidosis type I and Pompe disease. This observational study aims to evaluate the occurrence and epidemiology of these diseases using dried blood samples collected from newborns. The study is based on previous pilot work and seeks to include about 100,000 newborns over a period of three years. All newborns born in Normandy maternity hospitals who are participating in the national neonatal screening program will have additional blood samples collected on blotting paper for this study. The screening occurs within the first few days after birth, typically from day 2 to day 4. The study will continue until the target number of participants is reached. Participants will have blood samples collected as part of routine neonatal screening, with extra samples taken specifically for this research. The main outcome measured is the number of newborns screened relative to the number of samples collected. Secondary outcomes include the number of positive cases detected for Mucopolysaccharidosis type I and Pompe disease. The study involves parental consent and monitors newborns during these early days, with no further intervention or long-term follow-up described.

Fabry Disease is a rare inherited blood disorder caused by low levels of an enzyme called alpha-galactosidase A. This enzyme normally breaks down fat-like substances, but without enough of it, these substances can build up in blood vessels and harm vital organs such as the heart, kidneys, and brain over time. This study aims to learn more about the treatment effects of agalsidase alfa (Replagal4), an enzyme replacement therapy, in Chinese children and adults with Fabry disease by observing its impact on heart and kidney function, quality of life, and safety in routine clinical use. Participants in this study will receive enzyme replacement therapy with agalsidase alfa as part of their usual clinical care in China. This is a non-interventional, observational study where no additional study-specific visits are scheduled. The treatment follows routine practice settings, and researchers will monitor participants receiving this therapy over time. During the study lasting up to 18 months, participants will be observed for changes in heart function using measures like left ventricular mass index and ejection fraction, and kidney function using estimated glomerular filtration rate and urine analyses. Quality of life assessments and monitoring of adverse events will also be conducted. The study collects data from regular clinical visits without extra procedures, aiming to understand how agalsidase alfa works and its safety in real-world treatment of Fabry disease.

Researchers are evaluating the safety, pharmacokinetics, pharmacodynamics, and effectiveness of migalastat treatment in children aged 2 to less than 12 years with Fabry disease who have specific GLA gene variants that respond to this treatment. This Phase 3b, open-label, multicenter study includes pediatric subjects either new to enzyme replacement therapy (ERT) or who have stopped ERT at least 14 days before starting the study. The study consists of two consecutive treatment stages totaling 12 months of migalastat given every other day, with the initial dose based on body weight. Stage 1 lasts about 3 months, followed immediately by Stage 2 of 9 months. Participants are randomly assigned to one of three pharmacokinetic sampling groups, with blood samples collected at specified times during the study to measure migalastat levels. Participants will undergo regular safety monitoring, including tracking treatment-emergent adverse events, and blood tests to measure migalastat concentration and disease-related markers. Additional assessments include kidney function tests, heart measurements, symptom questionnaires, and quality of life surveys conducted at various times throughout the 12-month treatment and a 30-day follow-up after treatment ends. The study extends beyond the initial treatment period with an open-label extension phase for ongoing evaluation.

Researchers are evaluating the long-term effects of treatments on the effectiveness, safety, and health-related quality of life in patients with Fabry disease, focusing mainly on the drug migalastat. This prospective, observational study will enroll at least 450 patients worldwide, including those treated with migalastat, those receiving enzyme replacement therapy (ERT), and untreated patients. The study is designed to observe these patients over time to better understand disease progression and treatment impacts. Participants are grouped based on their treatment status: those treated with migalastat who started within 24 months before enrollment, those treated with ERT who also started within 24 months before enrollment, and untreated patients who have never been on treatment for Fabry disease but meet criteria for migalastat treatment. The study is non-interventional, meaning it observes patients receiving their usual care without assigning treatments. Enrollment will continue for five years, and each patient will be followed for up to five years after joining. During the study, participants will undergo various assessments, including monitoring kidney function by measuring the annualized rate of change in estimated glomerular filtration rate (eGFR). Researchers will also track clinical events related to Fabry disease, changes in relevant biomarkers, quality of life through patient-reported outcomes, and safety events over the observation period. Data will be collected both retrospectively and prospectively, with a focus on understanding long-term outcomes and treatment effects up to five years.

Researchers are evaluating the safety and effectiveness of Replagal in children and adults with Fabry disease in India. This open-label, single-arm Phase IV study aims to better understand the safety profile of Replagal by monitoring participants for about one year. Fabry disease participants must have a confirmed diagnosis based on gene mutation or enzyme deficiency and show clinical symptoms. Participants will receive Replagal at a dose of 0.2 mg per kilogram through intravenous infusion starting on Day 1 and then every two weeks up to Week 51. The treatment is given at the clinic and is designed to assess safety and potential benefits over approximately one year. This study does not include a comparison group and focuses on the effects of Replagal alone. During the study, participants will have regular assessments including kidney function tests, heart measurements, urine analyses, and quality of life questionnaires at various time points up to Week 53. Researchers will monitor adverse events, infusion reactions, and any treatment-related side effects throughout the study. Participants will be followed closely with scheduled visits to evaluate safety and any changes in their condition over the course of the year.

Researchers are evaluating the safety and effects of pegunigalsidase alfa (PRX-102), an enzyme replacement therapy, in children and adolescents with Fabry disease. This study includes boys and girls aged 2 to less than 18 years who have confirmed Fabry disease and symptoms such as neuropathic pain, cornea verticillata, or clustered angiokeratoma. The aim is to find the safest and most effective dose and understand how the drug affects symptoms like kidney and heart function, pain, and gastrointestinal problems. PRX-102 is given by intravenous infusion every two weeks. The study is divided into three parts: Stage I to find the correct dose, Stage II to confirm safety and effectiveness, and an optional Stage III extension until the drug becomes commercially available or the study ends. The drug dosing starts at 1.0 mg/kg every two weeks, with adjustments possible for younger children. Participants are grouped by age into three cohorts: 2 to 7 years, 8 to 12 years, and 13 to less than 18 years. Participants will have visits at least every two weeks for drug administration and various tests. These include physical exams, heart monitoring with ECG and ultrasound, symptom and quality of life questionnaires, and blood and urine tests to check safety, disease severity, and drug levels. Blood samples are collected multiple times over dosing intervals to study how the drug behaves in the body. Researchers will measure outcomes like adverse reactions, heart and kidney function, pain medication use, and disease severity over 12 months.