Phenylketonuria (PKU)

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.

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 conducting a Phase 3 randomized study to evaluate the safety, effectiveness, tolerability, and how the body processes pharmacokinetics the oral drug JNT-517 in adults aged 18 years or older who have phenylketonuria PKU. The study aims to compare JNT-517 with a placebo to understand its impact on plasma phenylalanine levels and other health outcomes related to PKU. Participants will be randomly assigned to receive either JNT-517 or a placebo for the first six weeks, with about a 67% chance of receiving JNT-517. After this initial period, all participants continuing in the study will receive one of two doses of JNT-517 75 mg or 150 mg twice daily for an additional 46 weeks. The study includes a screening period of up to 35 days to ensure dietary stability and proper amino acid levels before treatment begins. During the study, participants will take the study medication twice daily for up to 365 days. They will attend clinic visits or receive visits from a mobile health nurse for checkups and tests. Participants will also collect urine samples at home on specific days and keep a food diary for three days before each visit. Researchers will measure changes in plasma phenylalanine levels, ADHD symptoms, dietary intake, and monitor for any treatment-emergent adverse events throughout the study.

Researchers are evaluating the safety, tolerability, and effectiveness of MZE782 tablets in adults aged 18 to 75 years who have Phenylketonuria PKU, a genetic condition affecting amino acid metabolism. This Phase 2 study aims to assess how well MZE782 works and how safe it is for people with PKU by comparing different doses of the drug to a placebo. The study is sponsored by Maze Therapeutics and uses a randomized, parallel design with multiple groups. Participants will receive either a low or high dose of MZE782 or a matching placebo tablet. The treatment period lasts up to 17 weeks, during which plasma phenylalanine Phe levels and drug concentrations will be regularly measured. Some study groups may have specific requirements regarding blood Phe levels or background treatments, including stopping certain PKU medications before starting the study drug. The study includes multiple cohorts receiving different doses or placebo, with evaluations at baseline and multiple weeks throughout treatment. During the trial, participants will have regular blood tests to measure Phe levels and monitor drug levels at several time points up to week 13. Researchers will track safety by recording any adverse events from the start through week 17. Participants must maintain a consistent diet and protein intake during the study. The total participation lasts several months, with close monitoring to assess both the impact of MZE782 on PKU and its safety profile.

Researchers are evaluating the long-term effects of sepiapterin on preserving neurocognitive function in children with phenylketonuria PKU, focusing on treatment started in early childhood. This Phase 3b open-label study aims to assess whether sepiapterin can maintain intelligence scores and quality of life over several years in young participants with PKU. The study has two parts an initial open-label sepiapterin-responsiveness test followed by a longer open-label treatment period. Participants will receive sepiapterin orally once daily, with doses adjusted by age and weight, for up to six years. The sepiapterin powder will be mixed with water or apple juice before administration. Throughout the study, children will undergo regular assessments including intelligence quotient IQ testing at baseline, 2 years, and 4 years, as well as quality of life questionnaires and blood phenylalanine level measurements up to six years. Researchers will monitor cognitive function, quality of life, and blood markers associated with PKU, with the study concluding in 2031.

Researchers are evaluating the safety and tolerability of AG-181 in adults with Phenylketonuria PKU, a genetic condition affecting the metabolism of phenylalanine. This Phase 1b study aims to understand how the drug behaves in the body, including how it is processed and its effects on phenylalanine levels. The study is open-label and involves participants with specific genetic mutations related to PKU and elevated phenylalanine levels. Participants will receive AG-181 tablets daily from Day 1 to Day 28. The study includes up to two cohorts, both receiving the investigational drug, with dosing and treatment occurring over the 28-day period. The study is non-randomized and open-label, focusing on evaluating safety, drug levels in the blood, and pharmacodynamics during this treatment phase. During the study, participants will undergo assessments to monitor adverse events and serious side effects up to Day 42. Blood samples will be taken up to Day 28 to measure drug concentration, peak levels, time to peak concentration, overall exposure, clearance, volume of distribution, and changes in phenylalanine levels. These evaluations help researchers understand the drugs safety profile and its impact on the metabolic condition over the treatment duration.