Hochheim

Researchers are evaluating LY3884961, a genetic therapy delivered as a single intravenous infusion, in adults with peripheral symptoms of Gaucher Disease. This Phase 12, open-label, multicenter study aims to assess the safety and tolerability of different dose levels of LY3884961. The study includes dose-finding cohorts followed by an expansion cohort to better understand the therapys effects in this patient group. Participants will receive one dose of LY3884961 and will be monitored closely for 18 months to evaluate safety, tolerability, immune response, biomarkers, and treatment effects. The study may include up to three dose levels tested in small groups of patients, with an additional group enrolled afterward. The total study duration for each patient is about five years, including a screening period of up to 60 days. During the trial, participants will have regular evaluations including laboratory tests, imaging, and clinical assessments to track treatment-emergent adverse events and changes in spleen volume, platelet count, and relevant biomarkers. Researchers will also monitor the use and discontinuation of enzyme replacement or substrate reduction therapies. Long-term safety and immune response will be followed for up to 42 months after the initial 18-month period.

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 evaluating the safety, tolerability, and effectiveness of N-acetyl-L-leucine IB1001 compared to standard care for patients aged 4 years and older diagnosed with Niemann-Pick disease type C NPC. This is a pivotal, randomized, double-blind, placebo-controlled, multi-center study designed to provide important information on this treatments impact on NPC symptoms. The study includes a crossover design where participants receive both the study drug and placebo during separate periods. Participants will take N-acetyl-L-leucine or a placebo orally as granules suspended in water, orange juice, or almond milk. Patients aged 13 and older will receive a total daily dose of 4 grams divided into three doses, while those under 13 will receive weight-based dosing. The study consists of a baseline period followed by two treatment periods of about 12 weeks each, where participants switch from one treatment to the other. After completing the parent study, some patients may join an open-label extension phase providing up to three years of treatment. During the trial, participants will undergo assessments at several points, including before and after each treatment period. These include scales measuring ataxia severity, functional ability, disability, clinical global impressions from physicians, caregivers, and patients, and quality of life questionnaires. Researchers will monitor adherence and safety throughout the study. The trial continues until December 2030, with careful evaluation of the primary outcomes after each treatment phase and ongoing follow-up for those in the extension phase.

Researchers are evaluating the efficacy and safety of tividenofusp alfa DNL310, an investigational enzyme-replacement therapy that can penetrate the central nervous system, compared with the standard enzyme replacement treatment idursulfase in children and young adults with mucopolysaccharidosis type II MPS II, which includes neuronopathic and non-neuronopathic forms. This Phase 23, double-blind, randomized, controlled study also allows some participants to enter an open-label treatment phase based on specific criteria. The study includes two main groups Cohort A with participants aged 2 to under 6 years who have neuronopathic MPS II, and Cohort B with participants aged 6 to under 26 years who have non-neuronopathic MPS II. Both tividenofusp alfa and idursulfase are given by repeated intravenous doses. Participants who meet certain criteria may continue treatment in an open-label phase with either DNL310 or idursulfase. Participants will be closely monitored through various assessments during the study, including measurements of cerebrospinal fluid heparan sulfate levels, adaptive behavior scales, developmental tests, walking distance tests, and imaging for liver and spleen volume. Caregiver impressions of change are also collected. The primary outcomes are assessed at 24 and 96 weeks, with additional secondary outcomes measured up to 48 or 96 weeks. The study is designed to last until December 2027, ensuring thorough evaluation of safety and treatment effects.

Researchers are conducting an 18-month Phase 3 study to evaluate the safety and effectiveness of oral nizubaglustat AZ-3102 in children and adolescents with late-infantile and juvenile forms of Niemann-Pick type C disease. This randomized, double-blind, placebo-controlled trial aims to show whether nizubaglustat improves ataxic symptoms compared with placebo. The study also assesses other neurological and behavioral effects, pharmacokinetics, pharmacodynamics, and safety of the treatment. Participants receive either daily oral dispersible tablets of nizubaglustat or matching placebo. The study follows a parallel design with random assignment to treatment groups. The treatment period lasts for 18 months, during which participants take the assigned medication once daily. The study monitors treatment effects and safety throughout this period. During the trial, participants undergo assessments including the Scale for the Assessment and Rating of Ataxia SARA, Vineland Adaptive Behavior Scale, Penetration-Aspiration Scale, 9-Hole Peg Test, and other neurological and functional tests at baseline and at months 6, 12, and 18. Blood samples are collected to study drug levels and biomarkers. Researchers also track seizure frequency and adverse events. The primary outcome measures focus on changes in total and functional SARA scores from baseline to month 18, with safety and tolerability evaluated throughout participation.

Researchers are conducting an 18-month Phase 3 study to evaluate the safety and efficacy of oral nizubaglustat AZ-3102 in children aged 4 years and older diagnosed with late-infantile or juvenile forms of Niemann-Pick type C disease, GM1 gangliosidosis, or GM2 gangliosidosis. This randomized, double-blind, placebo-controlled, multicenter trial uses a Master Protocol Research Program to study these related conditions in separate subprotocols based on disease type. Participants are randomly assigned in a 21 ratio to receive either oral nizubaglustat tablets or a matching placebo. The treatment and procedures are specific to each disease subprotocol, detailing different eligibility requirements, safety assessments, and efficacy endpoints. The study includes subprotocols for Niemann-Pick type C disease and for GM1 or GM2 gangliosidosis, each with tailored treatment plans and monitoring. Throughout the study, participants will undergo evaluations as described in their respective subprotocols, which may include clinical assessments, safety monitoring, and outcome measurements over the 18-month period. Researchers will track participant allocation to each subprotocol as the primary outcome. The trial is designed to monitor safety and treatment effects closely until the study completes in 2028, with detailed procedures provided within each disease-specific subprotocol.

Researchers are evaluating the safety, effectiveness, pharmacokinetics PK, pharmacodynamics PD, and immune response to the treatment combination of cipaglucosidase alfa and miglustat in children with infantile-onset Pompe disease IOPD. This Phase 3, open-label, multicenter study includes both children who have previously received enzyme replacement therapy ERT and those who have not. The study focuses on pediatric subjects from birth up to 18 years old who have this rare genetic condition characterized by heart muscle thickening and muscle weakness. The study has two groups one includes children aged 6 months to under 18 years who have experienced clinical decline despite prior ERT, and the other includes infants younger than 6 months who have not received ERT before. Participants will receive intravenous infusions of cipaglucosidase alfa, a biological treatment, along with oral capsules of miglustat. The study also has a long-term extension phase for participants who benefit from the primary 104-week treatment period without major safety concerns. During the study, children will be monitored for infusion-related reactions and other safety measures over 104 weeks. Evaluations include physical tests like the six-minute walk test for older children, genetic confirmation of IOPD, and assessments of heart and muscle function. Researchers will track immune responses, drug levels in the body, and overall health status. The study aims to gather detailed data on how the treatment affects disease progression and safety in this young population.

Researchers are studying the safety, pharmacodynamics, and initial clinical effects of S-606001 in adults with late-onset Pompe disease LOPD. This study focuses on adding S-606001 to the existing enzyme replacement therapy ERT to evaluate its impact over time. Participants are randomly assigned to receive either a low dose or high dose of S-606001, or a matching placebo, taken orally twice daily after meals for 52 weeks. The study is double-blind, meaning neither participants nor researchers know who receives which dose or placebo during the trial. Throughout the 52 weeks, participants will be evaluated using lung function tests, 6-minute walk tests, muscle strength assessments, and patient-reported questionnaires on fatigue, pain, and physical function. Safety monitoring includes tracking adverse events and blood tests. Changes from baseline in forced vital capacity %FVC at week 52 is the primary outcome measured.