Phenylketonuria (PKU)

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 supplement's 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 infant's 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 participant's healthcare providers and the infant's 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, effectiveness, tolerability, and how the body processes (pharmacokinetics) an oral drug called JNT-517 in adults with phenylketonuria (PKU), a rare metabolic condition. This Phase 3 randomized study compares JNT-517 with a placebo, with participants unaware of which treatment they receive. The study is sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc., and includes a screening period to ensure participants have stable diet and amino acid levels. Participants will take either 75 mg or 150 mg of JNT-517, or a placebo, twice daily. The study has two parts: the first lasts about six weeks, where approximately two-thirds receive JNT-517 and one-third a placebo. After this, all participants continuing in the study receive one of two doses of JNT-517 for about 46 more weeks. Some study visits occur at the clinic, while others may be conducted by a mobile health nurse at home. During the study, participants will provide urine samples at home and bring them to the clinic on specific days. They will keep a food diary for three days before each visit to track dietary intake. Regular checkups, tests, and monitoring will be performed to assess changes in blood phenylalanine levels, cognitive and behavioral measures, dietary intake, and safety. Participation may last up to 400 days, including screening and treatment periods.

Researchers are evaluating the long-term effects of sepiapterin on maintaining brain function in children with Phenylketonuria (PKU) when treatment starts in early childhood. This Phase 3b open-label study aims to understand how sepiapterin impacts neurocognitive abilities over several years in young children with PKU, a condition affecting the body's processing of phenylalanine. The study has two parts: the first is an open-label test to see if participants respond to sepiapterin, and the second is a treatment phase where children receive daily oral doses of sepiapterin adjusted for their age and weight for up to six years. The medication is provided as a powder mixed with water or apple juice. Participants will be monitored regularly with intelligence tests at baseline, 2 years, and 4 years to observe changes in cognitive function. Quality of life and blood phenylalanine levels will also be assessed throughout the study, which may last up to six years. Safety and adherence will be tracked closely to evaluate the treatment’s impact over time.

Researchers are evaluating the safety and tolerability of AG-181, a drug being studied in people with Phenylketonuria (PKU), a genetic condition characterized by a specific mutation in the phenylalanine hydroxylase gene. This Phase 1b, open-label study is sponsored by Agios Pharmaceuticals, Inc. and aims to understand the drug's effects and behavior in the body in subjects aged 18 to 69 who have elevated phenylalanine levels. Participants will receive AG-181 tablets daily from Day 1 to Day 28 during the treatment period. The study includes two cohorts, both receiving the investigational drug without randomization or placebo control. The trial monitors various pharmacokinetic parameters, such as plasma concentration, peak concentration time, and drug clearance, alongside changes in phenylalanine levels. During the study, participants will be closely observed for any adverse events up to Day 42 to assess safety. Blood samples will be taken to measure drug levels and phenylalanine concentration, with dietary consistency maintained throughout the trial. The total participation time includes treatment and follow-up periods to ensure thorough monitoring of safety and drug effects.

Researchers are evaluating the safety and efficacy of NGGT002, a gene therapy using an adeno-associated viral vector carrying a functional copy of the human PAH gene, in adults with classic Phenylketonuria (PKU). This Phase 1/2, open-label, multiple-center study focuses on adults aged 18 to 55 with severe PAH deficiency and no residual enzyme activity. The aim is to assess the impact of NGGT002 in this population over a long-term period. Participants will receive a single intravenous infusion of NGGT002 at either a low or high dose. The study begins with a dose escalation phase where the first three subjects receive the low dose, followed by a decision to escalate or expand the cohort. If safety and efficacy are favorable, the study proceeds to a second part with the high dose in 3 to 6 subjects. The dosing is based on preclinical safety data to ensure the highest safe dose is selected. After receiving the gene therapy, participants will be followed for five years during which researchers will monitor safety by tracking adverse events, vital signs, ECGs, laboratory tests, and physical examinations. They will also measure changes in plasma phenylalanine levels and assess quality of life and protein intake. Participants are expected to record their diet and comply with study procedures. This long-term follow-up helps evaluate both the safety and the potential effects of NGGT002 over time.

This research investigates brain aging in adults with phenylketonuria (PKU), a rare metabolic disorder. It aims to understand how PKU and metabolic control affect cognitive and brain aging over time compared to healthy individuals. The study focuses on early- and mid-adulthood, using brain imaging and cognitive assessments to explore potential accelerated brain aging and its impact on brain health, cognition, and metabolic factors. Participants include adults with PKU who were early treated and healthy controls, with assessments at two time points separated by five years. Participants undergo brain scans using MRI, blood tests including phenylalanine levels, bone density measurements, and neuropsychological testing. The study evaluates biological brain age using advanced imaging analysis and machine learning models, comparing changes in brain structure and function over the follow-up period. During the study, participants will have fasting blood samples, DXA scans, MRI scans, and cognitive testing conducted both at baseline and after five years. Researchers will analyze brain aging trajectories, cognitive performance, metabolic control, and cardiometabolic risk factors. The study's findings aim to clarify how PKU influences brain health in adulthood and support future personalized treatment strategies. Total participation spans the baseline and a 5-year follow-up period with comprehensive evaluations at both times.