Hochheim

Researchers are evaluating LY3884961, a genetic therapy using a non-replicating viral vector, in adults with peripheral symptoms of Gaucher Disease, a rare genetic disorder. This Phase 1/2 open-label study aims to find safe dose levels and assess the treatment's safety and tolerability over a long period. The study includes patients with confirmed GBA1 gene variants who have been on stable treatment for at least two years. Participants will receive a single intravenous dose of LY3884961. The study starts with three dose-finding groups, each including three patients, followed by an expansion group with up to six patients. After dosing, the first 18 months focus on monitoring safety, immune response, biomarkers, and signs of treatment effect. Then, participants will be followed for an additional 42 months to continue safety and efficacy evaluations. Each participant's involvement lasts about five years, including up to 60 days for screening before treatment. Throughout the study, researchers will conduct medical assessments, laboratory tests, and biomarker analyses. They will closely monitor for any adverse events and immune reactions. The main goal is to track the occurrence and severity of any side effects that develop during the entire five-year period.

Researchers are conducting a global, multicenter, prospective observational registry to study patients with Pompe disease, including those with late-onset Pompe disease (LOPD) and infantile-onset Pompe disease (IOPD). The study includes both patients who are untreated and those receiving approved Pompe disease therapies. The main goals are to assess the long-term safety and real-world effectiveness of these treatments, understand their impact on quality of life and patient-reported outcomes, and describe the natural history of untreated Pompe disease. Participants may be treated with various therapies including enzyme replacement therapies such as cipaglucosidase alfa delivered by intravenous infusion, alglucosidase alfa or avalglucosidase alfa once approved locally, and miglustat co-administered with ATB200. Patients not receiving any medical therapy for Pompe disease are also included. The study gathers data from both treated and untreated patients as they are managed in routine clinical practice. Throughout the study, participant data will be collected to monitor the frequency of adverse events and serious adverse events over a period of five years. Researchers will also evaluate treatment effectiveness, quality of life, and patient-reported outcomes during this time. This observational approach allows for long-term safety monitoring and understanding of Pompe disease progression in a real-world setting.

Researchers are conducting a pivotal Phase III multinational study to evaluate the safety, tolerability, and effectiveness of N-acetyl-L-leucine (IB1001) in patients aged 4 and older with a confirmed diagnosis of Niemann-Pick disease type C (NPC). This randomized, double-blind, placebo-controlled trial compares N-acetyl-L-leucine to standard care. An extension phase follows the initial study, allowing continued open-label treatment for up to 3 years for participants who complete the parent study or enroll directly into the extension. Participants undergo three study periods starting with a baseline assessment of about two weeks. They are then randomized to receive either N-acetyl-L-leucine or placebo for approximately 12 weeks during the first intervention period (Period I), followed by a crossover to the opposite treatment for another 12 weeks in Period II. N-acetyl-L-leucine is given orally as granules for suspension in a sachet, while placebo is a matching sachet. The extension phase provides ongoing open-label access to N-acetyl-L-leucine. Throughout the study, patients are assessed twice during each period using scales measuring ataxia symptoms. Researchers monitor safety, efficacy, and treatment adherence. Participants must maintain stable background therapies for NPC symptoms and attend scheduled visits. Outcome measures include comparisons of ataxia rating scales between study periods. The total participation time includes initial randomized treatment and the option for extended open-label treatment lasting up to three years.

Researchers are studying the safety and effectiveness of tividenofusp alfa (DNL310), a new enzyme-replacement therapy designed to enter the central nervous system, for children and young adults with mucopolysaccharidosis type II (MPS II), including both neuronopathic and non-neuronopathic forms. This Phase 2/3 trial compares tividenofusp alfa to the standard treatment idursulfase, aiming to better understand its impact on this rare genetic condition. Participants receive either tividenofusp alfa or idursulfase through intravenous infusions as repeated doses. The study has a double-blind, randomized design with two groups receiving these treatments. Based on specific criteria, participants may also have the opportunity to enter an open-label phase where they receive either DNL310 or idursulfase openly. During the study, researchers will measure changes in cerebrospinal fluid heparan sulfate levels after 24 weeks to assess biochemical effects. They will also evaluate behavioral and adaptive functioning using the Vineland Adaptive Behavior Scale over 96 weeks. The study includes careful monitoring for safety and treatment response, with participants ranging from 2 to less than 26 years old involved in the trial.

Researchers are evaluating the safety and effectiveness of oral nizubaglustat (AZ-3102) in treating children and young people with late-infantile and juvenile forms of GM1 or GM2 gangliosidosis, rare inherited metabolic disorders. This Phase 3 study is designed as a double-blind, randomized, placebo-controlled trial lasting 18 months. It aims primarily to show improvements in ataxic symptoms, with additional goals to assess other neurological effects, the drug's behavior in the body, and its safety and tolerability. Participants will receive either oral nizubaglustat or a placebo daily over the 18-month treatment period. The study is conducted at multiple centers and includes careful monitoring of the drug's levels in the body and its impact on disease manifestations. The design ensures that neither the participants nor the researchers know which treatment is being given until the study concludes. During the study, participants will undergo assessments to measure changes in ataxia scores from baseline to month 18, along with evaluations of other functional symptoms. Safety will be closely monitored throughout. The total duration of participation is 18 months, during which researchers will collect data on neurological function, drug effects, and any side effects experienced by participants.

This research aims to assess the safety and effectiveness of oral nizubaglustat (AZ-3102) in treating late-infantile and juvenile forms of Niemann-Pick type C disease. It is an 18-month, double-blind, randomized, placebo-controlled, multicenter Phase 3 study focused on improving ataxic symptoms compared to placebo. Additional goals include evaluating other neurological symptoms, pharmacokinetics, pharmacodynamics, and overall safety and tolerability of the treatment. Participants will receive either oral nizubaglustat or a matching placebo once daily for 18 months. The study compares these two groups to measure the impact on ataxic manifestations and other disease symptoms. Pharmacokinetic assessments occur after the first dose and at steady state during multiple dosing. Safety monitoring continues throughout the treatment period. During the study, participants will undergo various assessments including the Scale for the Assessment and Rating of Ataxia (SARA) to measure changes in ataxia severity from baseline to month 18. Additional evaluations include functional assessments, safety monitoring, and tolerability checks. Researchers will also collect data on drug effects and side effects to understand how the treatment influences the disease over time.

Researchers are conducting an 18-month, Phase 3, randomized, double-blind, placebo-controlled, multicenter study to assess 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, GM1 gangliosidosis, or GM2 gangliosidosis. The study uses a Master Protocol Research Program where participants are assigned to different subprotocols according to their specific disease type. Additional details about eligibility, safety, and efficacy assessments are provided in disease-specific subprotocols. Participants will receive either oral nizubaglustat tablets or a matching placebo following the assigned subprotocol regimen. The study includes separate subprotocols for Niemann-Pick type C disease and for GM1 or GM2 gangliosidosis, each with its own specific procedures and endpoints. The treatment period lasts for 18 months, during which safety and efficacy are evaluated. Participants will be monitored and assessed throughout the 18-month treatment period, with evaluations tailored to the specific subprotocol. Researchers will measure the number of participants assigned to each subprotocol and track safety and efficacy outcomes. For detailed procedures and endpoints, participants and caregivers are referred to the corresponding clinical trial records for each disease subtype.

Researchers are evaluating the safety, effectiveness, how the body processes the drugs, and immune response of cipaglucosidase alfa combined with miglustat in children with infantile-onset Pompe disease (IOPD). This study includes both children who have previously received enzyme replacement therapy (ERT) and those who have not. The study is a Phase 3, open-label, multicenter trial designed to gather detailed information on these treatments in pediatric subjects aged from birth up to 18 years. Participants will receive cipaglucosidase alfa as a sterile lyophilized powder through intravenous infusion and miglustat as oral capsules of 65 mg. The study groups are divided into two cohorts based on age and prior ERT experience: Cohort 1 includes children aged 6 months to under 18 years who have received ERT for at least 6 months, and Cohort 2 includes infants younger than 6 months who have not received ERT. There is also a long-term extension phase for participants who benefit from the initial 104-week treatment without significant safety concerns. Throughout the study, participants will be closely monitored for infusion-associated reactions over 104 weeks. Assessments include walking tests for older children, heart condition history, and genotype documentation. Safety, drug levels, and immune responses will be tracked, along with evaluations of motor function and overall health. The study aims to provide comprehensive data on the treatment's impact and safety in managing infantile-onset Pompe disease over a two-year period.

This research aims to assess the safety, pharmacodynamics, and preliminary clinical effects of S-606001 when added to enzyme replacement therapy (ERT) in adults with late-onset Pompe disease (LOPD). The study focuses on participants who have been receiving ERT and evaluates the impact of the experimental treatment on lung function, particularly forced vital capacity (FVC). Participants will be randomly assigned to receive either oral S-606001 or a matching oral placebo alongside their ongoing ERT. This phase 2, double-blind, placebo-controlled study is conducted across multiple centers to carefully monitor and compare the effects of the investigational drug added to standard care over time. During the study, participants will undergo assessments including measurements of forced vital capacity at baseline and at week 52 to evaluate lung function changes. Other evaluations include safety monitoring, pharmacodynamic assessments, and exploratory clinical efficacy measures. The entire study duration includes screening, treatment, and follow-up visits to ensure thorough observation of participants' health and response to the therapy.