Amino Acid Metabolism Disorder

Urea cycle disorders UCD are rare diseases in China that can cause high mortality and disability, requiring long-term management due to recurring symptoms. This multi-center, prospective, single-arm study aims to evaluate the safety and effectiveness of Glycerol Phenylbutyrate in Chinese children with UCD. The goal is to provide more treatment options and improve clinical care for these patients in China. The study plans a total observation period of five years for patients on long-term treatment with this medication. The study involves 40 children aged from birth to 18 years diagnosed with various types of UCD, including carbamoyl phosphate synthetase I deficiency and others. Participants will receive Glycerol Phenylbutyrate oral liquid, with dosing based on body surface area and divided into multiple daily doses taken with meals. The study includes scheduled clinic visits at 1 month and 3 months after enrollment, followed by visits every 6 months up to 5 years. During these visits, researchers collect data on adverse events, dosage changes, hyperammonemic crises, and blood ammonia levels. Participants will undergo regular assessments including blood tests for ammonia and biochemistry, growth measurements height, weight, head circumference, and neurocognitive evaluations at specified intervals. The primary outcome is the mean blood ammonia level at 3 months after enrollment. Secondary outcomes include ammonia levels at multiple timepoints, frequency of crises, growth data, dosage adjustments, and various neurodevelopmental scores measured annually. This comprehensive follow-up aims to monitor safety, treatment effects, and overall development throughout the five-year period.

Researchers are evaluating the safety and tolerability of single and multiple doses of PL54 injections in adults aged 18 to 55 years with phenylketonuria PKU. This Phase I, open-label, dose-escalation study aims to compare the safety profiles between single and multiple dosing regimens and assess pharmacokinetics, pharmacodynamics, and immunogenicity of the drug. The study consists of two phases Phase Ia involves a single subcutaneous injection of PL54 at increasing doses from 0.01 mgkg to 0.5 mgkg, followed by a 28-day observation period with several clinic visits. Phase Ib includes multiple weekly subcutaneous injections for four weeks at doses from 0.04 mgkg to 0.25 mgkg, with a 35-day follow-up after the last dose and scheduled assessments. Dose escalation depends on safety data and committee review. Participants will attend multiple clinic visits for drug administration and monitoring, including assessments of adverse events and blood phenylalanine levels. Researchers will record the severity and relationship of any side effects and measure changes in blood phenylalanine concentration from baseline. The total participation duration is approximately six weeks for Phase Ia and up to nine weeks for Phase Ib, with safety and laboratory assessments throughout.

The GENESIS clinical study aims to map HLA genetic variation in the Greek population and evaluate possible correlations with selected underlying diseases. It is a multicenter, prospective, non-interventional clinical study targeting 12,000 subjects over an anticipated duration of 36 months, with the goal of creating a pilot HLA map for medical research and possible clinical applications. Each subject will complete one visit at a participating site and provide demographic information, including date of birth, gender, race, ancestry, height, and weight, as well as information about smoking or vaping, alcohol consumption, arterial blood pressure, diagnosed diseases, and current treatments. Recent clinical laboratory results from up to 12 months before sample collection may also be collected when available, including blood count, metabolic, liver enzyme, and biochemical parameters. Two buccal swabs will be collected from each subject for DNA extraction and HLA genotyping analysis. Selected DNA samples will also undergo low-pass whole genome sequencing to further investigate associations between the HLA region and autoimmune diseases. After the analysis is completed, an individualized ancestry report will be securely available to study subjects if they elect to access it.

Researchers are evaluating the effects of Diaberine, a berberine-based nutraceutical, on blood sugar regulation and metabolism in adults with metabolism disorder. This randomized, triple-blind, placebo-controlled trial will study 80 participants aged 18 to 70 over 24 weeks to assess how well this dietary supplement may aid in these health areas. Participants will be randomly assigned to one of two groups. One group will take Diaberine capsules containing Vitamin B12, berberine, magnesium citrate, cinnamon bark extract, chromium, and other ingredients three times daily, 15 minutes before meals. The other group will take placebo capsules with similar appearance but without the active ingredients. Both treatments will continue for 24 weeks with regular monitoring. During the study, participants will have their blood sugar regulation and metabolism measured at baseline, week 12, and week 24. Additionally, quality of life and weight changes will be tracked at multiple points throughout the 24 weeks. Participants will be monitored through questionnaires, blood tests, and weight assessments to evaluate the supplements effects and tolerance over time.

This research aims to observe the effects of Palynziq pegvaliase treatment in pregnant women with phenylketonuria PKU and on their babies exposed to pegvaliase during pregnancy and breastfeeding. The study is a Phase 4 observational trial that evaluates maternal, fetal, and infant outcomes related to pegvaliase exposure. It includes women diagnosed with PKU who were treated with pegvaliase from two weeks before their last menstrual period LMP or at any time during pregnancy. Participants are pregnant women prescribed pegvaliase by their healthcare provider who enroll through a centralized call center. The study collects data retrospectively from at least three months before the LMP, through pregnancy, and during the infants first year of life. The timing and duration of pegvaliase exposure during pregnancy and breastfeeding, including each trimester, are recorded. Individual participation lasts up to about 21 months. During the study, information will be gathered from the participants healthcare providers and the infants doctors. Researchers will monitor pregnancy outcomes and infant development over ten years, focusing on pegvaliase exposure effects. The study also tracks serious adverse events and pegvaliase use during breastfeeding. This long-term monitoring aims to provide detailed data on maternal and infant health following pegvaliase exposure.

Researchers are conducting a 10-year multi-center, prospective, longitudinal study in the United States to observe immunologic, inflammatory, and laboratory changes in people with phenylketonuria PKU who are treated with Palynziq pegvaliase. The study includes both new users starting pegvaliase within 30 days after enrolling in a related study 165-501 and those who have already been receiving the treatment before enrollment. The goal is to understand long-term immune and inflammatory responses to this treatment. Participants must already be enrolled in the 165-501 study to join this study. They will provide blood samples before dosing every three months for the first three years, then every six months for the remaining study period. Additional blood samples may be taken during safety events as defined in the related 165-501 study protocol, and standard care blood draws are also incorporated. Blood tests will measure phenylalanine levels and various immune and inflammatory markers, which will be processed centrally. During the study, data from this observational study will be combined with data from the 165-501 study to reduce duplicate reporting and lessen the burden on study sites. Participants may withdraw from this study while continuing in the 165-501 study, but not vice versa, to ensure safety monitoring. The research team will evaluate immune and inflammatory responses over up to 10 years of treatment, tracking changes through blood tests and clinical data collection for a comprehensive understanding of long-term effects.

Researchers are evaluating the long-term safety of JNT-517 in children and adults with Phenylketonuria PKU, a condition caused by a deficiency in the PAH enzyme. This Phase 3, open-label study includes participants who completed previous JNT-517 studies as well as those new to JNT-517 treatment. The goal is to understand how the drug performs over an extended period when used consistently in this population. All participants will receive JNT-517 orally twice daily with doses adjusted for age and weight. The study will follow a fixed dosing schedule regardless of prior exposure to JNT-517. Participants will be monitored for treatment-emergent adverse events and changes in blood and urine phenylalanine levels, dietary intake, and attention-related symptoms among children previously treated. Participants will attend regular visits for safety assessments, blood tests, dietary evaluations, and symptom rating scales. Plasma drug concentrations will be measured at specific times in younger children to understand drug levels. The study tracks adverse events from screening through two weeks after the last dose. Total participation duration may last up to approximately five years, allowing long-term safety and efficacy monitoring.

Researchers are conducting a 10-year global, multi-center observational study to better understand the safety profile of pegvaliase, a treatment for Phenylketonuria PKU. The study focuses on monitoring hypersensitivity reactions, long-term safety, tolerability, and the effectiveness of risk minimization measures used in the European Union. Both new users starting pegvaliase within 30 days of enrollment and those who have already been receiving pegvaliase can participate. Participants in this study will not receive any experimental treatments or undergo special procedures as part of the trial. Instead, their usual pegvaliase treatment and clinical care will continue as normal. Information about their medical history, pegvaliase use, other medications, and safety concerns such as allergic reactions and injection site issues will be collected by their primary physicians. Safety events will be reviewed periodically by an independent committee. Participants are followed according to routine clinical practice, with clinical outcomes assessed regularly, typically monthly during initial treatment phases and every six months during maintenance. The study measures risks of specific safety events over up to 10 years of pegvaliase treatment in a real-world setting. There are no mandatory study visits, and all data collection is based on regular medical care visits.

Researchers are evaluating the safety, pharmacokinetics, pharmacodynamics, and effectiveness of an investigational drug called GNR-055 in patients with Mucopolysaccharidosis Type II MPS II, also known as Hunter syndrome. This condition is a genetic disorder caused by a deficiency of the enzyme iduronate-2-sulfatase ID2S, leading to harmful buildup of certain substances in cells that affects growth, organs, and the nervous system. The study is a phase 23, multicenter, open-label trial involving different age groups to better understand how GNR-055 works and its safety profile. GNR-055 is a modified enzyme replacement therapy designed to cross the blood-brain barrier, potentially preventing neurological damage and improving quality of life for patients with MPS II. Participants receive weekly intravenous infusions of GNR-055 at doses ranging from 1.0 to 3.0 mgkg, depending on their study group. The study includes multiple cohorts, with adult and pediatric patients receiving specific dosing regimens over the trial period. During the study, participants will undergo various assessments including monitoring of adverse events, urine and serum levels of glycosaminoglycans GAG, cerebrospinal fluid analysis, joint motion measurements, MRI scans of liver, spleen, and brain, heart and lung function tests, neurocognitive evaluations, and biomarker analysis. These evaluations occur at baseline and multiple follow-up visits up to week 56. The study aims to gather detailed data on the drugs impact on disease symptoms, safety, and biological markers to inform future treatment options.

Researchers are investigating how metabolism, body composition, and body surface area relate in both healthy individuals and those with metabolic conditions such as diabetes, obesity, renal disease, or cancer. The study aims to improve the accuracy of metabolic rate measurements, which have traditionally relied on simple formulas using height and weight, which may not work well for everyone. Participants will spend two days and one night in the hospital during each visit. They will provide medical history, answer questions about their activity, diet, and lifestyle, and consume a special diet. They will undergo various tests including breathing gas measurements while lying under a clear hood, body scanning on a padded table and with a 3D scanner, electrical signal speed testing through the body, hand strength measurement, and collection of blood and urine after drinking salty water. Participants may return up to eight times per year with at least two weeks between visits. During the study, participants will be evaluated through these tests and questionnaires to understand their resting energy expenditure and body measurements. The primary outcomes include comparing measured versus predicted body surface area and determining how measured body surface area relates to energy expenditure independent of body composition. The study will continue until July 2031, and participants health and ability to complete tests will be monitored throughout their involvement.